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

: Collectively, our study compared, for the first time, the effects of three decoctions on SARS-CoV-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.

: 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 factor α (TNF-α), and interferon-β (IFN-β) were determined by enzyme-linked immunosorbent assay.

: 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.

: Three decoctions could decrease supernatant IL-6, MCP-1, nitric oxide (NO) and TNF-α to varying degrees in activated macrophages. Meanwhile, they did not increase the level of antiviral cytokine IFN-β induced 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 SARS-CoV-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.