Comparing the effects of three decoctions for coronavirus disease 2019 on severe acute respiratory syndrome coronavirus 2-related toll-like receptors-mediated inflammations

摘要

OBJECTIVE:To compare the anti-inflammatory effects of three decoctions for coronavirus disease 2019(COVID-19)[Qingfei Paidu Tang(清肺排毒汤),QF;Huashi Baidu Fang(化湿败毒方),HS;Xuanfei Baidu Fang(宣肺败毒方),XF]in parallelly experimental models by using severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)-related toll-like receptors(TLRs)ligands and its spike(S)protein as stimulators.METHODS:RAW264.7 macrophages were used to investigate the effects of three decoctions on the inflammations induced by R848,poly(I:C),lipopolysaccharide(LPS),as well as SARS-CoV-2 S protein,in vitro.Mouse endotoxemia model was used for evaluating their anti-inflammatory actions in vivo.The levels of monocyte chemoattractant protein-1(MCP-1),interleukin-6(IL-6),tumor necrosis factorα(TNF-α),and interferon-β(IFN-β)were determined by enzyme-linked immunosorbent assay.RESULTS:Three decoctions could decrease supernatant IL-6,MCP-1,nitric oxide(NO)and TNF-αto varying degrees in activated macrophages.Meanwhile,they did not increase the level of antiviral cytokine IFN-βinduced by TLR3 and TLR4 ligands,but rather suppressed it,suggesting that externally administrated type I interferons(IFN-Is)may be needed for the severe COVID-19 cases characterized by deficient IFN-Is.In mouse endotoxemia model,all three decoctions could suppress serum pro-inflammatory cytokines,but only QF could relieve hypothermia and antagonize diarrhea.CONCLUSIONS:Collectively,our study compared,for the first time,the effects of three decoctions on SARSCoV-2-related TLRs-mediated inflammations.In vitro,three decoctions exert similar suppressive effects on inflammatory cytokines induced by SARS-CoV-2-related TLRs ligands,as well as S protein.In vivo,QF possesses the strongest effects compared with HS and XF.These findings may provide not only experimental basis for the clinical use of three decoctions,but also a rationale for the combination therapy with IFN-Is.