Echinacoside alleviates acetaminophen-induced liver injury by attenuating oxidative stress and inflammatory cytokines in mice.

This study evaluates the protective effect of Echinacoside on acute liver toxicity induced by acetaminophen in mice and the mechanism behind it. Echinacoside and N-Acetyl Cysteine were intragastrically administrated for 7 days, and acetaminophen was intraperitoneally injected into mice 1 h after the last treatment on day 7. At the end of the experimental period, histological examination, parameters for the level of oxidative damage, hepatic malondialdehyde, serum pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1ß), UDP-glucuronosyltransferases, and sulfotransferases changes were examined using enzyme-linked immunosorbent assay and standard biochemical procedures. The expression of cytochrome P450 2E1 protein was assessed by western blot, followed by in silico molecular docking. Acetaminophen treatment obviously increased the levels of ALT and AST, changed hepatic histopathology, promoted oxidative stress, decreased antioxidant enzyme activities, and elevated the pro-inflammatory cytokines. Echinacoside significantly attenuated Acetaminophen-induced liver damage in a dose-dependent manner, with the most effective dose at 100 mg/kg. The pretreatments of Echinacoside in different concentrations altered the Acetaminophen-induced hepatotoxicity levels by decreasing the level of liver enzymes, reducing the liver necrosis with vacuolization, decreasing the hepatic malondialdehyde formation, increasing hepatic antioxidants activities, suppressing the pro-inflammatory cytokines (Tumor Necrosis Factor, Interleukin-6 and Interleukin-1beta), inhibiting Nitric Oxide production, enhancing sulfotransferases and UDP-glucuronosyltransferases activities. Notably, the expression of cytochrome P450 2E1 was inhibited by Echinacoside in a dose-dependent manner and the binding energy was -214.3 MeV. Echinacoside showed a significant protective effect against Acetaminophen-induced hepatotoxicity through the inhibition of oxidative stress, the expression of pro-inflammatory cytokines and cytochrome P450 2E1 protein expression.

Gambogic acid induces apoptotic cell death in T98G glioma cells.

Gambogic acid (GA), a natural product with a xanthone structure, has a broad range of anti-proliferative effects on cancer cell lines. We evaluated GA for its cytotoxic effects on T98G glioblastoma cells. GA exhibited potent anti-proliferative activity and induced apoptosis in T98G glioblastoma cells in a dose-dependent manner. Incubation of cells with GA revealed apoptotic features including increased Bax and AIF expression, cytochrome c release, and cleavage of caspase-3, -8, -9, and PARP, while Bcl-2 expression was downregulated. Furthermore, GA induced reactive oxygen species (ROS) generation in T98G cells. Our results indicate that GA increases Bax- and AIF-associated apoptotic signaling in glioblastoma cells.