The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats
| Autor: | Fang Liu, Qingwei Ruan, Deqiu Kong, Zhijun Bao, Xiaona Hu, Zhuowei Yu, Dongmei Shi, Zhanjuan Gao |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Senescence
Male medicine.medical_specialty Aging medicine.medical_treatment Anti-Inflammatory Agents Pharmacology Biology medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Alkaloids Internal medicine medicine Animals Cholinergic anti-inflammatory pathway Huperzine A Cellular Senescence Inflammation NF-kappa B Galactose Acetylcholinesterase Rats IκBα Oxidative Stress Endocrinology Cytokine Neuroprotective Agents chemistry Liver Cholinergic Cytokines Reactive Oxygen Species Sesquiterpenes Oxidative stress Developmental Biology medicine.drug |
| Zdroj: | Mechanisms of ageing and development. 134(3-4) |
| ISSN: | 1872-6216 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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