DOI QR코드

DOI QR Code

Study on the in vitro and in vivo anti-obesity effects of a combination of Syzygium aromaticum L. and Sorbus commixta Hedl.

정향과 마가목 복합물의 in vitro와 in vivo 항비만 효과 연구

  • Ji Heon Yu (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Hui Yeon An (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Seong-Soo Roh (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Mi-Rae Shin (Department of Herbology, College of Korean Medicine, Daegu Haany University)
  • 유지헌 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 안희연 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 신미래 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2024.03.05
  • Accepted : 2024.04.22
  • Published : 2024.04.30

Abstract

Purpose: This study investigated the anti-obesity effects of a combination of Syzygium aromaticum L. and Sorbus commixta Hedl. (SS) in vitro and in vivo. Methods: The extracts of Syzygium aromaticum extract (SA) and Sorbus commixta extract (SC) were prepared individually using distilled water. They were mixed in a 1:2 ratio for use in the experiment. To assess the anti-obesity potential of SS in vitro, we examined cell proliferation, cellular triglyceride (TG), and total cholesterol (TC) levels, as well as lipogenesis and β-oxidation in 3T3-L1 cells. To confirm its anti-obesity potential in vivo, C57BL/6J mice were fed a 60% high-fat diet (HFD) to induce obesity. SA alone, SC alone, and their combination compound, SS (at a dosage of 200 mg/kg) were orally administered for 6 weeks. Thereafter, to conduct a comparative evaluation, serum analysis, western blotting of liver tissues, and histopathological analysis were performed. Results: Both SS200 and SS400 significantly inhibited the cellular TG and TC contents in the 3T3-L1 cells. Furthermore, treatment of the cells with SS (at a dose 200 and 400 ㎍/mL) also led to a noticeable regulation of key lipogenic and β-oxidation factors. Treatment of obese mice with SS resulted in a greater reduction in serum leptin and TG levels compared to treatment with the individual compounds (SA and SC). Furthermore, activation of AMP-activated protein kinase α by SS treatment resulted in the suppression of sterol regulatory element-binding proteins (SREBP)-1, leading to the inhibition of acetyl-CoA carboxylase (ACC) expression. Conclusion: Our results suggest that SS may have the potential to prevent obesity through a reduction in the TG and TC levels and regulation of lipogenesis and β-oxidation.

본 연구에서는 정향과 마가목 복합물 (SS)의 항비만 효과를 알아보기 위해 실험을 진행하였다. SS 투여는 3T3-L1 세포 내 TG와 TC가 유의적으로 감소하는 효과를 나타냈으며, 지질 합성 관련 유전자와 지방산 산화 관련 유전자 발현을 조절하는 효과를 보여주었다. 비만이 유도된 C57BL/6 mice에서 SS 투여는 혈청 내 leptin 호르몬 수치를 감소시켰으며, AMPK/ACC/SREBP-1 경로를 경유하여 TG 합성을 억제하였다. 또한, 조직병리학적 분석을 통해 지질 축적과 지방세포의 크기가 감소된 것을 확인하였다. 따라서 SS는 비만의 예방과 치료를 위한 잠재력을 갖춘 소재로 사료된다.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Korea Government (MSIP) (No. 2018R1A5A2025272) and the Ministry of Education (2021R1I1A1A01059605).

References

  1. Jahangir E, De Schutter A, Lavie CJ. The relationship between obesity and coronary artery disease. Transl Res 2014; 164(4): 336-344. https://doi.org/10.1016/j.trsl.2014.03.010
  2. Seo YJ, Kim KJ, Choi J, Koh EJ, Lee BY. Spirulina maxima extract reduces obesity through suppression of adipogenesis and activation of browning in 3T3-L1 cells and high-fat diet-induced obese mice. Nutrients 2018; 10(6): 712. https://doi.org/10.3390/nu10060712
  3. Wang HN, Xiang JZ, Qi Z, Du M. Plant extracts in prevention of obesity. Crit Rev Food Sci Nutr 2022; 62(8): 2221-2234. https://doi.org/10.1080/10408398.2020.1852171
  4. Huang YH, Jung DW, Lee OH, Kang IJ. Fermented Platycodon grandiflorum extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mice. J Med Food 2016; 19(11): 1004-1014. https://doi.org/10.1089/jmf.2016.3805
  5. Chitraju C, Walther TC, Farese RV Jr. The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes. J Lipid Res 2019; 60(6): 1112-1120. https://doi.org/10.1194/jlr.M093112
  6. Shie PH, Yang CP, Huang GJ, Wang SY, Kuo YH. Sinensol-C isolated from Spiranthes sinensis inhibits adipogenesis in 3T3-L1 cells through the regulation of adipogenic transcription factors and AMPK activation. Molecules 2020; 25(18): 4204.
  7. Rojas A, Gallego P, Gil-Gomez A, Munoz-Hernandez R, Rojas L, Maldonado R, et al. Natural extracts abolished lipid accumulation in cells harbouring non-favourable PNPLA3 genotype. Ann Hepatol 2018; 17(2): 242-249. https://doi.org/10.5604/01.3001.0010.8642
  8. Cheng KT, Wang YS, Chou HC, Chang CC, Lee CK, Juan SH. Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes: roles of AMPK and PPARα in the lipolytic effect of kinsenoside. Phytomedicine 2015; 22(6): 641-647. https://doi.org/10.1016/j.phymed.2015.04.001
  9. Assifi MM, Suchankova G, Constant S, Prentki M, Saha AK, Ruderman NB. AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats. Am J Physiol Endocrinol Metab 2005; 289(5): E794-E800. https://doi.org/10.1152/ajpendo.00144.2005
  10. Lee SB, Keum DH, Lee MJ. Oriental and western medical study on the cause and treatment of obesity. Dongguk J Med 1996; 5: 33-52.
  11. Kim TR, Kim YJ, Woo CH. Anti-obesity effects of Banggihwnggi-tang-hap-yeonggyechulgam-tang in high fat diet induced obese mice model. J Korean Med Rehabi 2019; 29(4): 29-45. https://doi.org/10.18325/jkmr.2019.29.4.29
  12. Haro-Gonzalez JN, Castillo-Herrera GA, Martinez-Velazquez M, Espinosa-Andrews H. Clove essential oil (Syzygium aromaticum L. Myrtaceae): extraction, chemical composition, food applications, and essential bioactivity for human health. Molecules 2021; 26(21): 6387.
  13. Batiha GE, Alkazmi LM, Wasef LG, Beshbishy AM, Nadwa EH, Rashwan EK. Syzygium aromaticum L. (Myrtaceae): traditional uses, bioactive chemical constituents, pharmacological and toxicological activities. Biomolecules 2020; 10(2): 202.
  14. Radunz M, da Trindade ML, Camargo TM, Radunz AL, Borges CD, Gandra EA, et al. Antimicrobial and antioxidant activity of unencapsulated and encapsulated clove (Syzygium aromaticum, L.) essential oil. Food Chem 2019; 276: 180-186. https://doi.org/10.1016/j.foodchem.2018.09.173
  15. Moradi E, Rakhshandeh H, Rahimi Baradaran V, Ghadiri M, Hasanpour M, Iranshahi M, et al. HPLC/MS characterization of Syzygium aromaticum L. and evaluation of its effects on peritoneal adhesion: investigating the role of inflammatory cytokines, oxidative factors, and fibrosis and angiogenesis biomarkers. Physiol Rep 2023; 11(2): e15584.
  16. Moon SC, Choi HJ, Chung TW, Lee JH, Lee SO, Jung MH, et al. Sorbus commixta water extract induces apoptotic cell death via a ROS-dependent pathway. Oncol Lett 2018; 16(4): 4193-4200. https://doi.org/10.3892/ol.2018.9217
  17. Yang G, An HJ. β-sitosteryl-3-O-β-glucopyranoside isolated from the bark of Sorbus commixta ameliorates pro-inflammatory mediators in RAW 264.7 macrophages. Immunopharmacol Immunotoxicol 2014; 36(1): 70-77.
  18. Sohn EJ, Kang DG, Mun YJ, Woo WH, Lee HS. Anti-atherogenic effects of the methanol extract of Sorbus cortex in atherogenic-diet rats. Biol Pharm Bull 2005; 28(8): 1444-1449. https://doi.org/10.1248/bpb.28.1444
  19. Lee SO, Lee HW, Lee IS, Im HG. The pharmacological potential of Sorbus commixta cortex on blood alcohol concentration and hepatic lipid peroxidation in acute alcohol-treated rats. J Pharm Pharmacol 2006; 58(5): 685-693. https://doi.org/10.1211/jpp.58.5.0014
  20. Jeong IH, Ji SW, Roh SS. Liver protective effect of the co-treatment of Rhei Radix et Rhizoma and silymarin on TAA-induced liver injury. J Int Korean Med 2023; 44(3): 402-417. https://doi.org/10.22246/jikm.2023.44.3.402
  21. Lee JA, Kim MJ, Seo SW, Shin MR. Study of the effect and underlying mechanism of clove extract on monosodium iodoacetate-induced osteoarthritis in rats. J Int Korean Med 2022; 43(6): 1089-1104. https://doi.org/10.22246/jikm.2022.43.6.1089
  22. Bray GA, Paeratakul S, Popkin BM. Dietary fat and obesity: a review of animal, clinical and epidemiological studies. Physiol Behav 2004; 83(4): 549-555. https://doi.org/10.1016/j.physbeh.2004.08.039
  23. Feinle-Bisset C. Upper gastrointestinal sensitivity to meal-related signals in adult humans - relevance to appetite regulation and gut symptoms in health, obesity and functional dyspepsia. Physiol Behav 2016; 162: 69-82. https://doi.org/10.1016/j.physbeh.2016.03.021
  24. Hunt RH, Camilleri M, Crowe SE, El-Omar EM, Fox JG, Kuipers EJ, et al. The stomach in health and disease. Gut 2015; 64(10): 1650-1668. https://doi.org/10.1136/gutjnl-2014-307595
  25. Hoffmann KM, Herbrechter R, Ziemba PM, Lepke P, Beltran L, Hatt H, et al. Kampo medicine: evaluation of the pharmacological activity of 121 herbal drugs on GABAA and 5-HT3A receptors. Front Pharmacol 2016; 7: 219.
  26. Seo SW, Kim K, Shin MR. Anti-inflammatory effect of cloves in LPS-induced inflammation anti-inflammatory effect by cloves treatment in LPS-induced RAW264.7 cells. Pharmacogn Mag 2023; 19(1): 105-116. https://doi.org/10.1177/09731296221137420
  27. An HY, Rho SS, Shin MR. The anti-obesity activity of Syzygium aromaticum L. in high-fat diet-induced obese mice. Korean J Herbol 2024; 39(1): 11-21.
  28. Hu Q, Zhou M, Wei S. Progress on the antimicrobial activity research of clove oil and eugenol in the food antisepsis field. J Food Sci 2018; 83(6): 1476-1483. https://doi.org/10.1111/1750-3841.14180
  29. Peng C, Sang S, Shen X, Zhang W, Yan J, Chen P, et al. In vitro anti-Helicobacter pylori activity of Syzygium aromaticum and the preliminary mechanism of action. J Ethnopharmacol 2022; 288: 114995.
  30. Chan KW, Khong NM, Iqbal S, Ch'ng SE, Babji AS. Preparation of clove buds deodorized aqueous extract (CDAE) and evaluation of its potential to improve oxidative stability of chicken meatballs in comparison to synthetic and natural food antioxidants. J Food Qual 2012; 35(3): 190-199. https://doi.org/10.1111/j.1745-4557.2012.00445.x
  31. Jeon YG, Kim YY, Lee G, Kim JB. Physiological and pathological roles of lipogenesis. Nat Metab 2023; 5(5): 735-759. https://doi.org/10.1038/s42255-023-00786-y
  32. Alves-Bezerra M, Cohen DE. Triglyceride metabolism in the liver. Compr Physiol 2017; 8(1): 1-8. https://doi.org/10.1002/cphy.c170012
  33. Kraus NA, Ehebauer F, Zapp B, Rudolphi B, Kraus BJ, Kraus D. Quantitative assessment of adipocyte differentiation in cell culture. Adipocyte 2016; 5(4): 351-358. https://doi.org/10.1080/21623945.2016.1240137
  34. Yin Y, Li Z, Gao L, Li Y, Zhao J, Zhang W. AMPK-dependent modulation of hepatic lipid metabolism by nesfatin-1. Mol Cell Endocrinol 2015; 417: 20-26. https://doi.org/10.1016/j.mce.2015.09.006
  35. Huang LS, Yuen JJ, Trites MJ, Saha A, Epps CT, Hu Y, et al. Dietary macronutrient composition determines the contribution of DGAT1 to alcoholic steatosis. Alcohol Clin Exp Res 2018; 42(12): 2298-2312. https://doi.org/10.1111/acer.13881
  36. Day EA, Ford RJ, Steinberg GR. AMPK as a therapeutic target for treating metabolic diseases. Trends Endocrinol Metab 2017; 28(8): 545-560. https://doi.org/10.1016/j.tem.2017.05.004
  37. Ji R, Xiang X, Li X, Mai K, Ai Q. Effects of dietary curcumin on growth, antioxidant capacity, fatty acid composition and expression of lipid metabolism-related genes of large yellow croaker fed a high-fat diet. Br J Nutr 2021; 126(3): 345-354. https://doi.org/10.1017/S0007114520004171
  38. Cayli B, Ciftci G, Ciftci A, Savasan S. Effects of Lactobacillus acidophilus administration to anorexigenic neuropeptides and some biochemical parameters on rats fed with a high-fat diet. Prostaglandins Other Lipid Mediat 2023; 166: 106729.
  39. Li Y, 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): 376-388. https://doi.org/10.1016/j.cmet.2011.03.009
  40. Tian X, Ru Q, Xiong Q, Wen R, Chen Y. Catalpol attenuates hepatic steatosis by regulating lipid metabolism via AMP-activated protein kinase activation. BioMed Res Int 2020; 2020: 6708061.