Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Osteoarthritis (OA), characterized by progressive destruction of articular cartilage, is the most common form of human arthritis. Wogonin is a naturally occurring flavonoid found in root extract of Scutellaria baicalensis, and it has been shown to exhibit diverse biological activities. Here, we evaluated the potential anti-inflammatory and chondroprotective effects of Wogonin in IL-1β stimulated human OA chondrocytes.
Results: Wogonin completely suppressed the IL-1β-induced mRNA and protein expression of COX2, IL-6, iNOS, MMP-3, MMP-9, MMP-13, and ADAMTS-4 in human OA chondrocytes. Further, Wogonin significantly inhibited the NO and PGE2 production in IL-1β-stimulated human OA chondrocytes. Interestingly, Wogonin treatment increased the expression of type II collagen (COL2A1) and aggrecan (ACAN) in IL-1β-treated OA chondrocytes. Wogonin modulated the expression of IL-1β-induced phosphorylation of MAPKs (ERK1/2, JNK, and P38) in OA chondrocytes. Additionally, Wogonin activated redox sensitive transcription factor Nrf2, which has been shown to possess major chondroprotective role. Further, Wogonin upregulated the expression of Nrf2-dependent cytoprotective gene HO-1 in human OA chondrocytes. Inhibition of activity or knockdown of HO-1 expression abrogated the chondroprotective effect of Wogonin in IL-1β-stimulated human OA chondrocytes. Cellular uptake studies showed that Wogonin levels increased in a time dependent manner indicating the absence of metabolism of Wogonin in human OA chondrocytes. These data indicate that increased intracellular accumulation in due course of time activate Nrf2/HO-1 axis that may be responsible for the observed anti-inflammatory and chondroprotective activity of Wogonin under pathological conditions.
Conclusion: The present study suggests that Wogonin could be an effective chondroprotective and anti-inflammatory agent as it switched the chondrocyte gene expression from catabolic towards anabolic response and this effect was mediated, at least in part by the activation of Nrf2 and upregulation of HO-1 expression in OA chondrocytes.
To cite this abstract in AMA style:Khan MN, Haseeb A, Haynie S, Haqqi TM. Wogonin, a Plant-Derived Flavonoid, Exert Anti-Inflammatory and Chondroprotective Effects through the Activation Nrf2/HO-1 Signaling in Human OA Chondrocytes [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/wogonin-a-plant-derived-flavonoid-exert-anti-inflammatory-and-chondroprotective-effects-through-the-activation-nrf2ho-1-signaling-in-human-oa-chondrocytes/. Accessed .
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/wogonin-a-plant-derived-flavonoid-exert-anti-inflammatory-and-chondroprotective-effects-through-the-activation-nrf2ho-1-signaling-in-human-oa-chondrocytes/