By Thomas S. Ciraulo, MS, CL
Board Certified Holistic Health Practitioner

Yakugaku Zasshi. 2007 Oct;127(10):1701-7.

Effect of Anwala churna (Emblica officinalis GAERTN.): an ayurvedic preparation on memory deficit rats.
Vasudevan M, Parle M.

    Department of Pharmacology, Nandha College of Pharmacy, Koorapalayam Pirivu, Pitchandampalayam, Erode-District, Tamilnadu-638052, India. vasumpharmacol@yahoo.co.uk

    The present study was aimed at investigating the effects of Anwala churna (Emblica officinalis GAERTN.), an Ayurvedic preparation, on memory in rats. Anwala churna was administered orally in three doses (50, 100 and 200 mg/kg) for 15 days to different groups of young and aged rats. The elevated plus-maze and Hebb-Williams maze served as exteroceptive behavioral models for testing memory. Diazepam-, scopolamine-, and ageing induced amnesia served as the interoceptive behavioral models. Anwala churna (50, 100, and 200 mg/kg, p.o.) produced a dose-dependent improvement in memory scores of young and aged rats. Furthermore, it reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Based on these results, Anwala churna may prove to be a useful remedy for the management of Alzheimer's disease due to its multifarious beneficial effects such as memory improvement and reversal of memory deficits.  PMID: 17917427 [PubMed - indexed for MEDLINE]

J Ethnopharmacol. 1996 Feb;50(2):61-8.

Hypolipidaemic effect of fruit juice of Emblica officinalis in cholesterol-fed rabbits.
Mathur R, Sharma A, Dixit VP, Varma M.

    Department of Home Science (Food and Nutrition), University of Rajasthan, Jaipur, India.

    The lipid lowering and antiatherosclerotic effects of Emblica officinalis (Amla) fresh juice were evaluated in cholesterol-fed rabbits (rendered hyperlipidaemic by atherogenic diet and cholesterol feeding). E. officinalis fresh juice was administered at a dose of 5 ml/kg body weight per rabbit per day for 60 days. Serum cholesterol, TG, phospholipid and LDL levels were lowered by 82%, 66%, 77% and 90%, respectively. Similarly, the tissue lipid levels showed a significant reduction following E. officinalis juice administration. Aortic plaques were regressed. E. officinalis juice treated rabbits excreted more cholesterol and phospholipids, suggesting that the mode of absorption was affected. E. officinalis juice is an effective hypolipidaemic agent and can be used as a pharmaceutical tool in hyperlipidaemic subjects.     PMID: 8866725 [PubMed - indexed for MEDLINE]

J Nutr Sci Vitaminol (Tokyo). 2005 Dec;51(6):413-8.

Influence of amla (Emblica officinalis Gaertn.) on hypercholesterolemia and lipid peroxidation in cholesterol-fed rats.
Kim HJ, Yokozawa T, Kim HY, Tohda C, Rao TP, Juneja LR.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

    The effects of amla on low-density lipoprotein (LDL) oxidation and cholesterol levels were investigated in vitro and in vivo using Cu(2+)-induced LDL oxidation and cholesterol-fed rats. SunAmla and ethyl acetate (EtOAc) extract of amla significantly inhibited thiobarbituric acid (TBA)-reactive substance level in the Cu(2+)-induced LDL oxidation and the effects were stronger than those of probucol. In addition, the administration of SunAmla (at a dose of 20 or 40 mg/kg body weight/d) or EtOAc extract of amla (at a dose of 10 or 20 mg/kg body weight/d) for 20 d to rats fed 1% cholesterol diet significantly reduced total, free and LDL-cholesterol levels in a dose-dependent manner, and EtOAc extract of amla exhibited more potent serum cholesterol-lowering effect than SunAmla in the same amount. Furthermore, the oxidized LDL level in serum was markedly elevated in cholesterol-fed control rats as compared with normal rats, while it was significantly decreased by the administration of SunAmla or EtOAc extract of amla. Moreover, the serum TBA-reactive substance level was also significantly decreased after oral administration of SunAmla or EtOAc extract of amla. These results suggest that amla may be effective for hypercholesterolemia and prevention of atherosclerosis. PMID: 16521700 [PubMed - indexed for MEDLINE]

J Med Food. 2005 Fall;8(3):362-8.

Amla (Emblica officinalis Gaertn.) extracts reduce oxidative stress in streptozotocin-induced diabetic rats.
Rao TP, Sakaguchi N, Juneja LR, Wada E, Yokozawa T.

Bio-nutrition Division, Taiyo Kagaku Co. Ltd., Yokkaichi, Mie, Japan. tprao@taiyokagaku.co.jp

    The antioxidant properties of amla extracts and their effects on the oxidative stress in streptozotocin-induced diabetes were examined in rats. Amla in the form of either the commercial enzymatic extract SunAmla (Taiyo Kagaku Co. Ltd., Yokkaichi, Japan) (20 or 40 mg/kg of body weight/day) or a polyphenol-rich fraction of ethyl acetate extract (10 or 20 mg/kg of body weight/day) was given orally for 20 days to the streptozotocin-induced diabetic rats. Amla extracts showed strong free radical scavenging activity. Amla also showed strong inhibition of the production of advanced glycosylated end products. The oral administration of amla extracts to the diabetic rats slightly improved body weight gain and also significantly alleviated various oxidative stress indices of the serum of the diabetic rats. The elevated serum levels of 5-hydroxymethylfurfural, which is a glycosylated protein that is an indicator of oxidative stress, were significantly reduced dose-dependently in the diabetic rats fed amla. Similarly, the serum level of creatinine, yet another oxidative stress parameter, was also reduced. Furthermore, thiobarbituric acid-reactive substances levels were significantly reduced with amla, indicating a reduction in lipid peroxidation. In addition, the decreased albumin levels in the diabetic rats were significantly improved with amla. Amla also significantly improved the serum adiponectin levels. These results form the scientific basis supporting the efficacy of amla for relieving the oxidative stress and improving glucose metabolism in diabetes.  PMID: 16176148 PubMed - indexed for MEDLINE]

J Agric Food Chem. 2007 Sep 19;55(19):7744-52. Epub 2007 Aug 23.

Amla (Emblica officinalis Gaertn.) attenuates age-related renal dysfunction by oxidative stress.
Yokozawa T, Kim HY, Kim HJ, Tanaka T, Sugino H, Okubo T, Chu DC, Juneja LR.

Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. yokozawa@inm.u-toyama.ac.jp

    To investigate the effects of amla on renal dysfunction involved in oxidative stress during the aging process, we employed young (2 months old) and aged (13 months old) male rats and administered SunAmla (Taiyo Kagaku Co., Ltd., Japan) or an ethyl acetate (EtOAc) extract of amla, a polyphenol-rich fraction, at a dose of 40 or 10 mg/kg body weight/day for 100 days. The administration of SunAmla or EtOAc extract of amla reduced the elevated levels of serum creatinine and urea nitrogen in the aged rats. In addition, the tail arterial blood pressure was markedly elevated in aged control rats as compared with young rats, while the systolic blood pressure was significantly decreased by the administration of SunAmla or EtOAc extract of amla. Furthermore, the oral administration of SunAmla or EtOAc extract of amla significantly reduced thiobarbituric acid-reactive substance levels of serum, renal homogenate, and mitochondria in aged rats, suggesting that amla would ameliorate oxidative stress under aging. The increases of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression in the aorta of aging rats were also significantly suppressed by SunAmla extract or EtOAc extract of amla, respectively. Moreover, the elevated expression level of bax, a proapoptotic protein, was significantly decreased after oral administration of SunAmla or EtOAc extract of amla. However, the level of bcl-2, an antiapoptotic protein, did not show any difference among the groups. The expressions of renal nuclear factor-kappaB (NF-kappaB), inhibitory kappaB in cytoplasm, iNOS, and COX-2 protein levels were also increased with aging. However, SunAmla or EtOAc extract of amla reduced the iNOS and COX-2 expression levels by inhibiting NF-kappaB activation in the aged rats. These results indicate that amla would be a very useful antioxidant for the prevention of age-related renal disease.  PMID: 17715896 [PubMed - indexed for MEDLINE]

Physiol Behav. 2007 May 16;91(1):46-54. Epub 2007 Feb 8.

Memory enhancing activity of Anwala churna (Emblica officinalis Gaertn.): an Ayurvedic preparation.
Vasudevan M, Parle M.

Pharmacology Division, Department of Pharmaceutical Sciences, Post Box - 38, Guru Jambheshwar University of Science and Technology, Hisar, (Haryana) -125 001, India.

    Ayurveda means "the science of life". Ayur means "life" and Veda means "knowledge or science". It is the oldest medical system in the world. Its origins can be traced as far back as 4500 BC, to four ancient books of knowledge, (the "Vedas") and it is still officially recognized by the government of India. The present study was aimed at investigating the effects of Anwala churna (Emblica officinalis Gaertn.), an Ayurvedic preparation on memory, total serum cholesterol levels and brain cholinesterase activity in mice. Anwala churna was administered orally in three doses (50, 100 and 200 mg/kg) for fifteen days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. Total serum cholesterol levels and brain cholinesterase activity also estimated. Anwala churna (50, 100 and 200 mg/kg, p.o.) produced a dose-dependent improvement in memory scores of young and aged mice. Furthermore, it reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, brain cholinesterase activity and total cholesterol levels were reduced by Anwala churna administered orally for 15 days. Anwala churna may prove to be a useful remedy for the management of Alzheimer's disease on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.  PMID: 17343883 [PubMed - indexed for MEDLINE]

Phytomedicine. 2002 Mar;9(2):171-4.

Effect of bioactive tannoid principles of Emblica officinalis on ischemia-reperfusion-induced oxidative stress in rat heart.
Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S.

    The tannoid principles of the fruits of Emblica officinalis have been reported to exhibit antioxidant activity in vitro and in vivo. In the present study, an emblicanin-A (37%) and -B (33%) enriched fraction of fresh juice of Emblica fruits (EOT) was investigated for antioxidant activity against ischemia-reperfusion (IRI)-induced oxidative stress in rat heart. Vitamin E (VE) was used as the standard antioxidant agent. IRI was induced in isolated rat heart by perfusing it with modified Kreb-Hensleitt's solution for 5 min, followed by a period of ischemia (stoppage of perfusion) for 10 min and then restoring the perfusion (reperfusion) for 15 min. IRI induced a significant decrease in the activities of cardiac superoxide dismutase, catalase and glutathione peroxidase, with a concomitant increase in lipid peroxidation. These IRI-induced effects were prevented by the administration of EOT (50 and 100 mg/kg body wt.) and VE (200 mg/kg body wt.) given orally twice daily for 14 days prior to the sacrifice of the animals and initiation of the perfusion experiments. The study confirms the antioxidant effect of E. officinalis and indicates that the fruits of the plant may have a cardioprotective effect.  PMID: 11995952 [PubMed - indexed for MEDLINE]

Skin Pharmacol Appl Skin Physiol. 2002 Sep-Oct;15(5):374-80.

Emblica cascading antioxidant: a novel natural skin care ingredient.
Chaudhuri RK.

    Rona/EM Industries, Inc., Hawthorne, NY 10532, USA. rchaudhuri@emindustries.com

    A standardized extract of Phyllanthus emblica (trade named Emblica) was found to have a long-lasting and broad-spectrum antioxidant activity. The product has no pro-oxidation activity induced by iron and/or copper because of its iron and copper chelating ability. Emblica helps protect the skin from the damaging effects of free radicals, non-radicals and transition metal-induced oxidative stress. Emblica is suitable for use in anti-aging, sunscreen and general purpose skin care products. Copyright 2002 S. Karger AG, Basel  PMID: 12239434 [PubMed - indexed for MEDLINE]

J Ethnopharmacol. 1998 Sep;62(2):183-93.

Screening of some Indian medicinal plants for their antimicrobial properties.
Ahmad I, Mehmood Z, Mohammad F.

    Department of Agricultural Microbiology, Institute of Agriculture, Aligarh Muslim University, India.

    A total of 82 Indian medicinal plants traditionally used in medicines were subjected to preliminary antibacterial screening against several pathogenic and opportunistic microorganisms. Aqueous, hexane and alcoholic extracts of each plant were tested for their antibacterial activity using agar well diffusion method at sample concentration of 200 mg/ml. The results indicated that out of 82 plants, 56 exhibited antibacterial activity against one or more test pathogens. Interestingly, extracts of five plants showed strong and broad spectrum activity as compared to rest of 51 plant extracts which demonstrated moderate activity. On the whole the alcoholic extracts showed greater activity than their corresponding aqueous and hexane extracts. Among various extracts, only alcoholic extracts of Emblica officinalis, Terminalia chebula, Terminalia belerica, Plumbago zeylanica and Holarrhena antidysenterica were found to show potentially interesting activity against test bacteria. These active crude alcoholic extracts were also assayed for cellular toxicity to fresh sheep erythrocytes and found to have no cellular toxicity. PMID: 9741890 [PubMed - indexed for MEDLINE]

Mol Vis. 2004 Mar 12;10:148-54.

Inhibition of aldose reductase by tannoid principles of Emblica officinalis: implications for the prevention of sugar cataract.
Suryanarayana P, Kumar PA, Saraswat M, Petrash JM, Reddy GB.

Biochemistry Division, National Institute of Nutrition, Hyderabad, India.

    PURPOSE: Aldose reductase (AR) has been a drug target because of its involvement in the development of secondary complications of diabetes including cataract. Although numerous synthetic AR inhibitors (ARI) have been tested and shown to inhibit the enzyme, clinically synthetic ARIs have not been very successful. Therefore, evaluating natural sources for ARI potential may lead to the development of safer and more effective agents against diabetic complications. In the present study we have assessed the inhibition of AR by constituents of Emblica officinalis both in vitro and in lens organ culture. METHODS: E. officinalis is widely used against many chronic ailments including diabetes. Aqeous extract of E. officinalis and its major constituent tannoids were tested for inhibition against both rat lens and purified recombinant human AR. ARI potential of isolated tannoids of E. officinalis were also investigated against osmotic stress in rat lens organ culture. RESULTS: E. officinalis extract inhibited rat lens and recombinant human AR with IC50 values 0.72 and 0.88 mg/ml respectively. Since E. officinalis is a rich source of ascorbic acid, we investigated whether ascorbic acid was responsible for AR inhibition by E. officinalis extract. However, ascorbic acid did not inhibit AR even at 5 mM concentration. Further, we demonstrate that the hydrolysable tannoids of E. officinalis were responsible for AR inhibition, as enriched tannoids of E. officinalis exhibited remarkable inhibition against both rat lens and human AR with IC50 of 6 and 10 microg/ml respectively. The inhibition of AR by E. officinalis tannoids is 100 times higher than its aqueous extract and comparable to or better than quercetin. Furthermore, the isolated tannoids not only prevented the AR activation in rat lens organ culture but also sugar-induced osmotic changes. CONCLUSIONS: These results indicate that tannoids of E. officinalis are potent inhibitors of AR and suggest that exploring the therapeutic value of natural ingredients that people can incorporate into everyday life may be an effective approach in the management of diabetic complications.  PMID: 15031705 [PubMed - indexed for MEDLINE]

Mol Vis. 2007 Jul 24;13:1291-7.

Emblica officinalis and its enriched tannoids delay streptozotocin-induced diabetic cataract in rats.
Suryanarayana P, Saraswat M, Petrash JM, Reddy GB.

Biochemistry Division, National Institute of Nutrition, Hyderabad, India.

    PURPOSE: Aldose reductase (AR) has been a drug target because of its involvement in the development of secondary complications of diabetes including cataract. We have previously reported that the aqueous extract of Emblica officinalis and its constituent tannoids inhibit AR in vitro and prevent hyperglycemia-induced lens opacification in organ culture. The purpose of the current study was to investigate the effect of Emblica and its enriched tannoids on streptozotocin (STZ)-induced diabetic cataract in rats. METHODS: Diabetes was induced in Wistar-NIN rats by STZ (35 mg/kg body weight, intraperitoneally) and the animals were divided into three groups (Group II, III, and IV). The control rats (Group I) received only vehicle. While Group I and Group II animals received AIN-93 diet, rats in Groups III and IV received 0.2% of standardized mixture of Emblica tannoids and 2% of Emblica pericarp, respectively, in an AIN-93 diet for a period of eight weeks. Cataract progression due to hyperglycemia was monitored by slit-lamp biomicroscope and classified into four stages. At the end of the eight weeks, the animals were sacrificed and markers of the polyol pathway, oxidative stress, and alterations in protein content and crystallin profile in the lens were measured. Blood glucose and insulin levels were also determined. RESULTS: Both Emblica and its tannoids did not prevent STZ-induced hyperglycemia as assessed by blood glucose and insulin levels. However, slit lamp microscope observations indicated that these supplements delayed cataract progression. The present studies suggest that Emblica and its tannoids supplementation inhibited AR activity as well as sorbitol formation in the lens. The results also point out that Emblica and its tannoids might counter the polyol pathway-induced oxidative stress as there was a reversal of changes with respect to lipid peroxidation, protein carbonyl content, and activities of antioxidant enzymes. Emblica also prevented aggregation and insolubilization of lens proteins caused by hyperglycemia. CONCLUSIONS: The results provide evidence that Emblica and an enriched fraction of Emblica tannoids are effective in delaying development of diabetic cataract in rats.  PMID: 17679931 [PubMed - indexed for MEDLINE]

Biomed Pharmacother. 2003 Sep;57(7):296-300.
Immunomodulatory effects of agents of plant origin.
Ganju L, Karan D, Chanda S, Srivastava KK, Sawhney RC, Selvamurthy W.

Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi 110054, India. lganju@rediffmail.com

    The immunomodulatory properties of amla (Emblica officinalis) and shankhpushpi (Evolvulus alsinoides) were evaluated in adjuvant induced arthritic (AIA) rat model. Injecting Complete Freund's Adjuvant (CFA) in right hind paw of the animals induced inflammation. The crude extracts of both the herbs were administered intraperitonially following a repeated treatment profile. The anti-inflammatory response of both the extracts was determined by lymphocyte proliferation activity and histopathological severity of synovial hyperplasia. Both the extracts showed a marked reduction in inflammation and edema. At cellular level immunosuppression occurred during the early phase of the disease. There was mild synovial hyperplasia and infiltration of few mononuclear cells in amla or shankhpushpi treated animals. The induction of nitric oxide synthase (NOS) was significantly decreased in treated animals as compared to controls. These observations suggest that both the herbal extracts caused immunosuppression in AIA rats, indicating that they may provide an alternative approach to the treatment of arthritis.  PMID: 14499177 [PubMed - indexed for MEDLINE]


J Ethnopharmacol. 2002 Jun;81(1):5-10.

Cyto-protective and immunomodulating properties of Amla (Emblica officinalis) on lymphocytes: an in-vitro study.
Sai Ram M, Neetu D, Yogesh B, Anju B, Dipti P, Pauline T, Sharma SK, Sarada SK, Ilavazhagan G, Kumar D, Selvamurthy W.

Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, New Delhi 110054, India. sairam64@rediffmail.com

    The fruits extracts of Emblica officinalis (Amla) has been reported to have strong anti-oxidant properties. There is a paucity of studies on the immunomodulatory properties of fruit extracts of Amla in immuno-compromised states, with the emphasis on lymphocytes. Therefore, the aim of the study was to determine the anti-oxidant and immunomodulatory properties of Amla using chromium (VI) as an immunosuppressive agent. Chromium (Cr) treatment results in enhanced cytotoxicity, free radical production, lipid peroxidation and decreased glutathione peroxidase (GPx) activity and diminished glutathione (GSH) levels. There was a significant inhibition of both lipopolysaccharide and concanavalin-A-stimulated lymphocyte proliferation. Chromium also inhibited Con A stimulated interleukin-2 and gamma-interferon production significantly. Further, there was enhanced apoptosis and DNA fragmentation in the presence of Cr. Amla significantly inhibited Cr-induced free radical production and restored the anti-oxidant status back to control level. Amla also inhibited apoptosis and DNA fragmentation induced by Cr. Interestingly, Amla relieved the immunosuppressive effects of Cr on lymphocyte proliferation and even restored the IL-2 and gamma-IFN production considerably. PMID: 12020921 [PubMed - indexed for MEDLINE]

J Ethnopharmacol. 2004 Nov;95(1):83-5.

Evaluation of anti-pyretic and analgesic activity of Emblica officinalis Gaertn.
Perianayagam JB, Sharma SK, Joseph A, Christina AJ.

Pharmacognosy and Phytochemistry Division, Faculty of Pharmaceutical Sciences, Guru Jambheshwar University, Hisar-125001, India.

    The present study was designed to investigate the anti-pyretic and analgesic activity of ethanol (EEO) and aqueous (AEO) extracts of Emblica officinalis fruits in several experimental models. A single oral dose of EEO and AEO (500 mg/kg, i.p.) showed significant reduction in brewer's yeast induced hyperthermia in rats. EEO and AEO also elicited pronounced inhibitory effect on acetic acid-induced writhing response in mice in the analgesic test. Both, EEO and AEO did not show any significant analgesic activity in the tail-immersion test. These findings suggest that extracts of Emblica officinalis fruits possessed potent anti-pyretic and analgesic activity. Preliminary phytochemical screening of the extracts showed the presence of alkaloids, tannins, phenolic compounds, carbohydrates and amino acids, which may be responsible for anti-pyretic and analgesic activities. PMID: 15374611 [PubMed - indexed for MEDLINE]

J Trace Elem Med Biol. 2006;20(4):233-9. Epub 2006 Oct 2.

    Chemomodulatory effects of Terminalia chebula against nickel chloride induced oxidative stress and tumor promotion response in male Wistar rats.
    Prasad L, Husain Khan T, Jahangir T, Sultana S.

    Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.

    Nickel, a major environmental pollutant is a known potent nephrotoxic agent. In this communication we report the chemopreventive effect of Terminalia chebula on nickel chloride (NiCl(2)) induced renal oxidative stress, toxicity and cell proliferation response in male Wistar rats. Administration of NiCl(2) (250micromoL Ni/kg body weight) to male Wistar rats resulted in an increase in the reduced renal glutathione content (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO), H(2)O(2) generation, blood urea nitrogen (BUN) and serum creatinine with a concomitant decrease in the activity of glutathione peroxidase (p<0.001). Nickel chloride (NiCl(2)) treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [(3)H] incorporation into renal DNA (p<0.001). Prophylactic treatment of rats with T. chebula (25mg/kg body weight and 50mg/kg body weight) daily for one week resulted in the diminution of NiCl(2) mediated damage as evident from the down regulation of glutathione content, GST, GR, LPO, H(2)O(2) generation, BUN, serum creatinine, DNA synthesis (p<0.001) and ODC activity (p<0.01) with concomitant restoration of GPx activity. Thus, the present investigation suggests that T. chebula extract could be used as therapeutic agent for cancer prevention as evident from this study where it blocks or suppresses the events associated with chemical carcinogenesis.  PMID: 17098582 [PubMed - indexed for MEDLINE]

Biol Pharm Bull. 2003 Sep;26(9):1331-5.

    Antioxidant and free radical scavenging activities of Terminalia chebula.
    Cheng HY, Lin TC, Yu KH, Yang CM, Lin CC.

    Graduate Institute of Pharmaceutical Science, Kaohsiung Medical University, Taiwan.

    Free radicals react with biological molecules and destroy the structure of cells, which eventually causes free-radical induced disease such as cancer, renal failure, aging, etc. In this study, 6 extracts and 4 pure compounds of Terminalia chebula RETZ. were investigated for anti-lipid peroxidation, anti-superoxide radical formation and free radical scavenging activities. The superoxide radical scavenging of the 4 pure compounds was further evaluated using electron spin resonance (ESR) spectrometry. The results showed that all tested extracts and pure compounds of T. chebula exhibited antioxidant activity at different magnitudes of potency. The antioxidant activity of each pure compound was derived from different pathways and was suggested to be specific.  PMID: 12951481 [PubMed - indexed for MEDLINE]

Biol Pharm Bull. 2005 Sep;28(9):1639-44.

    Antioxidant effects of aqueous extract of Terminalia chebula in vivo and in vitro.
    Lee HS, Won NH, Kim KH, Lee H, Jun W, Lee KW.

    Department of Food Science, College of Life & Environmental Sciences, Korea University, Seoul, Korea.

    The ripe fruit of Terminalia chebula RETZIUS (T. chebula RETZ) (Combretsceae), which is a native plant in India and Southeast Asia, has traditionally been used as a popular folk medicine for homeostatic, antitussive, laxative, diuretic, and cardiotonic treatments. The objective of this study was to evaluate the protective effects of an aqueous extract of fruit of T. chebula on the tert-butyl hydroperoxide (t-BHP)-induced oxidative injury observed in cultured rat primary hepatocytes and rat liver. Both treatment and pretreatment of the hepatocytes with the T. chebula extract (TCE) significantly reversed the t-BHP-induced cell cytotoxicity and lactate dehydrogenase leakage. In addition, TCE exhibited in vitro ferric-reducing antioxidant activity and 2,2-diphenyl-1-picryhydrazyl free radical-scavenging activities. The in vivo study showed that pretreatment with TCE (500 or 1000 mg/kg) by gavage for 5 d before a single dose of t-BHP (0.1 mmol/kg i.p.) significantly lowered the serum levels of the hepatic enzyme markers aspartate aminotransferase and alanine aminotransferase and reduced the indicators of oxidative stress in the liver, such as the glutathine disulfide content and lipid peroxidation, in a dose-dependent manner. Histopathologic examination of the rat livers showed that TCE reduced the incidence of liver lesions, including hepatocyte swelling and neutrophilic infiltration, and repaired necrosis induced by t-BHP. Based on the results described above, we speculate that TCE has the potential to play a role in the hepatic prevention of oxidative damage in living systems.   PMID: 16141531 [PubMed - indexed for MEDLINE]

J Ethnopharmacol. 2002 Aug;81(3):327-36.

    Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit.
    Saleem A, Husheem M, Härkönen P, Pihlaja K.

    Department of Chemistry, University of Turku, Kiinamyllynkatu 10, FIN-20014 Turku, Finland. amsale@utu.fi

    A 70% methanol extract of Terminalia chebula fruit, was studied for its effects on growth in several malignant cell lines including a human (MCF-7) and mouse (S115) breast cancer cell line, a human osteosarcoma cell line (HOS-1), a human prostate cancer cell line (PC-3) and a non-tumorigenic, immortalized human prostate cell line (PNT1A) using assays for proliferation ([(3)H]-thymidine incorporation and coulter counting), cell viability (ATP determination) and cell death (flow cytometry and Hoechst DNA staining). In all cell lines studied, the extract decreased cell viability, inhibited cell proliferation, and induced cell death in a dose dependent manner. Flow cytometry and other analyses showed that some apoptosis was induced by the extract at lower concentrations, but at higher concentrations, necrosis was the major mechanism of cell death. ATP assay guided chromatographic fractionation of the extract yielded ellagic acid, 2,4-chebulyl-beta-D-glucopyranose (a new natural product), and chebulinic acid which were tested by ATP assay on HOS-1 cell line in comparison to three known antigrowth phenolics of Terminalia, gallic acid, ethyl gallate, luteolin, and tannic acid. Chebulinic acid (IC(50) = 53.2 microM +/- 0.16) > tannic acid (IC(50) = 59.0 microg/ml +/- 0.19) > and ellagic acid (IC(50) = 78.5 microM +/- 0.24), were the most growth inhibitory phenolics of T. chebula fruit in our study.  PMID: 12127233 [PubMed - indexed for MEDLINE]

Indian J Exp Biol. 2004 Feb;42(2):174-8.

    Protective effect of Terminalia chebula against experimental myocardial injury induced by isoproterenol.
    Suchalatha S, Shyamala Devi CS.

    Department of Biochemistry and Molecular Biology, University of Madras, Guindy Campus, Chennai 600 025, India.

    Cardioprotective effect of ethanolic extract of Terminalia chebula fruits (500 mg/kg body wt) was examined in isoproterenol (200 mg/kg body wt) induced myocardial damage in rats. In isoproterenol administered rats, the level of lipid peroxides increased significantly in the serum and heart. A significant decrease was observed in the activity of the myocardial marker enzymes with a concomitant increase in their activity in serum. Histopathological examination was carried out to confirm the myocardial necrosis. T. chebula extract pretreatment was found to ameliorate the effect of isoproterenol on lipid peroxide formation and retained the activities of the diagnostic marker enzymes.  PMID: 15282950 [PubMed - indexed for MEDLINE]

Phytother Res. 2007 May;21(5):476-80.

    Evaluation of the growth inhibitory activities of Triphala against common bacterial isolates from HIV infected patients.
    Srikumar R, Parthasarathy NJ, Shankar EM, Manikandan S, Vijayakumar R, Thangaraj R, Vijayananth K, Sheeladevi R, Rao UA.

    Department of Physiology, Faculty of Medicine, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamilnadu, India 600 113.

    The isolation of microbial agents less susceptible to regular antibiotics and the rising trend in the recovery rates of resistant bacteria highlights the need for newer alternative principles. Triphala has been used in traditional medicine practice against certain diseases such as jaundice, fever, cough, eye diseases etc. In the present study phytochemical (phenolic, flavonoid and carotenoid) and antibacterial activities of aqueous and ethanol extracts of Triphala and its individual components (Terminalia chebula, Terminalia belerica and Emblica officinalis) were tested against certain bacterial isolates (Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella sonnei, S. flexneri, Staphylococcus aureus, Vibrio cholerae, Salmonella paratyphi-B, Escherichia coli, Enterococcus faecalis, Salmonella typhi) obtained from HIV infected patients using Kirby-Bauer's disk diffusion and minimum inhibitory concentration (MIC) methods. T. chebula was found to possess high phytochemical content followed by T. belerica and E. officinalis in both aqueous and ethanol extracts. Further, most of the bacterial isolates were inhibited by the ethanol and aqueous extracts of T. chebula followed by T. belerica and E. officinalis by both disk diffusion and MIC methods. The present study revealed that both individual and combined aqueous and ethanol extracts of Triphala have antibacterial activity against the bacterial isolates tested. Copyright 2007 John Wiley & Sons, Ltd.    PMID: 17273983 [PubMed - indexed for MEDLINE]

Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis.
Funk JL, Oyarzo JN, Frye JB, Chen G, Lantz RC, Jolad SD, Sólyom AM, Timmermann BN.

Arizona Center for Phytomedicine Research, Department of Medicine, Department of Cell Biology and Anatomy, University of Arizona, Tucson, 85724, USA. jfunk@u.arizona.edu

Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of this traditional usage, dietary supplements containing turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding antiarthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well-characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW)-induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.  PMID: 16562833 [PubMed - indexed for MEDLINE]

Mol Carcinog. 2006 May;45(5):320-32.

Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis.
Divya CS, Pillai MR.

Department of Molecular Medicine, Regional Cancer Centre, Thiruvananthapuram, Kerala, India.

Curcumin (diferuloyl methane), the major yellow pigment from the rhizomes of turmeric (Curcuma longa Linn), has anticancer properties. Infection with high-risk human papillomaviruses (HPV) leads to development of cervical carcinoma, predominantly through the action of viral oncoproteins E6 and E7.The present study aims at analyzing the antitumor and antiviral properties of curcumin, on HPV associated cervical cancer cells. Our findings indicate curcumin to be cytotoxic to cervical cancer cells in a concentration-dependent and time-dependent manner. The cytotoxic activity was selectively more in HPV16 and HPV18 infected cells compared to non-HPV infected cells. Balance between tumor cell proliferation and spontaneous cell death via apoptosis had an important role in regulation of tumor cell growth. Curcumin-induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. Curcumin also selectively inhibited expression of viral oncogenes E6 and E7, evident from RT-PCR and Western blotting data. Electrophoretic mobility shift assay revealed that activation of NFkappaB-induced by TNFalpha is down regulated by curcumin. Curcumin blocked IkBalpha phosphorylation and degradation, leading to abrogation of NFkappaB activation. Curcumin also down regulated the expression of COX-2, a gene regulated by NFkappaB. Binding of AP-1, an indispensable component for efficient epithelial tissue-specific gene expression of HPV was also selectively down regulated by curcumin. These results provide attractive data for the possible use of curcumin in the management of HPV associated tumors. (c) 2006 Wiley-Liss, Inc. PMID: 16526022 [PubMed - indexed for MEDLINE]

Am J Chin Med. 2005;33(3):449-57.

Effect of curcuma herbs on vasomotion and hemorheology in spontaneously hypertensive rat.
Goto H, Sasaki Y, Fushimi H, Shibahara N, Shimada Y, Komatsu K.

Department of Kampo Diagnostics, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan. hiro510@ms.toyama-mpu.ac.jp

Curcuma herbs have a vasodilator effect. The effects of C. longa, which induces only endothelium-independent vasodilatation, and C. zedoaria, which induces both endothelium-dependent and -independent vasodilatation, were studied on vasomotion and hemorheology in spontaneously hypertensive rats. Spontaneously hypertensive eight-week-old male rats were assigned to five groups. For 12 weeks, the control group received standard chow. The 3%CL (C. longa) group received standard chow containing 3% (wt/wt) C. longa. The 1%CZ and 3%CZ (C. zedoaria) groups received standard chow containing 1% and 3% (wt/wt) C. zedoaria, respectively. The captoril group received standard chow and 100 mg/kg/day of captoril in drinking water. Blood pressure, vasomotion, hemorheology, etc. were examined. Systolic blood pressure of the 3%CZ and captoril groups decreased significantly as compared to the control group. Acetylcholine-induced endothelium-dependent relaxations of the 3%CZ and captoril groups were increased to a greater degree, significantly, than the control group. When testing xanthine oxidase-induced contraction, the 3%CZ group was significantly decreased as compared to the control group. Low shear stress of whole blood viscosity showed the 3%CL and 3%CZ groups to be decreased significantly compared to the control group. Thus, Curcuma herbs have hypotensive and protective effect on the endothelium in spontaneously hypertensive rats. Especially, C. zedoaria is more effective than C. longa, and its mechanism is thought to be related to a radical scavenging effect and improvement of hemorheology. PMID: 16047562 [PubMed - indexed for MEDLINE]

Curr Pharm Des. 2002;8(19):1695-706.

Chemotherapeutic potential of curcumin for colorectal cancer.
Chauhan DP.

Division of Gastroenterology, Department of Medicine, The University of California, San Diego, CA 92093-0688, USA. dchauhan@ucsd.edu

Colorectal cancer is one of the leading causes of cancer deaths in the Western world. More than 56,000 newly diagnosed colorectal cancer patients die each year in the United States. Available therapies are either not effective or have unwanted side effects. Epidemiological data suggest that dietary manipulations play an important role in the prevention of many human cancers. Curcumin the yellow pigment in turmeric has been widely used for centuries in the Asian countries without any toxic effects. Epidemiological data also suggest that curcumin may be responsible for the lower rate of colorectal cancer in these countries. Curcumin is a naturally occurring powerful anti-inflammatory medicine. The anticancer properties of curcumin have been shown in cultured cells and animal studies. Curcumin inhibits lipooxygenase activity and is a specific inhibitor of cyclooxygenase-2 expression. Curcumin inhibits the initiation of carcinogenesis by inhibiting the cytochrome P-450 enzyme activity and increasing the levels of glutathione-S-transferase. Curcumin inhibits the promotion/progression stages of carcinogenesis. The anti-tumor effect of curcumin has been attributed in part to the arrest of cancer cells in S, G2/M cell cycle phase and induction of apoptosis. Curcumin inhibits the growth of DNA mismatch repair defective colon cancer cells. Therefore, curcumin may have value as a safe chemotherapeutic agent for the treatment of tumors exhibiting DNA mismatch repair deficient and microsatellite instable phenotype. Curcumin should be considered as a safe, non-toxic and easy to use chemotherapeutic agent for colorectal cancers arise in the setting of chromosomal instability as well as microsatellite instability. PMID: 12171541 [PubMed - indexed for MEDLINE]

Cancer Lett. 2001 Oct 30;172(2):111-8.

Specific inhibition of cyclooxygenase-2 (COX-2) expression by dietary curcumin in HT-29 human colon cancer cells.
Goel A, Boland CR, Chauhan DP.

Division of Gastroenterology, Department of Medicine, The University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0688, USA.

Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory and anti-cancer activities. Cyclooxygenase (COX)-2 plays an important role in colon carcinogenesis. To investigate the effect of curcumin on COX-2 expression, we treated HT-29 human colon cancer cells with various concentrations of curcumin. Curcumin inhibited the cell growth of HT-29 cells in a concentration- and time-dependent manner. Curcumin markedly inhibited the mRNA and protein expression of COX-2, but not COX-1. These data suggest that a non-toxic concentration of curcumin has a significant effect on the in vitro growth of HT-29 cells, specifically inhibits COX-2 expression, and may have value as a safe chemopreventive agent for colon cancer.  PMID: 11566484 [PubMed - indexed for MEDLINE]

J Clin Rheumatol. 2004 Oct;10(5):236-245.

A 32-Week Randomized, Placebo-Controlled Clinical Evaluation of RA-11, an Ayurvedic Drug, on Osteoarthritis of the Knees.
Chopra A, Lavin P, Patwardhan B, Chitre D.

From the *Center for Rheumatic Diseases, Inlaks and Budhrani Hospital, Bharati Hospital Medical College (Deemed University), Pune, India; †Averion, Inc., Framingham, Massachusetts; the ‡School of Health Sciences, University of Pune, India; and §BIO-VED Pharmaceuticals, Inc., San Jose, California.

BACKGROUND:: The ancient Indian (Asian) Ayurvedic medicinal system uses herbomineral drugs to treat arthritis. Despite centuries of use, very few have been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa) is currently used to treat arthritis. OBJECTIVE:: The objective of this study was to evaluate the efficacy and safety of RA-11 in patients with symptomatic osteoarthritis (OA) of the knees. METHODS:: A total of 358 patients with chronic knee pain were screened free-of-cost in "arthritis camps" in an Indian metropolis. Ninety patients with primary OA of the knees (ACR classification; Arthritis Rheum 1986;29:1039-1049) were found eligible (postanalgesic washout pain visual analog score [VAS] >/=40 mm in either or both knees on body weight-bearing activities) to enroll into a randomized, double-blind, placebo-controlled, parallel efficacy, single-center, 32-week drug trial (80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the patient during the preceding 48 hours) and modified WOMAC (Western Ontario McMaster University OA Index, Likert scale, version 3.0) were the primary efficacy variables. The WOMAC section on "physical function difficulty" was modified for Indian use and validated before the trial. Routine laboratory testing was primarily done to monitor drug safety. At baseline, the groups (active = 45, placebo = 45) were well matched for several measures (mean pain VAS: active = 6.17; placebo = 6.5). RESULTS:: 1) Efficacy: Compared with placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3) and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly (P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in the WOMAC scores at week 16 and week 32 were also significantly superior (P <0.01, ANOVA) in the active group. 2) Safety: Both the groups reported mild adverse events (AE) without any significant difference. 3) Withdrawals: Twenty-eight patients were discontinued. None reported drug-related toxicity. The majority failed follow up/compliance. No differences were observed between the groups. CONCLUSION:: This controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32 weeks of therapy.  PMID: 17043520 [PubMed - as supplied by publisher]

1: Z Naturforsch [C]. 2006 Jan-Feb;61(1-2):6-10.

Seasonal variation and analgesic properties of different parts from Curcuma zedoaria Roscoe (Zingiberaceae) grown in Brazil.
Pamplona CR, de Souza MM, Machado Mda S, Cechinel Filho V, Navarro D, Yunes RA, Delle Monache F, Niero R.

Núcleo de Investigações Químico-Farmacêuticas (NIQFAR) e Programa de Mestrado em Ciências Farmacêuticas, Universidade do Vale do Itajaí (UNIVALI), 88.302-202 Itajaí, SC, Brazil.

This work describes the seasonal variation of curcumenol (1) and dihydrocurdione (2), two active terpenoids from different parts (roots, mother rhizome and rugous rhizome) of Curcuma zedoaria grown in Brazil. The analysis was carried out by high resolution gas chromatography, using external standards for determination. The results showed that both terpenoids are present in all the parts studied. However, C. zedoaria exhibited about three times more terpenoids in the mother rhizome in autumn than in other parts and seasons studied. The antinociceptive activity of the dichloromethane extracts from different parts and collected in different seasons was studied using the acetic acid-induced abdominal constriction model in mice. The extracts obtained from mother rhizome collected in autumn and winter at doses of 10 mg/kg body weight, i.p., caused considerable antinociceptive activity inhibiting 91.1 and 93.4% of the abdominal constrictions, respectively, whereas compounds 1 and 2 caused inhibitions of 64.0 and 46.0%, respectively. These results confirm that both compounds contribute to explain the antinociceptive effect (Anti-Pain Sensation) of the plant but suggest that other compounds are also acting as analgesics. An analgesic (colloquially known as a painkiller)-Wikipedia  PMID: 16610209 [PubMed - indexed for MEDLINE]

Adv Exp Med Biol. 2007;595:379-405.

Protection from acute and chronic lung diseases by curcumin.
Venkatesan N, Punithavathi D, Babu M.

Faculte de Medecine, UMR-7561, CNRS UHP, Vandoeuvre lès Nancy, France. vnar12@yahoo.com

The aim of this review has been to describe the current state of the therapeutic potential of curcumin in acute and chronic lung injuries. Occupational and environmental exposures to mineral dusts, airborne pollutants, cigarette smoke, chemotherapy, and radiotherapy injure the lungs, resulting in acute and chronic inflammatory lung diseases. Despite major advances in treating lung diseases, until now disease-modifying efficacy has not been demonstrated for any of the existing drugs. Current medical therapy offers only marginal benefit; therefore, there is an essential need to develop new drugs that might be of effective benefit in clinical settings. Over the years, there has been increasing evidence that curcumin, a phytochemical present in turmeric (Curcuma longa), has a wide spectrum of therapeutic properties and a remarkable range of protective effects in various diseases. Several experimental animal models have tested curcumin on lung fibrosis and these studies demonstrate that curcumin attenuates lung injury and fibrosis caused by radiation, chemotherapeutic drugs, and toxicants. The growing amount of data from pharmacological and animal studies also supports the notion that curcumin plays a protective role in chronic obstructive pulmonary disease, acute lung injury, acute respiratory distress syndrome, and allergic asthma, its therapeutic action being on the prevention or modulation of inflammation and oxidative stress. These findings give substance to the possibility of testing curcumin in patients with lung diseases.  PMID: 17569221 [PubMed - indexed for MEDLINE]

Cancer Lett. 1995 Jul 20;94(1):79-83.

Anti-tumour and antioxidant activity of natural curcuminoids.
Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R.

Amala Cancer Research Centre, Kerala, India.

Matural curcuminoids, curcumin, I, II and III isolated from turmeric (Curcuma longa) were compared for their cytotoxic, tumour reducing and antioxidant activities. Curcumin III was found to be more active than the other two as a cytotoxic agent and in the inhibition of Ehrlich ascites tumour in mice (ILS 74.1%). These compounds were also checked for their antioxidant activity which possibly indicates their potential use as anti-promoters. The amount of curcuminoids (I, II and III) needed for 50% inhibition of lipid peroxidation was 20, 14 and 11 g/m. Concentrations needed for 50% inhibition of superoxides were 6.25, 4.25 and 1.9 micrograms/ml and those for hydroxyl radical were 2.3, 1.8 and 1.8 micrograms/ml, respectively. The ability of these compounds to suppress the superoxide production by macrophages activated with phorbol-12-myristate-13-acetate (PMA) indicated that all the three curcuminoids inhibited superoxide production and curcumin III produced maximum effect. These results indicate that curcumin III is the most active of the curcuminoids present in turmeric. Synthetic curcumin I and III had similar activity to natural curcumins.  PMID: 7621448 [PubMed - indexed for MEDLINE]

Indian J Exp Biol. 2007 Sep;45(9):791-801.

Antischistosomal (Anti-Parasite) and liver protective effects of Curcuma longa extract in Schistosoma mansoni infected mice.
El-Ansary AK, Ahmed SA, Aly SA.

Medicinal Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.

With a view to clarify the induction of the "Crabtree consequence" in liver cells of S. mansoni infected mice, the curative effect of oil extract of C. longa was tested and compared to praziquantel (PZQ) the effective drug against all schistosome species occurring in man. Protein, glucose, glucose-6-phopsphatase, AMP-deaminase, adensoine deaminase, urea concentration, pyravate kinase (PK), phosphoenol pyruvate carboxykinase (PEPCK) and PK/PEPCK ratio were estimated. In addition, worm burden and ova count in mice infected with S. mansoni were elucidated. The result showed that C. longa normalized the concentration of protein, glucose, AMP-deaminase and adenosine deaminase, which were changed by infection. Moreover, it lowered pyruvate kinase level, while PZQ-treatment induced more elevation of this enzyme. PZQ was more effective in lowering worm burden while C. longa extract was more potent in reducing egg count.  PMID: 17907745 [PubMed - indexed for MEDLINE]

J Immunol. 2007 Jan 1;178(1):111-21.

Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.
Gururajan M, Dasu T, Shahidain S, Jennings CD, Robertson DA, Rangnekar VM, Bondada S.

Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY 40536, USA.

Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.  PMID: 17182546 [PubMed - indexed for MEDLINE]

Ann N Y Acad Sci. 2005 Nov;1056:206-17.

Curcumin: getting back to the roots.

Shishodia S, Sethi G, Aggarwal BB.

Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

The use of turmeric, derived from the root of the plant Curcuma longa, for treatment of different inflammatory diseases has been described in Ayurveda and in traditional Chinese medicine for thousands of years. The active component of turmeric responsible for this activity, curcumin, was identified almost two centuries ago. Modern science has revealed that curcumin mediates its effects by modulation of several important molecular targets, including transcription factors (e.g., NF-kappaB, AP-1, Egr-1, beta-catenin, and PPAR-gamma), enzymes (e.g., COX2, 5-LOX, iNOS, and hemeoxygenase-1), cell cycle proteins (e.g., cyclin D1 and p21), cytokines (e.g., TNF, IL-1, IL-6, and chemokines), receptors (e.g., EGFR and HER2), and cell surface adhesion molecules. Because it can modulate the expression of these targets, curcumin is now being used to treat cancer, arthritis, diabetes, Crohn's disease, cardiovascular diseases, osteoporosis, Alzheimer's disease, psoriasis, and other pathologies. Interestingly, 6-gingerol, a natural analog of curcumin derived from the root of ginger (Zingiber officinalis), exhibits a biologic activity profile similar to that of curcumin. The efficacy, pharmacologic safety, and cost effectiveness of curcuminoids prompt us to "get back to our roots."  PMID: 16387689 [PubMed - indexed for MEDLINE]

Biosci Biotechnol Biochem. 2007 Jun;71(6):1428-38.

Immunostimulating activity of crude polysaccharide extract isolated from Curcuma xanthorrhiza Roxb.
Kim AJ, Kim YO, Shim JS, Hwang JK.

Department of Biotechnology, Yonsei University, Korea.

Curcuma xanthorrhiza Roxb., commonly known as Javanese turmeric, has been reported to possess a variety of biological activities, including anti-inflammatory effects, anticarcinogenic effects, wound healing effects, and serum cholesterol-lowering effects. CPE, crude polysaccharide extract isolated from the rhizome of C. xanthorrhiza using 0.1 N NaOH, consisted of arabinose (18.69%), galactose (14.0%), glucose (50.67%), mannose (12.97%), rhamnose (2.73%), and xylose (0.94%), with an average molecular weight of 33,000 Da. In the present study, we investigated the effect of CPE on nitric oxide (NO), hydrogen peroxide (H2O2), tumor necrosis factor-alpha (TNF-alpha), and prostaglandin E2 (PGE2) production in RAW 264.7 cells. The uptake of fluorescein-labeled Escherichia coli was measured to determine whether CPE stimulates the phagocytic activity of RAW 264.7 cells. CPE significantly increased the phagocytosis of macrophages and the release of NO, H2O2, TNF-alpha, and PGE2 in a dose-dependent manner, and showed a similar activity to lipopolysaccharide (LPS). To study the mechanisms of CPE, we examined induction of iNOS and COX-2. NO and PGE2 were produced as a result of stimulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) respectively. Both modulations of iNOS and COX-2 expression by CPE were evaluated by Western immunoblotting and RT-PCR. Since transcription of these enzymes is under the control of nuclear factor-kappa B (NF-kappaB), we assessed the phosphorylation of inhibitor kappaBalpha (IkappaBalpha) through Western immunoblotting. CPE clearly induced phosphorylation of IkappaBalpha, suggesting a role as an NF-kappaB activator. Taking all this together, we conclude that CPE isolated from Curcuma xanthorrhiza stimulates the immune functions of macrophages, which is mediated in part by specific activation of NF-kappaB.  PMID: 17587672 [PubMed - indexed for MEDLINE]


Am J Epidemiol. 2006 Nov 1;164(9):898-906. Epub 2006 Jul 26.

Curry consumption and cognitive function in the elderly.
Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH.

Department of Psychological Medicine, National University of Singapore, Republic of Singapore. pcmngtp@nus.edu.sg

Curcumin, from the curry spice turmeric, has been shown to possess potent antioxidant and antiinflammatory properties and to reduce beta-amyloid and plaque burden in experimental studies, but epidemiologic evidence is lacking. The authors investigated the association between usual curry consumption level and cognitive function in elderly Asians. In a population-based cohort (n = 1,010) of nondemented elderly Asian subjects aged 60-93 years in 2003, the authors compared Mini-Mental State Examination (MMSE) scores for three categories of regular curry consumption, taking into account known sociodemographic, health, and behavioral correlates of MMSE performance. Those who consumed curry "occasionally" and "often or very often" had significantly better MMSE scores than did subjects who "never or rarely" consumed curry. The authors reported tentative evidence of better cognitive performance from curry consumption in nondemented elderly Asians, which should be confirmed in future studies.  PMID: 16870699 [PubMed - indexed for MEDLINE]

Adv Exp Med Biol. 2007;595:1-75.

Curcumin: the Indian solid gold.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H.

Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. aggarwal@mdanderson.org

Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".  PMID: 17569205 [PubMed - indexed for MEDLINE]

Adv Exp Med Biol. 2007;595:425-51.

Curcumin and autoimmune disease.
Bright JJ.

Neuroscience Research Laboratory, Methodist Research Institute, Clarian Health, Indianapolis, IN 46202, USA. jbright1@clarian.org

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.  PMID: 17569223 [PubMed - indexed for MEDLINE]

Phytother Res. 1999 Jun;13(4):318-22.

Efficacy of curcumin in the management of chronic anterior uveitis.
Lal B, Kapoor AK, Asthana OP, Agrawal PK, Prasad R, Kumar P, Srimal RC.

Department of Ophthalmology, K.G. Medical College, Lucknow, India.

    Curcumin, obtained from rhizomes of Curcuma longa, was administered orally to patients suffering from chronic anterior uveitis (CAU) at a dose of 375 mg three times a day for 12 weeks. Of 53 patients enrolled, 32 completed the 12-week study. They were divided into two groups: one group of 18 patients received curcumin alone, whereas the other group of 14 patients, who had a strong PPD reaction, in addition received antitubercular treatment. The patients in both the groups started improving after 2 weeks of treatment. All the patients who received curcumin alone improved, whereas the group receiving antitubercular therapy along with curcumin had a response rate of 86%. Follow up of all the patients for the next 3 years indicated a recurrence rate of 55% in the first group and of 36% in the second group. Four of 18 (22%) patients in the first group and 3 of 14 patients (21%) in the second group lost their vision in the follow up period due to various complications in the eyes, e.g. vitritis, macular oedema, central venous block, cataract formation, glaucomatous optic nerve damage etc. None of the patients reported any side effect of the drug. The efficacy of curcumin and recurrences following treatment are comparable to corticosteroid therapy, which is presently the only available standard treatment for this disease. The lack of side effects with curcumin is its greatest advantage compared with corticosteroids. A double blind multi-centric clinical trial with this drug in CAU is highly desirable to further validate the results of the present study.   PMID: 10404539 [PubMed - indexed for MEDLINE]

Biochem Pharmacol. 1995 Apr 18;49(8):1165-70.

Inhibition of human immunodeficiency virus type-1 integrase by curcumin.
Mazumder A, Raghavan K, Weinstein J, Kohn KW, Pommier Y.

Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, MD 20892-4255, USA.

    Curcumin (diferuloylmethane) is the yellow pigment in turmeric (Curcuma longa L.) that is widely used as a spice, food coloring (curry) and preservative. Curcumin exhibits a variety of pharmacological effects including antitumor, anti-inflammatory, and anti-infectious activities and is currently in clinical trials for AIDS patients. The effects of curcumin have been determined on purified human immunodeficiency virus type 1 (HIV-1) integrase. Curcumin has an inhibitory concentration50 (IC50) for strand transfer of 40 microM. Inhibition of an integrase deletion mutant containing only amino acids 50-212 suggests that curcumin interacts with the integrase catalytic core. Two structural analogs, methyl cinnamate and chlorogenic acid, were inactive. Energy minimization studies suggest that the anti-integrase activity of curcumin could be due to an intramolecular stacking of two phenyl rings that brings the hydroxyl groups into close proximity. The present data suggest that HIV-1 integrase inhibition may contribute to the antiviral activity of curcumin. These observations suggest new strategies for antiviral drug development that could be based upon curcumin as a lead compound for the development of inhibitors of HIV-1 integrase.  PMID: 7748198 [PubMed - indexed for MEDLINE]

Res Virol. 1998 Jan-Feb;149(1):43-52.

Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1 human immunodeficiency virus long terminal repeat.
Barthelemy S, Vergnes L, Moynier M, Guyot D, Labidalle S, Bahraoui E.

Laboratoire de Synthèse, Physico-Chimie et Radiobiologie, Faculté de Pharmacie, Toulouse, France.

    The transcription of HIV1 provirus is regulated by both cellular and viral factors. Various evidence suggests that Tat protein secreted by HIV1-infected cells may have additional action in the pathogenesis of AIDS because of its ability to also be taken up by non-infected cells. Curcumin [diferuloylmethane or 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the yellow pigment in turmeric Curcuma longa (Linn). It exhibits a variety of pharmacological effects including antiinflammatory and antiretroviral activities. Here, we demonstrated that curcumin used at 10 to 100 nM inhibited Tat transactivation of HIV1-LTR lacZ by 70 to 80% in HeLa cells. In order to develop more efficient curcumin derivatives, we synthesized and tested in the same experimental system the inhibitory activity of reduced curcumin (C1), which lacks the spatial structure of curcumin; allyl-curcumin (C2), which possesses a condensed allyl derivative on curcumin that plays the role of metal chelator; and tocopheryl-curcumin (C3), which enhances the antioxidant activity of the molecule. Results obtained with C1, C2 and C3 curcumin derivatives showed a significant inhibition (70 to 85%) of Tat transactivation. Despite the fact that tocopheryl-curcumin (C3) failed to scavenge O2.-, this curcumin derivative exhibited the most activity; 70% inhibition was obtained at 1 nM, while only 35% inhibition was obtained with the curcumin.  PMID: 9561563 [PubMed - indexed for MEDLINE]

Simultaneous determination of saponins and fatty acids in Ziziphus jujuba (Suanzaoren) by high performance liquid chromatography-evaporative light scattering detection and pressurized liquid extraction.
Zhao J, Li SP, Yang FQ, Li P, Wang YT.

Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau.

    The seed of Ziziphus jujube Mill. var. spinosa (Bunge) Hu ex H. F. Chou, Suanzaoren in Chinese, is one of commonly used Chinese medicines. Saponins and fatty oil contains several fatty acids in Suanzaoren are responsible for its therapeutic activities. In this study, a new HPLC coupled with evaporative light scattering detection (ELSD) and pressurized liquid extraction (PLE) method was developed for the simultaneous quantitative determination of 11 major components of 2 saponins and 9 fatty acids, namely jujuboside A, jujuboside B, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, arachidic acid and docosanoic acid in Suanzaoren. Simultaneous separation of these eleven compounds was achieved on a C18 analytical column. The mobile phase consisted of (A) 0.1% aqueous acetic acid and (B) methanol with 0.1% acetic acid using a gradient elution. The drift tube temperature of ELSD was set at 75 degrees C, and nitrogen flow-rate was 1.8l/min. All calibration curves showed good linearity (r(2)>0.9955) within test ranges. This method showed good reproducibility for the quantification of these eleven components in Suanzaoren with intra- and inter-day variations of less than 3.41 and 4.37%, respectively. The validated method was successfully applied to quantify 11 investigated components in nine commercial samples of Suanzaoren.  PMID: 16458908 [PubMed - indexed for MEDLINE]

Am J Chin Med. 2007;35(3):517-32.

Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells.
Huang X, Kojima-Yuasa A, Norikura T, Kennedy DO, Hasuma T, Matsui-Yuasa I.

Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.

    The Zizyphus jujuba fruit has been used as a traditional Chinese medicinal herb and considered to affect various physiological functions in the body for thousands of years. However, its anti-cancer activity and mechanism of action remain to be elucidated. We investigated the anti-cancer activity of Zizyphus jujuba Mill and its underlining mechanisms of action in human hepatoma cells (HepG2) and found that the extract of Z. jujuba decreased the viability of the cells. Further extraction of the initial Z. jujuba extract with organic solvents revealed that the chloroform fraction (CHCl(3)-F) was the most effective. Interestingly, the CHCl(3)-F induced not only apoptosis but also G1 arrest at a low concentration (100 mug/ml) and G2/M arrest at a higher concentration (200 mug/ml) by cell cycle assay. Apoptosis, an increase in intracellular ROS (reactive oxygen species) level, a decline of mitochondrial membrane potential at low Z. jujuba concentrations, and a ROS-independent mitochondrial dysfunction pathway at high concentrations were all observed. CHCl(3)-F-induced G1 arrest in HepG2 cells was associated with an increase in hypohosphorylation of Rb and p27(Kip1), and a decrease of phosphorylated Rb. However, CHCl(3)-F-induced G2/M arrest in HepG2 cells correlated with a decrease of the p27(Kip1) levels and generation of the phosphorylation of p27(Kip1), however the hypohosphorylation of Rb protein remained. Collectively, our findings suggest that the CHCl(3)-F extract of Z. jujuba extract induced a concentration dependent effect on apoptosis and a differential cell cycle arrest in HepG2 cells.  PMID: 17597510 [PubMed - indexed for MEDLINE]

Horm Metab Res. 2008 Jan;40(1):44-9. Epub 2007 Dec 18.

Prevention of Insulin Resistance by Ingesting Aqueous Extract of Ocimum sanctum to Fructose-fed Rats.
Reddy SS, Karuna R, Baskar R, Saralakumari D.

1Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, Andhra Pradesh, India.

    The study was aimed to examine if oral administration of the aqueous extract of the whole plant OCIMUM SANCTUM (OS) protects against the development of insulin resistance in fructose fed rats. Male Wister rats were randomly divided into four groups of eight animals each: group-S (starch diet), group-F (fructose diet), group-F+OS (fructose diet along with OCIMUM SANCTUM extract at a dose of 200 mg/kg), group-S+OS (starch diet along with OCIMUM SANCTUM). During the experimental period of 60 days body weight, plasma glucose, insulin, and triglycerides were measured at an interval of 15 days. Insulin sensitivity was assessed at the end of experimental period by measuring glucose-insulin index, which is the product of the areas under the curve of glucose and insulin during oral glucose tolerance test. The nontoxic nature of OS was revealed by unaltered body weight, plasma glucose, insulin, and triglyceride levels in group-S+OS when compared with group-S. A significant gain in body weight, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and insulin resistance were observed in group-F when compared with group-S. OS treatment prevented the observed fructose induced alterations in group-F+OS. In conclusion, our results suggests that oral administration of OS aqueous extract could delay the development of insulin resistance in rats and may be used as an adjuvant therapy for treating diabetic patients with insulin resistance.  PMID: 18085503 [PubMed - in process]

J Endocrinol. 2006 Apr;189(1):127-36.

Ocimum sanctum leaf extracts stimulate insulin secretion from perfused pancreas, isolated islets and clonal pancreatic beta-cells.
Hannan JM, Marenah L, Ali L, Rokeya B, Flatt PR, Abdel-Wahab YH.

Diabetes Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK.

    Ocimum sanctum leaves have previously been reported to reduce blood glucose when administered to rats and humans with diabetes. In the present study, the effects of ethanol extract and five partition fractions of O. sanctum leaves were studied on insulin secretion together with an evaluation of their mechanisms of action. The ethanol extract and each of the aqueous, butanol and ethylacetate fractions stimulated insulin secretion from perfused rat pancreas, isolated rat islets and a clonal rat beta-cell line in a concentration-dependent manner. The stimulatory effects of ethanol extract and each of these partition fractions were potentiated by glucose, isobutylmethylxanthine, tolbutamide and a depolarizing concentration of KCl. Inhibition of the secretory effect was observed with diazoxide, verapamil and Ca2+ removal. In contrast, the stimulatory effects of the chloroform and hexane partition fractions were associated with decreased cell viability and were unaltered by diazoxide and verapamil. The ethanol extract and the five fractions increased intracellular Ca2+ in clonal BRIN-BD11 cells, being partly attenuated by the addition of verapamil. These findings indicated that constituents of O. sanctum leaf extracts have stimulatory effects on physiological pathways of insulin secretion which may underlie its reported antidiabetic action.  PMID: 16614387 [PubMed - indexed for MEDLIN

Phytomedicine. 2002 May;9(4):346-51.

Extract of Ocimum canum lowers blood glucose and facilitates insulin release by isolated pancreatic beta-islet cells.
Nyarko AK, Asare-Anane H, Ofosuhene M, Addy ME.

Noguchi Memorial Institute for Medical Research, University of Ghana, Legon. anyarko@noguchi.mimcom.net

    Aqueous extract of Ocimum canum Sim, (Lamiaceae) is used by some Ghanaians to manage diabetes mellitus. In vivo modulation of levels of fasting blood glucose by 0. canum extract was evaluated in type-II diabetes mellitus using the C57BL/KsJ db/db genetically diabetic animal model, and its effects on glucose-stimulated insulin release in vitro were monitored using isolated rat pancreatic beta-islet cells. The results showed that fasting blood glucose levels and body weight decreased significantly (p < 0.05) in diabetic and non-diabetic C57BL/KsJ mice, which were administered aqueous extract of 0. canum. In vitro, the 0. canum extract significantly enhanced insulin release from isolated rat pancreatic beta-islet cells. Insulin release was found to be dependent on glucose concentration and increased with increasing O. canum concentration in the incubation medium up to an optimum extract concentration of 0.03 mg/ml. Release of the hormone decreased beyond this concentration of extract in the medium. Addition to the medium of Desmodium adscendens, a plant preparation used to manage inflammatory disorders, did not increase but rather inhibited insulin secretion by the pancreatic beta-islet cells. These results could explain the use of 0. canum in Ghanaian folk medicine to manage diabetes mellitus.  PMID: 12120816 [PubMed - indexed for MEDLINE]

Mol Cell Biochem. 2005 Oct;278(1-2):177-84.

Effect of herbal polyphenols on atherogenic transcriptome.
Kaul D, Shukla AR, Sikand K, Dhawan V.

Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. dkaul_24@hotmail.com

    The ancient Indian system of medicine supports the antiatherogenic properties of some herbs. The crosstalk amongst the genes coding for LDLR, LXRalpha, PPARs (alpha,gamma), CD-36 and c-myc may be important in atherogenesis because these genes control lipid metabolism, cytokine production and cellular activity within the arterial wall. Hence, we attempted for the first time to explore whether or not the polyphenols extracted from medicinal herbs had any effect on the transcription of these genes. Normal human mononuclear cells were cultured in the presence of polyphenols (and their HPLC purified sub-fractions) extracted from Green tea (Camellia sinensis), Neem (Azadirachta indica) and Tulsi (Ocimum sanctum). Transcriptional expression of these genes was measured by using RT-PCR and SCION IMAGE analysis software. These polyphenolic extracts were found to have the inherent capacity to inhibit the transcriptional expression of genes having direct involvement in atherogenic process. On the basis of these results, we propose for the first time that HPLC purified polyphenolic fraction IV of Tulsi may have a profound antiatherogenic effect. (arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries), atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque.)    PMID: 16180103 [PubMed - indexed for MEDLINE]

Res Vet Sci. 2005 Aug;79(1):37-43. Epub 2004 Dec 21.

Immunotherapeutic potential of Ocimum sanctum (L) in bovine subclinical mastitis.
Mukherjee R, Dash PK, Ram GC.

Division of Medicine, Indian Veterinary Research Institute, Izatnagar, UP 243 122, India. reena@ivri.up.nic.in

    Immunotherapeutic potential of aqueous extract of Ocimum sanctum (O. sanctum) leaf in bovine sub-clinical mastitis (SCM) was investigated. Somatic cell count (SCC), total bacterial count (TBC), milk differential leukocyte count (DLC), phagocytic activity and Phagocytic index and leukocyte lysosomal enzymes like myeloperoxidase and acid phosphatase content were evaluated after intramammary infusion of aqueous leaf extract of O. sanctum. The results revealed that the aqueous extract of O. sanctum treatment reduced the TBC and increased neutrophil and lymphocyte counts with enhanced phagocytic activity and phagocytic index. Similarly, the lysosomal enzymes contents of the milk polymorphonuclear cells (PMNs) were also enhanced significantly in animals treated with the extract. The results suggest that the crude aqueous extract of O. sanctum (leaf) possesses some biologically active principles that are antibacterial and immunomodulatory in nature. As such, the present wok substantiates the therapeutic use of medicinal herb and also emphasizes on the potential of the commonly available non-toxic substances to enhance the mammary immunity.  PMID: 15894022 [PubMed - indexed for MEDLINE]

J Ethnopharmacol. 2003 May;86(1):113-6.

Lens aldose reductase inhibiting potential of some indigenous plants.
Halder N, Joshi S, Gupta SK.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

    Cataract is the leading cause of blindness worldover. Diabetes is one of the major risk factors for cataractogenesis and aldose reductase (AR) has been reported to play an important role in sugar-induced cataract. In the present study, the AR inhibitory activity of Ocimum sanctum (OS), Withania somnifera (WS), Curcuma longa (CL), Azadirachta indica (AI) were studied together with their effect on sugar-induced cataractogenic changes in rat lenses in vitro. Aqueous extracts of the plants, procured from Dabur, India, were reconstituted with double distilled water to make various dilutions. AR inhibitory activity of these extracts and their anticataract potentials were evaluated in vitro in rat lenses. AR inhibitory activity of the aqueous extract of different plants was calculated considering the AR activity of normal rat lenses as 100%. The concentration of the plant extract that showed maximum AR inhibitory activity was selected to further study its effect on galactose-induced lens swelling and polyol accumulation in vitro. All the four plants were found to inhibit lens AR activity but to different extent. From dose-response curve, OS was found to be the most effective AR inhibitor followed by CL, AI and WS. The IC(50) values of OS, CL, AI and WS were calculated to be 20, 55, 57 and 89 microg/ml, respectively. OS showed a significant inhibition (38.05%) in polyol accumulation followed by CL and AI (28.4 and 25.04%, respectively). WS did not show any effect on polyol level in rat lenses. None of the plant extracts showed any significant effect on lens water content. OS (Ocimum sanctum) possesses a significant anticataract activity in vitro and its anticataract potential could be related with its AR inhibitory effect.  PMID: 12686449 [PubMed - indexed for MEDLINE]

Curr Eye Res. 2005 Jul;30(7):583-91.

Ocimum sanctum modulates selenite-induced cataractogenic changes and prevents rat lens opacification.
Gupta SK, Srivastava S, Trivedi D, Joshi S, Halder N.

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India. skgup@hotmail.com

    PURPOSE: To study the effect of Ocimum sanctum (OS) on selenite-induced morphological and biochemical changes in isolated rat lenses as well as on cataract incidence in rat pups. METHODS: Transparent rat lenses were divided into normal, selenite-only, and four treated groups. Selenite-only and treated group lenses were subjected to oxidative stress in vitro by incorporating sodium selenite (100 microM) in the culture medium. The effect of OS (70, 140, 280, and 560 microg/ml) was studied on the levels of reduced glutathione (GSH) and thiobarbituric acid reacting substances (TBARS) in selenite-challenged lenses. The lowest concentration of OS offering significant modulation on these two parameters was determined. Subsequently, the effect of prior and cotreatment with the lowest effective concentration of OS was studied on TBARS, GSH, and on lens antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), and glutathione-S-transferase (GST). Changes in lens protein profiles under different incubation conditions were analyzed by SDS gel-electrophoresis. In vivo, cataract was induced by a single subcutaneous injection of sodium selenite (25 micromole/kg b.w.) to 9-day-old rat pups. The anticataract effect of OS (5 and 10 mg/kg b.w.) injected intraperitoneally 4 hr prior to selenite challenge was evaluated by the presence of lens nuclear opacity in rat pups on the 16th postnatal day. Insolubilization of lens proteins post-selenite injection was monitored for 4 days. RESULTS: The lenses in the selenite-only group developed cortical opacities in 24 hr. OS showed different degrees of positive modulation in selenite-induced morphological as well as biochemical changes. The lowest effective dose of OS that significantly modulated glutathione and thiobarbituric acid reacting substances was found to be 140 microg/ml. At this dose, a significant increase in antioxidant enzyme levels and preservation of normal lens protein profile was observed. OS at the dose of 70 microg/ml did not show any significant protection with respect to either morphology or biochemistry of lenses. In vivo, 5 and 10 mg/kg of OS reduced the incidence of selenite cataract by 20% and 60%, respectively, and prevented protein insolubilization as well. CONCLUSIONS: Aqueous extract of OS possesses potential anticataract activity against selenite-induced experimental cataractogenesis. The protective effect was supported by restoration of the antioxidant defense system and inhibition of protein insolubilization of rat lenses as well.  PMID: 16020293 [PubMed - indexed for MEDLINE]

Zhongguo Zhong Yao Za Zhi. 2004 Jun;29(6):568-9, 593.

[Primary research of pharmacological effects of PEC on mice]
[Article in Chinese]

Wang LW, Liu XM, Lu GH, Gao NN, Xiao PG.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100094, China.

    OBJECTIVE: To study pharmacological effects of PEC (the oral liquid which consists of Panax quinquefolium, Epimedium brevicornum, Schisandra chinensis Bail and Cervus eplaphus) on mice. METHOD: Experiments were carried out through swimming test, step-through, spontaneous activity and sleeping time. RESULT: When 5-10 mL x kg(-1) of PEC was given orally for 7 days, it could prolong swimming duration of mice in water tank, and increase the tolerant ability against oxygen-deficiency. PEC could also improve cognitive-deficiency induced by taking off sleep with force in mice after given orally for 7 days. The PEC could increase the spontaneous activity in mice, antagonize the inhabitation induced by Valium, and shorten the sleeping time caused by sodium pentobarbital. CONCLUSION: PEC has strong potential neuro-pharmacological activities such as anti-fatigue, improving cognitive-deficiency in mice.  PMID: 15706926 [PubMed - indexed for MEDLINE]


J Med Food. 2005 Summer;8(2):125-32.

Ginger--an herbal medicinal product with broad anti-inflammatory actions.
Grzanna R, Lindmark L, Frondoza CG.

RMG Biosciences, Inc.

    The anti-inflammatory properties of ginger have been known and valued for centuries. During the past 25 years, many laboratories have provided scientific support for the long-held belief that ginger contains constituents with antiinflammatory properties. The original discovery of ginger's inhibitory effects on prostaglandin biosynthesis in the early 1970s has been repeatedly confirmed. This discovery identified ginger as an herbal medicinal product that shares pharmacological properties with non-steroidal anti-inflammatory drugs. Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase-1 and cyclooxygenase-2. An important extension of this early work was the observation that ginger also suppresses leukotriene biosynthesis by inhibiting 5-lipoxygenase. This pharmacological property distinguishes ginger from nonsteroidal anti-inflammatory drugs. This discovery preceded the observation that dual inhibitors of cyclooxygenase and 5-lipoxygenase may have a better therapeutic profile and have fewer side effects than non-steroidal anti-inflammatory drugs. The characterization of the pharmacological properties of ginger entered a new phase with the discovery that a ginger extract (EV.EXT.77) derived from Zingiber officinale (family Zingiberaceae) and Alpina galanga (family Zingiberaceae) inhibits the induction of several genes involved in the inflammatory response. These include genes encoding cytokines, chemokines, and the inducible enzyme cyclooxygenase-2. This discovery provided the first evidence that ginger modulates biochemical pathways activated in chronic inflammation. Identification of the molecular targets of individual ginger constituents provides an opportunity to optimize and standardize ginger products with respect to their effects on specific biomarkers of inflammation. Such preparations will be useful for studies in experimental animals and humans.      PMID: 16117603 [PubMed - indexed for MEDLINE]

Yakugaku Zasshi. 1992 Sep;112(9):645-55.

[Stomachic principles in ginger. II. Pungent and anti-ulcer effects of low polar constituents isolated from ginger, the dried rhizoma of Zingiber officinale Roscoe cultivated in Taiwan. The absolute stereostructure of a new diarylheptanoid]   [Article in Japanese]

Yamahara J, Hatakeyama S, Taniguchi K, Kawamura M, Yoshikawa M.

Kyoto Pharmaceutical University, Japan.

    By using the effects on HCl/ethanol-induced gastric lesions in rats, beta-sesquiphellandrene (2), beta-bisabolene (3), ar-curcumene (4) and 6-shogaol (5) were isolated as anti-ulcer active principles in ginger, the dried rhizoma of Zingiber officinale Roscoe (Shokyo in Japanese) which was cultivated in Taiwan, together with nine known compounds and a new diarylheptanoid. The absolute stereostructure of the diarylheptanoid was characterized as (3S,5S)-dihydroxy 1-(4'-hydroxy-3',5'-dimethoxyphenyl)-7-(4''-hydrox y-3''-methoxyphenyl)heptane (15) on the basis of chemical and spectroscopic evidence which included the application of the benzoate chirality method. The pungent effects of several constituents isolated from ginger were examined.  PMID: 1469612 [PubMed - indexed for MEDLINE]

Med Hypotheses. 1989 May;29(1):25-8.

Ginger (Zingiber officinale) and rheumatic disorders.
Srivastava KC, Mustafa T.

Department of Environmental Medicine, Odense University, Denmark.

    Oxygenation of arachidonic acid is increased in inflamed tissues. In this condition products of two enzymic pathways--the cyclooxygenase and the 5-lipoxygenase producing respectively prostaglandins and leukotrienes--are elevated. Of the cyclooxygenase products, PGE2 and of the lipoxygenase products, LTB4 are the strongest candidates for mediating inflammation. Non-steroidal anti-inflammatory drugs which inhibit the cyclooxygenase, and corticosteroids are used to treat such disorders. Both types of drugs produce adverse side-effects on prolonged use. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in rheumatic disorders. Seven patients suffering from such disorders reported relief in pain and associated symptoms on ginger administration.     PMID: 2501634 [PubMed - indexed for MEDLINE]

BMC Complement Altern Med. 2007 Dec 20;7(1):44

Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells.
Rhode J, Fogoros S, Zick S, Wahl H, Griffith KA, Huang J, Liu JR.

    ABSTRACT: BACKGROUND: Ginger (Zingiber officinale Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-KB. NF-KB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro. METHODS: The effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-KB and and production of VEGF and IL-8 was determined in the presence or absence of ginger. RESULTS: Ginger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that in vitro, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8. CONCLUSION: Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer.  PMID: 18096028 [PubMed - as supplied by publisher]

Toxicol Lett. 2007 Sep 28;173(3):151-60. Epub 2007 Jul 28.

Pro-apoptotic effects of 1'-acetoxychavicol acetate in human breast carcinoma cells.
Campbell CT, Prince M, Landry GM, Kha V, Kleiner HE.

Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA 71130, USA.

    The tropical ginger compound, 1'-acetoxychavicol acetate (ACA) possesses cancer chemopreventive properties in several models but its effects on breast cancer have not been fully evaluated. In this study, the effects of ACA on human breast carcinoma-derived MCF-7 and MDA-MB-231 cell viability were assessed using trypan blue exclusion analysis. ACA significantly decreased cell viability in a time- and dose-dependent manner, with effective concentrations 10-50 microM. Apoptosis was confirmed by morphological examination of cells through light microscopy, 4,6-diamidino-2-phenylindole dihydrochloride staining, and annexin V/Alexa Fluor 488 staining visualized using flow cytometry. ACA also increased protein expression of the activated form of caspase-3 in MDA-MB-231 cells. Addition of antioxidants N-acetylcysteine, ascorbic acid, or trolox prevented the loss of viability caused by ACA using trypan blue uptake as a marker. These results suggest ACA may have potential anticancer effects against breast carcinoma cells by inducing apoptosis.  PMID: 17766064 [PubMed - indexed for MEDLINE]

Dig Dis Sci. 2005 Oct;50(10):1889-97.

Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders.
Ghayur MN, Gilani AH.

Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, 74800, Pakistan.

    Ginger (rhizome of Zingiber officinale) has been widely used for centuries in gastrointestinal disorders, particularly dyspepsia, but its precise mode of action has yet to be elucidated. This study was undertaken to study the prokinetic action of ginger and its possible mechanism of action. Prokinetic activity of ginger extract (Zo.Cr) was confirmed in an in vivo test when it enhanced the intestinal travel of charcoal meal in mice. This propulsive effect of the extract, similar to that of carbachol, was blocked in atropine-pretreated mice, a standard cholinergic antagonist. Likewise, Zo.Cr showed an atropine-sensitive dose-dependent spasmogenic effect in vitro as well as in isolated rat and mouse stomach fundus tissues. In atropinized tissue, it showed spasmolytic activity as shown by the inhibition of 5-HT- and K+-induced contractions. A spasmolytic effect was also observed in other gut preparations either as noncompetitive inhibition of agonist dose-response curves, inhibition of high K+(80 mM)-induced contractions, or displacement of Ca2+ dose-response curves to the right, indicating a calcium antagonist effect. Phytochemical analysis revealed the presence of saponins, flavonoids, and alkaloids in the crude extract. These data indicate that Zo.Cr contains a cholinergic, spasmogenic component evident in stomach fundus preparations which provides a sound mechanistic insight for the prokinetic action of ginger. In addition, the presence of a spasmolytic constituent(s) of the calcium antagonist type may explain its use in hyperactive states of gut like colic and diarrhea.      PMID: 16187193 [PubMed - indexed for MEDLINE]

J Cardiovasc Pharmacol. 2005 Jan;45(1):74-80.

Ginger lowers blood pressure through blockade of voltage-dependent calcium channels.
Ghayur MN, Gilani AH.

    Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi, Pakistan.

    Ginger (Zingiber officinale Roscoe), a well-known spice plant, has been used traditionally in a wide variety of ailments including hypertension. We report here the cardiovascular effects of ginger under controlled experimental conditions. The crude extract of ginger (Zo.Cr) induced a dose-dependent (0.3-3 mg/kg) fall in the arterial blood pressure of anesthetized rats. In guinea pig paired atria, Zo.Cr exhibited a cardiodepressant activity on the rate and force of spontaneous contractions. In rabbit thoracic aorta preparation, Zo.Cr relaxed the phenylephrine-induced vascular contraction at a dose 10 times higher than that required against K (80 mM)-induced contraction. Ca2+ channel-blocking (CCB) activity was confirmed when Zo.Cr shifted the Ca2+ dose-response curves to the right similar to the effect of verapamil. It also inhibited the phenylephrine (1 microM) control peaks in normal-Ca2+ and Ca2+-free solution, indicating that it acts at both the membrane-bound and the intracellular Ca2+ channels. When tested in endothelium-intact rat aorta, it again relaxed the K-induced contraction at a dose 14 times less than that required for relaxing the PE-induced contraction. The vasodilator effect of Zo.Cr was endothelium-independent because it was not blocked by L-NAME (0.1 mM) or atropine (1 microM) and also was reproduced in the endothelium-denuded preparations at the same dose range. These data indicate that the blood pressure-lowering effect of ginger is mediated through blockade of voltage-dependent calcium channels.  PMID: 15613983 [PubMed - indexed for MEDLINE]

Biochem Biophys Res Commun. 2007 Oct 12;362(1):218-23. Epub 2007 Aug 10.

Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms.
Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K, Goto H.

Molecular Biology and Pathogenesis of Gastroenterology, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. kio@med.nagoya-u.ac.jp

    Ginger has been used throughout the world as spice, food and traditional herb. We found that 6-gingerol, a phenolic alkanone isolated from ginger, enhanced the TRAIL-induced viability reduction of gastric cancer cells while 6-gingerol alone affected viability only slightly. 6-Gingerol facilitated TRAIL-induced apoptosis by increasing TRAIL-induced caspase-3/7 activation. 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL-induced NF-kappaB activation. As 6-shogaol has a chemical structure similar to 6-gingerol, we also assessed the effect of 6-shogaol on the viability of gastric cancer cells. Unlike 6-gingerol, 6-shogaol alone reduced the viability of gastric cancer cells. 6-Shogaol was shown to damage microtubules and induce mitotic arrest. These findings indicate for the first time that in gastric cancer cells, 6-gingerol enhances TRAIL-induced viability reduction by inhibiting TRAIL-induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules. PMID: 17706603 [PubMed - indexed for MEDLINE]

Yakugaku Zasshi. 2005 Feb;125(2):213-7.

[Antiobesity actions of Zingiber officinale Roscoe] [Article in Japanese]

Han LK, Gong XJ, Kawano S, Saito M, Kimura Y, Okuda H.

Department of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto City 862-8502, Japan. hanlikun@hotmail.com

    Zingiber officinale Roscoe has been used as a folk medicine in China. An aqueous extract of Z. officinale Roscoe inhibited the hydrolysis of triolein emulsified with phosphatidylcholine by pancreatic lipase in vitro and it reduced the elevation of rat plasma triacylglycerol levels 1 and 2 h after oral administration of a lipid emulsion containing corn oil. These results suggest that the aqueous extract of Z. officinale Roscoe might inhibit the intestinal absorption of dietary fat by inhibiting its hydrolysis. Therefore we investigated the antiobesity effects of the aqueous extract of Z. officinale Roscoe by feeding a high-fat diet to mice for 8 weeks. Body weights at 2-8 weeks and final parametrial adipose tissue weights were significantly lower in mice fed the high-fat diet containing 3% aqueous extract of Z. officinale Roscoe than in the controls fed the high-fat diet. Feeding a high-fat diet containing 1% aqueous extract of Z. officinale Roscoe also significantly reduced final parametrial adipose tissue weights that were elevated in mice fed the high-fat diet alone. Our data suggest that the antiobesity effect of aqueous extract of Z. officinale Roscoe in mice fed a high-fat diet may be due in part to the inhibition of intestinal absorption of dietary fat by the active compounds of Z. officinale Roscoe.   PMID: 15684576 [PubMed - indexed for MEDLINE]

Harefuah. 2006 Oct;145(10):738-42, 782.

[Herbal medicine in womens' life cycle] [Article in Hebrew]

Ben-Arye E, Oren A, Ben-Arie A.

    The Complementary and Traditional Medicine Unit, Department of Family Medicine, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. eranben@netvision.net.il

    Women use herbs and other traditional and complementary modalities to treat various ailments throughout their life circle. This article reviewed 19 randomized controlled trials, which studied efficacy and safety of various herbs in the treatment of premenstrual syndrome (PMS), nausea and vomiting in the first trimester of pregnancy and menopausal hot flushes. Preliminary data support the efficacy of Chaste tree fruit (Vitex agnus) in the treatment of PMS, Ginger (Zingiber officinale) in the treatment of hyperemesis gravidarum and (Cimicifuga racemosa) in the treatment of menopausal hot flushes. Additional and more rigorous studies are warranted in order to support the efficacy and safety of these herbal remedies. PMID: 17111709 [PubMed - indexed for MEDLINE]

J Ethnopharmacol. 1990 Jul;29(3):267-73.

Ginger (Zingiber officinale) in migraine headache.
Mustafa T, Srivastava KC.

Institute of Biology, Odense University, Denmark.

    Migraine is considered as a neurological disorder with little convincing evidence of the involvement of some vascular phenomenon. Recent understanding of the mechanisms behind migraine pain generation and perception have considerably helped the development of modern migraine drugs. Most migraine drugs in use, i.e., ergotamine and dihydroergotamine, iprazochrome, pizotifen and diazepam; and non-steroidal antiinflammatory drugs (i.e. aspirin, paracetamol, persantin, etc.) have side-effects and are prescribed with caution for a limited duration. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in neurological disorders. It is proposed that administration of ginger may exert abortive and prophylactic effects in migraine headache without any side-effects.  PMID: 2214812 [PubMed - indexed for MEDLINE]