Protective Effects of Codium fragile Extract against Acetaminophen-Induced Liver Injury
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Acetaminophen (APAP) is a well-known analgesic used globally. Generally, APAP has been proven to be safe and effective at therapeutic doses; however, it can cause serious liver damage when administered at high levels. We prepared Codium fragile extract (CFE) using the seaweed C. fragile and confirmed that the CFE contains a substance called Loliolide with antioxidant activity. We performed the present study to determine whether CFE protects HEPG2 cells and BALB/c mice from oxidative stress-induced liver damage. We confirmed that CFE and Loliolide were non-cytotoxic and protected against liver damage by reducing the activities of ALT and AST, which were increased by APAP treatment, and that CFE reduced the mRNA expression of inflammatory cytokines TNF-α and IL-6 and inhibited the phosphorylation of ERK and p38 in HEPG2 cells as determined by RT-PCR and Western blot analyses. Furthermore, the TNF-α and IL-6 levels, which were increased after APAP treatment in BALB/c mice, decreased after CFE treatment. Therefore, we demonstrated that CFE exerts a protective effect against APAP-induced liver injury by suppressing the inflammatory response through anti-inflammatory activity. Our findings provide new perspectives for developing functional foods that utilize seaweeds to improve liver function.
Abstract
Acetaminophen (APAP) is a well-known analgesic used globally. Generally, APAP has been proven to be safe and effective at therapeutic doses; however, it can cause serious liver damage when administered at high levels. We prepared Codium fragile extract (CFE) using the seaweed C. fragile and confirmed that the CFE contains a substance called Loliolide with antioxidant activity. We performed the present study to determine whether CFE protects HEPG2 cells and BALB/c mice from oxidative stress-induced liver damage. We confirmed that CFE and Loliolide were non-cytotoxic and protected against liver damage by reducing the activities of ALT and AST, which were increased by APAP treatment, and that CFE reduced the mRNA expression of inflammatory cytokines TNF-α and IL-6 and inhibited the phosphorylation of ERK and p38 in HEPG2 cells as determined by RT-PCR and Western blot analyses. Furthermore, the TNF-α and IL-6 levels, which were increased after APAP treatment in BALB/c mice, decreased after CFE treatment. Therefore, we demonstrated that CFE exerts a protective effect against APAP-induced liver injury by suppressing the inflammatory response through anti-inflammatory activity. Our findings provide new perspectives for developing functional foods that utilize seaweeds to improve liver function.
참고문헌 (24)
- Mitra V, "Metabolic functions of the liver", Anaesth. Intensive Care Med, 10, pp.334~335 (2009)
- Fisher ES, "Evaluation and treatment of acetaminophen toxicity", Adv. Pharmacol, 85, pp.263~272 (2019)
- BinMowyna MN, "Kaempferol suppresses acetaminophen-induced liver damage by upregulation", activation of SIRT1, 2021, pp.59, 146~156
- Blazka ME, "Role of proinflammatory cytokines in acetaminophen hepatotoxicity", Toxicol. Appl. Pharmacol, 1133, pp.43~52 (1995)
- Yamada Y, "Initiation of liver growth by tumor necrosis factor : deficient liver regeneration in mice lacking type I tumor necrosis factor receptor", Proc. Natl. Acad. Sci. USA, 94, pp.1441~1446 (1997)
- Abad MJ, "Natural marine anti-inflammatory products", Mini. Rev. Med. Chem, 8, pp.740~754 (2008)
- Luthfi Adnan M, "The effects of seaweed supplementation consumption for improvement of liver injury in patients with non-alcoholic fatty liver disease : a systematic review", Clin. Exp. Hepatol, 8, pp.171~177 (2022)
- Sánchez-Valle V, "Role of oxidative stress and molecular changes in liver fibrosis : a review", Curr. Med. Chem, 19, pp.4850~4860 (2012)
- Meinita MDN, "A concise review of the bioactivity and pharmacological properties of the genus Codium(Bryopsidales, Chlorophyta)", J. Appl. Phycol, 34, pp.2827~2845 (2022)
- Ganesan P, "Anti-angiogenic effect of siphonaxanthin from green alga, Codium fragile", Phytomedicine, 17, pp.1140~1144 (2010)
- Moon SM, "Oleamide suppresses inflammatory responses in LPS-induced RAW264.7 murine macrophages and alleviates paw edema in a carrageenan-induced inflammatory rat model", Int. Immunopharmacol, 56, pp.179~185 (2018)
- Kim AD, "Cytotoxic effect of clerosterol isolated from Codium fragile on A2058human melanoma cells", Mar. Drugs, 11, pp.418~430 (2013)
- Hodges R, "The structure of Loliolide : a terpene from lolium perenne", Tetrahedron, 20, pp.1463~1467 (1964)
- Lever J, "Natural products of marine macroalgae from South Eastern Australia, with emphasis on the port Phillip Bay and heads regions of Victoria", Mar. Drugs, 18 (2020)[DOI]
- Silva J, "Loliolide, a new therapeutic option for neurological diseases? In vitro neuroprotective and anti-inflammatory activities of a monoterpenoid lactone isolated from Codium tomentosum", Int. J. Mol. Sci, 22 (2021)[DOI]
- Tzutzuy Ramirez, "Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells", Arch. Toxicol, 92, pp.893~906 (2018)
- Yamada Y, "Initiation of liver growth by tumor necrosis factor : deficient liver regeneration in mice lacking type I tumor necrosis factor receptor", Proc. Natl. Acad. Sci. USA, 94, pp.1441~1446 (1997)
- Giannini E, "Progressive liver functional impairment is associated with an increase in AST", ALT ratio, 1999, pp.44, 1249~1253
- Palabiyik SS, "The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines(HepG2)", Hum. Exp. Toxicol, 35, pp.1252~1263 (2016)
- Carol R Gardner, "Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1", Potential role of inflammatory mediators. Toxicol. Appl. Pharmacol, 192, pp.119~130 (2003)
- Toshio Tanaka, "IL-6 in inflammation, immunity, and disease", Cold Spring Harb. Perspect. Biol, 6, pp.a016295~ (2014)
- Moens U, "The role of mitogen-activated protein kinase-activated protein kinases(MAPKAPKs)in inflammation", Genes, 26, pp.101~133 (2013)
- Tan Q, "P38", ERK MAPK signaling pathways are involved in the regulation of filaggrin and involucrin by IL-17, 2017, pp.16, 8863~8867
- Xiaotong Li, "Bacillus amyloliquefaciens B10 can alleviate liver apoptosis and oxidative stress induced by aflatoxin B1", Food Chem. Toxicol, 151, pp.112124~ (2021)
