The Korea Journal of Herbology (대한본초학회지)

The Korea Association of Herbology (대한본초학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-Obesity Effect of Schizandrae Fructus Water Extract through Regulation of AMPK/Sirt1/PGC-1α signaling pathway

AMPK/Sirt1/PGC-1α 신호 전달 경로의 조절을 통한 오미자 추출물의 비만 개선 효과

  • Lee, Se Hui (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Park, Hae-Jin (DHU Bio Convergence Testing Center) ;
  • Shin, Mi-Rae (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Roh, Seong-Soo (Department of Herbology, College of Korean Medicine, Daegu Haany University)
  • 이세희 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 박해진 (대구한의대학교 DHU바이오융복합시험센터) ;
  • 신미래 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2022.02.16
  • Accepted : 2022.03.25
  • Published : 2022.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Although the anti-obesity effect of Schizandrae Fructus water extract has been demonstrated, its underlying mechanism is still unclear. Therefore, we aimed to evaluate the anti-obesity effect of Schizandrae Fructus water extract through the p-AMP-activated protein kinase (p-AMPK), sirtuin1 (Sirt1), and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling in 60% high-fat diet (HFD)-induced obese mouse model. Methods : Male C57BL/6 mice were divided into four groups. The Normal group was fed a normal diet and the obese groups were fed 60% HFD. Except for the Control group, the GG group was supplemented with 0.5% Garcinia gummigutta and the SCW group was supplemented with 0.5% Schizandrae Fructus water extract. After 6 weeks, obesity-related biomarkers in serum were measured and the expressions of protein for lipid-related factors in liver tissue were analyzed by western blot. Results : Treatment with SCW significantly down-regulated body weight compared to the Control group. SCW down-regulated levels of triglyceride and total cholesterol in serum and significantly increased p-AMPK, Sirt1, and PGC-1α in liver tissue. In addition, the expressions of fatty acid oxidation-related proteins such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1A (CPT-1A), uncoupling protein 1 (UCP1), and uncoupling protein 3 (UCP3) were significantly up-regulated. However, fatty acid synthesis-related proteins including sterol regulatory element-binding protein-1 (SREBP-1), phospho-Acetyl-CoA Carboxylase (p-ACC), and fatty acid synthase (FAS) were significantly down-regulated. Conclusions : Taken together, SCW treatment showed anti-obesity effect by regulating both fatty acid oxidation-related and fatty acid synthesis-related proteins through AMPK/Sirt1/PGC-1α signaling in 60% HFD-induced obese mice.

Keywords

Acknowledgement

본 연구는 농촌진흥청 연구사업 (과제번호: PJ014251022021)의 지원에 의해 수행되었습니다.

References

  1. Tang R, Liu H, Yuan Y, Xie K, Xu P, Liu X, Wen J. Genetic factors associated with risk of metabolic syndrome and hepatocellular carcinoma. Oncotarget. 2017;8:35403-35411. https://doi.org/10.18632/oncotarget.15893
  2. Solomon CG, Manson JE. Obesity and mortality: a review of the epidemiologic data. Am J Clin Nutr. 1997;66(4):1044S-1050S. https://doi.org/10.1093/ajcn/66.4.1044S
  3. Lee JH, Park SK, Oh NE, Park JH, Kwon MJ, Seo JM, Roh SH. Oral intake of Lactobacillus plantarum L-14 extract alleviates TLR2 and AMPK-mediated obesity associated disorders in high-fat-diet-induced obese C57BL/6J mice. Cell Prolif. 2021;54(6):e13039.
  4. Lee DS, Lee MH, Kim HS, Jeong TR, Hyun HS, Lee JM. Anti-Obesity Effect of Pine Cone (Pinus koraiensis) Supercritical Extract in High-Fat Diet-Induced Obese Mice. In Vivo. 2016;45(12):1701-1707.
  5. Reddy P, Chow MSS. Focus on orlistat: A nonsystemic inhibitor of gastrointestinal lipase for weight reduction in the management of obesity. Formulary. 1998;33 (10):943-959.
  6. Kang JG, Park CY. Anti-Obesity Drugs: A Review about Their Effects and Safety. Diabetes Metab. J. 2012;36:13-25. https://doi.org/10.4093/dmj.2012.36.1.13
  7. Woods A, Williams JR, Muckett PJ, et al. Liver-specific activation of AMPK prevents steatosis on a high-fructose diet. Cell Rep. 2017;18(13):3043-3051. https://doi.org/10.1016/j.celrep.2017.03.011
  8. Goldstein JL, Brown MS. From fatty streak to fatty liver: 33 years of joint publications in the JCI. J. Clin. Investig. 2008;118(4):1220-1222. https://doi.org/10.1172/JCI34973
  9. Bijland S, Mancini SJ, Salt IP. Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clin. Sci. 2013;124:491-507. https://doi.org/10.1042/CS20120536
  10. Mok C. Quality characteristics of Instant Tea prepared from spray-dried Omija(Schizandra chinensis Baillon) extracts/grape juice mixture. Food Eng. Prog. 2005;9(3):226-230.
  11. Hong YH, Yuhp PC, Shuenn JS, Chau SH, Chien CC, Sien CC. Oriental Materia Medica, Oriental Healing Arts Institute, California, UKroemer G. 1997. The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat. Med. 1986;3:614-620. https://doi.org/10.1038/nm0697-614
  12. Hung TM, Na MK, Min BS, Ngoc TM, Lee IS, Zhang XF, Bae KH. Acetylcholinesterase inhibitory effect of lignans isolated from Schizandra chinensis. Arch Pharm Res. 2007;30:685-690. https://doi.org/10.1007/BF02977628
  13. Choi YH, Takamatsu S, Khan SI, Srinivas PV, Ferreira D, Zhao J, Khan IA. Schisandrene, a dibenzocyclooctadiene lignan from Schisandra chinensis: structure-antioxidant activity relationships of dibenzocyclooctadiene lignans. J Nat Prod. 2006; 69:356-359. https://doi.org/10.1021/np0503707
  14. Yim SY, Lee YJ, Lee YK, Jung SE, Kim JH, Kim JE, Kim HJ, Son BG, Park YH, Lee YG, Choi YW, Hwang DY. Gomisin N isolated from Schisandra chinensis significantly induces anti-proliferative and pro-apoptotic effects in hepatic carcinoma. Mol Med Report. 2009;2(5):725-732. https://doi.org/10.3892/mmr_00000163
  15. Chen N, Chiu PY, Ko KM. Schisandrin B enhances cerebral mitochondrial antioxidant status and structural integrity, and protects against cerebral ischemia/reperfusion injury in rats. Biol Pharm Bull. 2008;31:1387-1391. https://doi.org/10.1248/bpb.31.1387
  16. Chang HS, Choi Il. Antimicrobial activities of medicinal herb extracts. J Korean Soc Food Sci Nutr. 2012;41261-41269.
  17. Bao TT, Xu GF, Liu GT, Sun RH, Song ZY. Comparison of the pharmacological actions of 7 constituents isolated from fructus schizandrae. J. Chin. Med. 1979;14(1): 1-7.
  18. Kim NK, Lee SY, Kang JJ, Kwon TK, Khang DW, Kim SH. Gomisin M2 alleviates psoriasis-like skin inflammation by inhibiting inflammatory signaling pathways. Mol. Med. Rep. 2021;24(6):859. https://doi.org/10.3892/mmr.2021.12499
  19. Ko YH, Jeong MR, Jang DS, Choi JH. Gomisin L1, a Lignan Isolated from Schisandra Berries, Induces Apoptosis by Regulating NADPH Oxidase in Human Ovarian Cancer Cells. Life (Basel). 2021;11(8):858.
  20. Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958;181(4617): 1199-1200. https://doi.org/10.1038/1811199a0
  21. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free radical biology and medicine. 1999; 26(9-10): 1231-1237. https://doi.org/10.1016/S0891-5849(98)00315-3
  22. Choi EO, Kwon DH, Kim MY, Hwang BH, Kim HJ, Ahn KI, $Jeong JW, Lee KW, Kim KY, Kim SG, Choi YH, Hong SH, Park C, Choi YH. Single Dose Oral Toxicity Test of Ethanol Extracts of Schisandrae fructus and Mori folium, and their Mixture in ICR Mice. Journal of Life Science. 2016;26(10):1207-1213. https://doi.org/10.5352/JLS.2016.26.10.1207
  23. NCD Risk Factor Collaboration (NCD-RisC) Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387:1377-1396. https://doi.org/10.1016/S0140-6736(16)30054-X
  24. Mayoral LP, Andrade GM, Mayoral EP, Huerta TH, Canseco SP, Rodal Canales FJ, Cabrera-Fuentes HA, Cruz MM, Perez Santiago AD, Alpuche JJ, Zenteno E, Ruiz HM, Cruz RM, Jeronimo JH, Perez-Campos E. Obesity subtypes, related biomarkers & heterogeneity. Indian J. Med. Res. 2020;151:11-21. https://doi.org/10.4103/ijmr.ijmr_1768_17
  25. Chang J, Xie J. Total synthesis of schizandrin, the main active ingredient isolated from the Chinese herbal medicine fructus schizandrae. Yao Xue Xue Bao. 1998;33(6):424-428.
  26. Go BS, Park SK, Choi SB, Jeon DH, Choi MK, Park SM. A Study on Hypoglycemic Effects of Crude Extracts of Schizandrae Fructus. Appl Biol Chem. 2004;47(2):258-264.
  27. Ju EJ. Effects of Fructus Schisandrae Water Extract on Cultured Mouse Myocardial Cells Induced by Xanthine Oxidase/Hypoxanthine. The Korean journal of nutrition. 2000;33(7):739-744.
  28. Gu M, Song H, Li Y, Jiang Y, Zhang Y, Tang Z, Ji G, Huang C. Extract of Schisandra chinensis fruit protects against metabolic dysfunction in high-fat diet induced obese mice via FXR activation. Phytotherapy Research. 2020;34(11):3063-3077. https://doi.org/10.1002/ptr.6743
  29. Chung MY, Shin EJ, Choi HK, Kim SH, Sung MJ, Park JH, Hwang JT. Schisandra chinensis berry extract protects against steatosis by inhibiting histone acetylation in oleic acid-treated HepG2 cells and in the livers of diet-induced obese mice. Nutr Res. 2017;46:1-10. https://doi.org/10.1016/j.nutres.2017.07.002
  30. Eisinger K, Rein-Fischboeck L, Neumeier M, Schmidhofer S, Pohl R, Haberl EM, Liebisch G, Kopp A, Schmid A, Krautbauer S, Buechler C. Alpha-syntrophin deficient mice are protected from adipocyte hypertrophy and ectopic triglyceride deposition in obesity. Experimental and Molecular Pathology. 2018;104(3):212-221. https://doi.org/10.1016/j.yexmp.2018.04.003
  31. Zhang BB, Zhou G, Li C. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab. 2009;9:407-416. https://doi.org/10.1016/j.cmet.2009.03.012
  32. Viollet B, Guigas B, Leclerc J, Hebrard S, Lantier L, Mounier R, Andreelli F, Foretz M. AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. Crit. Rev. Biochem. Mol. Biol. 2010;196: 81-98.
  33. Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA. Pfluger PT, Tschop MH. Sirtuin 1 and sirtuin 3: Physiological modulators of metabolism. Physiol. Rev. 2012;92:1479-1514. https://doi.org/10.1152/physrev.00022.2011
  34. Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009;458:1056-1060. https://doi.org/10.1038/nature07813
  35. Gurd BJ. Deacetylation of PGC-1α by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis. Appl Physiol Nutr Metab. 2011;36:589-597. https://doi.org/10.1139/h11-070
  36. Guo A, Li K, Tian HC, Fan Zm Chen QN, Yang YF, Yu J, Wu YX, Xiao Q. FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT-1/PGC-α pathway. J Cell Mol Med. 2021;25(1):3585-3600. https://doi.org/10.1111/jcmm.16448
  37. Ha SK, Kim J, Chae C. Role of AMP-activated protein kinase and adiponectin during development of hepatic steatosis in high-fat diet-induced obesity in rats. Journal of Comparative Pathology. 2011; 145(1):88-94. https://doi.org/10.1016/j.jcpa.2010.11.011
  38. Bronner M, Hertz R, Bar-Tana J. Kinasein-dependent transcriptional co-activation of peroxisome proliferator-activated receptor alpha by AMP-activated protein kinase. The Biochemical Journal. 2004;384(2):295-305. https://doi.org/10.1042/BJ20040955
  39. Bertolio R, Napoletano F, Mano M, Maurer-Stroh S, Fantuz M, Zannini A, Bicciato S, Sorrentino G, Del Sal G. Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nat. Commun. 2019;10:1326. https://doi.org/10.1038/s41467-019-09152-7
  40. Smith BK, Marcinko K, Desjardins EM, Lally JS, Ford RJ, Steinberg GR. Treatment of nonalcoholic fatty liver disease: role of AMPK, American journal of physiology. Endocrinol. Metabol. 2016;311(4): E730-E740.
  41. Na MK, Hung TM, Oh WK, Min BS, Lee SH, Bae KH. Fatty acid synthase inhibitory activity of dibenzocyclooctadiene lignans isolated from Schisandra chinensis. Phytotherapy Research. 2010;24(S2):S225-228. https://doi.org/10.1002/ptr.3149