Xiangying Zhang1, Jianbo Ding2, Chunyan Gou3, Tao Wen4, Li Li5, Xiaojun Wang6, Huasheng Yang7, Dan Liu8, Jinli Lou9, Dexi Chen10, Feng Ren11, Xiuhui Li12. 1. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China; Beijing Institute of Hepatology, Beijing 100069, PR China. Electronic address: zhangxiangying1984@163.com. 2. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: Jianbo1@163.com. 3. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: goucy@sina.vip.com. 4. Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100043, PR China. Electronic address: wentao5281@163.com. 5. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: bjfhlc@126.com. 6. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: 13718217343@126.com. 7. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: yangdoctor2000@qq.com. 8. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: liudanxy1219@163.com. 9. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: loujinli@163.com. 10. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China; Beijing Institute of Hepatology, Beijing 100069, PR China. Electronic address: dexichen@ccmu.edu.cn. 11. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China; Beijing Institute of Hepatology, Beijing 100069, PR China. Electronic address: renfeng7512@hotmail.com. 12. Beijing You-An Hospital, Capital Medical University, Beijing 100069, PR China. Electronic address: lixiuhui@sohu.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The Qingchangligan formula, a traditional Chinese medicine comprising five herbs, is useful for treatment of patients with liver failure; however, its protective and regulatory mechanisms remain elusive. AIM OF THE STUDY: To test the hypothesis that the Qingchangligan formula protects mice against acute liver failure by inhibiting liver inflammation. MATERIALS AND METHODS: Acute liver failure (ALF) was induced by intraperitoneal injection of D-GalN (700mg/kg) plus LPS (10μg/kg). The Qingchangligan formula was administered to mice in three doses of 50mg/kg (on day 1, day 2, and day 3) prior to D-GalN/LPS injection by intragastric administration. The mice in different groups were sacrificed at 6h after D-GalN/LPS injection, and liver samples and blood were collected for analysis. RESULTS: Administration of the Qingchangligan formula not only ameliorated liver injury, as evidenced by reduced transaminase levels and well-preserved liver architecture, but also decreased the lethality in ALF mice. Moreover, in the ALF model, pretreatment with the Qingchangligan formula alleviated liver inflammation and decreased hepatocyte apoptosis. Further demonstrating the protective effects of the Qingchangligan formula, we found that pretreatment with the Qingchangligan formula reduced the expression of inflammatory cytokines by decreasing the expression of components of the mitogen-activated protein kinase (MAPK) pathway and promoting autophagy in vitro and in vivo. CONCLUSIONS: Our findings demonstrated that the Qingchangligan formula exerts a protective effect against the pathophysiology of ALF, especially in regulating liver inflammation, and provide a rationale for using the Qingchangligan formula as a potential therapeutic strategy to ameliorate ALF.
ETHNOPHARMACOLOGICAL RELEVANCE: The Qingchangligan formula, a traditional Chinese medicine comprising five herbs, is useful for treatment of patients with liver failure; however, its protective and regulatory mechanisms remain elusive. AIM OF THE STUDY: To test the hypothesis that the Qingchangligan formula protects mice against acute liver failure by inhibiting liver inflammation. MATERIALS AND METHODS:Acute liver failure (ALF) was induced by intraperitoneal injection of D-GalN (700mg/kg) plus LPS (10μg/kg). The Qingchangligan formula was administered to mice in three doses of 50mg/kg (on day 1, day 2, and day 3) prior to D-GalN/LPS injection by intragastric administration. The mice in different groups were sacrificed at 6h after D-GalN/LPS injection, and liver samples and blood were collected for analysis. RESULTS: Administration of the Qingchangligan formula not only ameliorated liver injury, as evidenced by reduced transaminase levels and well-preserved liver architecture, but also decreased the lethality in ALFmice. Moreover, in the ALF model, pretreatment with the Qingchangligan formula alleviated liver inflammation and decreased hepatocyte apoptosis. Further demonstrating the protective effects of the Qingchangligan formula, we found that pretreatment with the Qingchangligan formula reduced the expression of inflammatory cytokines by decreasing the expression of components of the mitogen-activated protein kinase (MAPK) pathway and promoting autophagy in vitro and in vivo. CONCLUSIONS: Our findings demonstrated that the Qingchangligan formula exerts a protective effect against the pathophysiology of ALF, especially in regulating liver inflammation, and provide a rationale for using the Qingchangligan formula as a potential therapeutic strategy to ameliorate ALF.