The curative effect of ethanolic extract of Moringa oleifera leaf in an animal model of liver fibrosis
Abstract
Studies about the prevention effect of Moringa oleifera on liver fibrosis has been reported. However, its curative effect has not been reported, yet. This study was conducted to evaluate the curative effect of M. oleifera leaf extract on liver fibrosis. It was a laboratory experimental study with a post-test-only control group design. Rats were divided into 5 groups i.e. normal control which received intraperitoneally injections of 1 mL/kg BW of 0.9% NaCl solution twice a wk for 11 wk. Liver fibrosis control which received intraperitoneally injections of 1 mL/kg BW of 10% CCl4 solution twice a wk for 11 wk. Three M. oleifera treatment group which received intraperitoneally injections of 1 mL/kg BW of 10% CCl4 solution twice a wk for 11 wk continued by M. oleifera leaf ethanolic extract at dose of 600 mg/kg BW daily for 3 (MO3), 6 (MO6), and 10 (MO10) wk, respectively. The liver fibrosis level was assessed based on the METAVIR score. Histopathological analysis of liver tissues demonstrated that the 11-week CCl4 induction successfully resulted in liver fibrosis in rats (F3 and F4). The administration of M. oleifera leaf ethanolic extract decreased METAVIR scores ranged from F3 to F1. The optimal reduction of the METAVIR scores (F1) was observed in MO3 group after 6 wk administration (p<0.05). It was indicated that M. oleifera leaf ethanolic extract ameliorated liver fibrosis. In conclusion, M. oleifera leaf ethanolic extract has a curative effect against liver fibrosis.
References
Poulsen KL, Cajigas-Du Ross CK, Chaney JK, Nagy LE. Role of the chemokine system in liver fibrosis: a narrative review. Dig Med Res 2022; 5:30.
https://doi.org/10.21037/dmr-21-87
Roehlen N, Crouchet E, Baumert TF. Liver fibrosis: mechanistic concepts and therapeutic perspectives. Cells 2020; 9 (4): 875.
https://doi.org/10.3390/cells9040875
Qiao J. Occurrence, diagnosis and management of hepatic fibrosis and cirrhosis: an updated literature review. Arch Hepat Res 2019; 5(1):022-6.
https://doi.org/10.17352/ahr.000023
Wang F Da, Zhou J, Chen EQ. Molecular mechanisms and potential new therapeutic drugs for liver fibrosis. Front Pharmacol 2022; 13:787748.
https://doi.org/10.3389/fphar.2022.787748.
Acharya P, Chouhan K, Weiskirchen S, Weiskirchen R. Cellular mechanisms of liver fibrosis. Front Pharmacol 2021; 12:67640.
https://doi.org/10.3389/fphar.2021.671640
Garbuzenko DV. Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis. World J Clin Cases 2022; 10(12):3662-76.
https://doi.org/10.12998/wjcc.v10.i12.3662
Kou X, Li B, Olayanju JB, Drake JM, Chen N. Nutraceutical or pharmacological potential of Moringa oleifera Lam. Nutrients 2018; 10(3):343.
https://doi.org/10.3390/nu10030343.
Rani NZA, Husain K, Kumolosasi E. Moringa genus: a review of phytochemistry and pharmacology. Front Pharmacol 2018; 9:108.
https://doi.org/10.3389/fphar.2018.00108.
Kashyap P, Kumar S, Riar CS, Jindal N, Baniwal P, Guiné RPF, et al. Recent advances in drumstick (Moringa oleifera) leaves bioactive compounds: composition, health benefits, bioaccessibility, and dietary applications. Antioxidants (Basel) 2022; 11(2):402.
https://doi.org/10.2290/antiox11020402
Syahrin S, Kairupan C, Loho L, Manado SR, Patologi B, Fakultas A, et al. Gambaran histopatologik hati tikus Wistar yang diberi ekstrak daun kelor (Moringa oleifera) setelah diinduksi karbon tetraklorida (CCl4). e-Biomedik (eBm) 2016; 4(2).
Fathy SM, Mohammed MSM. Moringa oleifera Lam. leaf extract mitigates carbon tetrachloride-mediated hepatic inflammation and apoptosis via targeting oxidative stress and toll-like receptor 4/nuclear factor kappa B pathway in mice. Food Sci Human Wellness 2021; 10(3):383-91.
https://doi.org/10.1016/j.fshw.2021.02.030
Supriono S, Kalim H, Permatasari N, Susianti H. Moringa oleifera prevents in vivo carbon tetrachloride-induced liver fibrosis through targeting hepatic stellate cells. OAMJMS 2022;10(A):824-32.
https://doi.org/10.3889/oamjms.2022.9119
Supriono S, Kalim H, Permatasari N, Susianti H. Moringa oleifera inhibits liver fibrosis progression by inhibition of α-smooth muscle actin, tissue inhibitors of metalloproteinases-1, and collagen-1 in rat model liver fibrosis. OAMJMS 2020; 8(A):287-92.
https://doi.org/10.3889/oamjms.2020.4254
Li L, Hu Z, Li W, Hu M, Ran J, Chen P, et al. Establishment of a standardized liver fibrosis model with different pathological stages in rats. Gastroenterol Res Pract. 2012; 2012:560345.
https://doi.org/10.1155/2012/560345
Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol 2007; 47(4):598-607.
https://doi.org/10.1016/j.jhep.2007.07.006
Wu L, Zhang Q, Mo W, Feng J, Li S, Li J, et al. Quercetin prevents hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing autophagy via the TGF-β1/Smads and PI3K/Akt pathways. Sci Rep 2017; 7(1):9289.
https://doi.org/10.1038/s41598-017-09673-5
Scholten D, Trebicka J, Liedtke C, Weiskirchen R. The carbon tetrachloride model in mice. Lab Anim. 2015; 49(1 Suppl):4–11.
https://doi.org/10.1177/0023677215571192
Yanguas SC, Cogliati B, Willebrords J, Maes M, Colle I, van den Bossche B, et al. Experimental models of liver fibrosis. Arch Toxicol 2016; 90(5):1025-48.
https://10.1007/s00204-015-1543-4.
Knockaert L, Berson A, Ribault C, Prost PE, Fautrel A, Pajaud J, et al. Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver. Lab Invest 2012; 92(3):396-410.
https://doi.org/10.1038/labinvest.2011.193
Simon TG, Ma Y, Ludvigsson JF, Chong DQ, Giovannucci EL, Fucha CS, et al. Association between aspirin use and risk of hepatocellular carcinoma. JAMA Oncol 2018; 4(12):1683-90.
https://doi.org/10.1001/jamaoncol.2018.4154
Susanto H, Yunisa DT, Taufiq A, Putra WE, Jannah NR, Putri SA, et al. Anti fibrogenesis effect of green materials Moringa oleifera leaf powder (MOLP) on the progression of hepatocellular carcinoma. AIP Conference Proceedings 2021; 2353(1):030024.
https://doi.org/10.1063/5.0052554
Aly O, Abouelfadl DM, Shaker OG, Hegazy GA, Fayez AM, Zaki HH. Hepatoprotective effect of Moringa oleifera extract on TNF-α and TGF-β expression in acetaminophen-induced liver fibrosis in rats. Egyp J Med Hum Genet 2020; 2:69.
https://doi.org/10.1186/s43042-020-00106-z
Li X, Jin Q, Yao Q, Xu B, Li L, Zhang S, et al. The flavonoid quercetin ameliorates liver inflammation and fibrosis by regulating hepatic macrophages activation and polarization in mice. Front Pharmacol 2018; 9:72.
https://doi.org/10.3389/fphar.2018.00072
Shakerian E, Akbari R, Mohammadtaghvaei N, Gahrooie MM, Afarin R. Quercetin reduces hepatic fibrogenesis by inhibiting TGF-β/Smad3 signaling pathway in LX-2 cell line. Jundishapur J Nat Pharm Prod 2022; 17:e113484.
https://doi.org/10.5812/jjnpp.113484
Zhou G, Li C, Zhang R, Zhan Y, Lin L, Lang Z, et al. Kaempferol inhibits hepatic stellate cell activation by regulating miR-26b-5p/Jag1 axis and notch pathway. Front Pharmacol 2022; 13:881855.
https://doi.org/10.3389/fphar.2022.881855
Zheng H, Wang X, Zhang Y, Chen L, Hua L, Xu W. Pien-Tze-Huang ameliorates hepatic fibrosis via suppressing NF-κB pathway and promoting HSC apoptosis. J Ethnopharmacol 2019; 244:111856.
https://doi.org/10.1016/j.jep.2019.111856
Sadek KM, Abouzed TK, Abouelkhair R, Nasr S. The chemo-prophylactic efficacy of an ethanol Moringa oleifera leaf extract against hepatocellular carcinoma in rats. Pharm Biol 2017; 55(1):1458-66.