Department of Pharmacology, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
J Ethnopharmacol. 2020 May 23;254:112649. doi: 10.1016/j.jep.2020.112649. Epub 2020 Feb 14.
Calculus bovis (C. bovis), a widespread known traditional animal drug in China and Japan, has been widely used for a long time to treat various diseases, including high fever, convulsion and stroke. The aim of the present paper is to comprehensively review knowledge about C. bovis in terms of traditional usages, origin, chemical constituents, pharmacological activities and toxicology to seek an applicable substitute for NCB and provide potential new strategies utilizing C. bovis. Additionally, directions and perspectives for future investigations regarding C. bovis are also discussed.
In this paper, the traditional usages, origin, chemical constituents, pharmacology, and toxicology of C. bovis are comprehensively and systematically summarized by searching scientific databases, including Web of Science, PubMed, ScienceDirect, Springer, CNKI, Baidu Scholar and others. Additionally, some classic books of Chinese herbal medicine, academic papers authored by individuals with MSc and PhD degrees, local government reports as well as the state of local drug standards are also retrieved.
Currently, C. bovis mainly derives from four sources: natural Calculus bovis (NCB), Calculus bovis sativus (CBS), Cultured calculus bovis (CCB) and Calculus bovis artifactus (CBA). Owing to their different formation processes, the chemical constituents of the four kinds of C. bovis show certain differences. Additionally, over 44 chemical constituents have been isolated and identified from C. bovis, mainly including bile pigments, bile acids, cholesterols and amino acids. Further investigations have revealed a wide range of pharmacological effects of C. bovis, with effects on the nervous system, cardiovascular system, respiratory system, digestive system, immune system and others. Furthermore, NCB and CBA show hypotoxicity, but high concentrations of bilirubin can cause neurotoxicity and hearing impairment. Additionally, pharmacokinetic data for C. bovis are still lacking.
CBS contains analogous types and amounts of constituents and exerts similar therapeutic effects to NCB. Thus, CBS might be used as a sustainable substitute for NCB. Furthermore, the configuration and concentration of bile acids and bilirubin in C. bovis are responsible for the difference in pharmacological effects in the four types C. bovis. Further studies should focus on the structure-function relationship of bile acids and bilirubin in C. bovis by employing pharmacokinetics.
牛胆石（C. bovis），一种在中国和日本广泛应用的传统动物药物，长期以来一直被广泛用于治疗各种疾病，包括高热、惊厥和中风。本文旨在全面综述牛胆石的传统用途、来源、化学成分、药理活性和毒理学知识，寻求 NCB 的替代品，并为利用牛胆石提供潜在的新策略。此外，还讨论了牛胆石未来研究的方向和前景。
本文通过检索科学数据库，包括 Web of Science、PubMed、ScienceDirect、Springer、CNKI、百度学术等，全面系统地综述了牛胆石的传统用途、来源、化学成分、药理学和毒理学。此外，还检索了一些中草药经典著作、具有硕士和博士学位的个人学术论文、地方政府报告以及地方药品标准状况等。
目前，牛胆石主要来源于四种来源：天然牛胆石（NCB）、人工培育牛胆石（CBS）、养殖牛胆石（CCB）和人工牛胆石（CBA）。由于形成过程不同，四种牛胆石的化学成分存在一定差异。此外，从牛胆石中已分离鉴定出 44 种化学成分，主要包括胆色素、胆汁酸、胆固醇和氨基酸等。进一步研究发现，牛胆石具有广泛的药理作用，对神经系统、心血管系统、呼吸系统、消化系统、免疫系统等均有作用。此外，NCB 和 CBA 具有低毒性，但胆红素浓度过高可引起神经毒性和听力损伤。此外，牛胆石的药代动力学数据仍然缺乏。
CBS 含有类似的成分类型和含量，具有与 NCB 相似的治疗效果。因此，CBS 可能作为 NCB 的可持续替代品。此外，四种牛胆石中胆汁酸和胆红素的结构和浓度决定了其药理作用的差异。进一步的研究应侧重于运用药代动力学研究牛胆石中胆汁酸和胆红素的结构-功能关系。
