Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
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Forsythiae suspensa regulates SREBP-1c signaling pathway as mediated with LXR alpha nuclear orphan receptor

LXR 고아핵수용체 관련 신호 억제를 통한 연교의 sterol regulatory element-binding protein-1c 조절

  • 김영은 (동국대학교 한의학과 방제학교실) ;
  • 박선동 (동국대학교 한의학과 방제학교실) ;
  • 김영우 (동국대학교 한의학과 방제학교실)
  • Received : 2022.08.10
  • Accepted : 2022.08.25
  • Published : 2022.08.31
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Abstract

Objectives : Brain-Liver axis is an important target of the chronic human diseases. Hepatic steatosis is one of the most famous disorders in the chronic diseases. This study investigated the moderating effect of beneficial herbs on the fat accumulation, which is mediated by the LXR alpha-SREBP-1c signaling pathway. Methods : In order to confirm the SREBP-1c inhibitory effect, we performed immonoblotting ananlysis using HepG2 cells and Huh 7 cells treated by T0901317, the ligand of LXRα. Results : Forsythiae suspensa water extract (FSE) was not cytotoxicity in cell lines. FSE inhibited SREBP-1c protein expression in HepG2 and Huh7 cells induced by T0901317. In addition, FSE increased the phosphorylation of LKB1, which is associated with LXR-related pathway in HepG2 and Huh 7 cells. Conclusions : These results showed that FSE activated LKB1 to suppress SREBP-1c, which protects the cells against oxidative stress.

Keywords

Acknowledgement

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: HF21C0061) and (HF20C0212).

References

  1. Kim SJ, Park JW, Kim MG, Kim HJ, Hong YH, Han SH, Kim JG, et al. Clinical Predictors Reflecting the Pathologic Severity of Nonalcoholic Steatohepatitis in Patients with Nonalcoholic Fatty Liver. The Korean Journal of Gastroenterology. 2000;36(6):782-792.
  2. Jeon JH, Park KG. Definition, pathogenesis, and natural progress of non-alcoholic fatty liver disease. Journal of Korean Diabetes. 2014;15(2), 65. https://doi.org/10.4093/jkd.2014.15.2.65
  3. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science. 2011;332:1519-23. https://doi.org/10.1126/science.1204265
  4. O'MALLEY, Bert W. BULLER, Richard E. Mechanisms of steroid hormone action. Journal of Investigative Dermatology, 1977;68(1):1-4. https://doi.org/10.1111/1523-1747.ep12485116
  5. LEE EK, PARK YJ. Metabolic regulation of nuclear receptors. Journal of Korean Endocrine Society. 2008;23(3):155-164. https://doi.org/10.3803/jkes.2008.23.3.155
  6. Lai K, Harnish DC, Evans MJ. Estrogen receptor alpha regulates expression of the orphan receptor small heterodimer partner. J Biol Chem. 2003;278:36418-36429 https://doi.org/10.1074/jbc.M303913200
  7. Lee YK, Parker KL, Choi HS, et al. Activation of the promoter of the orphan receptor SHP by orphan receptors that bind DNA as monomers. J Biol Chem. 1999;274:20869-20873. https://doi.org/10.1074/jbc.274.30.20869
  8. GOODWIN, Bryan, et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Molecular cell, 2000, 6.3: 517-526. https://doi.org/10.1016/S1097-2765(00)00051-4
  9. Sinal, Christopher J., et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell. 2000;102(6):731-744. https://doi.org/10.1016/S0092-8674(00)00062-3
  10. Kim MJ, Im KR, Yoon KS. Anti-inflammatory effects of prescription extracts containing Forsythia viridissima L. Journal of the Society of Cosmetic Scientists of Korea. 2009;35(4),277-285.
  11. Jo MG, An BS, Mun YJ, Woo WH. Inhibitory effect of the methanol extract of Fructus Forsythiae on the melanogenesis. Korean Journal of Korean Medical Institute of Dermatology and Aesthetics. 2005;1(1),41-52.
  12. Bae, JH, Kim HY, Jang JY. Antimicrobial effect of Forsythiae fructus extracts on several food-borne pathogens. Korean journal of food and cookery science. 2005;21(3),319-325.
  13. Kim MJ, Kim JY, Jung TK, Choi SW, Yoon KS. Skin Anti-aging Effect of Forsythia viridissima L. Extract. KSBB journal. 2006;21(6),444-450.
  14. Yang SJ, Choe TB. Antioxidant activity and whitening effect of forsythiae fructus extracts. Korean Journal of Medicinal Crop Science. 2011;19(6),472-477. https://doi.org/10.7783/KJMCS.2011.19.6.472
  15. Yun UJ, Bae SJ, Song YR, Kim YW. A Critical YAP in Malignancy of HCC Is Regulated by Evodiamine. Int J Mol Sci. 2022 Feb 6;23(3):1855. https://doi.org/10.3390/ijms23031855
  16. Ulven SM, Dalen KT, Gustafsson JA, Nebb HI. LXR is crucial in lipid metabolism. Prostaglandins, leukotrienes and essential fatty acids. 2005;73(1),59-63. https://doi.org/10.1016/j.plefa.2005.04.009
  17. Houck KA, Borchert KM, Hepler CD, Thomas JS, Bramlett KS, Michael LF, Burris TP. T0901317 is a dual LXR/FXR agonist. Molecular Genetics and Metabolism. 2004;83(1-2),184-187. https://doi.org/10.1016/j.ymgme.2004.07.007
  18. Chisholm JW, Hong J, Mills SA, Lawn RM. The LXR ligand T0901317 induces severe lipogenesis in the db/db diabetic mouse. The Journal of Lipid Research. 2003;44(11),2039-2048. https://doi.org/10.1194/jlr.M300135-JLR200
  19. Cheng S, Liang S, Liu Q, Deng Z, Zhang Y, Du J, et al. Diosgenin prevents high-fat diet-induced rat non-alcoholic fatty liver disease through the AMPK and LXR signaling pathways. International Journal of Molecular Medicine. 2017;41(2),1089-1095.
  20. Kim J, Yang G, Kim Y, Kim, J, Ha J. AMPK activators: mechanisms of action and physiological activities. Experimental & molecular medicine. 2016;48(4),e224-e224. https://doi.org/10.1038/emm.2016.16
  21. Hardie DG. New roles for the LKB1-->AMPK pathway. Current Opinion in Cell Biology, 2005;17(2),167-173. https://doi.org/10.1016/j.ceb.2005.01.006
  22. Woods A, Johnstone SR, Dickerson K, Leiper FC, Wallimann T, Neumann D, et at. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Current Biology: CB. 2003;13(22),2004-2008. https://doi.org/10.1016/j.cub.2003.10.031
  23. Rodriguez C, Munoz M, Contreras C, Prieto D. AMPK, metabolism, and vascular function. The FEBS Journal, 2021;288(12),3746-3771. https://doi.org/10.1111/febs.15863
  24. Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, Carling D. Ca2+/calmodulin-dependent protein kinase kinase-β acts upstream of AMP-activated protein kinase in mammalian cells. Cell metabolism. 2005;2.1:21-33. https://doi.org/10.1016/j.cmet.2005.06.005
  25. Hawley SA, Pan DA, Mustard KJ, Ross L, Bain J, Edelman AM, et al. Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase. Cell metabolism, 2005;2(1),9-19. https://doi.org/10.1016/j.cmet.2005.05.009
  26. Fogarty S, Hawley SA, Green, KA, Saner N, Mustard KJ, Hardie DG. Calmodulin-dependent protein kinase kinase-β activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMP. Biochemical Journal. 2010;426(1),109-118. https://doi.org/10.1042/BJ20091372