Isovitexin Is a Direct Inhibitor of Staphylococcus aureus Coagulase

Abstract

Staphylococcus aureus (S. aureus) is a major pathogen that causes human pneumonia, leading to significant morbidity and mortality. S. aureus coagulase (Coa) triggers the polymerization of fibrin by activating host prothrombin, which then converts fibrinogen to fibrin and contributes to S. aureus pathogenesis and persistent infection. In our research, we demonstrate that isovitexin, an active traditional Chinese medicine component, can inhibit the coagulase activity of Coa but does not interfere with the growth of S. aureus. Furthermore, we show through thermal shift and fluorescence quenching assays that isovitexin directly binds to Coa. Dynamic simulation and structure-activity relationship analyses suggest that V191 and P268 are key amino acid residues responsible for the binding of isovitexin to Coa. Taken together, these data indicate that isovitexin is a direct Coa inhibitor and a promising candidate for drug development against S. aureus infection.

Inhibitory Effect of Salicin on Staphylococcus aureus Coagulase

“…Therefore, we found that salicin could directly bind to Coa, causing a change in the conformation of the protein to achieve inhibitory activity. We found that the binding constants of some Coa inhibitors of natural products, such as quercetin and isovitexin, with Coa were 2.64×10 3 L/ mol [13] and 9.98×10 4 L/mol, [15] respectively. Our study showed that the binding constant of 7.069×10 3 L/mol obtained for salicin and Coa falls within the range of reported binding constants for other ligands that interact with Coa, indicating that the binding affinity of salicin for Coa is consistent with, or slightly stronger than, other known interactions.…”

“…[12] According to previous studies, quercetin reduces catheter-related S. aureus infections by inhibiting Coa activity. [13] To date, several natural product inhibitors of Coa that have an inhibitory effect on Coa-induced coagulation by S. aureus have been reported, and these include isoquercitrin (quercetin-3-O-β-D-glucopyranoside), [14] quercetin (3,3',4',5,7-pentahydroxyflavone) [13] and isovitexin (apigenin-6-Cβ-glucopyranoside), [15] which are mainly flavonoid compounds. In this study, we screened dozens of natural compounds and ultimately identified salicin, a nonphenolic glucoside compound extracted from the roots of white willow bark (Salix alba), as a novel structural Coa inhibitor.…”

Ozone therapy for skin diseases: Cellular and molecular mechanisms

“…We previously reported that topical ozone treatment reduced the burden of S. aureus and increased the proportion of Acinetobacter species in atopic dermatitis. 112 In atopic dermatitis lesions, ozone therapy not only exhibits a bactericidal effect but also participates in restoring the skin microbial diversity. 11 In addition, we assessed the potential of ozone therapy in axillary hyperhidrosis and observed that ozonated oil could effectively decrease the skin pH value and inhibit the growth of Corynebacterium, the pathogenic bacteria of axillary hyperhidrosis.…”

Inquiry lipaseoring the mechanism of pancreatic lipase inhibition by isovitexin based on multispectral method and enzyme inhibition assay

“…As a common and abundant flavonoid glycoside, isovitexin is widely found in a variety of plant, such as the leaves of Ficus deltoidea, Gleditsia sinensis, and the coat of the mung bean [21][22][23]. It possesses manifold pharmacological activities, including lipid-lowering, hypoglycemic functions, anti-inflammatory, antioxidant, and antimicrobial effects [24][25][26]. For the past few years, isovitexin has been found to have the potential to prevent and treat obesity due to its PL inhibitory activity.…”