Grape-Leaf Extract Attenuates Alcohol-Induced Liver Injury via Interference with NF-κB Signaling Pathway

Abstract

Grape (Vitis vinifera) leaf extracts (GLEs) are known to be rich in phenolic compounds that exert potent antioxidant effects. Given the vulnerability of the liver to oxidative damage, antioxidants have been proposed as therapeutic agents and coadjuvant drugs to ameliorate liver pathologies. The current study was designed to characterize secondary metabolites and investigate the hepatoprotective effects of GLE and its underlying mechanisms. The secondary metabolites were profiled using HPLC–PDA–ESI-MS, and forty-five compounds were tentatively identified. In experimental in vivo design, liver injury was induced by oral administration of high doses of ethanol (EtOH) for 12 days to male Sprague Dawley rats that were split into five different groups. Blood samples and livers were then collected, and used for various biochemical, immunohistochemical, and histopathological analyses. Results showed that GLE-attenuated liver injury and promoted marked hepatic antioxidant effects, in addition to suppressing the increased heat-shock protein-70 expression. Moreover, GLE suppressed EtOH-induced expression of nuclear factor-κB (NF-κB) p65 subunit and proinflammatory cytokine tumor necrosis factor-α. Caspase-3 and survivin were enhanced by EtOH intake and suppressed by GLE intake. Finally, EtOH-induced histopathological changes in liver sections were markedly normalized by GLE. In conclusion, our results suggested that GLE interferes with NF-κB signaling and induces antioxidant effects, which both play a role in attenuating apoptosis and associated liver injury in a model of EtOH-induced liver damage in rats.

Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds

“…Many in vitro and in vivo studies confirmed that fruits such as the mango [ 144 ], grape [ 145 ], blueberry [ 110 ], mulberry [ 146 ], persimmon [ 147 ], pomegranate [ 148 ], cranberry [ 149 ], and wolfberry [ 150 ] play an important role against ALD. This ameliorative effect on ALD was mainly due to the presence of a tangible amount of bioactive compounds in fruits.…”

“…The results further show that grape leaf extract at a high dose of 100 mg/kg bw could significantly reduce lipid peroxidation level along with restoration of enzymic and non-enzymatic antioxidants level in the kidney and liver of alcohol-exposed rats. Recently, Amen et al [ 145 ] also confirmed that polyphenol-rich grape leaf extracts interfered with NF-κB signaling and exerted antioxidant effects, which further played a role in ameliorating apoptosis and associated hepatic injury in rats exposed to ethanol.…”

Lagotis brachystachya maxim attenuates chronic alcoholic liver injury combined with gouty arthritis in rats via its anti-inflammatory activity

“…The activation of NF-κB is closely related to alcoholic liver injury and gouty arthritis Liu et al, 2022). Accumulating studies have also confirmed that inhibiting the NF-κB signaling pathway can attenuate the symptoms of alcoholic liver injury and gouty arthritis by inhibiting the release of proinflammatory cytokines (Amen et al, 2020;Ouyang et al, 2021). In the present study, ELB could significantly inhibit TLR4/NF-κB/ MyD88 signaling pathway and proinflammatory cytokines in both the hepatic and synovial tissues, indicating that the therapeutical action of ELB is mediated by the inhibition of TLR4/NF-κB/MyD88/cytokine pathway.…”

Potency of Selected Berries, Grapes, and Citrus Fruit as Neuroprotective Agents

“…Carvalho et al [91] have reported that grape skin anthocyanins were active in weakening inflammatory events, including neutrophil infiltration, in addition to rescuing the ethidium bromide-induced demyelination of neurons in the pons of rat. e grape leaves extract intake for 12 days by male Sprague Dawley rats suppressed the ethanol-induced expression of nuclear factor-κB (NF-κB) p65 subunit, proinflammatory cytokine tumour necrosis factor-α, caspase-3, and surviving [92]. 3,4′,5-Trihydroxy-trans-stilbene (resveratrol) is a major compound present in grapes [93].…”