Toxicol Res.  2013 Sep;29(3):195-201.

Anti-inflammatory Effect of Isaria sinclairii Glycosaminoglycan in an Adjuvant-treated Arthritis Rat Model

• Ahn MY
• Jee SD
• Hwang JS
• Yun EY
• Ahn KS
• Kim YS

Abstract

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-kappaB activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin E2-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-alpha production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

Keyword

Isaria sinclairii; Glycosaminoglycan; Inflammation

MeSH Terms

Acetates
Animals
Arthritis*
Atherosclerosis
Cartilage
Cartilage, Articular
Edema
Freund's Adjuvant
Ganglia, Spinal
Human Umbilical Vein Endothelial Cells
Indomethacin
Inflammation
Jurisprudence
Methanol
NF-kappa B
Rats*
Tumor Necrosis Factor-alpha
Up-Regulation
Vascular Endothelial Growth Factor A
Acetates
Freund's Adjuvant
Indomethacin
Methanol
NF-kappa B
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A