Structural characterization of a Penicillium-derived exopolysaccharide and its hepatoprotective effects through regulation of oxidative stress and bile acid metabolism.

Exopolysaccharide (EPS) produced by a tea-derived endophytic Penicillium species has been reported to exhibit antioxidant activity in vitro; however, its in vivo effects and underlying structure-activity relationships remain largely unexplored. In the present study, the major EPS fraction, designated as EPS-B, was isolated and purified from the crude EPS. Structural analysis revealed that the backbone of EPS-B is mainly composed of →2)-α-D-Galp-(1 → and →2,6)-α-D-Galp-(1 → linkages, accompanied by minor →3)-α-D-Glcp-(1→, →6)-α-D-Manp-(1→, and →3,6)-β-D-Glcp-(1 → residues. A cyclophosphamide (CTX)-induced liver injury model was subsequently established to evaluate the regulatory effects of EPS at three different doses on liver function, oxidative stress, inflammation, apoptosis, and metabolic disturbances. EPS treatment markedly alleviated CTX-induced oxidative stress and inflammatory damage, activated the Nrf2/HO-1 antioxidant signaling pathway, and modulated cholesterol-bile acid metabolism, thereby contributing to the maintenance of hepatic metabolic homeostasis. In addition, EPS effectively reversed CTX-induced disturbances in energy, ribose, lipid, and amino acid metabolism, with the medium-dose group showing the most pronounced effects. These results indicate that EPS has potential as a bioactive ingredient in functional foods for liver protection. However, the high-dose EPS showed less pronounced anti-inflammatory effects and was associated with persistent inflammatory infiltration, suggesting a potential risk of lipotoxicity at excessive doses.