Concentrated extract of Prunus mume fruit exerts dual effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing beiging/browning

  • Su Bu College of Biology and the Environment, Nanjing Forestry University, Nanjing, China
  • Chunying Yuan College of Biology and the Environment, Nanjing Forestry University, Nanjing, China
  • Fuliang Cao Co-innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing, China
  • Qifeng Xu College of Biology and the Environment, Nanjing Forestry University, Nanjing, China
  • Yichun Zhang College of Forestry, Nanjing Forestry University, Nanjing, China
  • Ronghua Ju National Engineering Research Center of Biomaterials, Nanjing Forestry University, Nanjing, China
  • Longyun Chen Nanjing Longlijia Agricultural Development Co. Ltd., Nanjing, China
  • Zhong Li National Engineering Research Center of Biomaterials, Nanjing Forestry University, Nanjing, China
Keywords: Concentrated water extract of Prunus mume fruit (CEPM), beiging, browning, mitochondrial biogenesis, 3T3-L1 adipocytes


Background: The fruit Prunus mume has beneficial effects in the treatment of obesity and metabolic syndrome. However, its mechanism of action is unclear.

Objective: We assessed the effect of a concentrated water extract of P. mume fruit (CEPM) on adipogenesis and beiging/browning in 3T3-L1 cells.

Methods: The cell viability was determined by MTT assay. Lipid accumulation was assessed with Oil Red O (ORO) staining under different concentrations of CEPM. The effects of CEPM treatment during differentiation on beiging/browning and mitochondrial biogenesis in 3T3-L1 cells were investigated.

Results: CEPM treatment suppressed differentiation and decreased lipid accumulation by downregulating the expression of key adipogenic genes, including PPARγ, C/EBPα, SREBP-1c, FAS, and perilipin A. In contrast, CEPM treatment increased the mitochondrial DNA (mtDNA) content and mRNA levels of mitochondrial biogenesis genes, including NAMPTNrf1Nrf2, and CPT1α, and reduced reactive oxygen species levels. Importantly, CEPM increased the expression of brown/beige hallmark genes (Pgc-1α, Ucp1CideaCox7α1Cox8bCd137, and Pdk-4), as well as proteins (UCP1, PGC-1α, NRF1, TBX1, and CPT1α). The high-performance liquid chromatography (HPLC) analysis reveals that CEPM contains mumefural, naringin, 5-HMF, citric acid, caffeic acid, and hesperidin.

Conclusion: The first evidence we provided showed that CEPM has a dual role in 3T3-L1 cells inhibiting adipogenesis and promoting beiging/browning, and hence, could be a potential agent in the fight against obesity.


Download data is not yet available.


  1. Gonzalez-Muniesa P, Martinez-Gonzalez MA, Hu FB, Despres JP, Matsuzawa Y, Loos RJF, et al. Obesity. Nat Rev Dis Primers 2017; 3: 17034. doi: 10.1038/nrdp.2017.34

  2. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, et al. Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLoS Comput Biol 2009; 5(3): e1000324. doi: 10.1371/journal.pcbi.1000324

  3. Farmer SR. Transcriptional control of adipocyte formation. Cell Metab 2006; 4(4): 263–73. doi: 10.1016/j.cmet.2006.07.001

  4. Kim HL, Sim JE, Choi HM, Choi IY, Jeong MY, Park J, et al. The AMPK pathway mediates an anti-adipogenic effect of fruits of Hovenia dulcis Thunb. Food Funct 2014; 5(11): 2961–8. doi: 10.1039/c4fo00470a

  5. Shen S, Liao Q, Feng Y, Liu J, Pan R, Lee SM, et al. Myricanol mitigates lipid accumulation in 3T3-L1 adipocytes and high fat diet-fed zebrafish via activating AMP-activated protein kinase. Food Chem 2019; 270: 305–14. doi: 10.1016/j.foodchem.2018.07.117

  6. Zechner R, Zimmermann R, Eichmann TO, Kohlwein SD, Haemmerle G, Lass A, et al. FAT SIGNALS – lipases and lipolysis in lipid metabolism and signaling. Cell Metab 2012; 15(3): 279–91. doi: 10.1016/j.cmet.2011.12.018

  7. Houten SM, Wanders RJ. A general introduction to the biochemistry of mitochondrial fatty acid beta-oxidation. J Inherit Metab Dis 2010; 33(5): 469–77. doi: 10.1007/s10545-010-9061-2

  8. Chiu HF, Huang YC, Lu YY, Han YC, Shen YC, Golovinskaia O, et al. Regulatory/modulatory effect of prune essence concentrate on intestinal function and blood lipids. Pharm Biol 2017; 55(1): 974–9. doi: 10.1080/13880209.2017.1285323

  9. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014; 156(1–2): 20–44. doi: 10.1016/j.cell.2013.12.012

  10. Brand MD. The sites and topology of mitochondrial superoxide production. Exp Gerontol 2010; 45(7–8): 466–72. doi: 10.1016/j.exger.2010.01.003

  11. Yuliana A, Jheng HF, Kawarasaki S, Nomura W, Takahashi H, Ara T, et al. Beta-adrenergic receptor stimulation revealed a novel regulatory pathway via suppressing histone deacetylase 3 to induce uncoupling protein 1 expression in mice beige adipocyte. Int J Mol Sci 2018; 19(8): 2436. doi: 10.3390/ijms19082436

  12. Chouchani ET, Kazak L, Spiegelman BM. New advances in adaptive thermogenesis: UCP1 and beyond. Cell Metab 2019; 29(1): 27–37. doi: 10.1016/j.cmet.2018.11.002

  13. Ricquier D. UCP1, the mitochondrial uncoupling protein of brown adipocyte: a personal contribution and a historical perspective. Biochimie 2017; 134: 3–8. doi: 10.1016/j.biochi.2016.10.018

  14. Austin S, St-Pierre J. PGC1alpha and mitochondrial metabolism – emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 2012; 125(Pt 21): 4963–71. doi: 10.1242/jcs.113662

  15. Liang H, Ward WF. PGC-1alpha: a key regulator of energy metabolism. Adv Physiol Educ 2006; 30(4): 145–51. doi: 10.1152/advan.00052.2006

  16. Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 2008; 79(2): 208–17. doi: 10.1093/cvr/cvn098

  17. de Mello AH, Costa AB, Engel JDG, Rezin GT. Mitochondrial dysfunction in obesity. Life Sci 2018; 192: 26–32. doi: 10.1016/j.lfs.2017.11.019

  18. Kono R, Nakamura M, Nomura S, Kitano N, Kagiya T, Okuno Y, et al. Biological and epidemiological evidence of anti-allergic effects of traditional Japanese food ume (Prunus mume). Sci Rep 2018; 8(1): 11638. doi: 10.1038/s41598-018-30086-5

  19. Shin EJ, Hur HJ, Sung MJ, Park JH, Yang HJ, Kim MS, et al. Ethanol extract of the Prunus mume fruits stimulates glucose uptake by regulating PPAR-gamma in C2C12 myotubes and ameliorates glucose intolerance and fat accumulation in mice fed a high-fat diet. Food Chem 2013; 141(4): 4115–21. doi: 10.1016/j.foodchem.2013.06.059

  20. Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, et al. Identification and biological evaluation of flavonoids from the fruits of Prunus mume. Bioorg Med Chem Lett 2014; 24(5): 1397–402. doi: 10.1016/j.bmcl.2014.01.028

  21. Pi K, Lee K. Prunus mume extract exerts antioxidant activities and suppressive effect of melanogenesis under the stimulation by alpha-melanocyte stimulating hormone in B16-F10 melanoma cells. Biosci Biotechnol Biochem 2017; 81(10): 1883–90. doi: 10.1080/09168451.2017.1365591

  22. Lee MW, Kwon JE, Lee YJ, Jeong YJ, Kim I, Cho YM, et al. Prunus mume leaf extract lowers blood glucose level in diabetic mice. Pharm Biol 2016; 54(10): 2135–40. doi: 10.3109/13880209.2016.1147052

  23. Chuda Y, Ono H, Ohnishi-Kameyama M, Matsumoto K, Nagata T, Kikuchi Y. Mumefural, citric acid derivative improving blood fluidity from fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc). J Agric Food Chem 1999; 47(3): 828–31. doi: 10.1021/jf980960t

  24. Bu S, Yuan CY, Xue Q, Chen Y, Cao F. Bilobalide suppresses adipogenesis in 3T3-L1 adipocytes via the AMPK signaling pathway. Molecules 2019; 24(19): 3503. doi: 10.3390/molecules24193503

  25. Park WY, Choe SK, Park J, Um JY. Black raspberry (Rubus coreanus Miquel) promotes browning of preadipocytes and inguinal white adipose tissue in cold-induced mice. Nutrients 2019; 11(9): 2164. doi: 10.3390/nu11092164

  26. Torres-Villarreal D, Camacho A, Castro H, Ortiz-Lopez R, de la Garza AL. Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells. J Physiol Biochem 2019; 75(1): 83–8. doi: 10.1007/s13105-018-0659-4

  27. Liu M, Liu H, Xie J, Xu Q, Pan C, Wang J, et al. Anti-obesity effects of zeaxanthin on 3T3-L1 preadipocyte and high fat induced obese mice. Food Funct 2017; 8(9): 3327–38. doi: 10.1039/c7fo00486a

  28. Yesmin Simu S, Ahn S, Castro-Aceituno V, Yang DC. Ginsenoside Rg5: Rk1 exerts an anti-obesity effect on 3T3-L1 cell line by the downregulation of PPARgamma and CEBPalpha. Iran J Biotechnol 2017; 15(4): 252–9. doi: 10.15171/ijb.1517

  29. Kim YM, Jang MS. Anti-obesity effects of Laminaria japonica fermentation on 3T3-L1 adipocytes are mediated by the inhibition of C/EBP-alpha/beta and PPAR-gamma. Cell Mol Biol (Noisy-le-grand) 2018; 64(4): 71–7. doi: 10.14715/cmb/2018.64.4.12

  30. Sarparanta J, Garcia-Macia M, Singh R. Autophagy and mitochondria in obesity and type 2 diabetes. Curr Diabetes Rev 2017; 13(4): 352–69. doi: 10.2174/1573399812666160217122530

  31. Tormos KV, Anso E, Hamanaka RB, Eisenbart J, Joseph J, Kalyanaraman B, et al. Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab 2011; 14(4): 537–44. doi: 10.1016/j.cmet.2011.08.007

  32. Angelova PR, Abramov AY. Role of mitochondrial ROS in the braIn: from physiology to neurodegeneration. FEBS Lett 2018; 592(5): 692–702. doi: 10.1002/1873-3468.12964

  33. Cadenas S. Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim Biophys Acta Bioenerg 2018; 1859(9): 940–50. doi: 10.1016/j.bbabio.2018.05.019

  34. Yang Y, Karakhanova S, Hartwig W, D'Haese JG, Philippov PP, Werner J, et al. Mitochondria and mitochondrial ROS in cancer: novel targets for anticancer therapy. J Cell Physiol 2016; 231(12): 2570–81. doi: 10.1002/jcp.25349

  35. Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis 2017; 1863(5): 1037–45. doi: 10.1016/j.bbadis.2016.04.017

  36. Handschin C, Spiegelman BM. Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 2006; 27(7): 728–35. doi: 10.1210/er.2006-0037

  37. Piantadosi CA, Suliman HB. Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1. J Biol Chem 2006; 281(1): 324–33. doi: 10.1074/jbc.M508805200

  38. Kunkel GH, Chaturvedi P, Tyagi SC. Mitochondrial pathways to cardiac recovery: TFAM. Heart Fail Rev 2016; 21(5): 499–517. doi: 10.1007/s10741-016-9561-8

  39. Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 2015; 11(9): 535–46. doi: 10.1038/nrendo.2015.117

  40. Scarpulla RC. Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Ann N Y Acad Sci 2008; 1147: 321–34. doi: 10.1196/annals.1427.006

  41. Pettersson-Klein AT, Izadi M, Ferreira DMS, Cervenka I, Correia JC, Martinez-Redondo V, et al. Small molecule PGC-1alpha1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration. Mol Metab 2018; 9: 28–42. doi: 10.1016/j.molmet.2018.01.017

  42. Ikeda K, Maretich P, Kajimura S. The common and distinct features of brown and beige adipocytes. Trends Endocrinol Metab 2018; 29(3): 191–200. doi: 10.1016/j.tem.2018.01.001

  43. Milton-Laskibar I, Gomez-Zorita S, Arias N, Romo-Miguel N, Gonzalez M, Fernandez-Quintela A, et al. Effects of resveratrol and its derivative pterostilbene on brown adipose tissue thermogenic activation and on white adipose tissue browning process. J Physiol Biochem 2020; 76(2): 269–278. doi: 10.1007/s13105-020-00735-3

  44. Rodrigues AR, Salazar MJ, Rocha-Rodrigues S, Goncalves IO, Cruz C, Neves D, et al. Peripherally administered melanocortins induce mice fat browning and prevent obesity. Int J Obes (Lond). 2019; 43(5): 1058–69. doi: 10.1038/s41366-018-0155-5

  45. Liu M, Zheng M, Cai D, Xie J, Jin Z, Liu H, et al. Zeaxanthin promotes mitochondrial biogenesis and adipocyte browning via AMPKalpha1 activation. Food Funct 2019; 10(4): 2221–33. doi: 10.1039/c8fo02527d

  46. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481(7382): 463–8. doi: 10.1038/nature10777

  47. Christian M. In vitro models for study of brown adipocyte biology. Handb Exp Pharmacol 2019; 251: 85–96. doi: 10.1007/164_2018_122

  48. Zhang X, Li X, Fang H, Guo F, Li F, Chen A, et al. Flavonoids as inducers of white adipose tissue browning and thermogenesis: signalling pathways and molecular triggers. Nutr Metab (Lond). 2019; 16: 47. doi: 10.1186/s12986-019-0370-7

  49. Forbes-Hernández TY, Cianciosi D, Ansary J, Mezzetti B, Bompadre S, Quiles JL, et al. Strawberry (Fragaria × ananassa cv. Romina) methanolic extract promotes browning in 3T3-L1 cells. Food Funct 2020; 11(1): 297–304. doi: 10.1039/c9fo02285f

How to Cite
Bu S., Yuan C., Cao F., Xu Q., Zhang Y., Ju R., Chen L., & Li Z. (2021). Concentrated extract of Prunus mume fruit exerts dual effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing beiging/browning. Food & Nutrition Research, 65.
Original Articles