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A novel berberine‐metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats
Author(s) -
Jia Dan,
Li Zi Wen,
Zhou Xinxin,
Gao Ying,
Feng Yifan,
Ma Min,
Wu Zhengzhi,
Li Weimin
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13085
Subject(s) - endocrinology , medicine , lipogenesis , adipose tissue , metformin , chemistry , white adipose tissue , gluconeogenesis , type 2 diabetes , diabetes mellitus , biology , metabolism
Summary In this study, we investigated the biological activities of a novel berberine‐metformin hybrid compound ( BMH 473) as an anti‐diabetic agent. BMH 473 exhibited significant anti‐hyperglycaemic and anti‐hyperlipidaemic effects on T2 DM rats. In white adipose tissue, BMH 473 reduced the perirenal and epididymal adipose tissue mass and modulated the lesions in perirenal adipose tissue, by inhibiting the protein expressions of PPAR ‐Ɣ, C/ EBP ‐α and SREBP ‐1c as well as the mRNA expressions of lipogenic genes. Moreover, BMH 473 downregulated the levels of pro‐inflammatory cytokines in perirenal adipose tissue through the suppression of p‐ NF ‐κB. In liver, BMH 473 reduced liver ectopic fat accumulation, by regulating the protein expression levels of SREBP ‐1c and PPAR ‐α as well as the mRNA expression levels of lipogenic genes. In addition, BMH 473 inhibited hepatic gluconeogenesis by promoting the phosphorylation levels of AMPK α and ACC , and down‐regulating the mRNA expression levels of FBP ase , G6Pase and PEPCK . Furthermore, BMH 473 exhibited significant inhibitory effects on lipogenesis and lipid accumulation in 3T3‐L1 adipocytes by modulating the protein expression levels of PPAR ‐Ɣ, C/ EBP ‐α and SREBP ‐1 c as well as the mRNA expression levels of lipogenic genes. In conclusion, our results suggest that the newly synthesized BMH 473 is beneficial for maintaining glucose and lipid homeostasis in type 2 diabetic rats, and exhibits better anti‐hyperlipidaemic effects compared to metformin and berberine.