The present study investigated the efficacy of the hepatoprotective drug matrine (Mtr) for its new application for hepatosteatosis and associated disorders in glucose homeostasis. The study was performed in two nutritional models of hepatosteatosis in mice with various abnormal glucose homeostasis: (1) high-fructose diet (HFru) induced hepatosteatosis and glucose intolerance from hepatic, and (2) hepatosteatosis and hyperglycemia induced by high-fat (HF) diet in combination with low doses of streptozotocin (STZ). Administration of Mtr (100 mg/kg every day in diet for 4 weeks) abolished HFru-induced hepatosteatosis and glucose intolerance. These effects were associated with the inhibition of HFru-stimulated de novo lipogenesis (DNL) without altering hepatic fatty acid oxidation. Further investigation revealed that HFru-induced endoplasmic reticulum (ER) stress was inhibited, whereas heat-shock protein 72 (an inducible chaperon protein) was increased by Mtr. In a type 2 diabetic model induced by HF-STZ, Mtr reduced hepatosteatosis and improved attenuated hyperglycemia. The hepatoprotective drug Mtr may be repurposed for the treatment of hepatosteatosis and associated disorders in glucose homeostasis. The inhibition of ER stress associated DNL and fatty acid influx appears to play an important role in these metabolic effects.

中文翻译：

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重新使用苦参碱治疗肝脂肪变性和小鼠葡萄糖稳态中的相关疾病。

本研究调查了保护肝的药物苦参碱（Mtr）在肝脂肪变性和葡萄糖稳态中的相关疾病中的新应用的功效。这项研究是在两种具有各种葡萄糖稳态异常的小鼠的肝脂肪变性的营养模型中进行的：（1）高果糖饮食（HFru）诱导的肝脂肪变性和肝对葡萄糖的不耐受性；（2）高脂肪（HF）诱导的肝脂肪变性和高血糖症）与低剂量的链脲佐菌素（STZ）结合饮食。给予Mtr（每天100 mg / kg的饮食，持续4周）可消除HFru引起的肝硬皮病和葡萄糖耐受不良。这些作用与抑制HFru刺激的新生脂肪形成（DNL）而不改变肝脂肪酸氧化有关。进一步的研究表明，HFru诱导的内质网（ER）应激受到抑制，而Mtr增加了热休克蛋白72（一种诱导型伴侣蛋白）。在由HF-STZ诱导的2型糖尿病模型中，Mtr减少了肝脂肪变性并改善了减低的高血糖症。保肝药物Mtr可重新用于治疗肝脂肪变性和葡萄糖稳态的相关疾病。ER应激相关的DNL和脂肪酸流入的抑制作用似乎在这些代谢作用中起重要作用。保肝药物Mtr可重新用于治疗肝脂肪变性和葡萄糖稳态的相关疾病。ER应激相关的DNL和脂肪酸流入的抑制作用似乎在这些代谢作用中起重要作用。保肝药物Mtr可重新用于治疗肝脂肪变性和葡萄糖稳态的相关疾病。ER应激相关的DNL和脂肪酸流入的抑制作用似乎在这些代谢作用中起重要作用。