College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, P.R. China.
College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, P.R. China.
Sci Rep. 2017 Jan 5;7:40278. doi: 10.1038/srep40278.
Charred areca nut (CAN) is used to treat dyspepsia and abdominal distension in children. However, reports revealed that arecoline, the most important active constituent of CAN, possesses potential toxicities. This study was designed to investigate the optimum arecoline content in CAN, using the "target constituent removal combined with bioactivity assay" strategy. Based on PTLC method, we prepared CAN lacking all arecoline (WAC-100R) and a series of different ratios of arecoline-removed CAN samples (WAC-Rx). MTT and acute toxicity assays indicated that decreasing content by 50% decreased CAN toxicity significantly. Animal results revealed arecoline contents over 50% could guarantee the beneficial effects of CAN on gastrointestinal tract. Additionally, decreasing arecoline content in CAN by 50% decreased its pro-apoptotic effects significantly. Furthermore, decreasing 50% arecoline content in CAN down-regulated the expressions of Cleaved-Caspase-3, c-jun, c-fos, COX-2, PGE2, and IL-1α. Thus, our results revealed that CAN with 50% arecoline content (WAC-50R) has similar beneficial effects on the gastrointestinal tract to CAN, whereas its toxicity was decreased significantly. Collectively, our study suggested that the strategy of "target constituent removal combined with bioactivity assay" is a promising method to identify the optimum arecoline content in CAN, which is approximately 0.12%.
烤槟榔（CAN）被用于治疗儿童消化不良和腹胀。然而，有报道显示，CAN 中最重要的活性成分槟榔碱具有潜在的毒性。本研究旨在采用“靶向成分去除结合生物活性测定”策略，研究 CAN 中槟榔碱的最佳含量。基于 PTLC 方法，我们制备了不含任何槟榔碱的 CAN（WAC-100R）和一系列不同槟榔碱去除比例的 CAN 样品（WAC-Rx）。MTT 和急性毒性试验表明，槟榔碱含量降低 50%可显著降低 CAN 的毒性。动物实验结果表明，槟榔碱含量超过 50%可保证 CAN 对胃肠道的有益作用。此外，CAN 中槟榔碱含量降低 50%可显著降低其促凋亡作用。进一步研究发现，CAN 中槟榔碱含量降低 50%可下调 Cleaved-Caspase-3、c-jun、c-fos、COX-2、PGE2 和 IL-1α 的表达。因此，我们的研究结果表明，含有 50%槟榔碱含量的 CAN（WAC-50R）对胃肠道具有与 CAN 相似的有益作用，但其毒性显著降低。综上所述，本研究表明，“靶向成分去除结合生物活性测定”策略是确定 CAN 中槟榔碱最佳含量的一种有前途的方法，其最佳含量约为 0.12%。
