Xiaoting Tian1, Huan Liu1, Shida Qiao1, Hao Yin1, Mingcang Chen1, Pei Hu1, Yangyang Wang1, Huige Peng1, Fang Liu1, Guoyu Pan2, Chenggang Huang3. 1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai Ke Road Zhangjiang, Pudong, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. 2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai Ke Road Zhangjiang, Pudong, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: gypan@simm.ac.cn. 3. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai Ke Road Zhangjiang, Pudong, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: cghsimm@126.com.
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.
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 injuryrats, 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.
Authors: Ya Wang; Tianming Zhao; You Deng; Lijun Hou; Xiaofei Fan; Lin Lin; Wei Zhao; Kui Jiang; Chao Sun Journal: Oxid Med Cell Longev Date: 2019-12-11 Impact factor: 6.543