Recent studies have identified obesity as one of the world’s most serious chronic disorders. Adipogenesis, in which preadipocytes are differentiated into mature adipocytes, has a decisive role in establishing the number of adipocytes and determining the lipid storage capacity of adipose tissue and fat mass in adults. Fat accumulation in obesity is implicated with elevated oxidative stress in adipocytes induced by reactive oxygen species (ROS). Adipogenesis regulation by inhibiting adipogenic differentiation and ROS production has been selected as the strategy to treat obesity. The conventional anti-obesity drugs allowed by the U.S. Food and Drug Administration have severe adverse effects. Therefore, various natural products have been developed as a solution for obesity, suppressing adipogenic differentiation. Fraxetin is a major component extracted from the stem barks of Fraxinus rhynchophylla, with various bioactivities, including anti-inflammatory, anticancer, antioxidant, and antibacterial functions. However, the effect of fraxetin on adipogenesis is still not clearly understood. We studied the pharmacological functions of fraxetin in suppressing lipid accumulation and its underlying molecular mechanisms involving 3T3-L1 preadipocytes. Moreover, increased ROS production induced by a mixture of insulin, dexamethasone, and 3-isobutylmethylxanthine (MDI) in 3T3-L1 was attenuated by fraxetin during adipogenesis. These effects were regulated by mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, our findings imply that fraxetin possesses inhibitory roles in adipogenesis and can be a potential anti-obesity drug.

中文翻译：

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Fraxetin 通过调节 MAPK 信号通路抑制 3T3-L1 细胞的脂肪生成和活性氧生成

最近的研究已将肥胖确定为世界上最严重的慢性疾病之一。脂肪生成，其中前脂肪细胞分化为成熟的脂肪细胞，在确定脂肪细胞的数量和确定成人脂肪组织的脂质储存能力和脂肪量方面具有决定性作用。肥胖中的脂肪积累与活性氧 (ROS) 诱导的脂肪细胞氧化应激升高有关。通过抑制脂肪形成分化和 ROS 产生来调节脂肪形成已被选为治疗肥胖的策略。美国食品和药物管理局允许的常规抗肥胖药物具有严重的不良反应。因此，已经开发出各种天然产物作为肥胖症的解决方案，抑制脂肪形成分化。水曲柳，具有多种生物活性，包括抗炎、抗癌、抗氧化和抗菌功能。然而，fraxetin 对脂肪生成的影响仍不清楚。我们研究了 fraxetin 在抑制脂质积累中的药理功能及其涉及 3T3-L1 前脂肪细胞的潜在分子机制。此外，在脂肪生成过程中，由 3T3-L1 中的胰岛素、地塞米松和 3-异丁基甲基黄嘌呤 (MDI) 的混合物诱导的 ROS 产生增加被 fraxetin 减弱。这些影响受丝裂原活化蛋白激酶 (MAPK) 信号通路的调节。因此，我们的研究结果表明，fraxetin 在脂肪生成中具有抑制作用，并且可能是一种潜在的抗肥胖药物。