[1] Schwartz MW, Seeley RJ, Zeltser LM, Drewnowski A, Ravussin E, Redman LM, et al. Obesity pathogenesis: an endocrine society scientific statement. Endocr Rev. 2017;38(4):267–96. https://doi.org/10.1210/er.2017-00111. [2] Jin X, Qiu T, Li L, Yu R, Chen X, Li C, et al. Pathophysiology of obesity and its associated diseases. Acta Pharm Sin B. 2023;13(6):2403–24. https://doi.org/10.1016/j.apsb.2023.01.012. [3] World Health Organization. Obesity and overweight. 2025. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed 12 Aug 2025. [4] Gudzune KA, Kushner RF. Medications for obesity: a review. JAMA. 2024;332(7):571–84. https://doi.org/10.1001/jama.2024.10816. [5] Hadrich F, Sayadi S. Apigetrin inhibits adipogenesis in 3T3-L1 cells by downregulating PPARγ and CEBP-α. Lipids Health Dis. 2018;17(1):95. https://doi.org/10.1186/s12944-018-0738-0. [6] Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19(2):121–35. https://doi.org/10.1038/nrm.2017.95. [7] Zhang L, Zhang L, Wang X, Si H. Anti-adipogenic effects and mechanisms of ginsenoside Rg3 in pre-adipocytes and obese mice. Front Pharmacol. 2017;8:113. https://doi.org/10.3389/fphar.2017.00113. [8] Li Z, Ji GE. Ginseng and obesity. J Ginseng Res. 2018;42(1):1–8. https://doi.org/10.1016/j.jgr.2016.12.005. [9] Subha D, Harshnii K, Madhikiruba KG, Nandhini M, Tamilselvi KS. Plant derived exosome-like nanovesicles: an updated overview. Plant Nano Biol. 2023;3:100022. https://doi.org/10.1016/j.plana.2022.100022. [10] Kim HI, Park J, Zhu Y, Wang X, Han Y, Zhang D. Recent advances in extracellular vesicles for therapeutic cargo delivery. Exp Mol Med. 2024;56(4):836–49. https://doi.org/10.1038/s12276-024-01201-6. [11] Fang C, Pan J, Qu N, Lei Y, Han J, Zhang J, et al. The AMPK pathway in fatty liver disease. Front Physiol. 2022;13:970292. https://doi.org/10.3389/fphys.2022.970292. [12] Olzmann JA, Carvalho P. Dynamics and functions of lipid droplets. Nat Rev Mol Cell Biol. 2019;20(3):137–55. https://doi.org/10.1038/s41580-018-0085-z. [13] van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28. https://doi.org/10.1038/nrm.2017.125. [14] Emmanuela N, Muhammad DR, Iriawati WCH, Ratnadewi YMD, Takemori H, et al. Isolation of plant-derived exosome-like nanoparticles (PDENs) from Solanum nigrum L. berries and Their Effect on interleukin-6 expression as a potential anti-inflammatory agent. PLoS ONE. 2024;19(1):e0296259. https://doi.org/10.1371/journal.pone.0296259. [15] Cao YQ, Wu ZT, You Q, Xia YY, Zhao Q, de Marcos LC, et al. Chinese herbal medicine-derived extracellular vesicle-like particles: therapeutic potential and future research approaches. Interdiscip Med. 2025. https://doi.org/10.1002/INMD.20250038. [16] Ratnadewi D, Widjaja CH, Barlian A, Amsar RM, Ana ID, Hidajah AC, et al. Isolation of native plant-derived exosome-like nanoparticles and their uptake by human cells. HAYATI J Biosci. 2023;30(1):182–92. https://doi.org/10.4308/hjb.30.1.182-192. [17] Kyung KY, Lee YH, Lee SW. Anti-inflammatory properties of ginseng-derived exosome-like nanoparticles in LPS-induced RAW264.7. Res Sq. 2023. https://doi.org/10.21203/rs.3.rs-2836366/v1. [18] Seo K, Yoo JH, Kim J, Min SJ, Heo DN, Kwon IK, et al. Ginseng-derived exosome-like nanovesicles extracted by sucrose gradient ultracentrifugation to inhibit osteoclast differentiation. Nanoscale. 2023;15(12):5798–808. https://doi.org/10.1039/d2nr07018a. [19] Zhu J, Qiao Q, Sun Y, Xu Y, Shu H, Zhang Z, et al. Divergent sequences of tetraspanins enable plants to specifically recognize microbe-derived extracellular vesicles. Nat Commun. 2023;14(1):4877. https://doi.org/10.1038/s41467-023-40623-0. [20] Tsui L. Adipocyte-based high throughput screening for anti-obesity drug discovery: current status and future perspectives. SLAS Discovery. 2022;27(7):375–83. https://doi.org/10.1016/j.slasd.2022.08.001. [21] Ghasemi M, Turnbull T, Sebastian S, Kempson I. The MTT assay: utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis. Int J Mol Sci. 2021;22(23):12827. https://doi.org/10.3390/ijms222312827. [22] Wang H, Liu X, Wang C, Yu S, Yang X, Cao X, et al. Natural active botanical metabolites: targeting AMPK signaling pathway to treat metabolic dysfunction-associated fatty liver disease. Front Pharmacol. 2025;16:1611400. https://doi.org/10.3389/fphar.2025.1611400. [23] Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ, et al. C/EBPα induces adipogenesis through PPARγ: a unified pathway. Genes Dev. 2002;16(1):22–6. https://doi.org/10.1101/gad.948702. [24] Krahmer N, Farese RV Jr, Walther TC. Balancing the fat: lipid droplets and human disease. EMBO Mol Med. 2013;5(7):973–83. https://doi.org/10.1002/emmm.201100671. [25] Takahashi Y, Shinoda A, Furuya N, Harada E, Arimura N, Ichi I, et al. Perilipin-mediated lipid droplet formation in adipocytes promotes sterol regulatory element-binding protein-1 processing and triacylglyceride accumulation. PLoS ONE. 2013;8(5):e64605. https://doi.org/10.1371/journal.pone.0064605. [26] Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 2006;7(12):885–96. https://doi.org/10.1038/nrm2066. [27] Cristancho AG, Lazar MA. Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011;12(11):722–34. https://doi.org/10.1038/nrm3198. [28] TFuruhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008;7(6):489–503. https://doi.org/10.1038/nrd2589. [29] Fullerton MD, Galic S, Marcinko K, Sikkema S, Pulinilkunnil T, Chen ZP, et al. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat Med. 2013;19(12):1649–54. https://doi.org/10.1038/nm.3372. [30] Li YU, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13(4):376–88. https://doi.org/10.1016/j.cmet.2011.03.009. [31] Wu Z, Bucher NL, Farmer SR. Induction of peroxisome proliferator-activated receptor γ during the conversion of 3T3 fibroblasts into adipocytes is mediated by C/EBPβ, C/EBPδ, and glucocorticoids. Mol Cell Biol. 1996;16(8):4128–36. https://doi.org/10.1128/MCB.16.8.4128. [32] Wilson-Fritch L, Burkart A, Bell G, Mendelson K, Leszyk J, Nicoloro S, et al. Mitochondrial biogenesis and remodeling during adipogenesis and in response to the insulin sensitizer rosiglitazone. Mol Cell Biol. 2003;23(3):1085–94. https://doi.org/10.1128/MCB.23.3.1085-1094.2003. [33] Estandarte AK, Botchway S, Lynch C, Yusuf M, Robinson I. The use of DAPI fluorescence lifetime imaging for investigating chromatin condensation in human chromosomes. Sci Rep. 2016;6(1):31417. https://doi.org/10.1038/srep31417. [34] Bhumiratana S, Vunjak-Novakovic G. Engineering physiologically stiff and stratified human cartilage by fusing condensed mesenchymal stem cells. Methods. 2015;84:109–14. https://doi.org/10.1016/j.ymeth.2015.03.016. [35] Miranda L, Carpentier S, Platek A, Hussain N, Gueuning MA, Vertommen D, et al. AMP-activated protein kinase induces actin cytoskeleton reorganization in epithelial cells. Biochem Biophys Res Commun. 2010;396(3):656–61. https://doi.org/10.1016/j.bbrc.2010.04.151. [36] De Pauw A, Tejerina S, Raes M, Keijer J, Arnould T. Mitochondrial (dys) function in adipocyte (de) differentiation and systemic metabolic alterations. Am J Pathol. 2009;175(3):927–39. https://doi.org/10.2353/ajpath.2009.081155. [37] Siersbæk R, Madsen JGS, Javierre BM, Nielsen R, Bagge EK, Cairns J, et al. Dynamic rewiring of promoter-anchored chromatin loops during adipocyte differentiation. Mol Cell. 2017;66(3):420–35. https://doi.org/10.1016/j.molcel.2017.04.010. [38] Hagberg CE, Li Q, Kutschke M, Bhowmick D, Kiss E, Shabalina IG, et al. Flow cytometry of mouse and human adipocytes for the analysis of browning and cellular heterogeneity. Cell Rep. 2018;24(10):2746–56. https://doi.org/10.1016/j.celrep.2018.08.006. [39] Ahmad B, Serpell CJ, Fong IL, Wong EH. Molecular mechanisms of adipogenesis: the anti-adipogenic role of AMP-activated protein kinase. Front Mol Biosci. 2020;7:76. https://doi.org/10.3389/fmolb.2020.00076. [40] Zhang X, Zhang B, Zhang C, Sun G, Sun X. Effect of Panax notoginseng saponins and major anti-obesity components on weight loss. Front Pharmacol. 2021;11:601751. https://doi.org/10.3389/fphar.2020.601751. [41] Fan M, Lan X, Wang Q, Shan M, Fang X, Zhang Y, et al. Renal function protection and the mechanism of ginsenosides: current progress and future perspectives. Front Pharmacol. 2023;14:1070738. https://doi.org/10.3389/fphar.2023.1070738. [42] Mihaylova MM, Shaw RJ. Metabolic reprogramming by class I and II histone deacetylases. Trends Endocrinol Metab. 2013;24(1):48–57. https://doi.org/10.1016/j.tem.2012.09.003. |