Herbal Formula Science (대한한의학방제학회지)

The Korean Medicine Society for the Herbal Formula Study (대한한의학방제학회)
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Hepatocyte protection and antioxidant effect of Citri Unshius Pericarpium against cadmium-induced oxidative stress

카드뮴으로 유발된 산화 스트레스에 대한 진피의 간세포 보호 및 항산화 효과

  • 노규표 (대구한의대학교 한의과대학) ;
  • 변성희 (대구한의대학교 한의과대학) ;
  • 정대화 (디앤비바이오) ;
  • 이종록 (대구한의대학교 제약공학과) ;
  • 박숙자 (대구한의대학교 제약공학과) ;
  • 김상찬 (대구한의대학교 한의과대학)
  • Received : 2020.11.06
  • Accepted : 2020.11.25
  • Published : 2020.11.30
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Abstract

Objective : Citri Unshius Pericarpium is the dried peel of mature fruit of Citrus unshiu Markovich and has been used to treat indigestion, vomiting, and removal of phlegm. This study investigated the hepatoprotective and antioxidant effect of CEE (Ethanol extract of Citri Unshius Pericarpium) in cadmium (CdCl2)-treated HepG2 cells. Methods : Component analysis of Citri Unshius Pericarpium was analyzed by UPLC with C18 column. Cell viability was determined by MTT assay. The enzyme activity of superoxide dismutase (SOD) and the level of reactive oxygen species (ROS) and reduced glutathione (GSH) were analyzed using commercially available kits. Results : Cadmium caused severe HepG2 cell death. Cadmium also increased ROS production, consistent with depletion of GSH and inhibition of the SOD enzyme. However, CEE treatment reduced cell death and relieved oxidative stress caused by cadmium toxicity. CEE lowered ROS levels and improved depletion of GSH levels. CEE also enhanced the enzymatic activity of SOD. In component analysis, hesperidin was the most abundant of the five marker compounds (Narigenin, Narigin, Narirutin, Hesperidin and Hesperidin), which assumes that hesperidin partially contributed to the antioxidant activity of CEE. Conclusion : These results suggested that CEE could be a potential substance to solve heavy metal-related health problems. In particular, inhibition of oxidative stress by CEE can be a way to treat liver damage caused by cadmium.

Keywords

References

  1. Oriental Pharmacology Committee. Oriental Pharmacology. 2nd ed. Seoul:Shinil. 2006:670-5.
  2. Hung KC. The Pharmacology of Chinese herbs. 2nd ed. Cleveland:CRC Press. 1998:285-8.
  3. Hyon JS, Kang SM, Mahinda S, Koh WJ, Yang TS, Oh MC, Oh CK, Jeon YJ, Kim SH. Antioxidative activities of extracts from dried Citrus sunki and C. unshiu peels. J Korean Soc Food Sci Nutr. 2010;39(1):1-7. https://doi.org/10.3746/jkfn.2010.39.1.001
  4. Leelavinothan P, Kalist S. Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats. Exp Toxicol Pathol. 2012;64(5):513-20. https://doi.org/10.1016/j.etp.2010.11.007
  5. Nawrot TS, Staessen JA, Roels HA. Cadmium exposure in the population: From health risks to strategies of prevention. Biometals. 2010;23:769-82. https://doi.org/10.1007/s10534-010-9343-z
  6. Satarug S, Vesey DA, Gobe GC. Health risk assessment of dietary cadmium intake: Do current guidelines indicate how much is safe? Environ Health Perspect. 2017;125:284-8. https://doi.org/10.1289/EHP108
  7. Mezynska M, Brzoska MM. Environmental exposure to cadmium-A risk for health of the general population in industrialized countries and preventive strategies. Environ Sci Pollut Res. 2018;25:3211-32. https://doi.org/10.1007/s11356-017-0827-z
  8. Lin J, Zhang F, Lei Y. Dietary intake and urinary level of cadmium and breast cancer risk: A meta-analysis. Cancer Epidemiol. 2016;42:101-7. https://doi.org/10.1016/j.canep.2016.04.002
  9. Kang MY, Cho SH, Lim YH, Seo JC, Hong YC. Effects of environmental cadmium exposure on liver function in adults. Occup Environ Med. 2013;70:268-73. https://doi.org/10.1136/oemed-2012-101063
  10. Ramakrishnan R, Elangovan P, Pari L. Protective role of tetrahydrocurcumin: An active polyphenolic curcuminoid on cadmium-induced oxidative damage in rats. Appl Biochem Biotechnol. 2017;183:51-69. https://doi.org/10.1007/s12010-017-2430-7
  11. Brzoska MM, Rogalska J, Roszczenko A, Galazyn-Sidorczuk M, Tomczyk M. The mechanism of the osteoprotective action of a polyphenol-rich Aronia melanocarpa extract during chronic exposure to cadmium is mediated by the oxidative defense system. Planta Med. 2016;82:621-31. https://doi.org/10.1055/s-0042-103593
  12. Skipper A, Sims JN, Yedjou CG, Tchounwou PB. Cadmium chloride induces DNA damage and apoptosis of human liver carcinoma cells via oxidative stress. Int J Environ Res Public Health. 2016;13(1):88. https://doi.org/10.3390/ijerph13010088
  13. Rani A, Kumar A, Lal A, Pant M. Cellular mechanisms of cadmium-induced toxicity: A review. Int J Environ Health Res. 2013; 24:378-99. https://doi.org/10.1080/09603123.2013.835032
  14. Brzoska MM, Borowska S, Tomczyk M. Antioxidants as a potential preventive and therapeutic strategy for cadmium. Curr Drug Targets. 2016;17:1350-84. https://doi.org/10.2174/1389450116666150506114336
  15. Cha BJ. Changes in the constituents and antioxidant activity in accordance with the processing conditions of Citrus unshiu Markovich. Kor J Pharmacogn. 2015;46(1): 23-30.
  16. Borrelli F, Izzo AA. The plant Kingdom as a source of anti ulcer remedies. Phytother Res. 2000;14(8):581-91. https://doi.org/10.1002/1099-1573(200012)14:8<581::AID-PTR776>3.0.CO;2-S
  17. Kim DK, Lee KT, Eun JS, Zee OP, Lim JP, Eum SS, Kim SH, Shin TY. Anti-allergic components from the peels of Citrus unshiu. Arch Pharm Res. 1999;22(6):642-5. https://doi.org/10.1007/BF02975340
  18. Lee HI, Park AR, Chun SW. Effects of mitochondrial reactive oxygen species on neuronal excitability in rat spinal substantia gelatinosa neurons. Int J Oral Biol. 2012;37(1):17-23.
  19. Kwon GR, Moon IS, Lee WC. Neuroprotective effects of Pinelliae rhizoma water-extract by suppression of reactive oxygen species and mitochondrial membrane potential loss in a hypoxic model of cultured rat cortical cells. J Life Sci. 2009;19(5):598-606. https://doi.org/10.5352/JLS.2009.19.5.598
  20. Cichoz-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014;20(25):8082-91. https://doi.org/10.3748/wjg.v20.i25.8082
  21. Wang L, Yan B, Liu N, Li Y, Wang Q. Effects of cadmium on glutathione synthesis in hepatopancreas of freshwater crab, Sinopotamon yangtsekiense. Chemosphere. 2008;74(1):51-6. https://doi.org/10.1016/j.chemosphere.2008.09.025
  22. Noctor G, Foyer CH. Ascorbate and glutathione: keeping active oxygen under control. Annu Rev Plant Physiol Plant Mol Biol. 1998;49:249-79. https://doi.org/10.1146/annurev.arplant.49.1.249
  23. Romero MJ, Canada AT. The evaluation of Escherichia coli as a model for oxidant stress in mammalian hepatocytes: role of glutathione. Toxicol Appl Pharmacol. 1991;111: 485-95. https://doi.org/10.1016/0041-008X(91)90252-A
  24. Haouem S, Hmad N, Najjar MF, Hani AE, Sakly R. Accumulation of cadmium and its effects on liver and kidney functions in rats given diet containing cadmium-polluted radish bulb. Exp Toxicol Pathol. 2007;59:77-80. https://doi.org/10.1016/j.etp.2007.03.006
  25. Dkhil MA, Marwa SM, Diab MSM, Lokman MS, El-Sayed H, Aljawdah HMA, Al-Quraishy S, Bauomy AA. Hepato-protective effect of Pleurotus ostreatus extracts in cadmium-intoxicated rats. J King Saud Univ Sci. 2020;32(8):3432-6. https://doi.org/10.1016/j.jksus.2020.09.029
  26. Fridovich I. Superoxide dismutases. Annu Rev Biochem. 1975;44:147-59. https://doi.org/10.1146/annurev.bi.44.070175.001051
  27. Imlay JA, Fridovich I. Assay of metabolic superoxide production in Escherichia coli. J Biol Chem. 1991;266(11):6957-65. https://doi.org/10.1016/S0021-9258(20)89596-9
  28. Choi JH, Rhee SJ. Effects of green tea catechin on cadmium accumulation in chronic cadmium poisoned rats. Kor J Nutr. 2001;34(4):384-92.
  29. Cho EJ, Li L, Noriko Y, Kim HY. Antioxidative effects of hesperidin and hesperetin under cellular system. CNU J Agric Sci. 2011;38(4):717-22.