Ramulus Mori (Sangzhi) Alkaloids Alleviate High-Fat Diet-Induced Obesity and Nonalcoholic Fatty Liver Disease in Mice

  • Antioxidants (Basel). 2022 May 5;11(5):905. doi: 10.3390/antiox11050905.
Yan-Min Chen  1  2  3 ,  Chun-Fang Lian  1  2  3 ,  Qian-Wen Sun  1  2  3 ,  Ting-Ting Wang  4 ,  Yuan-Yuan Liu  4 ,  Jun Ye  1  2  3 ,  Li-Li Gao  1  2  3 ,  Yan-Fang Yang  1  2  3 ,  Shuai-Nan Liu  1  2 ,  Zhu-Fang Shen  1  2 ,  Yu-Ling Liu  1  2  3
Affiliations
  • 1. Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
  • 3. Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
  • 4. School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
PMID: 35624769 DOI: 10.3390/antiox11050905
Abstract

Nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes mellitus (T2DM) have highly related mechanisms. Ramulus Mori (Sangzhi) Alkaloids (SZ-A) from Morus alba L. were approved in 2020 for the treatment of T2DM. In this study, we examined the therapeutic effects and mechanism of SZ-A on obesity and NAFLD in mice. Mice (C57BL/6J) fed a high-fat diet (HFD) for 14 weeks were treated with SZ-A for another 6 weeks. HFD-induced weight gain was reduced by SZ-A in a dose-dependent manner. SZ-A treatment significantly stimulated Adiponectin expression and secretion in adipose tissue and 3T3-L1 adipocytes. Additionally, SZ-A markedly reduced hepatic steatosis (triglyceride, total Cholesterol) and expression of pro-inflammatory and pro-fibrotic genes. SZ-A regulated lipid metabolism and oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), Glutathione Peroxidase (GPx), and glutathione (GSH)) in the liver. Palmitic acid-induced Insulin resistance and lipid accumulation in HepG2 cells were also repressed by SZ-A. Collectively, SZ-A protected mice from HFD-induced NAFLD through an indirect effect of improved systemic metabolism reducing bodyweight, and a direct effect by enhancing the lipid metabolism of HepG2 cells. The weight-loss effect of SZ-A in mice was partly due to improved fatty oxidation instead of influencing food consumption.

Keywords
NAFLD; Ramulus Mori (Sangzhi) alkaloids; adiponectin; obesity; oxidative stress; steatosis.
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