title: Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing.
abstract: Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.affiliation: Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Science, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Pathology, Caritas Medical Center, Hong Kong, China.
authors.forename: Man-Shan
authors.initials: MS
authors.lastname: Tsui
authors.affiliation: Department of Pathology, Guangzhou University of Chinese Medicine, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yi
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Xiu-Qiong
authors.initials: XQ
authors.lastname: Fu
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Chi Leung
authors.initials: CL
authors.lastname: Chan
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Ya-Xi
authors.initials: YX
authors.lastname: Li
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Pei-Li
authors.initials: PL
authors.lastname: Zhu
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.|Institute of Integrated Bioinfomedicine &Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China.
authors.forename: Anfernee Kai Wing
authors.initials: AK
authors.lastname: Tse
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.|Institute of Integrated Bioinfomedicine &Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Lu
authors.affiliation: Consun Chinese Medicines Research Centre for Renal Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.|Institute of Integrated Bioinfomedicine &Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
mesh_terms: D000818:Animals; D066126:Cardiotoxicity / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000633:toxicity; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000097:blood; D005786:Gene Expression Regulation; D020939:Zingiber officinale / Q000737:chemistry; D008297:Male; D008516:Medicine, Chinese Traditional; D055432:Metabolomics; D030021:Pinellia / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000097:blood / Q000235:genetics; D013678:Technology, Pharmaceutical / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics
chemical_list: D004365:Drugs, Chinese Herbal; D005609:Free Radicals; D016212:Transforming Growth Factor beta; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases