Berberine Mitigates Betel-Nut Induced Hepatocarcinogenesis, Enhances Chemosensitivity to Cisplatin and Reduces Cisplatin- Induced Nephrotoxicity in Mice Exposed to an Aqueous Extract of Betel Nut

Background: There is a considerable correlation between the use of betel-nut (BN) as a chewing substance and the development of various malignancies. Objective: The bioactive phytocompound berberine was tested as monotherapy or in combination with cisplatin to reduce BN-induced carcinogenesis in mice. We also examined how berberine affected cisplatin-induced toxicity. Methods: Swiss Albino mice were exposed to aqueous extract of betel-nut (AEBN) at a dose of 2 mg ml-1 in drinking water, for 16 weeks. Following this, the mice were given a combination of AEBN and berberine (10 mg kg-1) for 8 weeks. Control mice were given drinking water without AEBN for 24 weeks. For the combination treatment, mice that had been exposed to AEBN (2 mg ml-1) for 16 weeks were given AEBN+sodiumchloride+cisplatin (5 mg kg-1) +berberine (10 mg kg-1) for 2 weeks. Histopathology, oxidative stress, proliferation, apoptosis, oncogenic and tumor suppressor proteins, hepatotoxicity, and nephrotoxicity were assessed in tissues retrieved at treatment endpoints. Results: Berberine monotherapy reduced tissue dysplasia, liver nodulation, oxidative stress, proliferation (Ki-67 and Cyclin D1) markers, Akt/mTOR signaling, and pP53 (Ser-15) levels and apoptosis in AEBN-treated mice to levels comparable to cisplatin alone. Berberine with cisplatin decreased nephrotoxicity, fur shedding, and cancer phenotype more than cisplatin alone. Conclusion: The study results imparted a new therapeutic approach in developing more effective and less harmful cancer treatments.