Zhongguo gonggong weisheng (Dec 2023)
Protective effect of ganoderma acid A on liver injury induced by α-amanitin in mice
Abstract
ObjectiveTo investigate the protective mechanism of ganoderma acid A against α-amanitin-induced liver injury in mice. MethodsForty Kunming mice were divided into 4 groups intraperitoneally injected with solution (10 mL/kg) containing α-amanitin at concentrations of 0.0, 0.1, 0.2 and 0.3 mg/kg to establish intoxicated mouse model. Another sixty Kunming mice were assigned into a blank control group, a α-amanitin intoxicated group, and four α-amanitin intoxicated groups administered with ganoderma acid A at dosages of 5, 10, 20, 40 mg/kg every 6 hours totally 4 times; the blank control group and the α-amanitin intoxicated group were treated with equal amount of normal saline. All the mice were sacrificed 48 hours after the first treatment. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and glutamyl transferase (GGT) were detected and hepatic reactive oxygen species (ROS), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), hepatic rat sarcoma (RAS) protein, nuclear factor kappa B (NF-κB), tumor necrosis factor receptor superfamily member 5 (TNFRSF5) protein were also determined. ResultsCompared with those of the blank control mice, significantly increased serum ALT, AST, ALP, GGT, hepatic expressions of ROS, IL-8, TNF-α, COX-2, rat sarcoma (RAS) protein (0.08 ± 0.02 vs. 12.55 ± 0.54), NF-κB (0.07 ± 0.01 vs. 10.58 ± 0.78), TNFRSF5 (0.09 ± 0.01 vs. 11.05 ± 0.83) protein were detected in the α-amanitin intoxicated mice (P < 0.05 for all). In comparison with the untreated α-amanitin intoxicated mice, the intoxicated mice administered with ganoderma acid A had significantly decreased serum ALT, AST, ALP, GGT and hepatic expressions of ROS, IL-8, TNF-α, COX-2 (all P < 0.05); the intoxicated mice with ganoderma acid A treatment also had dose-dependent decreased hepatic expressions of RAS protein (10.58 ± 0.89, 8.35 ± 0.73, 5.54 ± 0.44, and 3.74 ± 0.29 vs. 12.55 ± 0.54), NF-κB (8.53 ± 0.63, 6.82 ± 0.62, 4.24 ± 0.32, and 2.78 ± 0.21 vs. 10.58 ± 0.78), and TNFRSF5 (9.74 ± 0.78, 7.79 ± 0.71, 3.10 ± 0.34, and 2.81 ± 0.23 vs. 11.05 ± 0.83) (P < 0.05 for all). ConclusionGanoderma acid A can inhibit oxidative stress and inflammatory response to alleviate liver injury caused by α-amanitin in mice and the mechanism of the effect may be related to the activation of liver RAS/NF-κB/TNFRSF5 protein signaling pathway inhibited by ganoderma acid A.
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