Cuihua Jiang1, Nan Yao2, Qingqing Wang1, Jinghua Zhang3, Yan Sun3, Na Xiao3, Kang Liu3, Fang Huang3, Shengzuo Fang4, Xulan Shang4, Baolin Liu3, Yicheng Ni5, Zhiqi Yin6, Jian Zhang7. 1. Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing 210028, Jiangsu Province, PR China; Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China. 2. Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing 210028, Jiangsu Province, PR China. 3. Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China. 4. College of Forest Resources and Environment, Nanjing Forestry University, Nanjing 210037, PR China. 5. Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing 210028, Jiangsu Province, PR China; KU Leuven, Faculty of Medicine, Herestraat 49, 3000 Leuven, Belgium. 6. Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, PR China. Electronic address: chyzq2005@126.com. 7. Laboratory of Translational Medicine, Jiangsu Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing 210028, Jiangsu Province, PR China. Electronic address: zjwonderful@hotmail.com.
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.
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.