首页|Sappanwood-derived polyphenolic antidote of amyloidal toxins achieved detoxification via inhibition/reversion of amyloidal fibrillation
Sappanwood-derived polyphenolic antidote of amyloidal toxins achieved detoxification via inhibition/reversion of amyloidal fibrillation
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NSTL
Elsevier
? 2022The formidable virulence of methicillin-resistant staphylococcus aureus (MRSA) have thrown great challenges to biomedicine， which mainly derives from their autocrine phenol-soluble modulins (PSMs) toxins， especially the most toxic member termed phenol-soluble modulins α3 (PSMα3)。 PSMα3 cytotoxicity is attributed to its amyloidal fibrillation and subsequent formation of cross-α sheet fibrils。 Inspired by the multiple biological activity of Sappanwood， herein， we adopted brazilin， a natural polyphenolic compound originated from Caesalpinia sappan， as a potential antidote of PSMα3 toxins， and attempted to prove that the regulation of PSMα3 fibrillation was an effective alexipharmic way for MRSA infections。 In vitro results revealed that brazilin suppressed PSMα3 fibrillation and disassembled preformed amyloidal fibrils in a dose-dependent manner， in which molar ratio (brazilin: PSMα3) of efficient inhibition and disassembly were both 1:1。 These desired regulations dominated by brazilin benefited from its bonding to core fibrils-forming residues of PSMα3 monomers urged by hydrogen bonding and pi-pi stacking， and such binding modes facilitated brazilin-mediated inhibition or disruption of interactions between neighboring PSMα3 monomers。 In this context， these inhibited and disassembled PSMα3 assemblies could not easily insert into cell membrane and subsequent penetration， and thus alleviating the membrane disruption， cytoplasmic leakage， and reactive oxygen species (ROS) generation in normal cells。 As such， brazilin dramatically decreased the cytotoxicity borne by toxic PSMα3 fibrils。 In addition， in vivo experiments affirmed that brazilin relieved the toxicity of PSMα3 toxins and thus promoted the skin wound healing of mice。 This study provides a new antidote of PSMα3 toxins， and also confirms the feasibility of the assembly-regulation strategy in development of antidotes against supramolecular fibrillation-dependent toxins。
Xuan Q.、Zhou J.、Zhang W.、Wei A.、Zhang Q.、Chen C.、Jiang F.、Shen H.、Li H.、Wang P.
展开 >
State Key Laboratory of Bioreactor Engineering Biomedical Nanotechnology Center Shanghai Collaborative Innovation Center for Biomanufacturing Technology School of Biotechnology East China University of Science and Technology
Department of Orthopaedics Affiliated Sixth People's Hospital Shanghai Jiao Tong University
Institute for Environmental Pollution and Health School of Environmental and Chemical Engineering Shanghai University
Department of Bioproducts and Biosystems Engineering University of Minnesota
NSTL
Elsevier
