Do In Seung Gi‑Tang extract suppresses adipocyte differentiation in 3T3‑L1 cells

Shim,Eun Hyoung; Lee,Myeong Soo; Lee,Ju‑Ah; Lee,Hoyoung

doi:10.3892/mmr.2017.6446

Do In Seung Gi‑Tang extract suppresses adipocyte differentiation in 3T3‑L1 cells

Authors:
- Eun Hyoung Shim
- Myeong Soo Lee
- Ju‑Ah Lee
- Hoyoung Lee
View Affiliations

Affiliations: Korea Medicine Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 305‑811, Republic of Korea, Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon 305‑811, Republic of Korea
Published online on: April 7, 2017 https://doi.org/10.3892/mmr.2017.6446
Pages: 3549-3554
Copyright: © Shim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Blood stasis syndrome (BSS), additionally called Eohyul, is a basic pathological concept in Traditional Korean Medicine. Do In Seung Gi‑Tang (DISGT) is herbal medicine used for the treatment of BSS. It primarily treats metabolic diseases (MDs) including obesity, hypertension, diabetes mellitus and gynecological diseases, by promoting blood circulation. The present study aimed to investigate the anti‑adipogenesis effect of DISGT in 3T3‑L1 adipocytes using Oil Red O staining, and assessing levels of triglycerides (TGs) and leptin in adipocytes by ELISA and western blot analysis. The results demonstrated that DISGT treatment had inhibitory effects on fat droplet formation, TG accumulation, leptin production and cytokine content, during 3T3‑L1 adipocyte differentiation, without affecting cell viability. Additionally, DISGT treatment significantly suppressed the protein expression levels of peroxisome proliferator‑activated receptor γ and CAAT/enhancer binding protein α. These results provide evidence that DISGT has anti‑adipogenesis effects on preadipocytes and adipocytes by significantly blocking adipocyte differentiation and lipid accumulation, and suppressing adipogenic gene expression. Therefore, the present study demonstrated the potential of DISGT as a therapeutic agent for the treatment of MDs.

View Figures

View References

1	Eckel RH, Grundy SM and Zimmet PZ: The metabolic syndrome. Lancet. 365:1415–1428. 2005. View Article : Google Scholar : PubMed/NCBI
2	Kaur J: A comprehensive review on metabolic syndrome. Cardiol Res Pract. 2014:9431622014.PubMed/NCBI
3	Shin SS, Jung YS, Yoon KH, Choi S, Hong Y, Park D, Lee H, Seo BI, Lee HY and Yoon M: The Korean traditional medicine gyeongshingangjeehwan inhibits adipocyte hypertrophy and visceral adipose tissue accumulation by activating PPARalpha actions in rat white adipose tissues. J Ethnopharmacol. 127:47–54. 2010. View Article : Google Scholar : PubMed/NCBI
4	Pakala R, Kuchulakanti P, Rha SW, Cheneau E, Baffour R and Waksman R: Peroxisome proliferator-activated receptor gamma: Its role in metabolic syndrome. Cardiovasc Radiat Med. 5:97–103. 2004. View Article : Google Scholar : PubMed/NCBI
5	Farmer SR: Regulation of PPARgamma activity during adipogenesis. Int J Obes (Lond). 29 Suppl 1:S13–S16. 2005. View Article : Google Scholar : PubMed/NCBI
6	Li SM, Xu H and Chen KJ: The diagnostic criteria of blood-stasis syndrome: Considerations for standardization of pattern identification. Chin J Integr Med. 20:483–489. 2014. View Article : Google Scholar : PubMed/NCBI
7	Zhou XQ, Liang H, Sun X and Zhou HT: Correlation between TCM blood stasis pattern of coronary heart disease and coronary angiography result: A meta-analysis. Chin J Evid Based Med. 12:1470–1477. 2012.
8	Ji W, Zhou J, Wang S and Ji Z: Logistic regression analysis of relevance between different blood stasis syndromes and related factors in angina pectoris patients. Chin Arch Tradit Chin Med. 7(040)2013.(In Chinese).
9	Yu X, Zhang L and Xu H: Progress in research on relevant factors affecting TCM syndrome differentiation of CHD. Chin J Int Med Cardio/Cerebrovasc Dis. 7:581–584. 2009.(In Chinese).
10	Heo J: Donguibogam. Namsandang Publ. Corp.; Seoul: pp. 4622014
11	Lee YJ, Kim EK, Kim HY, Yoon JJ, Lee SM, Lee GM, Kang DG and Lee HS: Therapeutic effect of doinseunggi-tang on diabetic vascular dysfunction. HFS. 21:119–130. 2013.
12	Kosuge T, Ishida H and Ishii M: Studies on active substances in the herbs used for oketsu (‘stagnant blood’) in Chinese medicine. II. On the anticoagulative principle in persicae semen. Chem Pharm Bull (Tokyo). 33:1496–1498. 1985. View Article : Google Scholar : PubMed/NCBI
13	Ge RY, Zhou CH and She YC: Influences of stigma croci and semen persicae on function of ovary-uterus in pseudopregnant rats. J Tradit Chin Med. 3:23–26. 1983.PubMed/NCBI
14	Orban T, Palczewska G and Palczewski K: Retinyl ester storage particles (retinosomes) from the retinal pigmented epithelium resemble lipid droplets in other tissues. J Biol Chem. 286:17248–17258. 2011. View Article : Google Scholar : PubMed/NCBI
15	Columba-Cabezas S, Iaffaldano G, Chiarotti F, Alleva E and Cirulli F: Early handling increases susceptibility to experimental autoimmune encephalomyelitis (EAE) in C57BL/6 male mice. J Neuroimmunol. 212:10–16. 2009. View Article : Google Scholar : PubMed/NCBI
16	Engelman JA, Lisanti MP and Scherer PE: Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis. J Biol Chem. 273:32111–32120. 1998. View Article : Google Scholar : PubMed/NCBI
17	Chen KJ: Blood stasis syndrome and its treatment with activating blood circulation to remove blood stasis therapy. Chin J Integr Med. 12:891–896. 2012. View Article : Google Scholar
18	Spiegelman BM and Flier JS: Adipogenesis and obesity: Rounding out the big picture. Cell. 87:377–389. 1996. View Article : Google Scholar : PubMed/NCBI
19	Sartipy P and Loskutoff DJ: Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci USA. 100:pp. 7265–7270. 2003; View Article : Google Scholar : PubMed/NCBI
20	Wofford MR, Andrew ME, Brown A, King D, Pickett RA, Stevens J, Wyatt S and Jones DW: Obesity hypertension in the atherosclerosis risk in communities cohort: Implications of obesity guidelines. J Clin Hypertens. 1:27–32. 1999.
21	Pi-Sunyer FX: The obesity epidemic: Pathophysiology and consequences of obesity. Obes Res. 10 Suppl 2:S97–S104. 2002. View Article : Google Scholar
22	Yoon JJ, Lee YJ, Park OJ, Lee SM, Lee YP, Cho NG, Kang DG and Lee HS: Doinseunggitang ameliorates endothelial dysfunction in diabetic atherosclerosis. Evid Based Complement Alternat Med. 2013:7835762013. View Article : Google Scholar : PubMed/NCBI
23	Sung YY, Kim DS, Choi G, Kim SH and Kim HK: Dohaekseunggi-tang extract inhibits obesity, hyperlipidemia, and hypertension in high-fat diet-induced obese mice. BMC Complement Altern Med. 14:3722014. View Article : Google Scholar : PubMed/NCBI
24	Chen Q: Pharmacology and application of Chinese herbs. 16th. SMC Publ. Inc.; Taipei: pp. 4511989, (In Chinese).
25	Fasshauer M and Paschke R: Regulation of adipocytokines and insulin resistance. Diabetologia. 46:1594–1603. 2003. View Article : Google Scholar : PubMed/NCBI
26	Rosen ED and Spiegelman BM: Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 444:847–853. 2006. View Article : Google Scholar : PubMed/NCBI
27	Shao D, Rangwala SM, Bailey ST, Krakow SL, Reginato MJ and Lazar MA: Interdomain communication regulating ligand binding by PPAR-gamma. Nature. 396:377–380. 1998. View Article : Google Scholar : PubMed/NCBI
28	Lefterova MI and Lazar MA: New developments in adipogenesis. Trends Endocrinol Metab. 20:107–114. 2009. View Article : Google Scholar : PubMed/NCBI
29	Havel PJ: Role of adipose tissue in body-weight regulation: Mechanisms regulating leptin production and energy balance. Proc Nutr Soc. 59:pp. 359–371. 2000; View Article : Google Scholar : PubMed/NCBI
30	Auwerx J and Staels B: Leptin. Lancet. 351:737–742. 1998. View Article : Google Scholar : PubMed/NCBI
31	Isaia GC, D'Amelio P, Di Bella S and Tamone C: Is leptin the link between fat and bone mass? J Endocrinol Invest. 28(Suppl 10): S61–S65. 2005.
32	Liu M and Liu F: Regulation of adiponectin multimerization, signaling and function. Best Pract Res Clin Endocrinol Metab. 88:25–31. 2014. View Article : Google Scholar
33	Axelsson J, Bergsten A, Qureshi AR, Heimbürger O, Bárány P, Lönnqvist F, Lindholm B, Nordfors L, Alvestrand A and Stenvinkel P: Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int. 69:596–604. 2006. View Article : Google Scholar : PubMed/NCBI
34	Lefterova MI, Zhang Y, Steger DJ, Schupp M, Schug J, Cristancho A, Feng D, Zhuo D, CJ Jr, Liu XS Stoeckert and Lazar MA: PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev. 22:2941–2952. 2008. View Article : Google Scholar : PubMed/NCBI
35	Tang QQ, Zhang JW and Lane M Daniel: Sequential gene promoter interactions of C/EBPbeta, C/EBPalpha, and PPARgamma during adipogenesis. Biochem Biophys Res Commun. 319:235–239. 2004. View Article : Google Scholar : PubMed/NCBI
36	Rosen ED, Hsu CH, Wang X, Sakai S, Freeman MW, Gonzalez FJ and Spiegelman BM: C/EBPalpha, induces adipogenesis through PPARgamma: A unified pathway. Genes Dev. 16:22–26. 2002. View Article : Google Scholar : PubMed/NCBI
37	Schoonjans K, Staels B and Auwerx J: The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta. 1302:93–109. 1996. View Article : Google Scholar : PubMed/NCBI
38	Otto TC and Lane MD: Adipose development: From stem cell to adipocyte. Crit Rev Biochem Mol Biol. 40:229–242. 2005. View Article : Google Scholar : PubMed/NCBI