title: The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats.
abstract: 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 α-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-κB) 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, IκBα degradation, NF-κB p65 nuclear translocation and inflammatory responses. The expression levels of pro-inflammatory cytokine mRNA and proteins, such as TNFα, IL-1β 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-κB nuclear localization and activation.
authors: Central Laboratory, Shanghai Institute of Geriatrics, Huadong Hospital, Shanghai Medical College, Fudan University, 221 West Yan An Road, Shanghai 200040, PR China. qingweir@yahoo.com.cn
authors: Qingwei
authors: Q
authors: Ruan
authors: Fang
authors: F
authors: Liu
authors: Zhanjuan
authors: Z
authors: Gao
authors: Deqiu
authors: D
authors: Kong
authors: Xiaona
authors: X
authors: Hu
authors: Dongmei
authors: D
authors: Shi
authors: Zhijun
authors: Z
authors: Bao
authors: Zhuowei
authors: Z
authors: Yu
mesh_terms: D000375:Aging / Q000187:drug effects*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016922:Cellular Senescence; D016207:Cytokines / Q000378:metabolism; D005690:Galactose / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C050426:huperzine A; D005690:Galactose