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.
The effect of two different doses (50 and 100 mg/kg body wt/day for 14 days) of 80% ethanolic extract of the leaves of Adhatoda vesica were examined on drug metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of 8 weeks old Swiss albino mice. The modulatory effect of the extract was also examined on extra-hepatic organs viz. lung, kidney and forestomach for the activities of glutathione S-transferase, DT-diaphorase, superoxide dismutase and catalase. Significant increase in the activities of acid soluble sulfhydryl (-SH) content, cytochrome P450, NADPH-cytochrome P450 reductase, cytochrome b5, NADH-cytochrome b5 reductase, glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were observed in the liver at both dose levels of treatments. Adhatoda vesica acted as bifunctional inducer since it induced both phase I and phase II enzyme systems. Both the treated groups showed significant decrease in malondialdehyde (MDA) formation in liver, suggesting its role in protection against prooxidant induced membrane damage. The cytosolic protein was significantly inhibited at both the dose levels of treatment indicating the possibility of its involvement in the inhibition of protein synthesis. BHA has significantly induced the activities of GR and GSH in the present study. The extract was effective in inducing GST and DTD in lung and forestomach, and SOD and CAT in kidney. Thus, besides liver, other organs viz., lung, kidney and forestomach were also stimulated by Adhatoda, to increase the potential of the machinery associated with the detoxification of xenobiotic compounds. But, liver and lung showed a more consistent induction. Since the study of induction of the phase I and phase II enzymes is considered to be a reliable marker for evaluating the chemopreventive efficacy of a particular compound, these findings are suggestive of the possible chemopreventive role played by Adhatoda leaf extract.
Fruits or berries of Hippophae rhamnoides (sea buckthorn), a rich source of vitamins A, C, and E, carotenes, flavonoids, and microelements such as sulfur, selenium, zinc, and copper, are edible and have been shown to protect from atopic dermatitis, hepatic injury, cardiac disease, ulcer, and atherosclerosis. However, its mechanism of action is not clear. We show that Hippophae inhibits benzo(a)pyrene-induced forestomach and DMBA-induced skin papillomagenesis in mouse. This decrease in carcinogenesis may be attributed to the concomitant induction of phase II enzymes such as glutathione S-transferase and DT-diaphorase and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the mouse liver. This was accompanied by a remarkable induction of the transcription factor interferon regulatory factor-1 in the Hippophae-treated liver. Our results strongly suggest that Hippophae fruit is able to decrease carcinogen-induced forestomach and skin tumorigenesis, which might involve up-regulation of phase II and antioxidant enzymes as well as DNA-binding activity of IRF-1, a known antioncogenic transcription factor causing growth suppression and apoptosis induction for its anticancer effect.
Constant research work and evidences over the years indicate that consumption of tea, especially green tea, is good for preventing cancer. A growing body of evidence suggests beneficial role of green tea and its polyphenol in oral cancer. To elucidate the cancer preventive mechanisms of green tea, much effort has been devoted to investigate the anticancer effects of Epigallocatechin-3-gallate (EGCG), the major catechin of green tea. It has been revealed that EGCG restrained carcinogenesis in a variety of tissues through inhibition of growth factor-related cell signaling, reducing inflammatory mediators such as COX-2 and thereby limiting bioactivity of PGE2. It also enhances gene expression, modulates cellular proliferation and apoptosis. EGCG is a multi-potent anticancer agent, which not only provides solid evidence to support the anticancer potential of green tea, but also offers new ways for discovering multiple-targeted anticancer drugs.
Medicinal Plants have played a central role in the prevention and treatment of diseases since prehistoric times. In recent years, there has been growing interest in the study of medicinal plants and their extensive use in different countries. However, today it is essential to pay for the scientific proof as to whether it is rational to use a plant or its active principles. Hence the present communication constitutes a review with adequate information on the medicinal properties, ethno-medicinal uses, phytochemistry, and pharmacological activities of an Indian medicinal plant, Azima tetracantha Lam belonging to the family of Salvadoraceae. A wide range of phytochemical constituents have been isolated from A. tetracantha Lam which possesses activities like as stimulant, expectorant, anti-asthmatic activity, antispasmodic, analgesic, anti-inflammatory, anti-ulcer, anti-diarrhoeal, insecticidal, anti-microbial, antivenom activity, hepatoprotective, nephroprotective, hypoglycemic and hyperlipidemic activities. Hence, extracts of Azima tetracantha could form one of the best options for developing novel natural medicine.
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