Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No.1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400042, China.
Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Donghu District, Nanchang City, Jiangxi Province 330006, China.
Life Sci. 2021 Apr 1;270:119133. doi: 10.1016/j.lfs.2021.119133. Epub 2021 Jan 27.
Kaempferide (Ka, 3,5,7-trihydroxy-4'-methoxyflavone), an active ingredient of Tagetes erecta L., has been demonstrated to possess many pharmacological effects, including antioxidant, anti-inflammation, anticancer and antihypertension in previous study. However, there is no evidence of Ka on metabolic disorder in former studies. This study investigated the effects of Ka on glycolipid metabolism and explored the underlying mechanisms of action in vivo and vitro.
The mouse model of glycolipid metabolism disorder was induced by high-fat diet (HFD). The effects of Ka were evaluated on bodyweight, lipid metabolism and glucose metabolism. Hypolipidemic effect was examined by blood sample analysis. The hypoglycemic effect was detected by several indicators, like blood glucose, serum insulin, HOMA index and intraperitoneal glucose tolerance tests (IPGTT). The signaling pathways of lipid metabolism (PPARγ/LXRα/ABCA1) and glucose metabolism (PPARγ/PI3K/AKT) were evaluated using Real-Time PCR and Western blot. The primary culture of hepatocyte was prepared to confirm the target of Ka by co-culturing with PPARγ agonist or inhibitor.
The HFD mice developed obesity, hyperlipidemia, hyperglycemia and insulin resistance. Administration of Ka at a dose of 10 mg/kg.BW for 16 weeks effectively attenuated these changes. Further studies revealed the hypolipidemic and hypoglycemic effects of Ka depended on the activation of PPARγ/LXRα/ABCA1 and PPARγ/PI3K/AKT pathways, respectively. The primary hepatocyte test, co-cultured with PPARγ agonists or inhibitors, further confirmed the above signaling pathway and key protein.
These results suggested that Ka played an important role in improving glycolipid metabolism disorder. These favorable effects were causally associated with anti-obesity. The underlying mechanisms might have to do with the activation of the PPARγ and its downstream signaling pathway. Our study helped to understand the pharmacological actions of Ka, and played a role for Ka in the effective treatment of obesity, diabetes, nonalcoholic hepatitis and other metabolic diseases.
山柰酚（Ka，3,5,7-三羟基-4'-甲氧基黄酮）是万寿菊中的一种活性成分，先前的研究已经证明它具有许多药理作用，包括抗氧化、抗炎、抗癌和降血压。然而，以前的研究中没有关于 Ka 对代谢紊乱的证据。本研究旨在探讨 Ka 对糖脂代谢的影响，并在体内和体外探索其作用机制。
采用高脂饮食（HFD）诱导小鼠糖脂代谢紊乱模型。评价 Ka 对体重、脂代谢和糖代谢的影响。通过血液样本分析检测降脂作用。通过血糖、血清胰岛素、HOMA 指数和腹腔葡萄糖耐量试验（IPGTT）等指标检测降血糖作用。采用实时 PCR 和 Western blot 检测脂代谢（PPARγ/LXRα/ABCA1）和糖代谢（PPARγ/PI3K/AKT）信号通路。通过与 PPARγ 激动剂或抑制剂共培养，用原代肝细胞培养物进一步确定 Ka 的作用靶点。
HFD 小鼠出现肥胖、高血脂、高血糖和胰岛素抵抗。10mg/kg.BW 的 Ka 给药 16 周可有效改善这些变化。进一步的研究表明，Ka 的降脂和降血糖作用分别依赖于 PPARγ/LXRα/ABCA1 和 PPARγ/PI3K/AKT 通路的激活。与 PPARγ 激动剂或抑制剂共培养的原代肝细胞试验进一步证实了上述信号通路和关键蛋白。
这些结果表明，Ka 在改善糖脂代谢紊乱方面发挥了重要作用。这些有利作用与抗肥胖有关。其潜在机制可能与激活 PPARγ 及其下游信号通路有关。本研究有助于了解 Ka 的药理作用，并为 Ka 在肥胖、糖尿病、非酒精性肝炎等代谢性疾病的有效治疗中发挥作用提供了依据。
