Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1–STIM1 complex

Abstract

Background Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. Results In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. Conclusion These results indicated that resveratrol reduced store-operated Ca 2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1–STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis. Electronic supplementary material The online version of this article (10.1186/s40659-019-0250-7) contains supplementary material, which is available to authorized users.

Ellagic Acid Alleviates Rheumatoid Arthritis in Rats through Inhibiting MTA1/HDAC1-Mediated Nur77 Deacetylation

“…Emerging evidence indicated that FLSs exhibit abnormal proliferation and insufficient apoptosis, which drives Mediators of Inflammation synovial hyperplasia and inflammatory response in the pathophysiology of RA [3,4]. Current evidence indicated that natural products inhibited the biological behaviors of activated FLSs, which might provide new insights into the treatment of RA [5,17]. The natural polyphenol EA has been reported to have antioxidant, anti-inflammatory, and anticancer biological activities.…”

Resveratrol inhibits nicotine-induced conditioned place preference in mice

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Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports

“…Furthermore, 25 mg/kg of this compound can also decrease articular edema, NF-κB, and neutrophil elastase, and hence, diminish neutrophil extracellular traps, in RA rats, namely, by interfering with TLR-4, peptidyl arginine deiminase 4 enzyme and COX-2 [336]. Resveratrol at 45 mg/kg can also reduce store-operated Ca 2+ entry and enhance the apoptosis in an adjuvant arthritis rat model by targeting the ORAI1-STIM1 complex [329]. Additionally, Fernández-Rodríguez et al [330] reported that 12.5 mg/kg/day resveratrol can also induce the noncanonical autophagy pathway, reduce p62 expression, caspase-3 expression, and poly(ADP-ribose) polymerase, IL-1β, C-reactive protein, and prostaglandin E2, as well as NF-κB synovial tissue expression, which is correlated with p62 expression [330].…”