Comparison of inhibitory potency of three different curcuminoid pigments on nitric oxide and tumor necrosis factor production of rat primary microglia induced by lipopolysaccharide.
Microglia are the resident innate immune cells in the central nervous system. Evidence supports that the unregulated activation of microglia results in the production of pro-inflammatory cytokines and chemokines that propagate neuronal injury and finally cause neurodegenerative diseases. Curcuminn (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are curcuminoid pigments extracted from turmeric (Curcuma longa L.). Cur has been reported to suppress the activation of microglia by reducing toxic factors production, but little is known about whether the two natural demethoxy derivatives of Cur, DMC and BDMC, have the similar effects as Cur. In the present study, we found that all of the three curcuminoid pigments significantly suppressed nitric oxide (NO) production by LPS-activated microglia and the relative potency was DMC>BDMC>Cur. This result was verified by RT-PCR analysis of iNOS mRNA. The NO-scavenging abilities of three curcuminoid pigments are very weak, which suggested that the indirect effect may not be critical in inhibiting NO production by LPS-activated microglia. Moreover, these three curcuminoid pigments attenuated the expression of mRNA and proteins of tumor necrosis factor-alpha (TNF-alpha) in a concentration-dependent manner and the relative potency was also DMC>BDMC>Cur. In conclusion, Cur, DMC and BDMC were found as potent microglia-activation inhibitors, and DMC exhibited the strongest inhibitory activity on NO and TNF-alpha production. These results provided an interesting clue for designing new compounds which could have better potential therapeutic implications for various neurodegenerative diseases.
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, PR China.
Li Jia
LJ
Zhang
Chun Fu
CF
Wu
Xue Lian
XL
Meng
Dan
D
Yuan
Xu Dong
XD
Cai
Qi Long
QL
Wang
Jing Yu
JY
Yang
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D036381:Diarylheptanoids; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D036381:Diarylheptanoids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C034786:bisdemethoxycurcumin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D003474:Curcumin; C050229:demethoxycurcumin