Vialinin A, an Edible Mushroom-Derived p-Terphenyl Antioxidant, Prevents VEGF-Induced Neovascularization In Vitro and In Vivo

Abstract

Increased side toxicities and development of drug resistance are the major concern for the cancer chemotherapy using synthetic drugs. Therefore, identification of novel natural antioxidants with potential therapeutic efficacies is important. In the present study, we have examined how the antioxidant and anti-inflammatory activities of vialinin A, a p-terphenyl compound derived from Chinese edible mushroom T. terrestris and T. vialis, prevents human umbilical vascular endothelial cell (HUVEC) neovascularization in vitro and in vivo models. Pretreatment of HUVECs with vialinin A prevents vascular endothelial growth factor- (VEGF) induced HUVEC cell growth in a dose-dependent manner. Further, vialinin A also inhibits VEGF-induced migration as well as tube formation of HUVECs. Treatment of HUVECs prevents VEGF-induced generation of reactive oxygen species (ROS) and malondialdehyde (MDA) and also inhibits VEGF-induced NF-κB nuclear translocation as well as DNA-binding activity. The VEGF-induced release of various angiogenic cytokines and chemokines in HUVECs was also significantly blunted by vialinin A. Most importantly, in a mouse model of Matrigel plug assay, vialinin A prevents the formation of new blood vessels and the expression of CD31 and vWF. Thus, our results indicate a novel role of vialinin A in the prevention of neovascularization and suggest that anticancer effects of vialinin A could be mediated through its potent antioxidant and antiangiogenic properties.

Ubiquitously specific protease 4 inhibitor‐Vialinin A attenuates inflammation and fibrosis in S100‐induced hepatitis mice through Rheb/mTOR signalling

“…Vialinin A is a p‐terphenyl compound isolated from edible Chinese mushroom T. terrestris and T. vialis, 14 and also a specific inhibitor of USP4. Vialinin A has been shown to, significantly suppresses the expression of USP4 in vitro in previous studies 12,15,16 .…”

Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics

“…Vialinin A: Vialinin A, a non-specific USP4 inhibitor with an IC 50 value of 1.5 µM, also targets the catalytic activity of USP5/isopeptidase T (isoT) and UCH-L1 [211]. Vialinin A plays a role in the prevention of VEGF-induced neovascularization, and research suggests that its natural anti-oxidative properties could be developed as anti-angiogenic agents in cancer therapy [212].…”

Antimicrobial and Antioxidant Potential of Wild Edible Mushrooms

“…In addition, some researchers are investigated to study the antiangiogenic potential to prevent neurological disorders and hepatoprotective properties. A p-terphenyl compound is derived from two edible mushrooms that showed the anticancer effect to averts vascular endothelial growth factor with the presence of antioxidant and anti-inflammatory activity [63]. Few researchers reported that benzoic acid derivative compounds such as be p-hydroxybenzoic, protocatechuic, gallic, gentisic, homogentisic, vanillic, 5-sulphosalicylic, syringic, veratric, and vanillin obtained from diverse types of much room such as Phellinus rimosus, Ganoderma lucidum, Ganoderma tsugae, Coriolus versicolor, Lentinus edodes, Volvariella volvacea, Termitomyces heimii, Helvella crispa, Termitomyces tylerance, Lactarius sanguifluus, Morchella conica, Termitomyces mummiformis, Pleurotus sajor-caju, Termitomyces schimperi, Lentinus squarrulosus, Boletus edulis, Pleurotus djamor, Macrolepiota procera, Cantharellus clavatus, Morchella angusticeps, and Termitomyces microcarpus [25].…”