Effects of 7-Octenoic acid and 1-Phenyl-2-pentanol from Moringa oleifera Lam. Leaves Extract on the Hepatic Stellate Cells in an In Vitro Model of Liver Fibrosis
Keywords:
Liver fibrosis, Moringa oleifera Lam., 7-Octenoic acid, 1-Phenyl-2-pentanolAbstract
Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) proteins in the liver. Common causes include fatty liver disease and hepatitis C virus infection. Delayed or inaccurate diagnosis of liver fibrosis may elevate the risk of developing cirrhosis and liver cancer. Currently, there are no definitive pharmacological therapies for the treatment of liver fibrosis. Several studies have shown the anti-inflammatory effects of Moringa oleifera Lam. (MO) leaf extracts. In this study, we aimed to investigate the anti-fibrotic effect of two bioactive compounds identified in MO leaf crude extracts: 7-octenoic acid and 1-phenyl-2-pentanol. Hepatic stellate cells (HSCs) were treated with the active compounds, and cytokine levels were measured by using sandwich ELISA. In addition, protein expression in HSCs was analyzed by using proteomic technique. Proteomic analysis showed that 440 and 98 proteins were significantly upregulated and downregulated, respectively, in the 7-octenoic acid and 1-phenyl-2-pentanoltreated cells (p < 0.05). Additionally, there were decreases in expression of casein kinase II subunit alpha (CSNK2A1), guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 (GNB2), and low-density lipoprotein receptor-related protein 5 (LRP5), which are proteins related to the NF-κB, PI3K/Akt, and mTOR signaling pathways. TNF-α secretion was also suppressed by treatments with 7-octenoic acid and 1-phenyl-2-pentanol. In conclusion, these active compounds showed potent inhibitory activity on TGF-β1-induced HSCs and are promising candidates for anti-hepatic fibrosis drug research.
References
Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115: 209-18.
Menggensilimu, Yuan H, Zhao C, et al. Anti-liver fibrosis effect of total flavonoids from Scabiosa comosa Fisch. ex Roem. et Schult. on liver fibrosis in rat models and its proteomics analysis. Ann Palliat Med 2020; 9: 272-85.
Sarin SK, Kumar M, Eslam M, et al. Liver diseases in the Asia-Pacific region: a Lancet Gastroenterology & Hepatology Commission. Lancet Gastroenterol Hepatol 2020; 5: 167-228.
Poynard T, Lebray P, Ingiliz P, et al. Prevalence of liver fibrosis and risk factors in a general population using non-invasive biomarkers (FibroTest). BMC Gastroenterol 2010; 10: 1-13.
Khanam A, Saleeb PG, Kottilil S. Pathophysiology and treatment options for hepatic fibrosis: can it be completely cured? Cells 2021; 10: 1097.
Yang YM, Seki E. TNFoc in liver fibrosis. Curr Pathobiol Rep 2015; 3: 253-61.
Zelova H, Hosek J. TNF-alpha signalling and inflammation: interactions between old acquaintances. Inflamm Res 2013; 62: 641-51.
Tan Z, Sun H, Xue T, et al. Liver fibrosis: therapeutic targets and advances in drug therapy. Front Cell Dev Biol 2021; 9: 730176.
Camellia Seed Oil and Other Plant Oil Product Research and Development Center. (MORINGA) Chiang Rai, Thailand: [Available from: https://www.camelliaoilcenter.com/%E0%B8%A1%E0%B8%B0%E0%B8%A3%E0%B8%B8%E0%B8%A1-moringa/.
Kou X, Li B, Olayanju JB, Drake JM, Chen N. Nutraceutical or pharmacological potential of Moringa oleifera Lam. Nutrients 2018; 10: 343.
Wisitpongpun P, Suphrom N, Potup P, et al. In vitro bioassay-guided identification of anticancer properties from Moringa oleifera Lam. leaf against the MDAMB-231 cell line. Pharmaceuticals 2020;13: 464.
Yu J, Hu Y, Gao Y, et al. Kindlin-2 regulates hepatic stellate cells activation and liver fibrogenesis. Cell Death Discovery 2018; 4: 93.
Xu Z, Li T, Li M, et al. eRF3b-37 inhibits the TGF-β 1-induced activation of hepatic stellate cells by regulating cell proliferation, G0/G1 arrest, apoptosis and migration. Int J Mol Med 2018; 42: 3602-12.
Wei S, Wang Q, Zhou H, et al. miR-455- 3p alleviates hepatic stellate cell activation and liver fibrosis by suppressing HSF1 expression. Mol Ther Nucleic Acids 2019; 16: 758-69.
Wang Y, Wu C, Zhou J, Fang H, Wang J. Overexpression of estrogen receptor β inhibits cellular functions of human hepatic stellate cells and promotes the anti-fibrosis effect of calycosin via inhibiting STAT3 phosphorylation. BMC Pharmacol Toxicol 2022; 23: 77.
Kang H, Seo E, Oh YS, Jun H-S. TGF-β activates NLRP3 inflammasome by an autocrine production of TGF-β in LX-2 human hepatic stellate cells. Mol Cell Biochem 2022; 477: 1329-38.
Buakaew W, Krobthong S, Yingchutrakul Y, et al. Investigating the antifibrotic effects of β-Citronellol on a TGF-β 1-stimulated LX-2 hepatic stellate cell Model. Biomolecules 2024; 14: 800.
Szklarczyk D, Franceschini A, Wyder S, et al. STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res 2015; 43: 447-52.
Chen EY, Tan CM, Kou Y, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 2013; 14: 128.
Kuleshov MV, Jones MR, Rouillard AD, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 2016; 44: 90-7.
Xie Z, Bailey A, Kuleshov MV, et al. Gene set knowledge discovery with Enrichr. Current Protocols 2021; 1: 90.
Kanehisa M, Goto S. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28: 27-30.
Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Science 2019; 28: 1947-51.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res 2023; 51: 587-92.
Jodynis-Liebert J, Kujawska M. Biphasic dose-response induced by phytochemicals: experimental evidence. J Clin Med 2020; 9: 718.
Armando Ciiceresa’b AS, Sofia Rizzoa, Lorena Zabalaa, Edy De Leonb and Federico Naveb. Pharmacologic properties of Moringa oleifera. 2 : screening for antispasmodic, antiinflammatory and diuretic activity. J Ethnopharmacol 1992; 36: 233-7.
Vergara-Jimenez M, Almatrafi MM, Fernandez ML. Bioactive components in Moringa Oleifera leaves protect against chronic disease. Antioxidants (Basel). 2017; 6: 91.
Sharifudin SA, Fakurazi S, Hidayat MT, et al. Therapeutic potential of Moringa oleifera extracts against acetaminopheninduced hepatotoxicity in rats. Pharm Biol 2013; 51: 279-88.
Yang Y, Ding T, Xiao G, et al. Anti-Inflammatory Effects of allocryptopine via the target on the CX3CL1-CX3CR1 axis/GNB5/AKT/NF-kappaB/apoptosis in dextran sulfate-induced mice. Biomedicines 2023; 11: 464.
Li L, Zeng P, Yu L, et al. Salinomycin sodium exerts anti diffuse large B-cell lymphoma activity through inhibition of LRP6-mediated Wnt/β-catenin and mTORC1 signaling. Leukemia & Lymphoma 2023; 64: 1151-60.
Huang J, Hao J, Nie J, et al. Possible Mechanism of Dysphania ambrosioides (L.) Mosyakin & Clemants Seed Extract Suppresses the Migration and Invasion of Human Hepatocellular Carcinoma Cells SMMC-7721. Chem Biodivers 2023; 20: e202200768.
Li L, Xue J, Wan J, et al. LRP6 Knockdown ameliorates insulin resistance via modulation of autophagy by regulating GSK3beta signaling in human LO2 hepatocytes. Front Endocrinol (Lausanne) 2019; 10: 73.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Journal of the Medical Technologist Association of Thailand
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
