PMID- 23313706
OWN - NLM
STAT- MEDLINE
DCOM- 20130930
LR  - 20220318
IS  - 1872-6216 (Electronic)
IS  - 0047-6374 (Linking)
VI  - 134
IP  - 3-4
DP  - 2013 Mar
TI  - The anti-inflamm-aging and hepatoprotective effects of huperzine A in 
      D-galactose-treated rats.
PG  - 89-97
LID - S0047-6374(12)00182-0 [pii]
LID - 10.1016/j.mad.2012.12.005 [doi]
AB  - 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 alpha-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-kappaB) 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, IkappaBalpha degradation, NF-kappaB p65 nuclear 
      translocation and inflammatory responses. The expression levels of 
      pro-inflammatory cytokine mRNA and proteins, such as TNFalpha, IL-1beta 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-kappaB nuclear localization and 
      activation.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Ruan, Qingwei
AU  - Ruan Q
AD  - 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
FAU - Liu, Fang
AU  - Liu F
FAU - Gao, Zhanjuan
AU  - Gao Z
FAU - Kong, Deqiu
AU  - Kong D
FAU - Hu, Xiaona
AU  - Hu X
FAU - Shi, Dongmei
AU  - Shi D
FAU - Bao, Zhijun
AU  - Bao Z
FAU - Yu, Zhuowei
AU  - Yu Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130108
PL  - Ireland
TA  - Mech Ageing Dev
JT  - Mechanisms of ageing and development
JID - 0347227
RN  - 0 (Alkaloids)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesquiterpenes)
RN  - 0111871I23 (huperzine A)
RN  - X2RN3Q8DNE (Galactose)
SB  - IM
MH  - Aging/*drug effects
MH  - Alkaloids/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cellular Senescence
MH  - Cytokines/metabolism
MH  - Galactose/*metabolism
MH  - Inflammation/metabolism
MH  - Liver/*drug effects/metabolism
MH  - Male
MH  - NF-kappa B/metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - Oxidative Stress
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Sesquiterpenes/*pharmacology
EDAT- 2013/01/15 06:00
MHDA- 2013/10/01 06:00
CRDT- 2013/01/15 06:00
PHST- 2012/05/16 00:00 [received]
PHST- 2012/11/30 00:00 [revised]
PHST- 2012/12/11 00:00 [accepted]
PHST- 2013/01/15 06:00 [entrez]
PHST- 2013/01/15 06:00 [pubmed]
PHST- 2013/10/01 06:00 [medline]
AID - S0047-6374(12)00182-0 [pii]
AID - 10.1016/j.mad.2012.12.005 [doi]
PST - ppublish
SO  - Mech Ageing Dev. 2013 Mar;134(3-4):89-97. doi: 10.1016/j.mad.2012.12.005. Epub 
      2013 Jan 8.