Epoxy Clerodane Diterpene Attenuates the Differentiated Adipocyte Hypertrophy and Enhances Mitochondrial Metabolism

IF 3 4区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

ChemistryOpen Pub Date : 2026-06-18 DOI:10.1002/open.70230

Sahar Abdulaziz AlSedairy, Pandurangan Subash-Babu, Maha H. Alhussain, Manal Abdulaziz Binobead, Ali A. Alshatwi

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Abstract

Adipocyte hypertrophy is an obesity-related metabolic dysfunction, which is frequently associated with decreased mitochondrial activity during adipocyte development. The current study aimed to assess the potential of epoxy clerodane diterpene (ECD) (IUPAC: 5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone) extracted from Cassia tora on adipocyte differentiation, lipid accumulation, mitochondrial function, and inflammation. Human bone marrow mesenchymal stem cells (hMSCs) were stimulated into adipocytes using the standard differentiation medium. The methodological design included the evaluation of ECD cytotoxicity, lipid accumulation, mitochondrial membrane potential, qRT-PCR, and ELISA. ECD didn’t significantly reduce the cellular viability; however, it decreased lipid accumulation by 65%, 87%, and 87.5% at doses of 2, 4, and 8 μM, respectively. Also, at 4 µM of ECD, it decreased adipocyte hypertrophy, increased mitochondrial membrane potential, raised the expression of thermogenesis-related genes (UCP-1, PPARγC1α, SREBP1c), decreased the expression of adipogenic proteins (C/EBPα, PPARγ), increased adiponectin levels, and reduced inflammatory markers (IL-4, TNF-α) compared to untreated controls. Thus, ECD may hold tremendous promise as a natural agent for controlling adipogenesis, and its impacts on lipid metabolism, mitochondrial function, and inflammatory responses demonstrate its potential for therapeutic use in the treatment of obesity and associated metabolic diseases.

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环氧氯烷二萜减轻分化脂肪细胞肥大，促进线粒体代谢

脂肪细胞肥大是一种与肥胖相关的代谢功能障碍，通常与脂肪细胞发育过程中线粒体活性降低有关。本研究旨在评估决明子中环氧氯烷二萜（ECD）（IUPAC: 5R, 10R)-4R， 8r -二羟基- 2s， 3R: 15,16 -二羟基-13(16),17,12s: 18,1s -二内酯）对脂肪细胞分化、脂质积累、线粒体功能和炎症的影响。采用标准分化培养基将人骨髓间充质干细胞（hMSCs）诱导为脂肪细胞。方法学设计包括ECD细胞毒性、脂质积累、线粒体膜电位、qRT-PCR和ELISA评价。ECD未显著降低细胞活力；然而，在2 μM、4 μM和8 μM剂量下，它分别减少了65%、87%和87.5%的脂质积累。此外，在4µM ECD时，与未治疗的对照组相比，它减少了脂肪细胞的肥大，增加了线粒体膜电位，提高了产热相关基因（UCP-1, PPARγ c1 α, SREBP1c）的表达，降低了脂肪生成蛋白（C/EBPα, PPARγ）的表达，增加了脂联素水平，降低了炎症标志物（IL-4, TNF-α）。因此，ECD作为一种控制脂肪生成的天然药物可能具有巨大的前景，其对脂质代谢、线粒体功能和炎症反应的影响表明，它在治疗肥胖和相关代谢疾病方面具有潜在的治疗用途。

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来源期刊

ChemistryOpen CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

4.80

自引率

4.30%

发文量

143

审稿时长

1 months

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