ASPP-092, a Curcuma comosa diarylheptanoid, inhibits the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via activation of TGF-β/SMAD2/3 signaling
Issued Date
2025-12-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-105024104973
Journal Title
Biomedicine and Pharmacotherapy
Volume
193
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.193 (2025)
Suggested Citation
Sutjarit N., Yanukun K., Bhukhai K., Asavapanumas N., Rangketkarn S., Thongsa-ad U., Chaichompoo W., Suksamrarn A., Soodvilai S., Tantikanlayaporn D. ASPP-092, a Curcuma comosa diarylheptanoid, inhibits the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via activation of TGF-β/SMAD2/3 signaling. Biomedicine and Pharmacotherapy Vol.193 (2025). doi:10.1016/j.biopha.2025.118884 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113513
Title
ASPP-092, a Curcuma comosa diarylheptanoid, inhibits the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells via activation of TGF-β/SMAD2/3 signaling
Corresponding Author(s)
Other Contributor(s)
Abstract
Excessive 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.