Roots ofWithania somniferaInhibit Forestomach and Skin Carcinogenesis in Mice

Abstract

We evaluated the cancer chemopreventive efficacy of the Withania somnifera root, which has been used in the Indian traditional medicine system for many centuries for the treatment of various ailments. Since, studies showing its mechanism-based cancer chemopreventive efficacy are limited, this was investigated in the present study. We studied the effect of dietary administration of Withania root on hepatic phase I, phase II and antioxidant enzymes by estimation of its level/activity, as well as in attenuating carcinogen-induced forestomach and skin tumorigenesis in the Swiss albino mouse model. Our findings showed that roots of W.somnifera inhibit phase I, and activates phase II and antioxidant enzymes in the liver. Further, in a long-term tumorigenesis study, Withania inhibited benzo(a)pyrene-induced forestomach papillomagenesis, showing up to 60 and 92% inhibition in tumor incidence and multiplicity, respectively. Similarly, Withania inhibited 7,12-dimethylbenzanthracene-induced skin papillomagenesis, showing up to 45 and 71% inhibition in tumor incidence and multiplicity. In both studies, Withania showed no apparent toxic effects in mice as monitored by the body weight gain profile. Together, these findings suggest that W.somnifera root has chemopreventive efficacy against forestomach and skin carcinogenesis and warrants the identification and isolation of active compounds responsible for its anticancer effects, which may provide the lead for the development of antitumor agents.

Nephroprotective Effect ofWithania somnifera:A Dose-Dependent Study

“…Marked reduction in these levels might be due to the presence of W. somnifera's potent antioxidant substances, such as its alkaloids, withanolides, and few flavonoids. In particular, glycowithnolide substances sitoindosides VII-X and withaferin A, which are rich in antioxidant properties, [34][35][36] enhance the antioxidant status and in turn may quench the free radicals generated in GEN-induced nephrotoxicity. Former reports from our lab showed that W. somnifera normalized the levels of urea, creatinine, uric acid, and nonprotein nitrogen by increasing the antioxidant status in hyperammonemic conditions.…”

“…Furthermore, the antioxidant and free radical scavenging properties of W. somnifera were also studied in fore stomach and skin carcinogenesis in mice. [35][36][37] Taking into account the medicinal properties of W. somnifera, we hypothesize that W. somnifera would work in a dynamic way to give maximum therapeutic efficacy in the prevention or reversal of drug-induced nephrotoxicity without causing any side effects.…”

The protective effect of a purified extract of Withania somnifera against doxorubicin-induced cardiac toxicity in rats

“…Moreover, administration of WIT extract was found to reduce the myelosuppression (Davis and Kuttan 1998) and urotoxicity (Davis and Kuttan 2000) induced by antineoplastic agents such as cyclophosphamide in mice. WIT roots have also shown a specific chemopreventive efficacy against forestomach and skin carcinogenesis in mice (Padmavathi et al 2005).…”

Chemistry and pharmacology of withania somnifera: An update

“…Ashwagandha possesses anticancer properties against prostate, colon, lung, breast, leukemia, pancreatic, renal, head and neck cancer cells of humans (Nema et al, 2013;Patel et al, 2013;Yadav et al, 2010), forestomach and skin cancer cells in mice (Padmavathi et al, 2005). Recently the anticancerous potential of W. somnifera and its bioactive withanolides has been extensively studied by several research groups all around the world, which have discovered diverse mechanisms such as cytotoxicity, cell differentiation induction, cancer chemoprevention, cyclooxygenase-2 (COX-2) inhibition and a potential to inhibit the enzyme quinine reductase.…”