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A novel berberine-metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats

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机构: [1]Integrated Chinese and Western Medicine Post-doctoral Research Station, JinanUniversity, Guangzhou, China [2]The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China [3]Shenzhen Institute of Geriatrics, Shenzhen,China [4]Academy of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China [5]Central Laboratory of Guangdong Pharmaceutical University, GuangZhou,China
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关键词: glucose and lipid metabolism inflammatory cytokines novel berberine and metformin hybrid compound type 2 diabetic rats

摘要:
In this study, we investigated the biological activities of a novel berberine-metformin hybrid compound (BMH473) as an anti-diabetic agent. BMH473 exhibited significant anti-hyperglycaemic and anti-hyperlipidaemic effects on T2DM rats. In white adipose tissue, BMH473 reduced the perirenal and epididymal adipose tissue mass and modulated the lesions in perirenal adipose tissue, by inhibiting the protein expressions of PPAR-x194;, C/EBP-alpha and SREBP-1c as well as the mRNA expressions of lipogenic genes. Moreover, BMH473 downregulated the levels of pro-inflammatory cytokines in perirenal adipose tissue through the suppression of p-NF-kappa B. In liver, BMH473 reduced liver ectopic fat accumulation, by regulating the protein expression levels of SREBP-1c and PPAR-alpha as well as the mRNA expression levels of lipogenic genes. In addition, BMH473 inhibited hepatic gluconeogenesis by promoting the phosphorylation levels of AMPK alpha and ACC, and down-regulating the mRNA expression levels of FBPase, G6Pase and PEPCK. Furthermore, BMH473 exhibited significant inhibitory effects on lipogenesis and lipid accumulation in 3T3-L1 adipocytes by modulating the protein expression levels of PPAR-x194;, C/EBP-alpha and SREBP-1 c as well as the mRNA expression levels of lipogenic genes. In conclusion, our results suggest that the newly synthesized BMH473 is beneficial for maintaining glucose and lipid homeostasis in type 2 diabetic rats, and exhibits better anti-hyperlipidaemic effects compared to metformin and berberine.

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出版当年[2018]版:
大类 | 4 区 医学
小类 | 4 区 药学 4 区 生理学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 药学 4 区 生理学
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出版当年[2017]版:
Q3 PHYSIOLOGY Q3 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q2 PHYSIOLOGY Q3 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

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第一作者机构: [1]Integrated Chinese and Western Medicine Post-doctoral Research Station, JinanUniversity, Guangzhou, China [2]The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China [3]Shenzhen Institute of Geriatrics, Shenzhen,China
通讯作者:
通讯机构: [2]The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China [3]Shenzhen Institute of Geriatrics, Shenzhen,China [4]Academy of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China [*1]The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China. [*2]Guangzhou Higher Education Mega Center, Guangzhou, China.
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