Proanthocyanidins as a Potential Novel Way for the Treatment of Hemangioma.

Ran Tang,Shihong Pan,Dehai Xian,Jianqiao Zhong,Jixiang Xu,Huiling Peng,Yanming Xu

doi:10.1155/2021/5695378

Abstract

Hemangioma, the most common benign vascular tumor, not only affects the appearance and psychology but also has a life-threatening potential. It is considered that clonal vascular endothelial cell proliferation and excessive angiogenesis are responsible for hemangioma pathogenesis, in which abnormal cytokines/pathways are closely implicated, primarily including high expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) as well as their downstream pathways, especially phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt). These further stimulate the migration and proliferation of vascular endothelial cells and promote the formation of new vessels, ultimately leading to the occurrence and development of hemangioma. Proanthocyanidins are naturally active substance from plants and fruits. They possess multiple functions like antiproliferation, antiangiogenesis, and antitumor. It has been demonstrated that proanthocyanidins effectively work in various diseases via inhibiting the expression of various factors, e.g., HIF-1α, VEGF, PI3K, and Akt. Considering the pathogenesis of hemangioma and the effect of proanthocyanidins, we hold a hypothesis that proanthocyanidins would be applied in hemangioma via downregulating cytokine/pathway expression, suppressing vascular cell proliferation and arrest abnormal angiogenesis. Taken together, proanthocyanidins may be a potential novel way for the treatment of hemangioma.

Highlights

Hemangioma, a common benign vascular tumor, is closely associated with excessive angiogenesis/vasculogenesis that early emerges from childhood
The exact etiology of hemangioma still keeps unclear, emerging evidence indicates that hypoxia-induced vascular endothelial cell proliferation and abnormal angiogenesis are mainly involved in hemangioma
Several reports have implied that hypoxiainducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), highly expressing in hemangioma, are major two contributors to vascular endothelial cell proliferation and abnormal angiogenesis [9,10,11]

Summary

Introduction

Hemangioma, a common benign vascular tumor, is closely associated with excessive angiogenesis/vasculogenesis that early emerges from childhood. A clinical trial showed that propranolol exhibited a 100% of improvement rate in fast halt of hemangioma proliferation and a 87% of that in hemangioma regression after 31 patients with rapidly proliferating infantile hemangioma (IH), who had functional or cosmetic defects, were given with propranolol at a dose of 3 mg/kg/day [13]; undoubtedly, propranolol is effective, but some side effects, like bronchospasm, BioMed Research International bradycardia, hypotension, hyperkalemia, hypoglycemia, etc., frequently prevent its application in hemangioma [14,15,16,17] Another classical therapy, corticosteroid displays an optimistic effect on hemangioma; for example, daily systemic administration of prednisone at 2-3 mg/kg seemed to be available for hemangiomas of infancy, accompanied with a 84% of effective rate and a 36% of rebound rate [18]; this vehicle often stands still due to its numerous adverse reactions, e.g., reversible Cushing’s phase, mood disorders, gastric irritation, symptoms of weight gain, and adrenal suppression [19,20,21]. The potential evidence of proanthocyanidins for treating hemangioma is reviewed

Pathogenesis of Hemangioma

Characteristics and Applications of Proanthocyanidins

Findings

Conclusion