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Antioxidant and immunomodulatory activity induced by stevioside in liver damage: In vivo, in vitro and in silico assays.

ABSTRACT: AIMS:Stevioside is a diterpenoid obtained from the leaves of Stevia rebaudiana (Bertoni) that exhibits antioxidant, antifibrotic, antiglycemic and anticancer properties. Therefore, we aimed to study whether stevioside has beneficial effects in liver injury induced by long-term thioacetamide (TAA) administration and investigated the possible underlying molecular mechanism using in vivo, in vitro and in silico approaches. MAIN METHODS:Liver injury was induced in male Wistar rats by TAA administration (200?mg/kg), intraperitoneally, three times per week. Rats received saline or stevioside (20?mg/kg) twice daily intraperitoneally. In addition, cocultures were incubated with either lipopolysaccharide or ethanol. Liver injury, antioxidant and immunological responses were evaluated. KEY FINDINGS:Chronic TAA administration induced significant liver damage. In addition, TAA upregulated the protein expression of nuclear factor (NF)-?B, thus increasing the expression of proinflammatory cytokines and decreasing the antioxidant capacity of the liver through downregulation of nuclear erythroid factor 2 (Nrf2). Notably, stevioside administration prevented all of these changes. In vitro, stevioside prevented the upregulation of several genes implicated in liver inflammation when cocultured cells were incubated with lipopolysaccharide or ethanol. In silico assays using tumor necrosis factor receptor (TNFR)-1 and Toll-like receptor (TLR)-4-MD2 demonstrated that stevioside docks with TNFR1 and TLR4-MD2, thus promoting an antagonistic action against this proinflammatory mediator. SIGNIFICANCE:Collectively, these data suggest that stevioside prevented liver damage through antioxidant activity by upregulating Nrf2 and immunomodulatory activity by blocking NF-?B signaling.

SUBMITTER: Casas-Grajales S

PROVIDER: S-EPMC6556435 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Antioxidant and immunomodulatory activity induced by stevioside in liver damage: In vivo, in vitro and in silico assays.

Casas-Grajales Sael S Ramos-Tovar Erika E Chávez-Estrada Esmeralda E Alvarez-Suarez Diana D Hernández-Aquino Erika E Reyes-Gordillo Karina K Cerda-García-Rojas Carlos M CM Camacho Javier J Tsutsumi Víctor V Lakshman M Raj MR Muriel Pablo P

Life sciences 20190316

<h4>Aims</h4>Stevioside is a diterpenoid obtained from the leaves of Stevia rebaudiana (Bertoni) that exhibits antioxidant, antifibrotic, antiglycemic and anticancer properties. Therefore, we aimed to study whether stevioside has beneficial effects in liver injury induced by long-term thioacetamide (TAA) administration and investigated the possible underlying molecular mechanism using in vivo, in vitro and in silico approaches.<h4>Main methods</h4>Liver injury was induced in male Wistar rats by ...[more]

PMID: 30890404

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Project description:Introduction: Gnetum ula is a notable medicinal plant used to cure various ailments. The stem part of the plant is used traditionally to treat jaundice and other disorders. The present work is to investigate the in vitro hepatoprotective and antioxidant activity of ethanol extract of stem of G. ula (GUE) and its isolated compound gnetol. Methods: Column chromatography was carried out for GUE and various column fractions were obtained. DPPH and reducing power assays were performed for GUE and column fractions. The potent fraction was characterized, interpreted and tested for in vitro hepatoprotective activity on the BRL3A cell line. In silico docking studies of gnetol compound on the protein TGF-? (transforming growth factor - ?) and Peroxisome proliferator-activated receptor ? (PPAR?) was carried out. Results: DPPH scavenging and reducing power assay showed that the fourth column fraction has antioxidant potential than other fractions. The fourth column fraction was characterized to obtain gnetol compound. BRL3A cell line was used for the toxicity study of GUE and gnetol. Both, the extract and the isolated compound were found to be nontoxic with CTC50 value more than 1000 µg/mL. At the concentration of 200 µg/mL, GUE and gnetol offered cell protection of 50.2% and 54.3%, however, silymarin showed 77.15% protection at 200 µg/mL concentration against CCl4 treated BRL3A cell line. The docking results of the ligand molecule TGF-? showed that gnetol has the binding affinity of -7.0 and standard silymarin being -6.8. TGF-? showed good hydrophobic interactions and formed two hydrogen bonds with the amino acids. For PPAR? protein, gnetol showed the binding affinity of -8.4 and silymarin with -6.5. Hydrogen bonding and good hydrophobic interactions against the amino acid molecules in relation to the PPAR? protein are shown. Conclusion: Gnetum ula stem extract and its isolated compound are safe and offered significant hepatoprotection against CCl4 induced toxicity. Isolated compound gnetol exhibited a potent antioxidant activity offering protection to liver damage. However, in vivo studies need to be carried out to validate the traditional use of G. ula .

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Antioxidant and immunomodulatory activity induced by stevioside in liver damage: In vivo, in vitro and in silico assays.

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Antioxidant and immunomodulatory activity induced by stevioside in liver damage: In vivo, in vitro and in silico assays.

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