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

Abstract

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.

Keywords:

• proanthocyanidins
• Henoch-schönlein purpura
• TLR4/MyD88/NF-κB
• inflammation
• oxidative stress

Data Sharing Statement

The data used to support the findings of this study are included within the article.

Ethics Statement

This research was carried out following the ethical rules of the Declaration of Helsinki and was approved by the Clinical Trial Ethics Committee of the Affiliated Hospital of Southwest Medical University, with approval number KY2024088. All participants received detailed information about the study’s aims, methods, and potential benefits before joining.

Acknowledgments

We sincerely acknowledge the clinical medical research center of the Affiliated Hospital of Southwest Medical University for their support for our work. We highly appreciate all persons for their help in this manuscript.

Disclosure

The authors declare that they have no conflicts of interest.

Additional information

Funding

This study was supported by the grants from Health Commission of Sichuan Province [grant number 18PJ411] and Luzhou Science and Technology Bureau [grant number 2023JYJ039].