La hierba de S. Juan mejora la sintomatología depresiva en la abstinencia al tabaco-St John's herb ameliorates depression when quitting tobacco

Phytomedicine. 2007 Oct;14(10):645-51. Epub 2007 Aug 6.
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Serotonin mediates beneficial effects of Hypericum perforatum on nicotine withdrawal signs.

Mannucci C, Pieratti A, Firenzuoli F, Caputi AP, Calapai G.

Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, School of Medicine, University of Messina, Via Consolare Valeria, Policlinico Universitario, 98125 Messina, Italy.

Antidepressants may be effective treatment for smoking cessation and new evidence on relationship between smoking and depression is emerging. Extracts of the plant Hypericum perforatum possess antidepressant activity in humans and reduce nicotine withdrawal signs in mice. Both nicotine and H. perforatum administration elicit changes in serotonin (5-HT) formation in the brain. On this basis, we investigated the possible involvement of 5-HT in the beneficial effects of H. perforatum on nicotine withdrawal signs. With the aim to induce nicotine dependence, nicotine (2 mg/kg, four intraperitoneal injections daily) was administered for 14 days to mice (NM). Saline (controls, M) or H. perforatum extract (Ph 50, 500 mg/kg) were orally administered immediately after the last nicotine injection for 30 days after nicotine withdrawal. Another group of animals treated with nicotine (14 days) and successively with H. perforatum extract was intraperitoneally co-administered with selective 5-HT receptorial antagonist WAY 100635 (WAY) (1 mg/kg). All animals were evaluated for locomotor activity and abstinence signs, 24 after nicotine withdrawal. Brain 5-HT metabolism was evaluated in the cortex of mice sacrificed 30 days after nicotine withdrawal through evaluation of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio. After nicotine withdrawal measurement of 5-HT metabolism in the cortex showed a reduction of 5-HT content while animals treated only with Hypericum extract showed a significant reduction of total abstinence score compared to controls. WAY inhibited the reduction of total abstinence score induced by H. perforatum. Moreover, 5-HT1A expression has been evaluated 30 days after nicotine withdrawal. Our results, show a significant increase of cortical 5-HT content in NM treated with H. perforatum, with a concomitant significant increase of 5-HT1A receptor. So, it is possible to suggest an involvement of 5-HT in beneficial effects of H. perforatum on suffering produced by nicotine withdrawal in dependent mice.

PMID: 17689233 [PubMed - indexed for MEDLINE]

3: Planta Med. 2006 Mar;72(4):378-82.
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A pilot randomised, open, uncontrolled, clinical study of two dosages of St John's wort (Hypericum perforatum) herb extract (LI-160) as an aid to motivational/behavioural support in smoking cessation.

Barnes J, Barber N, Wheatley D, Williamson EM.

Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, London, UK. j.barnes@auckland.ac.nz

There is an association between smoking and depression, yet the herbal antidepressant St John's wort (Hypericum perforatum L.; SJW) herb extract has not previously been investigated as an aid in smoking cessation. In this open, uncontrolled, pilot study, 28 smokers of 10 or more cigarettes per day for at least one year were randomised to receive SJW herb extract (LI-160) 300 mg once or twice daily taken for one week before and continued for 3 months after a target quit date. In addition, all participants received motivational/behavioural support from a trained pharmacist. At 3 months, the point prevalence and continuous abstinence rates were both 18%, and at 12 months were 0%. Fifteen participants (54%) reported 23 adverse events up to the end of the 3-month follow-up period. There was no statistically significant difference in the frequency of adverse events for participants taking SJW once or twice daily (p > 0.05). Most adverse events were mild, transient and non-serious. This preliminary study has not provided convincing evidence that a SJW herb extract plus individual motivational/behavioural support is likely to be effective as an aid in smoking cessation. However, it may be premature to rule out a possible effect on the basis of a single, uncontrolled pilot study, and other approaches involving SJW extract may warrant investigation.

Publication Types:

* Randomized Controlled Trial
* Research Support, Non-U.S. Gov't

PMID: 16557483 [PubMed - indexed for MEDLINE]

4: J Altern Complement Med. 2005 Oct;11(5):909-15.
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Dietary supplements and weight control in a middle-age population.

Nachtigal MC, Patterson RE, Stratton KL, Adams LA, Shattuck AL, White E.

Bastyr University Research Institute, Kenmore, WA, USA.

OBJECTIVES: Obesity is rapidly becoming a health problem of epidemic proportions, bringing with it a host of health concerns. This study investigates the association of long-term (10-year) use of 14 nutritional supplements, marketed as weight-control aids, with weight change over the past 10 years among individuals age 53 to 57 years. METHODS: Data are from the VITamins And Lifestyle (VITAL) cohort study of western Washington. Participants (n = 15,655) completed questionnaires about 10-year supplement use, diet, health habits, height, and present and former weights. The following supplements that are sometimes marketed for weight control or loss were examined: multivitamins; vitamins B6 and B12; chromium; coenzyme Q10, dehydroepiandrosterone, essential fatty acids (EFAs), fiber, garlic (Allium sativum), ginkgo (Ginkgo biloba), ginseng (Panax spp.), melatonin, soy, and St. John's wort (Hypericum perforatum). Linear regression was used to model 10-year change in weight from age 45 to ages 53-57, stratified by sex and body mass index (BMI, kg/m2) (normal, overweight, or obese) at age 45 years. Models were controlled for race/ethnicity, education, energy intake, physical activity, weight at age 45 years, and smoking. RESULTS: Among overweight or obese men and women, long-term use of multivitamins, vitamins B6 and B12, and chromium were significantly associated with lower levels of weight gain. For example, with chromium, weight gain in the past 10 years for obese men was 11.7 lb for no use, 6.1 lb for <150 microg/day (10-year average), and a weight loss of 3.1 lb for > or = 150 microg/day (p for trend, <0.05). Among obese women, weight gain was 14.1 lb, 7.9 lb, and 3.2 lb for the three groups respectively (p for trend, <0.01). CONCLUSIONS: These data suggest that long-term users of certain supplements experienced less weight gain than individuals who did not use the supplements. Further study is necessary before recommendations regarding these supplements can be made.

PMID: 16296926 [PubMed - indexed for MEDLINE]

5: Psychopharmacology (Berl). 2003 Sep;169(2):186-9. Epub 2003 Apr 29.
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Hypericum perforatum attenuates nicotine withdrawal signs in mice.

Catania MA, Firenzuoli F, Crupi A, Mannucci C, Caputi AP, Calapai G.

Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, School of Medicine, University of Messina, Via Consolare Valeria, Policlinico Universitario Torre Biologica 5(o) piano, 98125 Messina, Italy.

RATIONALE: Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation. OBJECTIVE: We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice. METHODS: Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125-500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs. RESULTS: The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal. CONCLUSIONS: These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.


Neem tree-El árbol de neem

Neem, también llamado árbol de neem, es en el ayurveda un importante tónico de la piel. De este árbol particular se utilizan todas las partes, como la corteza, las hojas, las flores, las semillas y la resina. Han habido muchas investigaciones sobre el neem, sobre sus propiedades antibacterianas. Neem aumenta la inmunidad, la producción de interferones y la actividad de macrófagos y linfocitos. Sus propiedades antibacterianas son la causa de su actividad en enfermedades de la piel. Lo que es particular del neem, es que ayuda a regular el sistema inmune, de forma que tanto en el caso de una sobreinmunización (alergias), como en el caso de infecciones. Neem aumenta la actividad de la glutation-S-transferasa en el hígado, un enzima, que ayuda en la detoxificación de muchos agentes carcinógenos potentes. Las excavaciones muestran que el neem juega un papel importante en la cultura india desde hace 5000 años. A causa de sus propiedades limpiadoras y desintoxicantes en la sangre, con importancia en muchas enfermedades, se ha llamado popularmente al árbol de neem "El curandero de todos los males". Hay 37 artículos en la literatura científica, al menos, que describen la actividad anticancerosa del neem diversos modelos in vitro (células en cultivo), y animales.

Estos son los abstracts de algunas artículos científicos en los que investigan las propiedades anticancerosas del neem.

Phytother Res. 2007 Mar;21(3):245-50.
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Antiproliferative effect on human cancer cell lines after treatment with nimbolide extracted from an edible part of the neem tree (Azadirachta indica).

Roy MK, Kobori M, Takenaka M, Nakahara K, Shinmoto H, Isobe S, Tsushida T.

National Food Research Institute, 2-1-12, Kannondai, Tsukuba, Ibaraki 305-8642, Japan.

Nimbolide, a triterpenoid extracted from the flowers of the neem tree (Azadirachta indica), was found to have antiproliferative activity against some cancer cell lines. Treatment of cells with 0.5-5.0 microm concentrations of nimbolide resulted in moderate to very strong growth inhibition in U937, HL-60, THP1 and B16 cell lines. Flow cytometric analysis of U937 cells showed that nimbolide treatment (1-2.5 microm) resulted in cell cycle disruption by decreasing the number of cells in G0/G1 phase, with initial increases in S and G2/M phases. Cells exposed to a higher dose of nimbolide for a longer period displayed a severely damaged DNA profile, resulting in a remarkable increase in the number of cells in the sub-G1 fraction, with a reciprocal decrease of cells in all phases. Quantification of the expression of phosphatidylserine in the outer cell membrane showed that doses of nimbolide higher than 0.4 microm exerted remarkable lethality, with over 60% of cells exhibiting apoptotic features after exposure to 1.2 microm nimbolide. The antiproliferative effect of nimbolide and its apoptosis-inducing property raise hope for its use in anticancer therapy by enhancing the effectiveness of cell cycle disruption.

3: Int J Oncol. 2006 Nov;29(5):1269-78.
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Chemopreventative strategies targeting the MGMT repair protein: augmented expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts of several Indian medicinal plants.

Niture SK, Rao US, Srivenugopal KS.

Center for Cancer Biology, Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.

O6-alkylguanines are potent mutagenic, pro-carcinogenic and cytotoxic lesions induced by exogenous and endogenous alkylating agents. A facilitated elimination of these lesions by increasing the activity of O6-methylguanine-DNA methyltransferase (MGMT) is likely to be a beneficial chemoprevention strategy, which, however, has not been examined. Because, a marginal enhancement of this protein may be adequate for genomic protection, we studied alterations in MGMT activity and expression in human peripheral blood lymphocytes and cancer cell lines induced by water-soluble and alcohol-soluble constituents of several plants with established antioxidant and medicinal properties. Both the ethanolic and aqueous extracts from neem (Azadirachta indica), holy basil (Ocimum sanctum), winter cherry (Withania somnifera), and oregano (Origanum majorana) increased the levels of MGMT protein and its demethylation activity in a time-dependent manner with a maximum of 3-fold increase after 72-h treatment. The extracts from gooseberry (Emblica officinalis), common basil (Ocimum basilicum), and spearmint (Mentha viridis) were relatively less efficient in raising MGMT levels. Increased levels of MGMT mRNA accounted at least, in part, for the increased activity of the DNA repair protein. The herbal treatments also increased glutathione S-transferase-pi (GSTP1) expression, albeit to a lesser extent than MGMT. These data provide the first evidence for the upregulation of human MGMT by plant constituents and raise the possibility of rational dietary approaches for attenuating alkylation-induced carcinogenesis. Further, they reveal the putative antioxidant responsiveness of the MGMT gene in human cells.

4: Planta Med. 2006 Aug;72(10):917-23. Epub 2006 Jul 20.
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Inhibition of colon cancer (HT-29) cell proliferation by a triterpenoid isolated from Azadirachta indica is accompanied by cell cycle arrest and up-regulation of p21.

Roy MK, Kobori M, Takenaka M, Nakahara K, Shinmoto H, Tsushida T.

National Food Research Institute, Kannondai, Ibaraki, Tsukuba, Japan. mkroy@affrc.go.jp

Nimbolide, a natural triterpenoid present in the edible parts of the neem tree ( Azadirachta indica), was found to be growth-inhibitory in human colon carcinoma HT-29 cells. Nimbolide treatment of cells at 2.5 - 10 microM resulted in moderate to very strong growth inhibition. Flow cytometric analysis of HT-29 cells showed that nimbolide treatment (2.5 microM, 12 h) caused a 6.5-fold increase in the number of cells (55.6 %) in the G2/M phase compared with the control cells (8.8 %). At 48 h, the cell population in the G2/M phase decreased to 18 %, while that in the G0/G1 phase increased to 52.3 %. Western blot analysis revealed that nimbolide-mediated G2/M arrest was accompanied by the up-regulation of p21, cyclin D2, Chk2; and down-regulation of cyclin A, cyclin E, Cdk2, Rad17. At G0/G1 cell cycle arrest, modulation in the expression of the cell cycle regulatory molecules was also observed. We found that nimbolide-induced growth inhibition and cell cycle arrest were not associated with cellular differentiation. Quantification of cells with respect to the expression of phosphatidylserine in the outer cell membrane showed an increase in apoptotic cells by about 13 % after 48 h of nimbolide treatment.

5: Phytother Res. 2006 Sep;20(9):814-8.
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Pretreatment with neem (Azadirachta indica) leaf preparation in Swiss mice diminishes leukopenia and enhances the antitumor activity of cyclophosphamide.

Ghosh D, Bose A, Haque E, Baral R.

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata-700026, India.

Cancer chemotherapy is associated with several life threatening complications, including bone marrow suppression and leucopenia. To overcome this problem, colony stimulating factor (CSF), granulocyte colony stimulating factor (GCSF) and granulocyte macrophage colony stimulating factor (GMCSF), can be used, however, these therapeutics are expensive and have several disadvantages, including tumor growth promoting activities. This study attempted to use an immunostimulatory neem (Azadirachta indica) leaf preparation (NLP) to prevent the cyclophosphamide (CYP) induced reduction in the WBC count. Pretreatment of mice with NLP reduced the extent of leucopenia and neutropenia in normal and tumor bearing CYP treated mice. NLP pretreatment enhanced in vitro tumor cell cytotoxicity by peripheral blood mononuclear cells (PBMC) from CYP treated mice in either normal or tumor bearing conditions. Similarly, NLP pretreatment of mice enhanced the CYP mediated in vivo tumor growth inhibition and survivability of the host. Based on these observations, it is concluded that NLP would be an effective tool to reduce CYP-induced hematological complications. Copyright (c) 2006 John Wiley & Sons, Ltd.

6: Bioorg Med Chem Lett. 2006 Aug 15;16(16):4391-4. Epub 2006 Jun 21.
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Synthesis and biological activity of amide derivatives of nimbolide.

Sastry BS, Suresh Babu K, Hari Babu T, Chandrasekhar S, Srinivas PV, Saxena AK, Madhusudana Rao J.

Natural Products Laboratory, Division of Organic Chemistry-I, Indian Institute of Chemical Technology, Hyderabad.

Nimbolide (1), a limonoid isolated from Azadirachta indica, is the chief cytotoxic principle in Neem leaves extract. Using nimbolide as a lead compound for anti-cancer analogue design, a series of nimbolide derivatives have been synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Out of 10 compounds screened 2g, 2h and 2i showed potent activity.

7: Asian Pac J Cancer Prev. 2005 Oct-Dec;6(4):515-20.
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Ethanolic neem (Azadirachta indica) leaf extract induces apoptosis in the hamster buccal pouch carcinogenesis model by modulation of Bcl-2, Bim, caspase 8 and caspase 3.

Subapriya R, Bhuvaneswari V, Nagini S.

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.

Induction of apoptosis is one of the most active strategies in cancer chemoprevention and the ability of medicinal plants in this regard has attracted major research interest. The present study was designed to investigate the apoptosis inducing capacity of an ethanolic neem leaf extract (ENLE) during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis using the apoptosis-associated proteins Bcl-2, Bim, caspase 8 and caspase 3 as markers. Topical application of DMBA to the hamster cheek pouch for 14 weeks resulted in well developed squamous cell carcinomas associated with increased expression of Bcl-2 and decreased expression of Bim, caspase 8 and caspase 3. Administration of ENLE inhibited DMBA-induced hamster buccal pouch (HBP) carcinogenesis, as revealed by the absence of neoplasms, with induction of Bim and caspases 8 and 3 and inhibition of Bcl-2 expression. Our results suggest that the chemopreventive effects of ENLE may be mediated by induction of apoptosis.

8: J Ethnopharmacol. 2006 Apr 21;105(1-2):246-50. Epub 2005 Dec 27.
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Anticancer effects of ethanolic neem leaf extract on prostate cancer cell line (PC-3).

Kumar S, Suresh PK, Vijayababu MR, Arunkumar A, Arunakaran J.

Department of Biotechnology, Karpagam Arts and Science college, Coimbatore 641 021, India.

Prostate cancer (PC) is the most prevalent cancer and the leading cause of male cancer death. Azadirachta indica (neem tree) has been used successfully centuries to reduce tumors by herbalists throughout Southeast Asia. Here the present study indicated that an ethanolic extract of neem has been shown to cause cell death of prostate cancer cells (PC-3) by inducing apoptosis as evidenced by a dose-dependent increase in DNA fragmentation and a decrease in cell viability. Western blot studies indicated that treatment with neem extract showed decreased level of Bcl-2, which is anti-apoptotic protein and increased the level of Bax protein. So the neem extract could be potentially effective against prostate cancer treatment.

9: Asian Pac J Cancer Prev. 2005 Jul-Sep;6(3):263-9.
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Quinone reductase inducers in Azadirachta indica A. Juss flowers, and their mechanisms of action.

Sritanaudomchai H, Kusamran T, Kuakulkiat W, Bunyapraphatsara N, Hiransalee A, Tepsuwan A, Kusamran WR.

Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.

We have previously shown that the flowers of neem tree (Azadirachta indica A. Juss, family Meliaceae), Thai variety, strongly induced the activity of glutathione S-transferase (GST) while resulting in a significant reduction in the activities of some cytochrome P(450)-dependent monooxygenases in rat liver, and possess cancer chemopreventive potential against chemically-induced mammary gland and liver carcinogenesis in rats. In the present study, 2 chemicals possessing strong QR inducing activity were fractionated from neem flowers using a bioassay based on the induction of QR activity in mouse hepatoma Hepa 1c1c7 cultured cells. Spectroscopic characteristics revealed that these compounds were nimbolide and chlorophylls, having CD (concentration required to double QR specific activity) values of 0.16 and 3.8 mug/ml, respectively. Nimbolide is a known constituent of neem leaves, but was found for the first time here in the flowers. Both nimbolide and chlorophylls strongly enhanced the level of QR mRNA in Hepa 1c1c7 cells, as monitored by northern blot hybridization, indicating that the mechanism by which these constituents of neem flowers induced QR activity is the induction of QR gene expression. These findings may have implication on cancer chemopreventive potential of neem flowers in experimental rats previously reported.

10: J Exp Clin Cancer Res. 2005 Jun;24(2):223-30.
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Modulation of xenobiotic-metabolizing enzymes by ethanolic neem leaf extract during hamster buccal pouch carcinogenesis.

Subapriya R, Velmurugan B, Nagini S.

Dept. of Biochemistry, Faculty of Science Annamalai University, Annamalainagar, India.

Chemoprevention by medicinal plants is a promising approach for controlling cancer. There is substantial evidence to indicate that chemopreventive agents exert their anticarcinogenic effects by modulation of phase I and phase II xenobiotic-metabolizing enzymes. Therefore, we examined the chemopreventive potential of ethanolic neem leaf extract (ENLE) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into four groups of six animals each. The right buccal pouches of animals in Group I were painted with 0.5 per cent DMBA in liquid paraffin three times per week. Animals in Group 2 painted with DMBA as in group 1, received in addition, intragastric administration of ENLE at a concentration of 200 mg/kg bw three times per week on days alternate to DMBA application. Group 3 was given ENLE alone. Animals in Group 4 served as controls. All animals were killed after an experimental period of 14 weeks. Five out of six hamsters painted with DMBA alone developed squamous cell carcinomas in the buccal pouch. The HBP tumours showed an increase in phase I carcinogen activation (cytochrome P450 and b5) and phase II detoxification enzyme (glutathione-S-transferase, DT-diaphorase and NADPH-diaphorase) activities. In the liver of tumour-bearing animals, enhanced cytochrome P450 and b5 levels were accompanied by a decrease in phase II detoxification enzyme activities. Administration of ENLE effectively suppressed DMBA-induced HBP tumours, decreased cytochrome P450 and b5 levels, and enhanced phase II enzyme activities in the pouch and liver. Our results suggest that the modulation of DMBA metabolism is a possible mechanism for the chemopreventive effects of ethanolic neem leaf extract.

11: J Ethnopharmacol. 2005 May 13;99(1):109-12.
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Antioxidant activity of Siamese neem tree (VP1209).

Sithisarn P, Supabphol R, Gritsanapan W.

Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayuthaya Rd., Ratchatewi, Bangkok 10400, Thailand.

Leaves, fruits, flowers and stem bark extracts from the Siamese neem tree (Azadirachta indica A. Juss var. siamensis Valeton, Meliaceae) were assessed for antioxidant activity in vitro using the 1,1-diphenyl-2-picryl hydrazyl (DPPH) scavenging assay, total antioxidant activity and inhibition of lipid peroxidation in Chago K1 cancer cell culture by the thiobarbituric acid reactive substances (TBARS) method. The results showed that leaf aqueous extract, flower and stem bark ethanol extracts exhibited higher free radical scavenging effect on the DPPH assay with 50% scavenging activity at 26.5, 27.9 and 30.6 microg/ml, respectively. The total antioxidant activity of these extracts was found to be 0.959, 0.988 and 1.064 mM of standard trolox, respectively. At 100 microg/ml, the flower ethanol and leaf aqueous extracts significantly decreased malondialdehyde (MDA) levels (46.0 and 50.6%, respectively) by the TBARS method. The results suggest that extracts from leaf, flower and stem bark of the Siamese neem tree have strong antioxidant potential. This report supports the ethnomedical use of young leaves and flowers of this plant as a vegetable bitter tonic to promote good health.

12: J Med Food. 2004 Fall;7(3):334-9.
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Effects of aqueous extracts of garlic (Allium sativum) and neem (Azadirachta indica) leaf on hepatic and blood oxidant-antioxidant status during experimental gastric carcinogenesis.

Arivazhagan S, Velmurugan B, Bhuvaneswari V, Nagini S.

Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.

The modifying effects of aqueous extracts of garlic and neem leaf during the pre-initiation and post-initiation phases of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in male Wistar rats. The extent of lipid peroxidation and the status of phase II biotransformation enzymes such as glutathione peroxidase and glutathione-S-transferase that use reduced glutathione (GSH) as substrate were used to biomonitor the chemopreventive potential of these extracts. Enhanced lipid peroxidation in the liver and blood of tumor-bearing animals was accompanied by significant decreases in the activities of GSH-dependent antioxidants in the pre-initiation as well as in the post-initiation phases. Our results suggest that the modulatory effects of garlic and neem leaf on hepatic and blood oxidant-antioxidant status may play a key role in preventing cancer development at extrahepatic sites.

13: Trans R Soc Trop Med Hyg. 2004 Jul;98(7):435-7.
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An antimalarial extract from neem leaves is antiretroviral.

Udeinya IJ, Mbah AU, Chijioke CP, Shu EN.

Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA.

An acetone-water neem leaf extract with antimalarial activity was evaluated in vitro at 5 microg/ml for inhibition of adhesion of malaria parasite-infected erythrocytes and cancer cells to endothelial cells, and at 10 microg/ml for protection of lymphocytes against invasion by HIV. The extract was also evaluated in 10 patients with HIV/AIDS at 1000 mg daily for 30 d. The mean binding of infected erythrocytes and cancer cells per endothelial cell was 15 and 11 respectively in the absence of the extract, and 0 and 2 respectively in with the extract. In the absence and presence of the extract, 0% and 75%, respectively, of lymphocytes were protected. In the treated patients, haemoglobin concentration, mean CD4+ cell count and erythrocyte sedimentation rate, which were initially 9.8 g/dl, 126 cells/microl and 90 mm/h respectively, improved to 12.1 g/dl, 241 cells/microl and 49 mm/h. Mean bodyweight and platelet count, initially 57 kg and 328 x 10(3)/mm3 respectively, increased to 60 kg and 359 x 10(3)/mm3. No adverse effects were observed during the study. The extract showed antiretroviral activity with a mechanism of action that may involve inhibition of cytoadhesion. The results may help in the development of novel antiretroviral and antimalarial drugs.

14: Toxicology. 2004 May 20;198(1-3):83-90.
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Pesticide exposure--Indian scene.

Gupta PK.

Toxicology Consulting Services Inc., C-44, Rajinder Nagar, Bareilly 243122, UP, India. drpkg_brly@sancharnet.in

Use of pesticides in India began in 1948 when DDT was imported for malaria control and BHC for locust control. India started pesticide production with manufacturing plant for DDT and benzene hexachloride (BHC) (HCH) in the year 1952. In 1958, India was producing over 5000 metric tonnes of pesticides. Currently, there are approximately 145 pesticides registered for use, and production has increased to approximately 85,000 metric tonnes. Rampant use of these chemicals has given rise to several short-term and long-term adverse effects of these chemicals. The first report of poisoning due to pesticides in India came from Kerala in 1958 where, over 100 people died after consuming wheat flour contaminated with parathion. Subsequently several cases of pesticide-poisoning including the Bhopal disaster have been reported. Despite the fact that the consumption of pesticides in India is still very low, about 0.5 kg/ha of pesticides against 6.60 and 12.0 kg/ha in Korea and Japan, respectively, there has been a widespread contamination of food commodities with pesticide residues, basically due to non-judicious use of pesticides. In India, 51% of food commodities are contaminated with pesticide residues and out of these, 20% have pesticides residues above the maximum residue level values on a worldwide basis. It has been observed that their long-term, low-dose exposure are increasingly linked to human health effects such as immune-suppression, hormone disruption, diminished intelligence, reproductive abnormalities, and cancer. In this light, problems of pesticide safety, regulation of pesticide use, use of biotechnology, and biopesticides, and use of pesticides obtained from natural plant sources such as neem extracts are some of the future strategies for minimizing human exposure to pesticides.

15: J Ethnopharmacol. 2004 May;92(1):23-36.
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Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model systems.

Dasgupta T, Banerjee S, Yadava PK, Rao AR.

Cancer Biology and Applied Molecular Biology Laboratories, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

Numerous laboratory studies reveal that various naturally occurring dietary substances can modify the patho-physiological process of various metabolic disorders and can be an effective preventive strategy for various diseases, including cancer. Indian Neem tree, Azadirachta indica A. Juss. (family: Meliaceae), contains at least 35 biologically active principles and is widely grown all over the tropics. The effect of two different doses (250 and 500 mg per kilogram body weight) of 80% ethanolic extract of the leaves of Azadirachta indica were examined on drug metabolizing Phase-I and Phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase, and lipid peroxidation in the liver of 7-week-old Swiss albino mice. Also anticarcinogenic potential of Azadirachta indica leaf extract was studied adopting protocol of benzo(a)pyrene-induced fore-stomach and 7,12-dimethyl benz(a)anthracene (DMBA)-induced skin papillomagenesis. Our primary findings reveal its potential to induce only the Phase-II enzyme activity associated mainly with carcinogen detoxification in liver of mice. The hepatic glutathione S-transferase (P < 0.005) and DT-diaphorase specific activities (P < 0.01) were elevated above basal level. With reference to antioxidant enzymes the investigated doses were effective in increasing the hepatic glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT) activities significantly (from P < 0.005 to P < 0.001). Reduced glutathione measured as non-protein sulphydryl was found to be significantly elevated in liver (P < 0.005) and in extrahepatic organs (from P < 0.005 to P < 0.001) examined in our study. Glutathione S-transferase (GST) and DT-diaphorase (DTD) showed a dose-dependent increase in extrahepatic organs. Chemopreventive response was measured by the average number of papillomas per mouse, as well as percentage of tumor-bearing animals. There was a significant inhibition of tumor burden, in both the tumor model system studied (from P < 0.005 to P < 0.001). Tumor incidence was also reduced by both the doses of Azadirachta indica extract. Copyright 2003 Elsevier Ireland Ltd.

16: J Nat Prod. 2002 Dec;65(12):1886-91.
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Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and related euphane triterpenes from the tree Melia dubia.

Pettit GR, Numata A, Iwamoto C, Morito H, Yamada T, Goswami A, Clewlow PJ, Cragg GM, Schmidt JM.

Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki, Osaka 569-1094, Japan.

The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED(50) 1.7-5.6 microg/mL). Four of the others, the previously known methyl kulonate (8), kulinone (9), 16-hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED(50) 2.5-6.2 microg/mL) the P388 cancer cell line. In addition, two new euphane triterpenes were isolated and named dubione A (6) and dubione B (7). Structures for each of the 11 euphane triterpenes were established by spectral techniques that included HRMS and 2D NMR.

17: Phytother Res. 2000 Jun;14(4):291-3.
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Garlic and neem leaf extracts enhance hepatic glutathione and glutathione dependent enzymes during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in rats.

Arivazhagan S, Balasenthil S, Nagini S.

Department of Biochemistry, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.

The protective effect of garlic (Allium sativum L.) and neem leaf (Azadirachta indica A. Juss.) was investigated on hepatic lipid peroxidation and antioxidant status during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in male Wistar rats. Enhanced lipid peroxidation in the liver of tumour-bearing animals was accompanied by significant decreases in the activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (GGT) and reduced glutathione (GSH) levels. Administration of garlic and neem leaf extracts significantly lowered lipid peroxidation and enhanced the hepatic levels of glutathione and glutathione dependent enzymes. We speculate that garlic and neem leaf significantly alter cancer development at extrahepatic sites by influencing hepatic biotransformation enzymes and antioxidants. Copyright 2000 John Wiley & Sons, Ltd.

19: IDRC Rep. 1995 Jan;22(4):10.
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India's vaccine inventor: Gursaran Talwar.

Rai U.

PIP: Dr Gursaran Talwar, 68, has worked for almost 20 years to find a safe, long-lasting, and reversible contraceptive vaccine. The Director of India's National Institute of Immunology began his research in the mid 1970s with financial support from the Indian government and IDRC. Toxicology studies were conducted for 10 years. The vaccine increases production of antibodies against human chorionic gonadotropin (HCG), a hormone which assists in preparing the uterus for embryo implantation. The vaccine blocks this process and prevents pregnancy. Without the vaccine, 50-75% of embryos fail to be implanted because of antibodies to HCG; with the vaccine, 100% do. The vaccine is administered once a month for 3 months. Although another form of contraception must be used during this time, protection afterwards lasts for a year. Boosters are given annually. In a clinical study of 88 vaccinated women, 1 pregnancy occurred in 821 menstrual cycles. Fertility returns with discontinuation of the vaccinations. Dr Talwar is also working on a contraceptive for the 3-month period using the purified extract of the neem tree, a male contraceptive, a treatment for prostate cancer, and a vaccine against leprosy.

20: Indian J Exp Biol. 1990 Nov;28(11):1008-11.
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Plant products as protective agents against cancer.

Aruna K, Sivaramakrishnan VM.

Isotope Division, Cancer Institute, Madras, India.

Out of various spices and leafy vegetables screened for their influence on the carcinogen-detoxifying enzyme, glutathione-S-transferase (GST) in Swiss mice, cumin seeds, poppy seeds, asafoetida, turmeric, kandathipili, neem flowers, manathakkali leaves, drumstick leaves, basil leaves and ponnakanni leaves increased GST activity by more than 78% in the stomach, liver and oesophagus, - high enough to be considered as protective agents against carcinogenesis. Glutathione levels were also significantly elevated in the three tissues by these plant products. All of them except neem flowers, significantly suppressed (in vivo) the chromosome aberrations (CA) caused by benzo(a)pyrene in mouse bone marrow cells. Multiple CA and exchanges reflecting the severity of damage within a cell were significantly suppressed by these nine plant products. The results suggest that these nine plant products are likely to suppress carcinogenesis and can act as protective agents against cancer.

La hierba china Astragalus membranaceus ayuda a eliminar el virus del papiloma humano

La cervicitis crónica ha sido relacionada con infecciones por el virus del papiloma humano tipo 16, virus del herpes simple 2 y citomegalovirus (CMV), como ha sido demostrado mediante la técnica de hibridación de DNA y el método de aislamiento de virus a partir de muestras tomadas de las cérvix normales y erosionadas. Un equipo de investigación del Hospital Tian Tan de Beijing demuestra en este estudio que tras una tanda de tratamiento con interferón alpha1 recombinante, el 98% de los casos mostró una mejora clínica y el 60% una clara mejora. Asimismo, las tasas de detección del virus del papiloma humano y del virus del herpes simple disminuyeron significativamente tras el tratamiento con rIFN-alpha1, cuando se comparó con los que no habían recibido tratamiento. La hierba china Astragalus membranaceus mostró un efecto sinérgico cuando fue administrada junto con la terapia a base de interferón. La hierba china Astragalus membranaceus (o huáng qí en el idioma chino) es una de las 50 hierbas principales utilizadas en la medicina tradicional china. Esta hierba es utilizada tradicionalmente para aumentar el sistema inmunitario y en la curación de heridas.

Chin Med J (Engl). 1990 Aug;103(8):647-51.Links
Viral etiology of chronic cervicitis and its therapeutic response to a recombinant interferon.Qian ZW, Mao SJ, Cai XC, Zhang XL, Gao FX, Lu MF, Shao XS, Li YY, Yang XK, Zhuo YA, et al.
Beijing Tian Tan Hospital.

Chronic cervicitis was shown to be related to papillomavirus type 16(HPV-16), herpes simplex virus type 2 and cytomegalovirus (CMV) infections as demonstrated by DNA hybridization technique and virus isolation method from samples taken from erosive and normal cervices. After one course of treatment with recombinant interferon alpha 1 (rIFN-alpha 1), 93.8% of cases showed clinical improvement and 60% marked improvement. The HPV-16 and HSV detection rates dropped down significantly after rIFN-alpha 1 treatment as compared with those before treatment. Astragalus membranaceus, a Chinese herbal drug, was shown to be synergic to interferon therapy.