Baiying qingmai formulation ameliorates thromboangiitis obliterans by inhibiting HMGB1/RAGE/NF-κB signaling pathways

Abstract

Baiying Qingmai Formulation (BF) is a classical clinical prescription used for decades to treat thromboangiitis obliterans (TAO). Although it effectively relieves pain and ischemic ulcers in patients with TAO, its anti-TAO mechanisms remain unclear. The chemical components of BF were analyzed using high-performance liquid chromatography and the potential targets of the compounds identified in BF were analyzed using molecular docking. Further, the signaling pathways and molecular mechanism of BF in treating TAO were studied using a rat model of TAO. Seven compounds (gallic acid, catechin, chlorogenic acid, caffeic acid, paeoniflorin, quercetin, and paeonol) were identified in BF, and molecular docking predicted their high affinities with HMGB1/RAGE/NF-κB proteins. In in vivo studies, BF not only inhibited the protein expression of HMGB1, RAGE, ICAM-1, and VCAM-1; mRNA levels of HMGB1 and RAGE; and the phosphorylation of NF-κB, ERK, Janus kinase (JNK) and p38 MAPK in the femoral artery, but also reduced the levels of inflammatory cytokines (IL-6, TNF-α, IL-1β, HMGB1) and stable metabolite (TXB2) of cytokine promoting thrombosis (TXA2) in the plasma. Moreover, BF stimulated the secretion of stable metabolite (6-keto-PGF1α) of cytokine inhibiting thrombosis (PGI2) in the plasma. BF inhibited the inflammatory response and thrombosis in the femoral artery, thus reducing the degree of vascular occlusion, which alleviated the symptoms in rats with TAO. Our findings suggest that BF ameliorates TAO by inhibiting the activation of the ERK, JNK, p38 MAPK and HMGB1/RAGE/NF-κB signaling pathways, thereby providing novel ideas for the treatment of TAO and essential information for the further development and utilization of BF as a promising drug to treat TAO.

Ethnobotanical Uses and Pharmacological Activities of Moroccan Ephedra Species

“…6 ). This is not surprising because these phenolic derivatives present high affinities for the different proteins of the HMGB1/RAGE/NF- κ B signaling pathway and gallic acid is known to reduce the risk of AGE-mediated cellular complications, preventing fibrosis induced by advanced glycation end products 126 , 127 , 128 .…”

Iliac crest bone distraction surgery for the treatment of thromboangiitis obliterans of lower limbs: A cohort-prospective preliminary study

“…The manifestation of resting pain, the underlying mechanisms of which are still incompletely understood, stands as a pivotal symptom in patients with TAO. Current literature presents several potential causative factors of rest pain, such as circulatory disorders, neuroin ammatory agents, in ammation-mediated vascular endothelial dysfunction, and other immunomodulated mechanisms [28][29][30]. The widely accepted view is that TAO is postulated as an immunomodulated disease due to abnormal immune system activation inducing in ammatory reactions, possibly contributing to pain generation [31,32].…”

“…Simultaneously, early initiation of the SDF-1/CXCR4 signaling axis is observed to modulate the migration, chemotaxis, and activation of immune cells [29,34]. Additionally, bone fractures may instigate the differentiation of bone marrow stem cells and induce the release of various growth factors and nutritional components.…”

Knowledge Mapping of Global Status and Trends for Thromboangiitis Obliterans: A Bibliometrics and Visual Analysis

“… 34 Zou C. et al concluded that Baiying qingmai formulation improves TAO by inhibiting activation of JNK, ERK, p38 MAPK, and HMGB1/RAGE/NF-κB signaling pathways. 35 As for rheumatology: there are 12.5% of patients with TAO who had joint problems in the pre-occlusive stage, they presented with recurrent episodes of large joints with signs of local inflammation (swelling due to stasis edema). At this stage, patients are likely to consult rheumatologists, so the differential diagnosis between TAO and rheumatism is very important.…”