Isovitexin Depresses Osteoarthritis Progression via the Nrf2/NF-κB Pathway: An in vitro Study

Abstract

Purpose Osteoarthritis (OA) is a multifactorial joint disease and inflammatory processes contribute to joint destruction. Isovitexin (IVX) is a flavone component found in passion flower, Cannabis and, and the palm that is known for its anti-inflammatory properties. Materials and Methods This study investigated in vitro the role and underlying mechanism used by IVX in its regulation of OA development. Effects of IVX on the viability of chondrocytes were measured by CCK-8 assays. The phenotypes of extracellular matrix (ECM) degeneration and inflammation were measured by qPCR, Western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and Western blot. Molecular docking was applied to predict the interacting protein of IVX, while Nrf2 was knocked down by siRNAs to confirm its role. Results We demonstrated that IVX suppressed ECM degeneration and suppressed pro-inflammatory factors in IL-1β-treated chondrocytes. Additionally, IVX impact on NF-κB signaling in IL-1β-exposed chondrocytic cells; Mechanistically, it was also demonstrated in molecular docking and knock down studies that IVX might bind to Nrf2 to suppress NF-κB pathway. Conclusion Our data suggest that IVX halts OA disease advancement through the Nrf2/NF-κB axis, suggesting a possibility of IVX as a target for OA therapy.

Isovitexin alleviates acute gouty arthritis in rats by inhibiting inflammation via the TLR4/MyD88/NF-κB pathway

“…Previous study indicated that isovitexin suppresses NF-κB pathway in osteoarthritis (Hu et al. 2021 ). In our study, isovitexin can significantly inhibit the expression of TLR4 protein in the synovium of rats with acute gout, and can also significantly antagonize the expression of NF-κB p65 in the synovium.…”

“…Recent results indicate that isovitexin could suppress osteoarthritis progression (Hu et al. 2021 ). Isovitexin has the advantages of easy extraction, high content and stable performance, which is expected to become an alternative drug for biodiversity (Liu et al.…”

Carbon dots derived from folic acid attenuates osteoarthritis by protecting chondrocytes through NF-κB/MAPK pathway and reprogramming macrophages

“…In agreement with previous studies [ 48 , 49 ], excessive oxidative stress induced by IL-1β in this study significantly activated Nrf2 signaling in primary chondrocytes. Most published studies suggested Nrf2 signaling activation relates with its protective ability to inflammatory responses [ 50 – 52 ]. Nevertheless, we found that CDs inhibited the activation of Nrf2 signaling and HO-1 expression.…”

Natural compounds protect against the pathogenesis of osteoarthritis by mediating the NRF2/ARE signaling

“…In addition, Moracin ( 3 , isolated from Cortex Mori. Radicis, Moraceae ), Isovitexin ( 4 , isolated from the passion flower ( Passiflora edulis Sims, Passifloraceae ), Cannabis ( Cannabis sativa L., Moraceae ), and palm ( Elaeis guineensis Jacq., Arecaceae )), Eriodictyol ( 5 , isolated from citrus fruits ( Citrus reticulata Blanco, Rutaceae )), Licochalcone A (Lico A, 6 , isolated from the licorice root ( Glycyrrhiza uralensis Fisch., Leguminosae )), and Epigallocatechin-3-O-gallate (EGCG, 7 , isolated from tea leaves) exhibit similar effects against inflammatory responses by activating the NRF2 signaling in OA chondrocytes ( Jia et al, 2017 ; Wang Y. et al, 2018 ; Zhou et al, 2020 ; Hu et al, 2021 ; Zhu et al, 2022a ) ( Tables 1 , 2 ). In addition, EGCG (100 μM) also suppresses the JNK/MAPK signaling and inhibits inflammatory responses in IL-1β-treated human chondrocytes ( Akhtar and Haqqi, 2011 ).…”