Abstract
Arthritis is a chronic inflammatory disease accompanied by pathological reactions such as swelling, redness, fever, and pain in various joint areas. The drugs currently available to treat arthritis are associated with diverse side-effects. Therefore, there is a need for safer and more effective treatments to alleviate the inflammation of arthritis with fewer side-effects. In this study, a new sterol, Δ8(14)-ergostenol, was discovered, and its glycosides were synthesized and found to be more efficient in terms of synthesis or anti-inflammatory activity than either spinasterol or 5,6-dihydroergosterol is. Among these synthetic glycosides, galactosyl ergostenol inhibited the expression of inflammatory mediators in TNF-α-stimulated FLS and TNF-α-induced MMPs and collagen type II A1 degradation in human chondrocytes. These results suggest the new galactosyl ergostenol as a treatment candidate for arthritis.
Keywords:
arthritis; collagen type II A1; ergostenol; ergostenol glycosides; matrix metalloproteinase.
MeSH terms
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology*
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Cell Line
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Cell Survival / drug effects
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Chondrocytes / cytology
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Chondrocytes / drug effects*
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Chondrocytes / metabolism
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Collagen Type II / genetics
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Collagen Type II / metabolism
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Ergosterol / chemistry
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Ergosterol / pharmacology*
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Gene Expression Regulation / drug effects*
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Glycosides / chemical synthesis
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Glycosides / pharmacology*
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Humans
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Inflammation / prevention & control
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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Matrix Metalloproteinases / genetics
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Matrix Metalloproteinases / metabolism
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Models, Biological
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Signal Transduction
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Synoviocytes / cytology
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Synoviocytes / drug effects*
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Synoviocytes / metabolism
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Anti-Inflammatory Agents
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COL2A1 protein, human
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CXCL8 protein, human
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Collagen Type II
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Glycosides
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IL1B protein, human
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IL6 protein, human
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Interleukin-1beta
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Interleukin-6
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Interleukin-8
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Tumor Necrosis Factor-alpha
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NOS2 protein, human
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Nitric Oxide Synthase Type II
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Matrix Metalloproteinases
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Ergosterol