Prevention of inflammation-mediated neurotoxicity by Rg3 and its role in microglial activation.
Considering the importance of inflammation and apoptosis in neurodegenerative conditions, the potential suppressive effects of the Rg3, a by-product obtained during the steaming of red ginseng, may indicate that Rg3 could provide a beneficial therapeutic approach to treating or preventing neurodegenerative disease. We investigated the effect of Rg3 on Abeta42-mediated microglial activation and inflammation-mediated neurotoxicity in murine BV-2 microglial and Neuro-2a neuroblastoma cells, respectively. Rg3 effectively reduced inflammatory cytokine expression in Abeta42-treated BV-2, and inhibited the binding of NF-kappaB p65 to its DNA consensus sequences, and significantly reduced the expression of TNF-alpha in activated microglia. Pretreatment with Rg3 increased the survival rate of Neuro-2a exposed to TNF-alpha. These observations suggest that Rg3 reduced neurotoxicity by inhibiting chronic inflammation through the suppression of activated microglia. In addition, the expression of pro-inflammatory cytokines in BV-2 stimulated by Abeta42 was decreased but not eliminated by Rg3 when binding to the macrophage scavenger receptor type A (MSRA) was blocked with fucoidan. This implies that the inflammatory response may not be exclusively triggered via MSRA. More interestingly, iNOS was almost completely inhibited in the presence of Rg3 when MSRA binding was blocked with fucoidan. Moreover, Rg3 increased the expression of MSRA in BV-2 transfected with siRNA targeting MSRA mRNA, and this increased MSRA expression may play a role in the phagocytosis of Abeta42 peptides. Our results indicate that inhibition of the inflammatory repertoire of microglia, neuroprotection, and increased MSRA expression induced by Rg3 may at least partly explain its therapeutic effects in chronic neurodegenerative diseases.
Joo
Seong Soo
SS
Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea. larryjoo@hanmail.net
Yoo
Yeong Min
YM
Ahn
Byung Woo
BW
Nam
Sang Yun
SY
Kim
Yun-Bae
YB
Hwang
Kwang Woo
KW
Lee
Do Ik
DI
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000633:toxicity; D004797:Enzyme-Linked Immunosorbent Assay; D036145:Ginsenosides / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology* / Q000517:prevention & control*; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000473:pathology* / Q000517:prevention & control*; D005894:Panax / Q000737:chemistry; D011134:Polysaccharides / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D036145:Ginsenosides; D011134:Polysaccharides; D034741:RNA, Small Interfering; C097367:ginsenoside Rg3; C007789:fucoidan