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Content decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri.
Environ Toxicol Pharmacol 2017; 52:129-137ET

Abstract

Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and 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 the cytotoxicities induced by SSa and SSd. In parallel, none of SSc, SSb1, or SSb2 caused cell injury. Our study reveals how changes in chemical ingredients are connected to the toxicity of Chaihu during vinegar baking process and also provides a guidance for structure optimization to reduce drug induced toxicity.

Authors+Show Affiliations

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.ACEA Biosciences Inc., Hangzhou 310030, China.HD Biosciences Co., Ltd, Shanghai 201201, China.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: lishiyou@big.ac.cn.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China. Electronic address: yjqiao@bucm.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28412648

Citation

Wang, Shifeng, et al. "Content Decline of SERCA Inhibitors Saikosaponin a and D Attenuates Cardiotoxicity and Hepatotoxicity of Vinegar-baked Radix Bupleuri." Environmental Toxicology and Pharmacology, vol. 52, 2017, pp. 129-137.
Wang S, Zhang Y, Zhang Q, et al. Content decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri. Environ Toxicol Pharmacol. 2017;52:129-137.
Wang, S., Zhang, Y., Zhang, Q., Peng, S., Shen, C., Yu, Y., ... Qiao, Y. (2017). Content decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri. Environmental Toxicology and Pharmacology, 52, pp. 129-137. doi:10.1016/j.etap.2017.04.002.
Wang S, et al. Content Decline of SERCA Inhibitors Saikosaponin a and D Attenuates Cardiotoxicity and Hepatotoxicity of Vinegar-baked Radix Bupleuri. Environ Toxicol Pharmacol. 2017;52:129-137. PubMed PMID: 28412648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Content decline of SERCA inhibitors saikosaponin a and d attenuates cardiotoxicity and hepatotoxicity of vinegar-baked Radix bupleuri. AU - Wang,Shifeng, AU - Zhang,Yuxin, AU - Zhang,Qiao, AU - Peng,Sha, AU - Shen,Chen, AU - Yu,Yangyang, AU - Zhang,Minyu, AU - Yang,Wei, AU - Wu,Qinghua, AU - Zhang,Yanling, AU - Li,Shiyou, AU - Qiao,Yanjiang, Y1 - 2017/04/04/ PY - 2016/12/18/received PY - 2017/03/29/revised PY - 2017/04/02/accepted PY - 2017/4/17/pubmed PY - 2017/10/17/medline PY - 2017/4/17/entrez KW - Autophagy KW - Cardiotoxicity KW - Hepatotoxicity KW - Radix bupleuri KW - SERCA SP - 129 EP - 137 JF - Environmental toxicology and pharmacology JO - Environ. Toxicol. Pharmacol. VL - 52 N2 - Improper usage of unprocessed Radix bupleuri root (chaihu) may cause cardiotoxicity and liver injury. Baking herb with vinegar is believed to attenuate the adverse responses. However, the chemical and molecular basis involved remained unclear. To this end, we investigated the in vitro toxicity of saikosaponin a, c, d, and their hydrolysates saikosaponin b1 and 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 the cytotoxicities induced by SSa and SSd. In parallel, none of SSc, SSb1, or SSb2 caused cell injury. Our study reveals how changes in chemical ingredients are connected to the toxicity of Chaihu during vinegar baking process and also provides a guidance for structure optimization to reduce drug induced toxicity. SN - 1872-7077 UR - https://www.unboundmedicine.com/medline/citation/28412648/Content_decline_of_SERCA_inhibitors_saikosaponin_a_and_d_attenuates_cardiotoxicity_and_hepatotoxicity_of_vinegar_baked_Radix_bupleuri_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1382-6689(17)30102-3 DB - PRIME DP - Unbound Medicine ER -