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

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.