Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response

Qiaoling Yang; Fangfang Shu; Junting Gong; Ping Ding; Rongrong Cheng; Jinmei Li; Renchao Tong; Lili Ding; Huajun Sun; Wendong Huang; Zhengtao Wang; Li Yang

doi:10.1016/j.jep.2020.112556

Sweroside ameliorates NAFLD in high-fat diet induced obese mice through the regulation of lipid metabolism and inflammatory response

J Ethnopharmacol. 2020 Jun 12:255:112556. doi: 10.1016/j.jep.2020.112556. Epub 2020 Jan 9.

Authors

Qiaoling Yang¹, Fangfang Shu², Junting Gong³, Ping Ding³, Rongrong Cheng², Jinmei Li³, Renchao Tong³, Lili Ding⁴, Huajun Sun⁵, Wendong Huang⁶, Zhengtao Wang³, Li Yang⁷

Affiliations

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.

PMID: 31926984
DOI: 10.1016/j.jep.2020.112556

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.

Keywords: Inflammation; Lipid metabolism; NAFLD; PPAR-α; weroside.

MeSH terms

Animals
CD36 Antigens / genetics
CD36 Antigens / metabolism
Diet, High-Fat*
Disease Models, Animal
Fibroblast Growth Factors / genetics
Fibroblast Growth Factors / metabolism
Gene Regulatory Networks
HEK293 Cells
Humans
Inflammation Mediators / metabolism*
Insulin Resistance
Iridoid Glucosides / pharmacology*
Lipid Metabolism / drug effects*
Lipid Metabolism / genetics
Liver / drug effects*
Liver / metabolism
Liver / pathology
Male
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease / etiology
Non-alcoholic Fatty Liver Disease / metabolism
Non-alcoholic Fatty Liver Disease / pathology
Non-alcoholic Fatty Liver Disease / prevention & control*
Obesity / etiology
Obesity / metabolism
Obesity / physiopathology
Obesity / prevention & control*
PPAR alpha / genetics
PPAR alpha / metabolism
Transcriptome
Weight Gain / drug effects*

Substances

CD36 Antigens
Cd36 protein, mouse
Inflammation Mediators
Iridoid Glucosides
PPAR alpha
Ppara protein, mouse
fibroblast growth factor 21
Fibroblast Growth Factors
sweroside