Department of Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
J Tradit Chin Med. 2023 Feb;43(1):51-59. doi: 10.19852/j.cnki.jtcm.2023.01.006.
: 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.
: 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, . Mouse endotoxemia model was used for evaluating their anti-inflammatory actions . 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.
: 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.
: Collectively, our study compared, for the first time, the effects of three decoctions on SARS-CoV-2-related TLRs-mediated inflammations. , three decoctions exert similar suppressive effects on inflammatory cytokines induced by SARS-CoV-2-related TLRs ligands, as well as S protein., 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.
通过使用严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）相关 Toll 样受体（TLR）配体及其刺突（S）蛋白作为刺激物，比较三种用于治疗 2019 年冠状病毒病（COVID-19）的方剂[清肺排毒汤（QF）、化湿败毒方（HS）、宣肺败毒方（XF）]在平行实验模型中的抗炎作用。
采用 RAW264.7 巨噬细胞研究三种方剂对 R848、多聚（I：C）、脂多糖（LPS）以及 SARS-CoV-2 S 蛋白诱导的炎症的影响。采用小鼠内毒素血症模型评价其抗炎作用。通过酶联免疫吸附试验测定单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和干扰素-β（IFN-β）的水平。
三种方剂均可不同程度地降低活化巨噬细胞上清液中白细胞介素-6（IL-6）、MCP-1、一氧化氮（NO）和 TNF-α的水平。同时，它们没有增加 TLR3 和 TLR4 配体诱导的抗病毒细胞因子 IFN-β的水平，反而抑制了它，这表明对于 IFN-Is 缺乏的严重 COVID-19 病例，可能需要外源性 I 型干扰素（IFN-Is）。在内毒素血症小鼠模型中，三种方剂均可抑制血清促炎细胞因子，但只有 QF 可缓解体温过低和拮抗腹泻。
本研究首次比较了三种方剂对 SARS-CoV-2 相关 TLR 介导的炎症的影响。结果表明，三种方剂对 SARS-CoV-2 相关 TLR 配体诱导的炎症细胞因子均有相似的抑制作用，对 S 蛋白也有相似的抑制作用。与 HS 和 XF 相比，QF 具有最强的作用。这些发现不仅为三种方剂的临床应用提供了实验依据，也为 IFN-Is 的联合治疗提供了理论依据。
