Polydatin inhibits mast cell-mediated allergic inflammation by targeting PI3K/Akt, MAPK, NF-κB and Nrf2/HO-1 pathways

Abstract

Polydatin(PD) shows anti-allergic inflammatory effect, and this study investigated its underlying mechanisms in in vitro and in vivo models. IgE-mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) models were used to confirm PD effect in vivo. Various signaling pathway proteins in mast cell were examined. RT-PCR, ELISA and western blotting were applied when appropriate. Activity of Lyn and Fyn kinases in vitro was measured using the Kinase Enzyme System. PD dose-dependently reduced the pigmentation of Evans blue in the PCA model and decreased the concentration of serum histamine in PSA model, and attenuated the degranulation of mast cells without generating cytotoxicity. PD decreased pro-inflammatory cytokine expression (TNF-α, IL-4, IL-1β, and IL-8). PD directly inhibited activity of Lyn and Syk kinases and down-regulated downstream signaling pathway including MAPK, PI3K/AKT and NF-kB. In addition, PD also targets Nrf2/HO-1 pathway to inhibit mast cell-derived allergic inflammatory reactions. In conclusion, the study demonstrates that PD is a possible therapeutic candidate for allergic inflammatory diseases. It directly inhibited activity of Lyn and Syk kinases and down-regulates the signaling pathway of MAPK, PI3K/AKT and NF-κB, and up-regulates the signaling pathway of Nrf2/HO-1 to inhibit the degranulation of mast cells.

Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats

“…19 Also, the property of PD on Nrf2 activation has been proved in different diseases models but not IVDD. [20][21][22] In this study, we report that PD exerts properties of antisenescence and anti-ECM catabolism in NPCs treated with TNF-α. Further, we discover that PD decreases the ROS production and protects NPCs from mitochondrial dysfunction induced by TNF-α.…”

“…Similar to RSV structurally, PD possesses multiple pharmacological properties of antioxidation, anti‐inflammation and antitumour . Also, the property of PD on Nrf2 activation has been proved in different diseases models but not IVDD …”

Polydatin ameliorates pulmonary fibrosis by suppressing inflammation and the epithelial mesenchymal transition via inhibiting the TGF-β/Smad signaling pathway

“…Specially, the level of pro-inammatory factor (TNF-a) was strongly reduced by PD, this was in accordance with many other reports. 10,33,34 Besides, the adding of TNF-a counteracted PD-induced NLRP3 inammasome inactivation via enhancing NF-kB pathway. 35 These researches hent that PD may interact with TNF-a.…”

“…Polydatin (3,4 0 ,5-trihydroxystibene-3-b-mono-D-glucoside; PD), is a natural component extracted from perennial herb Polygonum cuspidatum and a traditional Chinese herbal medicine. 10 Previous studies indicated that PD exerted multiple biological activities including anti-inammation and antioxidation. Chen reported that PD attenuated kidney inammation by inhibiting NF-kB/NLRP3 inammasome activation.…”

NF‐κB activation mediates LPS‐or zymosan‐induced hypotension and inflammation reversed by BAY61‐3606, a selective Syk inhibitor, in rat models of septic and non‐septic shock

“…Likewise, Hossen et al has shown that Src and Syk are likely to bridge TLR stimulation with NF‐κB activation. Ye et al has also reported that the possible underlying mechanism of the antiallergic effect exerted by polydatin (PD) in allergic inflammatory diseases demonstrated that these effects of PD seem to depend on direct inhibition of Syk kinase activity and down‐regulation of the NF‐κB signalling pathway. In the light of all these reports together with our findings, it can be claimed that Syk activation seems to be critical not only for NF‐κB activation but also for the modulation of transactivation of this transcription factor.…”