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-ß 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.
Subject(s)
Cardiotoxicity/prevention & control , Drugs, Chinese Herbal/chemistry , Metabolomics , Pinellia/chemistry , Technology, Pharmaceutical/methods , Animals , Drugs, Chinese Herbal/toxicity , Free Radicals/antagonists & inhibitors , Free Radicals/blood , Gene Expression Regulation , Zingiber officinale/chemistry , Male , Medicine, Chinese Traditional , Pinellia/toxicity , Rats , Rats, Sprague-Dawley , Signal Transduction , TOR Serine-Threonine Kinases/blood , TOR Serine-Threonine Kinases/genetics , Transforming Growth Factor beta/blood , Transforming Growth Factor beta/geneticsABSTRACT
We describe a PFIC2 patient with a good response to ursodeoxycholic acid for 9 years. We found two novel ABCB11 gene mutations in the patient, i.e. I498T and 2098delA. The correlation of the patient's genotypes with the clinical course supports the existence of a phenotypic continuum between BRIC2 and PFIC2.
