Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory Effect of Cymbopogon Citratus Ethanol Extracts on Adipogenesis in 3T3-L1 Preadipocytes

레몬그라스 에탄올 추출물의 3T3-L1 지방세포 분화 억제효과

  • Jo, Yong Seok (Department of Pathology, College of Korean Medicine, Wonkwang University) ;
  • Ju, Sung Min (Department of Pathology, College of Korean Medicine, Wonkwang University) ;
  • Hwang, Keum Hee (Department of Pathology, College of Korean Medicine, Wonkwang University) ;
  • Kim, Min Sook (Hisol Co., Ltd.) ;
  • Kim, Kwang Sang (Hisol Co., Ltd.) ;
  • Jeon, Byung Hun (Department of Pathology, College of Korean Medicine, Wonkwang University)
  • 조용석 (원광대학교 한의과대학 병리학교실) ;
  • 주성민 (원광대학교 한의과대학 병리학교실) ;
  • 황금희 (원광대학교 한의과대학 병리학교실) ;
  • 김민숙 (하이솔) ;
  • 김광상 (하이솔) ;
  • 전병훈 (원광대학교 한의과대학 병리학교실)
  • Received : 2019.01.21
  • Accepted : 2019.02.19
  • Published : 2019.02.25
Download PDF
⟨ Previous Next ⟩

Abstract

Cymbopogon citratus, commonly know as lemongrass, prossesses strong antioxidant, anti-tumor and anti-inflammatory properties. Howerver, its anti-obesity activity remains to be elucidated. This study investigated the effect of ethanol extract of Cymbopogon citratus on adipogenesis, and its underlying mechanism, in 3T3-L1 preadipocytes. The results demonstrated that ethanol extracts of Cymbopogon citratus effectively suppressed intercellular lipid accumulation at non-toxic concentrations, and was associated with the down-regulation of adipocyte-specific transcription factors, including $C/EBP{\alpha}$ and $PPAR{\gamma}$, and phosphorylation of $AMPK{\alpha}$. Furthermore, ethanol extracts of Cymbopogon citratus increased p21 and p21 expression, while the expression of CDK2, cyclin A and cyclin B1 was reduced. As a result, ethanol extracts of Cymbopogon citratus seems to induce G0/G1 cell cycle arrest of 3T3-L1 cells. On the other hand, ERK and Akt signaling pathways were not involved in anti-adipogenesis by ethanol extracts of Cymbopogon citratus. Taken together, theses results suggest that ethanol extracts of Cymbopogon citratus inhibits adipocyte differentiation in 3T3-L1 cells and can be used as a safe and efficient natural substance to manage anti-obesity.

Keywords

References

  1. Peng Y, Yu S, Li H, Xiang H, Peng J, Jiang S. MicroRNAs: Emerging roles in adipogenesis and obesity. Cell Signal. 2014;26(9):1888-96. https://doi.org/10.1016/j.cellsig.2014.05.006
  2. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, Cushman SW, Periwal V. Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLoS Comput Biol. 2009;5(3):e1000324. https://doi.org/10.1371/journal.pcbi.1000324
  3. Oh JS, Kim JS, Lee BM, Lee SK, Chung MY. A Comparative Study on Obesity-related Eating Habits and Lifestyle Behaviors of Depressed and Normal Middle-aged Female in Korea. Kor J Aesthet Cosmetol. 2013;11(2):231-8.
  4. Chung MY, Kim SH, Oh JS. Comparison of obesity-related life patterns with according to body mass index and self-awareness of body shape. Kor J Aesthet Cosmetol. 2013;11(6):1109-1115.
  5. Gwon SY, Ahn JY, Jung CH, Moon BK, Ha TY. Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells. BMC Complem Altern Med. 2013;13:207. https://doi.org/10.1186/1472-6882-13-207
  6. Cornelius P, MacDougald OA, Lane MD. Regulation of adipocyte development. Annu Rev Nutr. 1994;14:99-129. https://doi.org/10.1146/annurev.nu.14.070194.000531
  7. Prusty D, Park BH, Davis KE, Farmer SR. Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma ) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes. J Biol Chem. 2002;277(48):46226-32. https://doi.org/10.1074/jbc.M207776200
  8. Xu J, Liao K. Protein kinase B/AKT 1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation. J Biol Chem. 2004;279(34):35914-22. https://doi.org/10.1074/jbc.M402297200
  9. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell. 1999;4(4):611-7. https://doi.org/10.1016/S1097-2765(00)80211-7
  10. Wu Z, Rosen ED, Brun R, Hauser S, Adelmant G, Troy AE, McKeon C, Darlington GJ, Spiegelman BM. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell. 1999;3(2):151-8. https://doi.org/10.1016/S1097-2765(00)80306-8
  11. Shon MS, Shin YJ, Lee SC, Kim GN. Anti-obese activities of Kaki-tannins prepared from various persimmons through inhibition of 3T3-L1 adipogenesis. Kor J Aesthet Cosmetol. 2014;12(4):539-46.
  12. Gupta R, Rathi P, Gupta N, Bradoo S. Lipase assays for conventional and molecular screening: an overview. Biotechnol Appl Biochem. 2003;37(Pt 1):63-71. https://doi.org/10.1042/BA20020059
  13. Kim SH, Kim JY, Ryu KA, Sohn CM. Evaluation of the dietary diversity and nutrient intakes in obese adults. Korean J Community Nutr. 2007;12(5):583-91.
  14. Yi MR, Kang CH, Bu HJ. Acetic acid fermentation properties and antioxidant activity of lemongrass vinegar. Korean J Food Preserv. 2017;24(5):680-7. https://doi.org/10.11002/kjfp.2017.24.5.680
  15. Bhattacharya AK, Kaul PN, Rajeswara Rao BR. Effect of Prolonged Storage on the Quality of Lemongrass (Cymbopogon flexuosus (Nees ex Steud.) Wats.) Essential Oil. J Essent Oil Bear Pl. 1998;1(2-3):104-9.
  16. Sforcin JM, Amaral JT, Fernandes A Jr, Sousa JP, Bastos JK. Lemongrass effects on IL-1beta and IL-6 production by macrophages. Nat Prod Res. 2009;23(12):1151-9. https://doi.org/10.1080/14786410902800681
  17. Francisco V, Figueirinha A, Costa G, Liberal J, Lopes MC, Carmen GR, Carlos FG, Cruz MT, Batista MT. Chemical characterization and anti-inflammatory activity of luteolin glycosides isolated lemongrass. J Funct Foods. 2014;10:436-43. https://doi.org/10.1016/j.jff.2014.07.003
  18. Silva CB, Guterres SS, Weisheimer V, Schapoval ES. Antifungal activity of the lemongrass oil and citral against Candida spp. Braz J Infect Dis. 2008;12(1):63-6.
  19. Sri Devi S, Ashokkumar N. Citral, a Monoterpene Inhibits Adipogenesis Through Modulation of Adipogenic Transcription Factors in 3T3-L1 Cells. Indian J Clin Biochem. 2018;33(4):414-21. https://doi.org/10.1007/s12291-017-0692-z
  20. Modak T, Mukhopadhaya A. Effects of citral, a naturally occurring antiadipogenic molecule, on an energy-intense diet model of obesity. Indian J Pharmacol. 2011, 43(3):300-5. https://doi.org/10.4103/0253-7613.81515
  21. Cheel J, Theoduloz C, Rodriguez J, Schmeda-Hirschmann G. Free radical scavengers and antioxidants from Lemongrass (Cymbopogon citratus (DC.) Stapf.). J Agric Food Chem. 2005;53(7):2511-7. https://doi.org/10.1021/jf0479766
  22. Lee MS, Cho SM, Lee MH, Lee EO, Kim SH, Lee HJ. Ethanol extract of Pinus koraiensis leaves containing lambertianic acid exerts anti-obesity and hypolipidemic effects by activating adenosine monophosphate-activated protein kinase (AMPK). BMC Complement Altern Med. 2016;16:51. https://doi.org/10.1186/s12906-016-1031-2
  23. Tang QQ, Otto TC, Lane MD. Mitotic clonal expansion: a synchronous process required for adipogenesis. Proc Natl Acad Sci USA. 2003;100(1):44-9. https://doi.org/10.1073/pnas.0137044100
  24. Shon MS, Kim GN. Anti-oxidant and anti-obese activities of turmeric (Curcuma longa L.) extract in 3T3-L1 Cells. Kor J Aesthet Cosmetol. 2014;12(2):169-5.
  25. Farmer SR (2006) Transcriptional control of adipocyte formation. Cell Metab. 2006;4(4):263-3. https://doi.org/10.1016/j.cmet.2006.07.001
  26. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994;79(7):1147-56. https://doi.org/10.1016/0092-8674(94)90006-X
  27. Carling D, Zammit VA, Hardie DG. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 1987;223(2):217-22. https://doi.org/10.1016/0014-5793(87)80292-2
  28. Hardie DG, Corton J, Ching YP, Davies SP, Hawley S. Regulation of lipid metabolism by the AMP-activated protein kinase. Biochem Soc Trans. 1997;25(4):1229-31. https://doi.org/10.1042/bst0251229
  29. Hardie DG, Pan DA. Regulation of fatty acid synthesis and oxidation by the AMP-activated protein kinase. Biochem Soc Trans. 2002;30(Pt 6):1064-70. https://doi.org/10.1042/bst0301064
  30. Chen S, Li Z, Li W, Shan Z, Zhu W. Resveratrol inhibits cell differentiation in 3T3-L1 adipocytes via activation of AMPK. Can J Physiol Pharmacol. 2011;89(11):793-9. https://doi.org/10.1139/y11-077
  31. Lee YK, Lee WS, Hwang JT, Kwon DY, Surh YJ, Park OJ. Curcumin exerts antidifferentiation effect through AMPKalpha-PPAR-gamma in 3T3-L1 adipocytes and antiproliferatory effect through AMPKalpha-COX-2 in cancer cells. J Agric Food Chem. 2009;57(1): 305-10. https://doi.org/10.1021/jf802737z
  32. Rosen ED, Spiegelman BM. PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem. 2001;276(41):37731-4. https://doi.org/10.1074/jbc.R100034200
  33. 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
  34. Smith PJ, Wise LS, Berkowitz R, Wan C, Rubin CS. Insulin-like growth factor-I is an essential regulator of the differentiation of 3T3-L1 adipocytes. J Biol Chem. 1988;263(19):9402-8. https://doi.org/10.1016/S0021-9258(19)76555-7
  35. Bost F, Aouadi M, Caron L and Binetruy B. The role of MAPKs in adipocyte differentiation and obesity. Biochimie 2005;87(1):51-6. https://doi.org/10.1016/j.biochi.2004.10.018
  36. Magun R, Burgering BM, Coffer PJ, Pardasani D, Lin Y, Chabot J, Sorisky A. Expression of a constitutively activated form of protein kinase B (c-Akt) in 3T3-L1 preadipose cells causes spontaneous differentiation. Endocrinology. 1996;137(8):3590-3. https://doi.org/10.1210/endo.137.8.8754791
  37. Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, Sundararajan D, Chen WS, Crawford SE, Coleman KG, Hay N. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 2003;17(11):1352-65. https://doi.org/10.1101/gad.1089403
  38. Kim SH, Park HS, Lee MS, Cho YJ, Kim YS, Hwang JT, Sung MJ, Kim MS, Kwon DY. Vitisin A inhibits adipocyte differentiation through cell cycle arrest in 3T3-L1 cells. Biochem Biophys Res Commun. 2008;372(1):108-13. https://doi.org/10.1016/j.bbrc.2008.04.188
  39. Jang YJ, Koo HJ, Sohn EH, Kang SC, Rhee DK, Pyo S. Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathways. Food Funct. 2015;6(7):2365-74. https://doi.org/10.1039/C5FO00397K