Proanthocyanidins: A novel approach to Henoch‑Schonlein purpura through balancing immunity and arresting oxidative stress via TLR4/MyD88/NF‑κB signaling pathway (Review)

Abstract

Henoch-Schonlein purpura (HSP), a recurrent and immunoglobulin (Ig)A-mediated vasculitis, presents not only as skin lesions but also as systemic involvement that can be life-threatening. Although the etiology of HSP remains unknown, immune imbalance and oxidative stress (OS) are primary contributors to its pathogenesis, alongside the abnormal activation of Toll-like receptor (TLR)/myeloid differentiation primary response gene 88 (MyD88)/nuclear factor-κB (NF-κB) pathway. TLRs, especially TLR4, stimulate downstream signaling molecules such as NF-κB and proinflammatory cytokines, which are released when TLRs combine with the key adapter molecule MyD88. This leads to the activation of T helper (Th) cell 2/Th17 and overproduction of reactive oxygen species (ROS). The function of regulatory T (Treg) cells is suppressed in the process. Th17/Treg imbalance then produces various inflammatory cytokines to promote proliferation and differentiation of B cells and the secretion of antibodies. IgA is secreted, and it binds to vascular endothelial surface receptors where the complex induces injury of the vascular endothelial cells. Additionally, excessive ROS creates OS that leads to an inflammatory response and vascular cell apoptosis or necrosis, thereby contributing to vascular endothelial damage and HSP occurrence. Proanthocyanidins are active compounds naturally enriched in fruits, vegetables and plants. Proanthocyanidins have diverse properties, including anti-inflammatory, antioxidant, antibacterial, immunoregulatory, anticarcinogenic and vascular protective effects. Proanthocyanidins are used in the management of various diseases. Proanthocyanidins regulate T cells, equilibrate immunity and arrest OS by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Considering the pathogenesis of HSP and the properties of proanthocyanidins, the present study hypothesized that these compounds may potentially lead to HSP recovery through modulating the immune equilibrium and preventing OS by inhibiting the TLR4/MyD88/NF-κB pathway. To the best of our knowledge, however, little is known about the positive effects of proanthocyanidins against HSP. The present review summarizes the potential of proanthocyanidins to treat HSP.

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

“…Then TLR4, by binding to MyD88, excites downstream NF-κB signaling pathway to encourage inflammatory factors release and ROS production, further irritating inflammatory responses and OS occurrence. 30 , 58 Above molecular events in turn exacerbate vascular endothelial cells injury and vascular permeability, eventually lead to the onset of HSP. 45 , 57 , 59 These confirm the importance of TLR4/MyD88 /NF-κB in HSP pathogenesis.…”

“… 11 , 28 , 29 Given that the functions of PCs and the pathogenesis of HSP, PCs would be a promising treatment for HSP. 30 However, reports about PCs treating HSP scarcely exist. In the previous study, we initially revealed that PCs obviously relieved the clinical and pathological lesions of HSP-like rats, decreased the levels of inflammatory factors, ROS and MDA, and increased those of CAT, SOD and GSH, possibly involving the attenuation of inflammatory reaction and oxidative damage (as a separate paper to publish).…”