Qiaoling Yang1, Fangfang Shu2, Junting Gong3, Ping Ding3, Rongrong Cheng2, Jinmei Li3, Renchao Tong3, Lili Ding4, Huajun Sun5, Wendong Huang6, Zhengtao Wang3, Li Yang7. 1. The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China; Department of Diabetes Complications & Metabolism, Institute of Diabetes Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA. 2. The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. 3. The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. 4. The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Department of Diabetes Complications & Metabolism, Institute of Diabetes Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA. 5. Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China. 6. Department of Diabetes Complications & Metabolism, Institute of Diabetes Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA. 7. The MOE Key Laboratory of Standardization of Chinese Medicines and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: yl7@shutcm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. AIM OF THE STUDY: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. MATERIALS AND METHODS: C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. RESULTS: The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. CONCLUSION: Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α.
ETHNOPHARMACOLOGICAL RELEVANCE: Sweroside, an iridoid derived from Traditional Chinese Medicine, is an active component in Swertia pseudochinensis Hara. Swertia pseudochinensis Hara is first recorded in "Inner Mongolia Chinese Herb Medicine"and is considered as a folk medicine for treating hepatitis in northern China. AIM OF THE STUDY: This study sought to elucidate the role of sweroside in high fat diet induced obesity and fatty liver by using mouse model and investigated the primary molecular mechanism via transcriptomics analysis. MATERIALS AND METHODS: C57BL/6 mice were fed high-fat diet (HFD) for 14 weeks to induce obesity, hyperglycemia, and fatty liver. These mice were subsequently treated with HFD alone or mixed with sweroside (at a daily dosage of 60 mg per kg of BW, 120 mg per kg of BW and 240 mg per kg of BW) for 6 weeks. BW and food intake was monitored weekly. Biochemical and pathological analysis were conducted to investigate the effect of sweroside on NAFLD. RNA-sequence and RT-qPCR analysis were performed to analyze the potential mechanism. RESULTS: The mice treated with sweroside were resistant to HFD-induced body weight gain, insulin resistance and hepatic steatosis. Ingenuity pathway analysis (IPA) demonstrated that hepatic gene networks related to lipid metabolism and inflammatory response were down-regulated in the HFD + sweroside group. PPAR-ɑ was located in the center of the hepatic gene network, and the significantly altered genes were CD36 and FGF21, which are related to hepatic inflammation and lipid metabolism. Consistently, upstream-regulators analysis revealed that the main enriched upstream-regulator was PPAR-ɑ. CONCLUSION: Our results indicate that sweroside may ameliorate obesity with fatty liver via the regulation of lipid metabolism and inflammatory responses. The beneficial effects of sweroside might be closely associated with the regulation of PPAR-α.
Authors: Jun Li; Cuiting Zhao; Qing Zhu; Yonghuai Wang; Guangyuan Li; Xinxin Li; Yuhong Li; Nan Wu; Chunyan Ma Journal: Front Cardiovasc Med Date: 2021-03-19