Liying Ren1, Dongmei Sun2, Xia Zhou3, Yifan Yang4, Xiaoqian Huang5, Yangxue Li6, Chunxia Wang7, Yuhao Li8. 1. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: 1775885301@qq.com. 2. Analysis Department of Chinese Medicine, Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China. Electronic address: tcmgdp@163.com. 3. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: 771741266@qq.com. 4. Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW 2000, Australia. Electronic address: yifanyang@sitcm.edu.au. 5. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: 302804664@qq.com. 6. Analysis Department of Chinese Medicine, Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine, Guangzhou 510095, China. Electronic address: efongzg@126.com. 7. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: wangcx@smu.edu.cn. 8. Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW 2000, Australia. Electronic address: yuhao@sitcm.edu.au.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The modified Longdan Xiegan Tang (mLXT) has been used clinically for various neuropsychiatric disorders and liver diseases. The use of antipsychotics is associated with nonalcoholic fatty liver disease. AIM OF THE STUDY: To investigate the effect and underlying mechanisms of mLXT on antipsychotic-induced fatty liver. MATERIALS AND METHODS: The representative active components in the formula were identified and quantified by a HPLC method. Fatty liver in male rats was induced by olanzapine (5 mg/kg) (p.o., × 8 weeks), and the rats were co-treated with mLXT extract (50 and 500 mg/kg). Blood and liver variables were determined enzymatically or histologically. Gene/protein expression was analyzed by real-time PCR and Western blot. RESULTS: Treatment of rats with mLXT decreased olanzapine-induced increases in hepatic triglyceride content, cell vacuolar degeneration and Oil Red O-stained area, accompanied by suppression of olanzapine-stimulated hepatic mRNA and/or protein overexpression of sterol regulatory element-binding protein (SREBP)-1c, and its downstream lipogenic enzymes for de novo lipogenesis. Besides, mLXT also activated hepatic expression of peroxisome proliferator-activated receptor-alpha and its target genes associated with fatty acid beta-oxidation, phosphorylated Thr172 in AMP-activated protein kinase (AMPK)-alpha (the upstream enzyme of SREBP-1c and PPAR-alpha), and its ratio to total AMPK-alpha. CONCLUSIONS: The present results suggest that chronic treatment with mLXT ameliorates olanzapine-induced fatty liver by regulating hepatic de novo lipogenesis- and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c and PPAR-alpha, respectively, through activation of AMPK-alpha. Our findings provide the evidence that supports clinical use of the formula for antipsychotic medication-induced fatty liver.
ETHNOPHARMACOLOGICAL RELEVANCE: The modified Longdan Xiegan Tang (mLXT) has been used clinically for various neuropsychiatric disorders and liver diseases. The use of antipsychotics is associated with nonalcoholic fatty liver disease. AIM OF THE STUDY: To investigate the effect and underlying mechanisms of mLXT on antipsychotic-induced fatty liver. MATERIALS AND METHODS: The representative active components in the formula were identified and quantified by a HPLC method. Fatty liver in male rats was induced by olanzapine (5 mg/kg) (p.o., × 8 weeks), and the rats were co-treated with mLXT extract (50 and 500 mg/kg). Blood and liver variables were determined enzymatically or histologically. Gene/protein expression was analyzed by real-time PCR and Western blot. RESULTS: Treatment of rats with mLXT decreased olanzapine-induced increases in hepatic triglyceride content, cell vacuolar degeneration and Oil Red O-stained area, accompanied by suppression of olanzapine-stimulated hepatic mRNA and/or protein overexpression of sterol regulatory element-binding protein (SREBP)-1c, and its downstream lipogenic enzymes for de novo lipogenesis. Besides, mLXT also activated hepatic expression of peroxisome proliferator-activated receptor-alpha and its target genes associated with fatty acid beta-oxidation, phosphorylated Thr172 in AMP-activated protein kinase (AMPK)-alpha (the upstream enzyme of SREBP-1c and PPAR-alpha), and its ratio to total AMPK-alpha. CONCLUSIONS: The present results suggest that chronic treatment with mLXT ameliorates olanzapine-induced fatty liver by regulating hepatic de novo lipogenesis- and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c and PPAR-alpha, respectively, through activation of AMPK-alpha. Our findings provide the evidence that supports clinical use of the formula for antipsychotic medication-induced fatty liver.
Authors: Inga Bae-Gartz; Philipp Kasper; Nora Großmann; Saida Breuer; Ruth Janoschek; Tobias Kretschmer; Sarah Appel; Lisa Schmitz; Christina Vohlen; Alexander Quaas; Michal R Schweiger; Christina Grimm; Axel Fischer; Nina Ferrari; Christine Graf; Christian K Frese; Sonja Lang; Münevver Demir; Christoph Schramm; Gregor Fink; Tobias Goeser; Jörg Dötsch; Eva Hucklenbruch-Rother Journal: Sci Rep Date: 2020-09-22 Impact factor: 4.379
Authors: Jozaa Z ALTamimi; Ghedeir M Alshammari; Nora A AlFaris; Reham I Alagal; Dalal H Aljabryn; Norah A Albekairi; Mahmoud Ahmad Alkhateeb; Mohammed Abdo Yahya Journal: Pharm Biol Date: 2022-12 Impact factor: 3.503