Content decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri

Publication date: Available online 4 April 2017 Source:Environmental Toxicology and Pharmacology Author(s): Shifeng Wang, Yuxin Zhang, Qiao Zhang, Sha Peng, Chen Shen, Yangyang Yu, Minyu Zhang, Wei Yang, Qinghua Wu, Yanling Zhang, Shiyou Li, Yanjiang Qiao Improper usage of unprocessed Radix bupleuri (chaihu) may cause fetal toxicity. Baking herb with vinegar is believed to attenuate the toxicity. However, the chemical and molecular basis remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1, b2. Results showed that SSa and SSd possessed higher affinity with sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) by molecular docking, and exhibited stronger toxic responses on cardiomyocytes and hepatocytes than the other three saikosaponins in equivalent concentrations. Further, SSa and SSd induced LC3 puncta formation in U2OS-mCherry-EGFP-LC3 cells. Blockage of autophagy by 3-methyladenine did not abrogate HepG2 or H9c2 induced cytotoxicity. In parallel, none of SSc, SSb1, or SSb2 induced cell injury. Our study provides a rationale for revealing how changes in chemical ingredients is connected to the toxicity of Chaihu during the vinegar baking process and also provides a guidance for structure optimization to reduce drug induced toxicity. Graphical abstract
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research