Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure

Abstract

Inflammation and oxidative stress are essential for the pathogenesis of fulminant hepatic failure (FHF). Asiatic acid (AA), which is a pentacyclic triterpene that widely occurs in various vegetables and fruits, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of AA against lipopolysaccharide (LPS) and d-galactosamine (GalN)-induced FHF and the underlying molecular mechanisms. Our findings suggested that AA treatment effectively protected against LPS/d-GalN-induced FHF by lessening the lethality; decreasing the alanine transaminase and aspartate aminotransferase levels, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production, malondialdehyde formation, myeloperoxidase level and reactive oxygen species generation (i.e., H2O2, NO, and O2−), and increasing the glutathione and superoxide dismutase contents. Moreover, AA treatment significantly inhibited mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway activation via the partial induction of programmed cell death 4 (PDCD4) protein expressions, which are involved in inflammatory responses. Furthermore, AA treatment dramatically induced the expression of the glutamate-cysteine ligase modifier subunit, the glutamate-cysteine ligase catalytic subunit, heme oxygenase-1, and NAD (P) H: quinoneoxidoreductase 1 (NQO1), which are largely dependent on activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) through the induction of AMP-activated protein kinase (AMPK) and glycogen synthase kinase-3β (GSK3β) phosphorylation. Accordingly, AA exhibited protective roles against LPS/d-GalN-induced FHF by inhibiting oxidative stress and inflammation. The underlying mechanism may be associated with the inhibition of MAPK and NF-κB activation via the partial induction of PDCD4 and upregulation of Nrf2 in an AMPK/GSK3β pathway activation-dependent manner.

Asiatic acid ameliorates CC l₄-induced liver fibrosis in rats: involvement of Nrf2/ARE, NF-κB/IκBα, and JAK1/STAT3 signaling pathways

“…AA has been known as a natural compound extracted from the Terminalia catappa L ., which has antioxidative and anti-inflammatory properties. 21 Our previous studies have suggested that AA protects the liver against hepatocyte apoptosis, and inhibits HSC activation and ECM synthesis. 23 , 24 In this study, the results demonstrated that AA alleviated oxidative stress-mediated hepatocyte damage, inflammation, and HSCs activation in rats, which suggested that AA has therapeutic potential against mild liver injury and liver fibrosis.…”

Modified distribution in the polyphenolic profile of rosemary leaves induced by plant inoculation with an arbuscular mycorrhizal fungus

“…6. From this study, it was concluded that several polyphenolic compounds hosting strong antioxidant properties such as ferulic acid, 29 asiatic acid, 30 carnosol, 31 and vanillin 32 were clearly related to mycorrhizal rosemary plant samples, whereas other polyphenolic compounds, such as caffeic and chlorogenic acids, have a higher influence in the non-inoculated plants. These results are in accordance with those previously reported by López-Ráez et al 33 in tomato roots; the levels of ferulic acid increased after the establishment of a mycorrhizal colonization by two AM fungi, Glomus intraradices and Glomus mosseae, while the levels of chlorogenic and caffeic acids decreased.…”

Overexpression of C‑sis inhibits H2O2‑induced Buffalo rat liver cell apoptosis in�vitro and alleviates liver injury in a rat model of fulminant hepatic failure

“…Under stress conditions, the structure of the nucleolus is perturbed and certain nucleolar proteins, including ribosomal proteins, are released from the nucleolus to the nucleoplasm where they associate with Mouse Double Minute 2 (MDM2) to inhibit its activity and stabilize p53 ( 53 , 54 ). Reactive oxygen species are crucial in FHF ( 55 ). The present study used H 2 O 2 to induce oxidative stress in order to induce the apoptosis of BRL cells.…”