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<p>The rising global incidence of obesity underscores the urgent demand for effective therapeutic interventions. Natural products have emerged as promising alternatives; however, identifying candidates that effectively target the complex mechanisms underlying obesity remains a critical challenge. In this study, the specialized metabolites of <i>Dendrobium albosanguineum</i> were investigated for their anti-obesity potential. Methanolic extraction was performed on the entire plant, followed by systematic fractionation and compound elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy. A set of in vitro colorimetric assays was employed to assess pancreatic lipase inhibition, cytotoxicity, intracellular lipid storage, triglyceride content, and glycerol release in murine (3T3-L1) and/or human (PCS-210-010) adipocyte models. In addition, flow cytometry, western blotting analysis, and RT-qPCR were used to evaluate the effects of a chosen metabolite on cell cycle progression and the expression of adipogenesis-related genes and proteins. Eight metabolites were isolated, including bibenzyls (moscatilin, chrysotoxine), lignans (syringaresinol, foliachinenoside C), a sterol (daucosterol), a phenylpropanoid (<i>n</i>-octacosyl-<i>trans</i>-<i>p</i>-coumarate), and flavonoids (rhoifolin, kaempferol-3-<i>O</i>-(2″,6″-dirhamnosyl)glucoside). Among them, foliachinenoside C exhibited the most potent activity, with 94.77 ± 0.85% inhibition of pancreatic lipase (IC<sub>50</sub> = 40.73 ± 0.74 µM). It significantly reduced triglyceride levels and promoted glycerol release in both murine and human adipocytes. Mechanistically, foliachinenoside C induced cell cycle arrest at the G0 phase in 3T3-L1 cells and downregulated key adipogenic transcription factors (PPARγ, C/EBPα, SREBP1c) and lipogenic proteins (FAS, PLIN1, LPL, ADPN, FABP4). Moreover, it modulated the AKT/GSK3β and AMPK-ACC signaling pathways, collectively suppressing adipocyte differentiation. These findings position foliachinenoside C as a promising plant-derived compound for obesity pharmacotherapy, warranting further investigation to facilitate its clinical development.</p>

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Regulatory effects of specialized metabolites from Dendrobium albosanguineum on lipid metabolism and adipocyte differentiation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月24日

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  • Jittima Wuttiin,
  • Poomraphie Nuntawong,
  • Hnin Ei Ei Khine,
  • Rungroch Sungthong,
  • Tharita Kitisripanya,
  • May Thazin Thant,
  • Chatchai Chaotham,
  • Wanwimon Mekboonsonglarp,
  • Kittisak Likhitwitayawuid,
  • Boonchoo Sritularak

摘要

The rising global incidence of obesity underscores the urgent demand for effective therapeutic interventions. Natural products have emerged as promising alternatives; however, identifying candidates that effectively target the complex mechanisms underlying obesity remains a critical challenge. In this study, the specialized metabolites of Dendrobium albosanguineum were investigated for their anti-obesity potential. Methanolic extraction was performed on the entire plant, followed by systematic fractionation and compound elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy. A set of in vitro colorimetric assays was employed to assess pancreatic lipase inhibition, cytotoxicity, intracellular lipid storage, triglyceride content, and glycerol release in murine (3T3-L1) and/or human (PCS-210-010) adipocyte models. In addition, flow cytometry, western blotting analysis, and RT-qPCR were used to evaluate the effects of a chosen metabolite on cell cycle progression and the expression of adipogenesis-related genes and proteins. Eight metabolites were isolated, including bibenzyls (moscatilin, chrysotoxine), lignans (syringaresinol, foliachinenoside C), a sterol (daucosterol), a phenylpropanoid (n-octacosyl-trans-p-coumarate), and flavonoids (rhoifolin, kaempferol-3-O-(2″,6″-dirhamnosyl)glucoside). Among them, foliachinenoside C exhibited the most potent activity, with 94.77 ± 0.85% inhibition of pancreatic lipase (IC50 = 40.73 ± 0.74 µM). It significantly reduced triglyceride levels and promoted glycerol release in both murine and human adipocytes. Mechanistically, foliachinenoside C induced cell cycle arrest at the G0 phase in 3T3-L1 cells and downregulated key adipogenic transcription factors (PPARγ, C/EBPα, SREBP1c) and lipogenic proteins (FAS, PLIN1, LPL, ADPN, FABP4). Moreover, it modulated the AKT/GSK3β and AMPK-ACC signaling pathways, collectively suppressing adipocyte differentiation. These findings position foliachinenoside C as a promising plant-derived compound for obesity pharmacotherapy, warranting further investigation to facilitate its clinical development.