Yan Gao1,2, Jiaqing Yan2,3, Juntong Li4, Xun Li5, Songwei Yang5, Naihong Chen2,5, Lin Li1, Lan Zhang1. 1. Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing, China. 2. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica and Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3. Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 4. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China. 5. College of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.
Abstract
OBJECTIVES: Improper usage of acetaminophen (APAP) leads to morbidity and also mortality secondary to liver damage. Ginseng could suppress APAP-induced hepatotoxicity and ginsenoside Rg3 is a kind of major component in ginseng against liver damage. Herein, we intended to estimate the beneficial function and molecular mechanism of Rg3 on APAP-caused hepatotoxicity and identified hepatoprotection. METHODS: A total of 50 C57BL/6J mice were divided into five random groups, and each contains 10 mice as the control, acetaminophen (350 mg/kg) and Rg3 (5, 10 and 20 mg/kg) + acetaminophen (350 mg/kg) groups. These mice were intragastric administration a single dose of acetaminophen by oral treatment behind pre-administered with several doses of ginsenoside Rg3 for six hours. KEY FINDINGS: According to our data, the injection of APAP (350 mg/kg) enhanced the basal levels of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and lactic dehydrogenase. However, these abnormal added were alleviated by Rg3. Moreover, Rg3 treatment obviously relieved APAP-caused inflammation and oxidant in liver tissues. The depletion of glutathione, glutathione peroxidase, total antioxidant capacity and generation of malondialdehyde induced by APAP treatment were reduced by Rg3. By H&E staining, Rg3 effectively reduced APAP-caused apoptosis and inflammatory infiltration. Moreover, Rg3 attenuated APAP-caused hepatic damage in part by regulating the pro-inflammatory and anti-inflammatory cytokines. Moreover, we found that Rg3 could bind to NLRP3 suggesting the anti-inflammatory effects of Rg3 by molecular docking study. CONCLUSIONS: In summary, Rg3 showed hepatic protective function in APAP-induced hepatotoxicity as evidenced by a reduction of the oxidant and the inflammatory reply, relieve of hepatocellular damage, showing potential in Rg3 as a potential therapeutic medicine to prevent hepatic injury.
OBJECTIVES: Improper usage of acetaminophen (APAP) leads to morbidity and also mortality secondary to liver damage. Ginseng could suppress APAP-induced hepatotoxicity and ginsenoside Rg3 is a kind of major component in ginseng against liver damage. Herein, we intended to estimate the beneficial function and molecular mechanism of Rg3 on APAP-caused hepatotoxicity and identified hepatoprotection. METHODS: A total of 50 C57BL/6J mice were divided into five random groups, and each contains 10 mice as the control, acetaminophen (350 mg/kg) and Rg3 (5, 10 and 20 mg/kg) + acetaminophen (350 mg/kg) groups. These mice were intragastric administration a single dose of acetaminophen by oral treatment behind pre-administered with several doses of ginsenoside Rg3 for six hours. KEY FINDINGS: According to our data, the injection of APAP (350 mg/kg) enhanced the basal levels of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and lactic dehydrogenase. However, these abnormal added were alleviated by Rg3. Moreover, Rg3 treatment obviously relieved APAP-caused inflammation and oxidant in liver tissues. The depletion of glutathione, glutathione peroxidase, total antioxidant capacity and generation of malondialdehyde induced by APAP treatment were reduced by Rg3. By H&E staining, Rg3 effectively reduced APAP-caused apoptosis and inflammatory infiltration. Moreover, Rg3 attenuated APAP-caused hepatic damage in part by regulating the pro-inflammatory and anti-inflammatory cytokines. Moreover, we found that Rg3 could bind to NLRP3 suggesting the anti-inflammatory effects of Rg3 by molecular docking study. CONCLUSIONS: In summary, Rg3 showed hepatic protective function in APAP-induced hepatotoxicity as evidenced by a reduction of the oxidant and the inflammatory reply, relieve of hepatocellular damage, showing potential in Rg3 as a potential therapeutic medicine to prevent hepatic injury.