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연교의 항산화 효과 연구

Anti-oxidant effect of forsythia suspensa on cellular damage in the chronic disease

  • 김영은 (동국대학교 한의과대학 방제학교실) ;
  • 김민진 (동국대학교 한의과대학 방제학교실) ;
  • 배수진 (동국대학교 한의과대학 방제학교실) ;
  • 박선빈 (동국대학교 한의과대학 방제학교실) ;
  • 박선동 (동국대학교 한의과대학 방제학교실) ;
  • 박광일 (경상대학교 수의과대학 생리학 실험실) ;
  • 김영우 (동국대학교 한의과대학 방제학교실)
  • Young-Eun Kim (AI-Bio Convergence DDI Basic Research Laboratory (BRL), School of Korean Medicine, Dongguk University) ;
  • Min-Jin Kim (AI-Bio Convergence DDI Basic Research Laboratory (BRL), School of Korean Medicine, Dongguk University) ;
  • Su-Jin Bae (AI-Bio Convergence DDI Basic Research Laboratory (BRL), School of Korean Medicine, Dongguk University) ;
  • Seon Been Bak (AI-Bio Convergence DDI Basic Research Laboratory (BRL), School of Korean Medicine, Dongguk University) ;
  • Sun-Dong Park (AI-Bio Convergence DDI Basic Research Laboratory (BRL), School of Korean Medicine, Dongguk University) ;
  • Kwang-Il Park (Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University) ;
  • Young Woo Kim (AI-Bio Convergence DDI Basic Research Laboratory (BRL), School of Korean Medicine, Dongguk University)
  • 투고 : 2024.01.31
  • 심사 : 2024.02.13
  • 발행 : 2024.02.28

초록

Objectives : This study induced oxidative stress in HepG2 cells by treating them with AA+iron and investigated the effects of forsythia suspensa extract on this stress, as well as elucidated the molecular mechanisms underlying its hepatoprotective effects. Methods : To confirm the antioxidative effects of FSE, HepG2 cells were induced with AA+iron to induce oxidative stress, followed by MTT assay. Additionally, the effect of FSE in reducing the increased ROS levels and mitochondrial damage induced by AA+iron in HepG2 cells was confirmed using FACS. Furthermore, western blot analysis were conducted to investigate the molecular mechanisms underlying the hepatoprotective effects of FSE. Results : FSE increased the decreased cell viability induced by AA+iron. Additionally, FSE normalized the expression of apoptosis-related proteins induced by AA+iron. The elevated ROS levels in HepG2 cells induced by AA+iron were reduced by FSE, and the increase in Rh123-negative cells induced by AA+iron was attenuated by FSE. Moreover, FSE activated the protein expression of AMPK and its related phosphorylating enzymes, LKB1 and ACC. Furthermore, FSE activated YAP and its upstream phosphorylating enzyme, LATS1. Conclusions : These results demonstrate that FSE has an inhibitory effect on oxidative stress induced by AA+iron and may have potential hepatoprotective effects.

키워드

과제정보

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (number: HF20C0212). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government [MSIT] (RS-2023-00218419) (NRF-2022R1I1A3053818) (2022R1A2C1092168). 그리고, 본 연구는 교육부와 한국연구재단의 재원으로 지원을 받아 수행된 3단계 산학협력 선도대학 육성사업(LINK 3.0) (No.202306390001)에 의하여 연구되었다.

참고문헌

  1. Prasad S, Gupta SC, Tyagi AK. Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals. Cancer Lett. 2017;387:95-105.
  2. Jomova K, Raptova R, Alomar SY, Alwasel SH, Nepovimova E, Kuca, K, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol. 2023;97(10):2499-2574.
  3. Mittler R. ROS Are Good. Trends Plant Sci. 2017; 22(1):11-19.
  4. Yang YC, Zhu Y, Sun SJ, Zhao CJ, Bai Y, Wang J, et al. ROS regulation in gliomas: implications for treatment strategies. Front Immunol. 2023;14:1259797.
  5. Fu PP, Xia Q, Hwang HM, Ray PC, Yu H. Mechanisms of nanotoxicity: generation of reactive oxygen species. J Food Drug Anal. 2014;22(1):64-75.
  6. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 2015;97:55-74.
  7. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int J Mol Sci. 2015;16(11):26087-26124.
  8. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World allergy organization journal. 2012;5;9-19.
  9. Bloomer SA, Brown KE. Iron-Induced Liver Injury: A Critical Reappraisal. Int J Mol Sci. 2019;20(9):2132.
  10. Britton LJ, Subramaniam VN, Crawford DH. (2016). Iron and non-alcoholic fatty liver disease. World journal of gastroenterology. 2016;22(36):8112.
  11. Lunova M, Goehring C, Kuscuoglu D, Mueller K, Chen Y, Walther P, et al. Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload. J Hepatol. 2014;61(3):633-641.
  12. Liu Y, Li G, Lu F, Guo Z, Cai S, Huo T. Excess iron intake induced liver injury: The role of gut-liver axis and therapeutic potential. Biomed Pharmacother. 2023;168:115728.
  13. Tallima H, El Ridi R. Arachidonic acid: Physiological roles and potential health benefits - A review. J Adv Res. 2017;11:33-41.
  14. Sztolsztener K, Chabowski A, Harasim-Symbor E, Bielawiec P, Konstantynowicz-Nowicka K. Arachidonic Acid as an Early Indicator of Inflammation during Non-Alcoholic Fatty Liver Disease Development. Biomolecules. 2020;10(8):1133.
  15. Zheng Z, Li Y, Jin G, Huang T, Zou M, Duan S. The biological role of arachidonic acid 12-lipoxygenase (ALOX12) in various human diseases. Biomed Pharmacother. 2020;129:110354.
  16. Lee EH, Baek SY, Kim KY, Lee SG, Kim SC, Lee HS, et al. Effect of Rheum undulatum Linne extract and Glycyrriza uralensis Fischer extract against arachidonic acid and iron-induced oxidative stress in HepG2 cell and CCl 4-induced liver injury in mice. Herbal Formula Science. 2016;24(3):163-174. https://doi.org/10.14374/HFS.2016.24.3.163
  17. Jang M, Seo HL, Kim SC, Kim YW. Effect of Prunellae Spica on oxidative stress and mitochondrial dysfunction in the hepatocyte. Journal of Physiology & Pathology in Korean Medicine. 2016;30(1):20-26.
  18. Kim KY, Lee SG, Baek SY, Lee EH, Jang EJ, Lee JH, et al. Salinomycin ameliorates oxidative hepatic damage through AMP-activated protein kinase, facilitating autophagy. Toxicol Appl Pharmacol. 2018;360:141-149.
  19. Wang Z, Xia Q, Liu X, Liu W, Huang W, Mei X, et al. Phytochemistry, pharmacology, quality control and future research of Forsythia suspensa (Thunb.) Vahl: A review. J Ethnopharmacol. 2018;210:318-339.
  20. Wang W, Yu H, Wang J, Lei W, Gao J, Qiu X, et al. The Complete Chloroplast Genome Sequences of the Medicinal Plant Forsythia suspensa (Oleaceae). Int J Mol Sci. 2017;18(11):2288.
  21. Weng D, Zha SH, Zhu Y, Li H, Hou SB, Zhao QS, et al. Effect of particle size on the physicochemical and antioxidant properties of Forsythia suspensa (Thunb.) Vahl leaf powders. Powder Technology. 2022;410:117866.
  22. Long SF, He TF, Wu D, Yang M, Piao XS. Forsythia suspensa extract enhances performance via the improvement of nutrient digestibility, antioxidant status, anti-inflammatory function, and gut morphology in broilers. Poult Sci. 2020;99(9):4217-4226.
  23. Weng D, Tian R, Jin H, Zha S, Zhao Q, Zhao B. Study on extraction, purification, and biological activities of forsythiaside A from Forsythia suspensa (Thunb.) Vahl leaf. Biomass Conversion and Biorefinery. 2023;1-17.
  24. Gui L, Wang S, Wang J, Liao W, Chen Z, Pan D, et al. Effects of forsythin extract in Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet. Food Science and Human Wellness. 2024;13(2): 659-667.
  25. Ramos-Tovar E, Muriel P. Free radicals, antioxidants, nuclear factor-E2-related factor-2 and liver damage. J Appl Toxicol. 2020;40(1):151-168.
  26. Gu X, Manautou JE. Molecular mechanisms underlying chemical liver injury. Expert Rev Mol Med. 2012;14:e4.
  27. Nishina H. Physiological and pathological roles of the Hippo-YAP/TAZ signaling pathway in liver formation, homeostasis, and tumorigenesis. Cancer Sci. 2022;113(6):1900-1908.
  28. Ezhilarasan D. Oxidative stress is bane in chronic liver diseases: Clinical and experimental perspective. Arab J Gastroenterol. 2018;19(2):56-64.
  29. Han D, Hanawa N, Saberi B, Kaplowitz N. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. Am J Physiol Gastrointest Liver Physiol. 2006;291(1):G1-G7.
  30. Seo E, Kang H, Choi H, Choi W, Jun HS. Reactive oxygen species-induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging. Aging Cell. 2019;18(2):e12895.
  31. Pieczenik SR, Neustadt J. Mitochondrial dysfunction and molecular pathways of disease. Exp Mol Pathol. 2007;83(1):84-92.
  32. Mansouri A, Gattolliat CH, Asselah T. Mitochondrial Dysfunction and Signaling in Chronic Liver Diseases. Gastroenterology. 2018;155(3):629-647.
  33. Wei YH, Lu CY, Lee HC, Pang CY, Ma YS. Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann N Y Acad Sci. 1998;854:155-170.
  34. Omidkhoda N, Mahdiani S, Hayes AW, Karimi G. Natural compounds against nonalcoholic fatty liver disease: A review on the involvement of the LKB1/AMPK signaling pathway. Phytother Res. 2023;37(12):5769-5786.
  35. Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245.
  36. Smith BK, Marcinko K, Desjardins EM, Lally JS, Ford RJ, Steinberg GR. Treatment of nonalcoholic fatty liver disease: role of AMPK. Am J Physiol Endocrinol Metab. 2016;311(4):E730-E740.
  37. Fang C, Pan J, Qu N, Lei Y, Han J, Zhang J, et al. The AMPK pathway in fatty liver disease. Front Physiol. 2022;13:970292.
  38. Joshi T, Singh AK, Haratipour P, Sah AN, Pandey AK, Naseri R, et al. Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications. J Cell Physiol. 2019;234(10):17212-17231.
  39. Bates J, Vijayakumar A, Ghoshal S, Marchand B, Yi S, Kornyeyev D, et al. Acetyl-CoA carboxylase inhibition disrupts metabolic reprogramming during hepatic stellate cell activation. J Hepatol. 2020;73(4):896-905.
  40. Wang M, Dong Y, Gao S, Zhong Z, Cheng C, Qiang R, et al. Hippo/YAP signaling pathway protects against neomycin-induced hair cell damage in the mouse cochlea. Cell Mol Life Sci. 2022;79(2):79.
  41. Miyamura N, Hata S, Itoh T, Tanaka M, Nishio M, Itoh M, et al. YAP determines the cell fate of injured mouse hepatocytes in vivo. Nat Commun. 2017;8:16017.
  42. Boopathy GTK, Hong W. Role of Hippo Pathway-YAP/TAZ Signaling in Angiogenesis. Front Cell Dev Biol. 2019;7:49.