One of Ayurveda’s most powerful herbs, Withania somnifera has been the subject of over 100 international clinical studies. The role of the herb in various immune disorders, endocrine disorders, its anti-inflammatory activity, the anxiolytic activity of its extracts has been established beyond doubt. Yet, the most important activity of Withania remains its potent immunomodulating activity. A study Davis L, & Kuttan G, showed the effect of Withania somnifera on the cellular immune responses (CMI) was studied in normal as well as tumour bearing animals. Administration of Withania extract was found to enhance the proliferation of lymphocytes, bone marrow cells and thymocytes in responses to mitogens. Both PHA and Con A mitogens along with Withania treated splenocytes, bone marrow cells and thymocytes could stimulate proliferation twice greater than the normal. Withania treated splenocytes along with the mitogen LPS (10 microg/ml) could stimulate the lymphocyte proliferation six times more than the normal. Natural killer cell activity (NK) was found to be enhanced significantly in both the normal and the tumour bearing group and it was found to be earlier than the control (48.92% cell lysis). Antibody dependent cellular cytotoxicity (ADCC) was found to be enhanced in the Withania treated group on the 9th day (65% cell lysis). An early Antibody dependent complement mediated cytotoxicity (ACC) was observed in the Withania treated group on day 13 (47% cell lysis).
J Prakash and co workers demonstrated the chemopreventive effect of Withania somnifera hydroproprietory root extract (WSRE) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer in Swiss albino mice. The skin lesions were induced by the twice-weekly topical application of DMBA (100 nmol/ 100 microliters acetone) for 8 wk on the shaved back of mice. WSRE was administered at the maximal tolerated dose of 400 mg/kg p.o. three times per week on alternate days 1 wk before DMBA and continued for 24 wk thereafter. The results of the study revealed a significant decrease in incidence and average number of skin lesions in mice compared with DMBA alone at the end of Week 24. Biochemical parameters were assessed in the lesions of WSRE-treated and untreated control mice. A significant impairment was noticed in the levels of reduced glutathione, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase in skin lesions of DMBA-treated control mice compared with vehicle-treated mice. These parameters were returned to near normal by administration of WSRE to DMBA-treated mice. The above findings were supported by histopathological studies. From the present study, it can be inferred that WRSE possesses potential chemopreventive activity in this experimental model of cancer. The chemopreventive activity may be linked to the antioxidant/free radical-scavenging constituents of the extract. The anti-inflammatory and immunomodulatory properties of WSRE are also likely to contribute to its chemopreventive action.
In a study by Russo A, and co workers the free radical scavenging capacity of methanolic extracts from Witania Somnifera was investigated as well as and the effect on DNA cleavage induced by H2O2 UV-photholysis. In addition, the investigators investigated whether the plant extracts are capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. The extract showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage;. These results were confirmed by a significant protective effect on H2O2-induced cytoxicity and DNA damage in human non-immortalized fibroblasts. These antioxidant effects of active principle of Withania Somnifera may explain, at least in part, the reported anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory and antiaging effects produced by the plant extracts in experimental animal and in clinical situations and may justify the further investigation of its other beneficial biological properties.
A reputed immunoprotector, this herb is used in Ayurveda for longevity. Its role as an immunoprotector has been established in various clinical trials and the extract of this herb has demonstrated significant immunomodulating properties.
Aqueous extract of T. cordifolia inhibited Fenton (FeSO4) reaction and radiation mediated 2-deoxyribose degradation in a dose dependent fashion with an IC50 value of 700 microg/ml for both Fenton and radiation mediated 2-DR degradation. Similarly, it showed a moderate but dose dependent inhibition of chemically generated superoxide anion at 500 microg/ml concentration and above with an IC50 value of 2000 microg/ml. Aqueous extract inhibited the formation of Fe2+-bipiridyl complex and formation of comet tail by chelating Fe2+ ions in a dose dependent manner with an IC50 value of 150 microg/ml for Fe2+-bipirydyl formation and maximally 200 microg/ml for comet tail formation, respectively. The extract inhibited ferrous sulphate mediated lipid peroxidation in a dose-dependent manner with an IC50 value of 1300 microg/ml and maximally (70%) at 2000 microg/ml. The results reveal that the direct and indirect antioxidant actions of T. cordifolia probably act in corroboration to manifest the overall radioprotective effects.
Jagetia and co workers have shown that the exposure of HeLa cells to 0, 5, 10, 25, 50 and 100 microg/ml of Tinospora cordifolia extracts (methanol, aqueous and methylene chloride) resulted in a dose-dependent but significant increase in cell killing, when compared to non-drug-treated controls. The effects of methanol and aqueous extracts were almost identical. However, methylene chloride extract enhanced the cell killing effect by 2.8- and 6.8-fold when compared either to methanol or aqueous extract at 50 and 100 microg/ml, respectively. Conversely, the frequency of micronuclei increased in a concentration-dependent manner in Tinospora cordifolia-treated groups and this increase in the frequency of micronuclei was significantly higher than the non-drug-treated control cultures and also with respect to 5 microg/ml Tinospora cordifolia extract-treated cultures, at the rest of the concentrations evaluated. Furthermore, the micronuclei formation was higher in the methylene chloride extract-treated group than in the other two groups. The dose response relationship for all three extracts evaluated was linear quadratic. The effect of Tinospora cordifolia extracts was comparable or better than doxorubicin treatment. The micronuclei induction was correlated with the surviving fraction of cells and the correlation between cell survival and micronuclei induction was found to be linear quadratic. Our results demonstrate that Tinospora cordifolia killed the cells very effectively in vitro and deserves attention as an antineoplastic agent
Holy Basil as it is commonly known is considered a herb of the Gods. Its adaptogenic properties make this a particularly important plants in the prevention of immune disorders. Researchers at the Department of Horticulture and National Food Safety and Toxicology, Michigan State University, USA. have demonstrated the antioxidant activity of the herb extracts.Two Researchers, Vrinda B & Uma Devi P , have shown that Orientin (Ot) and Vicenin (Vc), two water-soluble flavonoids isolated from the leaves of Indian holy basil Ocimum sanctum have shown significant protection against radiation lethality and chromosomal aberrations in vivo.
Other researchers at The Department of Horticulture and National Food Safety and Toxicology, Michigan State University, USA have demonstrated the anti-oxidant activity by bioassay-directed extraction of the fresh leaves and stems of Ocimum sanctum and purification of the extract yielded the following compounds; cirsilineol , cirsimaritin , isothymusin , isothymonin , apigenin , rosmarinic acid , and appreciable quantities of eugenol. The structures of compounds 1-6 were established using spectroscopic methods. Compounds 1 and 5 were isolated previously from O. sanctum whereas compounds 2 and 3 are here identified for the first time from O. sanctum. Eugenol, a major component of the volatile oil, and compounds 1, 3, 4, and 6 demonstrated good antioxidant activity at 10-microM concentrations. Anti-inflammatory activity or cyclooxygenase inhibitory activity of these compounds were observed. Eugenol demonstrated 97% cyclooxygenase-1 inhibitory activity when assayed at 1000-microM concentrations. Compounds 1, 2, and 4-6 displayed 37, 50, 37, 65, and 58% cyclooxygenase-1 inhibitory activity, respectively, when assayed at 1000-microM concentrations.
Researchers studying the incidence of papillomas and squamous cell carcinomas have shown that these significantly reduced, and treatment with extracts of Ocimum sanctum increased the survival rate in the topically applied leaf paste and orally administered extracts to animals. Orally administered aqueous extract have showed profound effect in Histopathological observations made on the mucosa confirmed these findings. Further fluorescent spectral studies at 405 nm excitation on the mucosa of control, DMBA and extracts orally administered experimental animals showed a prominent maxima at 430 nm for control, 628 nm for DMBA induced carcinomas while aqueous and ethanolic extracts administered animals showed at 486 nm and 488 nm, respectively. The fluorescent intensity at 630 nm (FI630 nm) was significantly reduced and the ratio of fluorescent intensities at 520 nm and 630 nm (FI520 nm/630 nm) were significantly increased in orally administered extracts compared to DMBA treated animals. These observations suggest that the orally administered extract of O. sanctum may have the ability to prevent the early events of carcinogenesis.
A study by Banerjee S and co workers, reports the modulatory influence of proprietory extract from the leaves of Ocimum sanctum on the activities of cytochrome p-450, cytochrome b5, and aryl hydrocarbon hydroxylase enzymes in the liver and glutathione-S-transferase and reduced glutathione level in the liver, lung, and stomach of the mouse. Oral treatment with the leaf extract at 400 and 800 mg/kg body wt for 15 days would significantly elevate the activities of cytochrome p-450 (p < 0.05), cytochrome b5 (p < 0.01, p < 0.001), aryl hydrocarbon hydroxylase (p < 0.05), and glutathione S-transferase (p < 0.05, p < 0.01), all of which are important in the detoxification of carcinogens as well as mutagens. Moreover treatment with 400 and 800 mg/kg body wt of Ocimum extract for 15 days also significantly elevated extrahepatic glutathione-S-transferase (p < 0.05, p < 0.01). The reduced glutathione level was also elevated by treatment with the leaf extract in liver, lung, and stomach tissues (p < 0.01, p < 0.001). Mice fed a diet containing 0.75% butylated hydroxyanisole (positive control) revealed no alteration in the basal hepatic cytochrome p-450 and aryl hydrocarbon hydroxylase level, but hepatic cytochrome b5 and glutathione S-transferase activity in hepatic and extrahepatic organs were elevated in a time-responsive manner (p < 0.05, p < 0.001). The observations suggest further exploitation of the Ocimum leaf extract or its active principle(s) for the chemoprevention of chemical carcinogenesis in different animal model systems.
Modified pectins extracted from this plant yield compounds that have anti-metastatic activity. Avraham Raz, PhD, director of the tumor progression and metastasis lab at Detroit's Barbara Ann Karamanos Cancer Institute, became interested in the way cancer cells clump together to form tumors. He found that this clumping needed sticky sugars -- and that pectins can keep these sugars from sticking. Normal pectins won't work in the blood stream. But Raz's team found a way to alter pectin so that it could be digested and enter the blood. And that's not all. In a recent issue of the Journal of the National Cancer Institute, Raz and colleagues showed that these modified citrus pectins cut the size of tumors in mice with implanted human breast and colon cancers.
A team of researchers at Wayne State University, School of Medicine, and Department of Pathology, Karmanos Cancer Institute, Detroit, MI, USA. studied the effects of high pH- and temperature-modified citrus pectin (MCP), a nondigestible, water-soluble polysaccharide fiber derived from citrus fruit that specifically inhibits the carbohydrate-binding protein galectin-3, on tumor growth and metastasis in vivo and on galectin-3-mediated functions in vitro. METHODS: In vivo tumor growth, angiogenesis, and metastasis were studied in athymic mice that had been fed with MCP in their drinking water and then injected orthotopically with human breast carcinoma cells (MDA-MB-435) into the mammary fat pad region or with human colon carcinoma cells (LSLiM6) into the cecum. Galectin-3-mediated functions during tumor angiogenesis in vitro were studied by assessing the effect of MCP on capillary tube formation by human umbilical vein endothelial cells (HUVECs) in Matrigel. The effects of MCP on galectin-3-induced HUVEC chemotaxis and on HUVEC binding to MDA-MB-435 cells in vitro were studied using Boyden chamber and labeling assays, respectively. The data were analyzed by two-sided Student's t test or Fisher's protected least-significant-difference test.
Tumor growth, angiogenesis, and spontaneous metastasis in vivo were statistically significantly reduced in mice fed MCP. In vitro, MCP inhibited HUVEC morphogenesis (capillary tube formation) in a dose-dependent manner. In vitro, MCP inhibited the binding of galectin-3 to HUVECs: At concentrations of 0.1% and 0.25%, MCP inhibited the binding of galectin-3 (10 micro g/mL) to HUVECs by 72.1% (P =.038) and 95.8% (P =.025), respectively, and at a concentration of 0.25% it inhibited the binding of galectin-3 (1 micro g/mL) to HUVECs by 100% (P =.032). MCP blocked chemotaxis of HUVECs toward galectin-3 in a dose-dependent manner, reducing it by 68% at 0.005% (P<.001) and inhibiting it completely at 0.1% (P<.001). Finally, MCP also inhibited adhesion of MDA-MB-435 cells, which express galectin-3, to HUVECs in a dose-dependent manner. CONCLUSIONS: MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effects on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.
Researchers at Texas A&M University-Kingsville Citrus Center, Weslaco, TX 78596, USA.undertook a study to characterize the pectin from four citrus species and to determine their in vitro inhibitory activities on the binding of fibroblast growth factor (FGF) to the FGF receptor (FGFR). Pectin from various parts of lemon, grapefruit, tangerine, and orange were isolated and characterized. Tangerine had the highest pectin content among the four citrus species. Segment membrane contained as much as or more pectin than flavedo/albedo. Anhydrogalacturonic content was highest in pectin from segment membrane of tangerine and flavedo/albedo of grapefruit. Lemon pectin contained the highest methoxyl content (MC), and grapefruit contained the largest proportion of lower molecular weight (<10000 Da) pectin. Tangerine contained the highest neutral sugar in both flavedo/albedo and segment membrane. The interdependency of heparin on factor-receptor interaction provides a means for identifying new antagonists of growth factor activity and thus for treatment of various diseases. These results showed that pectin significantly inhibited the binding of FGF-1 to FGFR1 in the presence of 0.1 microg/mL heparin. The pectin from the segment membrane of lemon was the most potent inhibitor. The inhibition activity was significantly correlated with sugar content, MC, and size of pectin. Kinetic studies revealed a competitive nature of pectin inhibition with the heparin, a crucial component of the FGF signal transduction process. The observation that the heparin-dependent biological activity of FGF signal transduction is antagonized by citrus pectin should be further investigated for the use of these pectins as anti-growth factor agents for potential health benefits.