Vitexin alleviates interleukin‐1β‐induced inflammatory responses in chondrocytes from osteoarthritis patients: Involvement of HIF‐1α pathway

Abstract

It has been reported that vitexin has anti‐inflammatory effects in osteoarthritis (OA) rats. However, the effects of vitexin on interleukins‐1β (IL‐1β)‐stimulated OA patient‐derived chondrocytes have not been reported. The purpose of this study was to investigate the anti‐inflammatory effects of vitexin on IL‐1β‐stimulated human osteoarthritis chondrocytes and to reveal the involvement of hypoxia‐inducible factor 1α (HIF‐1α) pathway. Enzyme‐linked immunosorbent assay, quantitative real‐time PCR and Western blotting assays were employed. ELISA results demonstrated that the proinflammatory cytokine levels of interleukins‐6 (IL‐6) and tumour necrosis factor α (TNF‐α) in the serum and synovial fluid and HIF‐1α level in the synovial fluid were significantly elevated in OA patients compared to normal healthy subjects. Moreover, the Western blotting results indicated that the protein expression of HIF‐1α was significantly higher in the cartilage tissues of OA patients. OA patient‐derived chondrocytes were stimulated by IL‐1β and treated with different concentration of vitexin for 24 hours. Vitexin showed no cytotoxicity and increased the survival of chondrocytes under IL‐1β stimulation. Vitexin suppressed IL‐1β‐induced production of NO and prostaglandin E2 (PGE2) in chondrocytes culture. The treatment of vitexin significantly inhibited IL‐1β‐induced expressions of proinflammatory cytokine levels of IL‐6, TNF‐α, matrix metalloproteinase (MMP)‐1, MMP‐3 and MMP‐13. Furthermore, Western blotting results demonstrated that HIF‐1α is involved in vitexin's protective effects on IL‐1β‐stimulated injuries in OA patient‐derived chondrocytes. Our study demonstrates that vitexin alleviates IL‐1β‐induced inflammatory responses in chondrocytes from osteoarthritis patients, which may be attributed partly to the inhibition of HIF‐1α pathway.

Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development

“…Vitexin, a flavone C-glycoside (5,7,4-trihydroxyflavone-8-glucoside) found in medicinal and other plants, presents anti-inflammatory activities by preventing the oxidative stress, inhibiting pro-inflammatory cytokines production, and increasing the anti-inflammatory cytokine IL-10 [38]. Vitexin inhibited the production of TNF-α, IL-6, nitric oxide (NO), and PGE 2 in human osteoarthritis chondrocytes [110]. Furthermore, vitexin prevents mast cells degranulation [111], reduces the production of pro-inflammatory mediators by neutrophils [112,113] and macrophages [113].…”

Multitargeted Effects of Vitexin and Isovitexin on Diabetes Mellitus and Its Complications

“…In both in vivo and in vitro models, vitexin and 2″-O-α-L-rhamnopyranosyl vitexin treatment suppressed the secretion of activator-inflammatory cytokines TNF, IL-6, and IL-1β proteins' content compared with controls [5,55,97,[100][101][102][103]. Yang et al [104] suggested that the vitexin inhibitory effect on IL-1β-induced inflammatory responses and may be attributed partly to the inhibition of the HIF-1α pathway. In the inflammation model, vitexin exhibited pronounced activity in blocking the expression of TNF-α and the subsequent neutrophil activation [74,105,106].…”

Relationship Between Magnetic Resonance T2-Mapping and Matrix Metalloproteinase 1,3 in Knee Osteoarthritis

“…At present, there are reported clinical cases of applying MMPS inhibitors in treating OA [ 24 , 25 ], the underlying mechanism of which is to inhibit the inflammation of articular cartilage and the degradation of cartilage by reducing the production of MMPS, thereby inhibiting inflammation and degradation of articular cartilage. Hence, achieving better protection of chondrocytes, improved outcome of clinical symptoms; helping with the ease and repair of inflammation.…”