Fuziline 通过激活 β 肾上腺素能受体刺激产热来改善葡萄糖和脂质代谢,International Journal of Molecular Sciences

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Fuziline 通过激活 β 肾上腺素能受体刺激产热来改善葡萄糖和脂质代谢
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2023-05-06 , DOI: 10.3390/ijms24098362
He Gao ₁ , Zhenqiang Li ₁ , Chuanjing Cheng ₁ , Jing Cui ₁ , Jiamin Peng ₁ , Xiaoying Wang ₂ , Man Zhang ₁ , Yuanyuan Hou ₁ , Gang Bai ₁

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附子是一种广泛使用的中药，已被发现可有效治疗心血管疾病和代谢紊乱。患有这些疾病的患者常常会出现生热障碍，其特点是怕冷，并且会加剧疾病的进展。本研究建立了结合细胞线粒体膜电位和线粒体温度检测的体外筛选模型，筛选具有产热活性的药物。经过对含药血清血液成分特征代谢物含量的区分和含量测定，发现附子碱（FZL）是附子的关键生热特性，其生热作用的相对重要性高达33%。。实验通过评估直肠、肝脏和棕色脂肪组织等不同器官的温度变化来评估附子和 FZL 的体内生热活性。此外，使用瞬时 β3-AR 转染和双荧光素酶测定系统评估了细胞内 β3-肾上腺素能受体 (β3-AR) 激动作用的效果。通过验证β-肾上腺素受体（β-AR）下游信号通路，研究FZL促进产热、改善线粒体功能的分子机制。结果表明，FZL 非选择性激活 β-AR，进而激活下游 cAMP-PKA 信号通路，导致肝糖原分解和甘油三酯水解增加，同时增强线粒体能量代谢。因此，肝脏和棕色脂肪组织接收能量来产生热量。总之，这些发现提供了对附子治疗与生热障碍相关的代谢障碍的治疗应用的见解。

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Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis

Radix aconiti carmichaeli is a widely used traditional Chinese medicine that has been found to be effective in treating cardiovascular diseases and metabolic disorders. Patients with these diseases often experience a heat generation disorder, which is characterized by chilliness and can worsen the progression of the disease. This study established an in vitro screening model combining the examination of cellular mitochondrial membrane potential and mitochondrial temperature to screen drugs with thermogenic activity. After differentiation and determination of the content of characteristic metabolites of the drug-containing serum blood components, it was found that Fuziline (FZL) is the key thermogenic property in Radix aconiti carmichaeli, responsible for its thermogenic effects with a high relative importance of 33%. Experiments were conducted to evaluate the thermogenic activity of Radix aconiti carmichaeli and FZL in vivo by assessing temperature changes in various organs, including the rectum, liver, and brown adipose tissue. Moreover, the effects of intracellular β3-adrenergic receptor (β3-AR) agonistic effects were evaluated using transient β3-AR transfection and dual-luciferase assay systems. The molecular mechanism by which FZL promotes thermogenesis and improves mitochondrial function was investigated by verifying the β-adrenergic receptors (β-AR) downstream signaling pathway. The results suggest that FZL activates β-AR nonselectively, which in turn activates the downstream cAMP-PKA signaling pathway and leads to an increase in liver glycogenolysis and triglyceride hydrolysis, accompanied by enhancing mitochondrial energy metabolism. Consequently, the liver and brown adipose tissue receive energy to generate heat. In summary, these findings provide insight into the therapeutic application of Radix aconiti carmichaeli for metabolic disorders associated with heat generation disorders.

更新日期：2023-05-07

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