Protection of Proanthocyanidins Against HSP Serum-Induced Inflammation and Oxidative Stress on Human Umbilical Vein Endothelial Cells

Background: Immune-mediated inflammation and oxidative stress play pivotal roles in Henoch-Schonlein purpura (HSP), primarily through the TLR4/MyD88/NF-κB pathway.Proanthocyanidins (PCs) exert anti-inflammatory and antioxidant effects by regulating some signals like TLR4/MyD88/NF-κB.Previous research uncovered that PCs could alleviate purpura-like lesions and pathological changes on rats likely through attenuating inflammation and OS damage.The mechanism of PCs on HSP deserves further investigation.Objective: To clarify the potential mechanism of PCs to HUVECs induced by the serum of HSP patients.Methods: HUVECs were randomly divided into blank, control, model, and low-, medium-, and high-concentration PCs group.Then, 25% HSP serum was assigned to the latter four groups, while 25% serum from healthy subjects to control group and serum-free culture medium to blank one.The last three groups separately received different concentrations of PCs.In addition, TAK-242, a TLR4 inhibitor, was applied to investigate the effect of TLR4-related signals in PCs against HSP serum-induced damage.Finally, inflammatory and OS-related parameters were detected by using cytological/molecular-biological techniques.Results: Treated with HSP serum later, the levels of immuno-inflammatory and oxidative indicators obviously went up (P < 0.05), and those of antioxidants remarkably went down (P < 0.05).PCs, however, reversed above phenomena (P < 0.05).Moreover, TLR4, MyD88 and NF-κB proteins/genes highly expressed in the model group; but significantly fell off in the presence of PCs (P < 0.05).Amazingly, all of above indicators showed no significant difference among the groups of different PCs concentrations (P > 0.05).These alterations likewise occurred after TAK-242 pretreatment with or without PCs, ie a notable drop of TLR4, MyD88 and NF-κB appeared in TAK-242 presence, few differences existing when compared to the PCs groups.Conclusion: PCs effectively protect HUVECs from inflammatory and OS damage provoked by HSP serum via blocking TLR4/ MyD88/NF-κB signals.