Assessment of safety through mutagenicity and subchronic toxicity studies with black pepper extract preparation.

Lee Chae, Sungwon Lee, Swetha Mahadevan, Mark R Bauter, Colleen Wojenski, Kristin Robertson, Brian Premkumar, Brinda Mahadevan
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Abstract

Introduction: Black pepper (Piper nigrum) is a rich source of natural and bioactive components such as N-trans-feruloyltyramine (NFT). In this paper, we discuss the results of the subchronic toxicity and mutagenicity studies conducted to understand the potential for adverse effects if any, of Black Pepper Extract Preparation (BPE).

Methods: To evaluate mutagenicity, an Ames test was conducted with BPE in the presence and absence of S9 metabolic activation. Long-term safety was inferred through a 90-day subchronic toxicology study using adult rats. Dose levels were selected with expected human intake levels of NFT (120 mg/kg/day), with an acceptable safety factor, for preclinical safety and tolerability. Sprague Dawley rats were fed diets targeting dietary intakes (doses) of 0, 125, 350, or 700 mg/kg/day of BPE for 90 days, an NFT dose level equivalent to 68, 190, and 380 mg/kg/day.

Results: In vitro Ames test up to 5000 µg/plate with and without S9 metabolic activation showed no BPE-related increases in revertant colony numbers and was non-mutagenic. There were no BPE-related changes in viability, clinical signs, body weight, food consumption, and organ weights. BPE dietary administration did not induce any treatment-related changes in hematology, clinical chemistry, other macroscopic or microscopic endpoints.

Discussion and conclusion: The highest dose tested with BPE (700 mg/kg/day) was the no-observed-adverse-effect level (NOAEL) that revealed no adverse effects. Based on toxicological endpoints evaluated, this NOAEL for BPE corresponded to a human equivalent NFT dose level of 380 mg/kg/day, dependent upon a (∼50%) concentration of NFT in BPE.

通过黑胡椒提取物制剂的诱变性和亚慢性毒性研究评估其安全性。
简介黑胡椒(Piper nigrum)含有丰富的天然生物活性成分,如 N-反式阿魏酰酪胺(N-trans-feruloyltyramine,NFT)。本文讨论了亚慢性毒性和诱变性研究的结果,以了解黑胡椒提取物制剂(BPE)的潜在不良影响(如果有的话):为了评估诱变性,在有 S9 代谢活化和没有 S9 代谢活化的情况下对 BPE 进行了 Ames 试验。通过对成年大鼠进行为期 90 天的亚慢性毒理学研究,推断其长期安全性。剂量水平是根据人类对 NFT 的预期摄入水平(120 毫克/千克/天)和可接受的安全系数选定的,以确保临床前安全性和耐受性。给 Sprague Dawley 大鼠喂食目标膳食摄入量(剂量)为 0、125、350 或 700 毫克/千克/天的 BPE,持续 90 天,NFT 剂量水平相当于 68、190 和 380 毫克/千克/天:结果:体外阿姆斯试验(5000 微克/板)(含或不含 S9 代谢活化)显示,逆转菌落数的增加与 BPE 无关,且无突变性。存活率、临床症状、体重、食量和器官重量都没有发生与 BPE 相关的变化。BPE 膳食给药不会引起血液学、临床化学、其他宏观或微观终点发生任何与治疗相关的变化:BPE 测试的最高剂量(700 毫克/千克/天)为无观测不良效应水平(NOAEL),未发现任何不良影响。根据评估的毒理学终点,BPE 的无观测不良效应水平相当于 380 毫克/千克/天的人体等效 NFT 剂量水平,这取决于 BPE 中 NFT 的浓度(∼50%)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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