Sutjarit N.Yanukun K.Bhukhai K.Asavapanumas N.Rangketkarn S.Thongsa-ad U.Chaichompoo W.Suksamrarn A.Soodvilai S.Tantikanlayaporn D.Mahidol University2025-12-142025-12-142025-12-01Biomedicine and Pharmacotherapy Vol.193 (2025)07533322https://repository.li.mahidol.ac.th/handle/123456789/113513Excessive bone marrow adipose tissue (BMAT) is a key contributor to postmenopausal osteoporosis. It is associated with bone marrow-derived mesenchymal stem cells (BM-MSCs), which favor differentiation into adipocytes, thereby compromising osteoblast and bone formation. In addition, BMAT secretes anti-osteogenic factors that exacerbate bone loss. In this study, we investigated the effects of ASPP-092, a diarylheptanoid compound isolated from Curcuma comosa , on BM-MSC differentiation. ASPP-092 inhibited adipogenic differentiation and lipid accumulation by downregulating key adipogenic transcription factors and enzymes, including peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein 1 (SREBP1), lipoprotein lipase (LPL), and fatty acid-binding protein 4 (FABP4). ASPP-092 also reduced the secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) while increasing anti-inflammatory interleukin-10 (IL-10) and adipokines such as leptin, adiponectin, and resistin. Transcriptomic analysis revealed upregulation of genes involved in the transforming growth factor-beta (TGF-β), Hippo, and Wnt/beta-catenin signaling pathways. Pharmacological inhibition of TGF-β/SMAD2/3 signaling abolished the anti-adipogenic effects of ASPP-092. These findings identify a novel mechanism by which ASPP-092 suppresses BMAT formation and supports its potential as an anti-osteoporotic agent.Pharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/j.biopha.2025.1188842-s2.0-10502410497319506007