1. Department of Pharmacology R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India;
2. Department of Pharmacology, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India;
3. Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India;
4. Department of Pharmacognosy, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, Maharashtra, India;
5. Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box- 17666, Al Ain, Abu Dhabi, UAE.
*Authors contribute equally to this work.
Barringtonia racemosa fruits are believed to be useful in cancer treatment in Ayurveda, the Indian system of medicine. In present study, bartogenic acid (BA), a triterpenoid constituent of Barringtonia fruits was evaluated for its cytotoxicity property using the human skin carcinoma cell line (SCC-13) and human peripheral blood mononuclear cells (PBMC). The chemopreventive efficacy of BA was evaluated against the DMBA/Croton oil-induced skin carcinogenesis in mice.BA was orally administered at the doses of 1, 2 or 4 mg/kg/day or applied topically every day for 12 weeks following DMBA application. The in vitro data from cell lines revealed that BA induces cytotoxicity against the SCC-13 cells (IC50=7.5 µM). It was found 4.05 times more selective to exert cytotoxicity against SCC-13 as compared to the PBMC (IC50=30.4 µM). The in vivo datacollected from mice model of DMBA/Croton oil-induced skin carcinogenesis revealed that BA administered orally or applied topically, both reduced the precancerous skin lesions andthe incidence of tumor bearing. The oral doses of BA (2 and 4 mg/kg) and topical treatment significantly reduced the incidence and number of skin papillomas. At these doses, BA also increased the activities of catalase and superoxide dismutase and induced an increase in glutathionecontent and inhibited lipid peroxidation in the skin. These findings reveal the chemopreventive efficacy of BA and also demonstrate that it contributes to the cytotoxic and antioxidative effects of Barringtonia racemosa fruits. The study also validates the traditional claims of Barringtonia fruits and provides a scientific basis of its chemopreventive property.
Keywords: Bartogenic acid, Two-stage skin carcinogenesis, DMBA/Croton oil, Skin Cancer, Chemoprevention, Natural products, Phytochemicals.