Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 2: Hepatic disposition in vivo and hepatoprotective activity in vitro. (23rd May 2019)

• Record Type: Journal Article
• Authors: Tian, Xiaoting; Liu, Huan; Qiao, Shida; Yin, Hao; Chen, Mingcang; Hu, Pei; Wang, Yangyang; Peng, Huige; Liu, Fang; Pan, Guoyu; Huang, Chenggang
• Is Part Of: Journal of ethnopharmacology. Volume 236(2019)
• Page Start: 161
• Page End: 172
• Publication Date: 2019-05-23
• Subjects: YCHT Yin-Chen-Hao Tang -- TCM traditional Chinese medicine -- HPLC-QQQ-MS/MS high performance liquid chromatography coupled to triple quadrupole mass spectrometry -- IS internal standard -- AST aspartate transaminase -- ALT alanine transaminase -- LDH lactate dehydrogenase -- SOD superoxide dismutase -- TLC thin-layer chromatography -- ESI electrospray ionization -- SRM selective reaction monitoring -- QC quality control -- LLOQ the lower limit of quantification -- DMEM Dulbecco's modified Eagle medium -- MTT 3-[4, 5-dimethylthiazol-2-yl]−2, 5 diphenyl tetrazolium bromide -- DMSO dimethyl sulfoxide -- VC Vitamin C -- ER liver extraction ratio -- UGT UDP-glucuronosyltransferase -- P-gp P-glycoprotein -- Mrp2 multidrug resistance-associated protein 2; Yin-Chen-Hao Tang -- Hepatic disposition -- Pharmacokinetics -- Hepatoprotection -- HepG2 -- Carbon tetrachloride; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2019.02.022
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Yin-Chen-Hao Tang (YCHT) has been a very popular, hepatoprotective three-herb formula with an unclear chemical base. Aim of this study: To reveal the hepatoprotective chemical base of oral-dosed YCHT, we bridged the hepatic disposition of six compounds in vivo and their hepatoprotection in vitro . Materials and methods: In vivo, following the oral administration of YCHT in normal and CCl4 -induced liver injury rats, the determinations of chlorogenic acid, 4-hydroxyacetophenone, geniposide, genipin, rhein and emodin were conducted in the portal vein plasma, the liver, and the systemic plasma. In vitro, the hepatoprotective activities of these compounds were determined in the CCl4 -induced HepG2 cells. Results: Consistent with the highest content in YCHT, geniposide had the highest exposure in vivo . Inconsistent with the negligible content, rhein, 4-hydroxyacetophenone, emodin and genipin showed substantial hepatic accumulations. In contrast, chlorogenic acid, an ingredient that has a high content in YCHT, elicited no hepatic exposure. In normal rats, the hepatic disposition prevented the compounds entering into the systemic plasma from the portal vein plasma by 44.9–100%, except for rhein. CCl4 -induced liver injury caused a decreased hepatic exposure of 4-hydroxyacetophenone, rhein and emodin by 50%. In vitro, all six compounds exerted the hepatoprotection by increasing cell viability, decreasing hepatic marker enzymes and inhibiting lipid peroxidation at varying levels. Conclusion: Geniposide, rhein, emodin, 4-hydroxyacetophenone and genipin directly resisted liver injury in oral-dosed YCHT, while chlorogenic acid likely played an indirect role. This study proved that YCHT exerted hepatoprotection through multiple components and multiple actions. However, close attention should be paid to the possible side effects and oral dosage of YCHT in clinics. Graphical abstract: fx1