To evaluate the protective effects of ergothioneine against D-galactose (D-gal)-induced oxidative damage in rats and elucidate the underlying molecular mechanisms.
Oxidative damage in rats was induced by intraperitoneal injection of D-gal (200 mg/kg) once daily for 6 consecutive weeks. Male SD rats were randomly assigned to 5 groups: The control group, which received intraperitoneal saline injection, and the model group as well as the low-dose (EGT-L, 1.4 mg/kg), mid-dose (EGT-M, 2.8 mg/kg) and high-dose (EGT-H, 5.6 mg/kg)ergothioneine groups, which were administered intraperitoneal D-gal. Starting from week 3 and continuing through week 6, each treatment group received daily intragastric administration of ergothioneine, while the control and model groups were given an equal volume of saline, for a total duration of 4 weeks. The levels of oxidative stress markers,including malondialdehyde (MDA) as a marker of lipid peroxidation and protein carbonyls as markers of protein oxidation, antioxidants such as reduced glutathione (GSH), and antioxidant enzymes including catalase (CAT) and superoxide dismutase (SOD) were measured in the serum and liver of rats using colorimetric assays. A preliminary network pharmacology analysis was performed to investigate the potential mechanisms underlying the antioxidant effects of ergothioneine, and further validation was carried out using western blotting to assess the impact of ergothioneine on the hepatic protein expression levels of Acetyl-FOXO1, FOXO1 and SIRT1.
Compared with the model group, ergothioneine-treated groups decreased MDA and protein carbonyl levels in serum and liver,and increased SOD and CAT activities and GSH content. Western blotting indicated that ergothioneine administration reduced the ratio of Acetyl-FOXO1/FOXO1 and upregulated SIRT1 protein expression in liver tissue.
Ergothioneine exhibits significant protective effects against D-gal-induced oxidative damage in rats. The underlying mechanism may predominantly involve modulation of the FoxO signaling pathway.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |