Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Anti-inflammatory Immune Drugs Collaborative Innovation Center, Hefei, 230032, China.
Acta Pharmacol Sin. 2020 Nov;41(11):1387-1394. doi: 10.1038/s41401-020-00510-6. Epub 2020 Sep 3.
Total glycoside of paeony (TGP) has been widely used to treat inflammation and immune diseases in China. Paeoniflorin (Pae) is the major active component of TGP. Although TGP has few adverse drug reactions, the slow onset and low bioavailability of Pae limit its clinical use. Enhanced efficacy without increased toxicity is pursued in developing new agents for inflammation and immune diseases. As a result, paeoniflorin-6'-O-benzene sulfonate (CP-25) derived from Pae, is developed in our group, and exhibits superior bioavailability and efficacy than Pae. Here we describe the development process and research advance on CP-25. The pharmacokinetic parameters of CP-25 and Pae were compared in vivo and in vitro. CP-25 was also compared with the first-line drugs methotrexate, leflunomide, and hydroxychloroquine in their efficacy and adverse effects in arthritis animal models and experimental Sjögren's syndrome. We summarize the regulatory effects of CP-25 on inflammation and immune-related cells, elucidate the possible mechanisms, and analyze the therapeutic prospects of CP-25 in inflammation and immune diseases, as well as the diseases related to its potential target G-protein-coupled receptor kinases 2 (GRK2). This review suggests that CP-25 is a promising agent in the treatment of inflammation and immune diseases, which requires extensive investigation in the future. Meanwhile, this review provides new ideas about the development of anti-inflammatory immune drugs.
白芍总苷（TGP）已广泛用于中国的炎症和免疫性疾病的治疗。芍药苷（Pae）是 TGP 的主要活性成分。尽管 TGP 的不良反应较少，但芍药苷的起效慢和生物利用度低限制了其临床应用。为了开发用于炎症和免疫性疾病的新药物，人们追求在不增加毒性的情况下提高疗效。因此，我们小组开发了来源于芍药苷的苯磺酸酯（CP-25），其具有比芍药苷更高的生物利用度和疗效。本文描述了 CP-25 的开发过程和研究进展。比较了 CP-25 和芍药苷的体内和体外药代动力学参数。还比较了 CP-25 与一线药物甲氨蝶呤、来氟米特和羟氯喹在关节炎动物模型和实验性干燥综合征中的疗效和不良反应。总结了 CP-25 对炎症和免疫相关细胞的调节作用，阐明了可能的机制，并分析了 CP-25 在炎症和免疫性疾病以及与其潜在靶标 G 蛋白偶联受体激酶 2（GRK2）相关疾病中的治疗前景。本综述表明 CP-25 是一种有前途的炎症和免疫性疾病治疗药物，未来需要进一步广泛研究。同时，这篇综述为抗炎免疫药物的开发提供了新的思路。
