Xiaoming Sun1, Yi Lv2, Lu Huang3, Hao Gao4, Chaoran Ren3, Jingjing Li3, Man Bie3, Wei Li5, Kazuo Koike5, Kwok-Fai So6, Jia Xiao7. 1. Center for Clinical Precision Medication, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, 510006, China; Clinical Pharmacy (School of Integrative Pharmacy, Institute of Integrative Pharmaceutical Research), Guangdong Pharmaceutical University, Guangzhou, 510006, China. 2. Laboratory of Neuroendocrinology, Fujian Key Laboratory of Developmental and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou, 350007, China. 3. Guangdong-HongKong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, 510632, China; Guangdong Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, 510632, China. 4. College of Pharmacy, Jinan University, Guangzhou, 510632, China. 5. Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan. 6. Laboratory of Neuroendocrinology, Fujian Key Laboratory of Developmental and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou, 350007, China; Guangdong-HongKong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, 510632, China; Guangdong Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, 510632, China; Department of Ophthalmology, The University of Hong Kong, Pokfulam, Hong Kong, China. Electronic address: hrmaskf@hku.hk. 7. Laboratory of Neuroendocrinology, Fujian Key Laboratory of Developmental and Neurobiology, College of Life Sciences, Fujian Normal University, Fuzhou, 350007, China; School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China; Institute of Clinical Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, China. Electronic address: edwinsiu@connect.hku.hk.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Gogi berry is a traditional food supplement and medical herbal which has been widely used in Eastern Asian countries. Lycium barbarum polysaccharides (LBP) are the major active components of Gogi berry and have been proved to possess a lot of biological activities. AIM OF THE STUDY: We aimed to delineate the protective effect and mechanism of LBP on hepatic encephalopathy (HE). MATERIALS AND METHODS: We investigated the protective mechanism of LBP in a thioacetamide (TAA, intraperitoneally injected, 400 mg/kg) induced acute HE mice model. Key phenotypes of clinical HE were phenocopied in the mice model, including high mortality, severe hepatic histology injury, increased hepatic oxidative stress, apoptosis, enhanced circulating levels of pro-inflammatory cytokines and ammonia, suppressed tryptophan hydroxylase activity, and deficits in locomotor activity. RESULTS: The pathological alterations were effectively ameliorated by the oral administration with LBP (5 mg/kg, oral gavage, everyday), which were mediated by regulating MAPK pathways in both the liver and brain. Knockout of pro-inflammatory cytokines TNF-α or IL-6 effectively ameliorated impaired mice locomotor activity and MAPK activation in the brain. In an in vitro TNF-α-, IL-6-, or ammonia-induced microglia damaged cell model, cell injuries were evidently protected by the co-administration with LBP (50 μg/ml). CONCLUSION: LBP ameliorated the hepatic/brain injuries and impaired locomotor activities in a HE mice model. Pro-inflammatory cytokines may serve as communicating molecules linking the liver and brain for the HE pathogenesis, partly through MAPK regulation.
ETHNOPHARMACOLOGICAL RELEVANCE: Gogi berry is a traditional food supplement and medical herbal which has been widely used in Eastern Asian countries. Lycium barbarum polysaccharides (LBP) are the major active components of Gogi berry and have been proved to possess a lot of biological activities. AIM OF THE STUDY: We aimed to delineate the protective effect and mechanism of LBP on hepatic encephalopathy (HE). MATERIALS AND METHODS: We investigated the protective mechanism of LBP in a thioacetamide (TAA, intraperitoneally injected, 400 mg/kg) induced acute HEmice model. Key phenotypes of clinical HE were phenocopied in the mice model, including high mortality, severe hepatic histology injury, increased hepatic oxidative stress, apoptosis, enhanced circulating levels of pro-inflammatory cytokines and ammonia, suppressed tryptophan hydroxylase activity, and deficits in locomotor activity. RESULTS: The pathological alterations were effectively ameliorated by the oral administration with LBP (5 mg/kg, oral gavage, everyday), which were mediated by regulating MAPK pathways in both the liver and brain. Knockout of pro-inflammatory cytokines TNF-α or IL-6 effectively ameliorated impaired mice locomotor activity and MAPK activation in the brain. In an in vitro TNF-α-, IL-6-, or ammonia-induced microglia damaged cell model, cell injuries were evidently protected by the co-administration with LBP (50 μg/ml). CONCLUSION: LBP ameliorated the hepatic/brain injuries and impaired locomotor activities in a HEmice model. Pro-inflammatory cytokines may serve as communicating molecules linking the liver and brain for the HE pathogenesis, partly through MAPK regulation.
Authors: Heba M A Khalil; Islam A Khalil; Asmaa K Al-Mokaddem; Marwa Hassan; Riham A El-Shiekh; Hesham A Eliwa; Azza M Tawfek; Walaa H El-Maadawy Journal: Drug Deliv Transl Res Date: 2022-06-07 Impact factor: 4.617