Inhibitory effects of Angelica sinensis ethyl acetate extract and major compounds on NF-kappaB trans-activation activity and LPS-induced inflammation.
OBJECTIVE
Previous study showed that the ethyl acetate (EtOAc) fraction from Angelica sinensis (Oliv.) Diels (Apiaceae) (AS) inhibited nitric oxide (NO) and prostaglandin E(2) secretions in vitro. This study was to evaluate anti-inflammatory activity of AS EtOAc extract and its major compounds in vivo and in vitro.


METHODS
NF-kappaB luciferase activity and pro-inflammatory cytokine secretions from lipopolysaccharide (LPS) plus interferon (IFN)-gamma-stimulated RAW 264.7 cells pre-treated with EtOAc extract or compounds were analyzed. For further in vivo study, BALB/c mice were tube-fed with 1.56 (AS1 group), 6.25 (AS2 group) mg/kg body weight/day in 100 microl soybean oil, while the control and PDTC (pyrrolidine dithiocarbamate, an anti-inflammatory agent) groups were tube-fed with 100 microl soybean oil/day only. After 1 week of tube-feeding, the PDTC group was injected with 50 mg/kg BW PDTC and 1 h later, all of the mice were injected with 15 mg/kg BW LPS. The pro-inflammatory cytokine levels and lifespan of LPS-challenged mice were determined.


RESULTS
The results showed that AS EtOAc extract significantly inhibited NF-kappaB luciferase activity and TNF-alpha, IL-6, macrophage inflammatory protein-2 (MIP-2) and NO secretions from LPS/IFN-gamma-stimulated RAW 264.7 cells. The AS1 and PDTC groups, but not AS2, had significantly higher survival rate than the control group. This was characterized by the inhibition of the serum TNF-alpha and IL-12p40 levels after LPS injection (p<0.05). The major compounds of AS, ferulic acid and Z-ligustilide, also significantly decreased NF-kappaB luciferase activity, which may contribute to the anti-inflammatory activity of AS.


CONCLUSIONS
Low dose of AS EtOAc extract that inhibits the production of inflammatory mediators alleviates acute inflammatory hazards and protect mice from endotoxic shock.
Chao
Wen-Wan
WW
Department of Biochemical Science and Technology, Institute of Microbiology and Biochemistry, National Taiwan University, Taipei, Taiwan, ROC.
Hong
Yong-Han
YH
Chen
Miaw-Ling
ML
Lin
Bi-Fong
BF
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D003373:Coumaric Acids / Q000494:pharmacology; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D003373:Coumaric Acids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C027820:ligustilide; C004999:ferulic acid; D008156:Luciferases; D015107:4-Butyrolactone