Tianjin University of Traditional Chinese Medicine, Tianjin-301617, China.
Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin-300250, China.
J Ethnopharmacol. 2021 Mar 25;268:113566. doi: 10.1016/j.jep.2020.113566. Epub 2020 Nov 7.
Bisbenzylisoquinoline (BBIQ) alkaloids are generally present in plants of Berberidaceae, Monimiaceae and Ranunculaceae families in tropical and subtropical regions. Some species of these families are used in traditional Chinese medicine, with the effects of clearing away heat and detoxification, promoting dampness and defecation, and eliminating sores and swelling. This article offers essential data focusing on 13 representative BBIQ compounds, which are mainly extracted from five plants. The respective botany, traditional uses, phytochemistry, pharmacokinetics, and toxicity are summarized comprehensively. In addition, the ADME prediction of the 13 BBIQ alkaloids is compared and analyzed with the data obtained.
We have conducted a systematic review of the botanical characteristics, traditional uses, phytochemistry, pharmacokinetics and toxicity of BBIQ alkaloids based on literatures collected from PubMed, Web of Science and Elsevier during 1999-2020. ACD/Percepta software was utilized to predict the pharmacokinetic parameters of BBIQ alkaloids and their affinity with enzymes and transporters.
Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity of 13 alkaloids, namely, tetrandrine, dauricine, curine, trilobine, isotrilobine, cepharanthine, daurisoline, thalicarpine, thalidasine, isotetrandrine, liensinine, neferine and isoliensinine, have been summarized in this paper. It can't be denied that these alkaloids are important material basis of pharmacological effects of family Menispermaceae and others, and for traditional and local uses which has been basically reproduced in the current studies. The 13 BBIQ alkaloids in this paper showed strong affinity and inhibitory effect on P-glycoprotein (P-gp), with poor oral absorption and potent binding ability with plasma protein. BBIQ alkaloids represented by tetrandrine play a key role in regulating P-gp or reversing multidrug resistance (MDR) in a variety of tumors. The irrationality of their usage could pose a risk of poisoning in vivo, including renal and liver toxicity, which are related to the formation of quinone methide during metabolism.
Although there is no further clinical evaluation of BBIQ alkaloids as MDR reversal agents, their effects on P-gp should not be ignored. Considering their diverse distribution, pharmacokinetic characteristics and toxicity reported during clinical therapy, the quality standards in different plant species and the drug dosage remain unresolved problems.
双苄基异喹啉（BBIQ）生物碱一般存在于热带和亚热带地区的小檗科、防己科和毛茛科植物中。这些科的一些物种被用于传统中药，具有清热解毒、祛湿通便、消肿止痛的功效。本文提供了 13 种代表性 BBIQ 化合物的基本数据，这些化合物主要从 5 种植物中提取。全面总结了它们各自的植物学、传统用途、植物化学、药代动力学和毒性。此外，还比较分析了这 13 种 BBIQ 生物碱的 ADME 预测结果与文献中获得的数据。
我们对 1999 年至 2020 年期间从 PubMed、Web of Science 和 Elsevier 收集的文献进行了系统综述，综述了 BBIQ 生物碱的植物学特征、传统用途、植物化学、药代动力学和毒性。ACD/Percepta 软件用于预测 BBIQ 生物碱的药代动力学参数及其与酶和转运体的亲和力。
本文总结了 13 种生物碱，即粉防己碱、蝙蝠葛碱、小檗碱、汉防己甲素、汉防己乙素、千金藤碱、头花千金藤碱、蝙蝠葛苏林碱、蝙蝠葛任碱、异粉防己碱、莲心碱、小檗胺和去甲异波尔定碱的植物学、传统用途、植物化学、药代动力学和毒性。不可否认的是，这些生物碱是防己科和其他科的药理作用的重要物质基础，也是目前研究中基本重现的传统和地方用途的重要物质基础。本文中的 13 种 BBIQ 生物碱对 P-糖蛋白（P-gp）具有很强的亲和力和抑制作用，口服吸收差，与血浆蛋白结合能力强。以粉防己碱为代表的 BBIQ 生物碱在多种肿瘤中对 P-gp 具有调节或逆转多药耐药（MDR）的作用。它们的不合理使用可能会导致体内中毒的风险，包括肾毒性和肝毒性，这与代谢过程中形成醌亚甲基有关。
虽然尚未对 BBIQ 生物碱作为 MDR 逆转剂进行进一步的临床评价，但不应忽视其对 P-gp 的影响。考虑到它们在临床治疗中的分布广泛、药代动力学特征和毒性报道，不同植物物种的质量标准和药物剂量仍然是未解决的问题。
