The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats.

Mechanisms of ageing and development

PubMedID: 23313706

Ruan Q, Liu F, Gao Z, Kong D, Hu X, Shi D, Bao Z, Yu Z. The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats. Mech Ageing Dev. 2013;134(3-4):89-97.
Oxidative stress contributes to a chronic inflammatory process referred to as "inflamm-aging". Acetylcholinesterase inhibitors (AChEI) can enhance cholinergic transmission and act as anti-inflammatory agents via immunocompetent cells expressing a-7 acetylcholine receptors (AChR). The present study explores the possible role of huperzine A, a reversible and selective AChEI, against D-gal-induced oxidative damage, cell toxicity and inflamm-aging in rat livers. In two-month-old rats with normal liver function, an 8-week administration of D-gal (300 mg/kg subcutaneously (s.c.) injected), significantly increased hepatic impairment, ROS generation and oxidative damage, hepatic senescence, nuclear factor-kappa B (NF-?B) activation and inflammatory responses. An 8-week co-administration of both D-gal (300 mg/kg s.c.) and huperzine A (0.1 mg/kg s.c.) not only significantly decreased hepatic function impairment, ROS generation, oxidative damage, but also suppressed inflamm-aging by inhibiting hepatic replicative senescence, AChE activity, I?Ba degradation, NF-?B p65 nuclear translocation and inflammatory responses. The expression levels of pro-inflammatory cytokine mRNA and proteins, such as TNFa, IL-1ß and IL-6 decrease significantly, and the protein levels of the anti-inflammatory cytokine IL-10 display an obvious increase. These findings indicated that D-gal-induced hepatic injury and inflamm-aging in the rat liver was associated with the development of a pro-inflammatory phenotype in this organ. D-gal induced damage-associated molecular patterns (DAMPs) because oxidative damages might play an important role in D-gal-induced hepatic sterile inflammation. Huperzine A exhibited protective effects against D-gal-induced hepatotoxicity and inflamm-aging by inhibiting AChE activity and via the activation of the cholinergic anti-inflammatory pathway. The huperzine A mechanism might be involved in the inhibition of DAMPs-mediated NF-?B nuclear localization and activation.