Kinsenoside isolated from Anoectochilus formosanus suppresses LPS-stimulated inflammatory reactions in macrophages and endotoxin shock in mice.
In the present study, we reported that kinsenoside, a major component of Anoectochilus formosanus, inhibited inflammatory reactions in mouse peritoneal lavage macrophages and protects mice from endotoxin shock. In LPS-stimulated mouse peritoneal lavage macrophages, kinsenoside inhibited the inflammatory mediators, such as nitric oxide, TNF-[alpha], IL-1[beta], monocyte chemoattractant protein 1, and macrophage migration inhibitory factor production. Furthermore, kinsenoside decreased the formation of a nuclear factor [kappa]B-DNA complex and nuclear p65 and p50 protein levels. Kinsenoside inhibited nuclear factor [kappa]B translocation through both I[kappa]B[alpha]-dependent and -independent pathway. In contrast, it stimulated anti-inflammatory cytokine IL-10 generation and enhanced the mRNA expression of IL-10 and suppressor of cytokine signaling 3 in the same cells induced by LPS. In an animal model, both pretreatment and posttreatment of kinsenoside increased the survival rate of ICR mice challenged by LPS (80 mg/kg, i.p.). Pretreatment with kinsenoside decreased serum levels of TNF-[alpha], IL-1[beta], IL-10, monocyte chemoattractant protein 1, and migration inhibitory factor at 1 h after sublethal dose of LPS (40 mg/kg, i.p.) in mice. In contrast, kinsenoside enhanced serum IL-10 level at 24 h after LPS injection in mice. In conclusion, kinsenoside inhibited the production of inflammatory mediators and enhanced anti-inflammatory cytokine generation. Therefore, kinsenoside can alleviate acute inflammatory hazards.
Hsiao
Hung-Bo
HB
Department of Life Science, National Chung Hsing University, Taichung, Taiwan.
Wu
Jin-Bin
JB
Lin
Ho
H
Lin
Wen-Chuan
WC
D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009005:Monosaccharides / Q000737:chemistry / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
C422363:3-glucopyranosyloxybutanolide; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009005:Monosaccharides; D016328:NF-kappa B; D015107:4-Butyrolactone