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Cyclocarya paliurus extract modulates adipokine expression and improves insulin sensitivity by inhibition of inflammation in mice
Authors:Cuihua Jiang  Nan Yao  Qingqing Wang  Jinghua Zhang  Yan Sun  Na Xiao  Kang Liu  Fang Huang  Shengzuo Fang  Xulan Shang  Baolin Liu  Yicheng Ni  Zhiqi Yin  Jian Zhang
Affiliation:1. Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing 210028, Jiangsu Province, PR China;2. Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China;3. College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210037, PR China;4. KU Leuven, Faculty of Medicine, Herestraat 49, 3000 Leuven, Belgium
Abstract:

Ethnopharmacological relevance

Cyclocarya paliurus Batal., a Chinese native plant, is the sole species in its genus and its leaves have been widely used as a remedy for diabetes in traditional folk medicine. The study was undertaken to evaluate the effects of Cyclocarya paliurus leaves extracts (CPE) on adipokine expression and insulin sensitivity in mice.

Materials and methods

Mice were stimulated with conditioned medium (prepared from activated macrophages, Mac-CM) to induce adipose dysfunction and insulin resistance. Then mice were treated with CPE (100, 200 and 500 mg/kg, ig.) or metformin (200 mg/kg, ig.), followed by glucose and insulin intolerance, adipokine expression, phosphorylation of insulin receptor substrate (IRS-1) and glucose consumption measurement.

Results

CPE, as well as metformin effectively promoted glucose disposal in oral glucose tolerance test in normal mice. Mac-CM challenge induced glucose and insulin intolerance, but CPE reversed these alternations with increased glycogen content in muscle and liver, well demonstrating its beneficial effects on glucose homeostasis. RT-qPCR analysis showed that CPE inhibited TNF-a, IL-6, MCP-1 and resistin overexpression and effectively enhanced adiponectin expression in adipose tissue when mice were exposed to Mac-CM stimulation. Inflammation impaired insulin signaling in muscle, whereas CPE inhibited inflammation-induced serine phosphorylation of IRS-1 and effectively restored the phosphorylation of both IRS-1 at tyrosine residues and downstream Akt phosphorylation in response to insulin. Moreover, independently of insulin, CPE promoted glucose consumption in adipocytes under normal and inflammatory conditions.

Conclusion

Above-mentioned results demonstrated that CPE beneficially regulated adipokines expression and ameliorated insulin resistance through inhibition of inflammation in mice.
Keywords:Cyclocarya paliurus   Macrophages-derived conditioned medium   Adipokine expression   Insulin resistance   Inflammation
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