Inhibition of monosodium urate crystal-induced inflammation by withaferin A.
OBJECTIVE
Gouty arthritis is a characteristically intense acute inflammatory reaction resulting from the formation of sodium urate crystals in the joint cavity. In the present study, the effect of withaferin A, a steroidal lactone was investigated on monosodium urate crystal-induced inflammation in mice; an experimental model for gouty arthritis and compared it with that of the non-steroidal anti-inflammatory drug, indomethacin.


METHODS
Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-alpha were determined in control and monosodium urate crystal-induced mice. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL).


RESULTS
Paw volume, the levels of lysosomal enzymes, lipid peroxidation, and inflammatory mediator tumour necrosis factor-alpha were found to be increased significantly and the activities of antioxidant status were in turn decreased in monosodium urate crystal-induced mice; however these changes were reverted back to near normal levels in withaferin A (30 mg/kg/b.wt, i.p.) treated monosodium urate crystal-induced mice. In addition, beta-glucuronidase and lactate dehydrogenase level were reduced in withaferin A (100microg/ml) treated monosodium urate crystal-incubated polymorphonuclear leucocytes.


CONCLUSIONS
The present findings clearly indicated that withaferin A exerted a strong anti-inflammatory effect against gouty arthritis.
Sabina
Evan Prince
EP
1School of Biotechnology, Chemical and Biomedical engineering, VIT University Vellore - 632 014, Tamil Nadu, India.
Chandal
Sonal
S
Rasool
Mahaboob Khan
MK
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D004195:Disease Models, Animal; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D007213:Indomethacin / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D016898:Interferon-alpha / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D014527:Uric Acid; D054358:Withanolides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016898:Interferon-alpha; D054358:Withanolides; D014527:Uric Acid; C009684:withaferin A; D007213:Indomethacin; D004875:Ergosterol