病毒性肺炎是 SARS-CoV-2 感染后死亡的主要原因。尽管糖皮质激素在早期有效，但长期治疗可能会导致多种不良反应和有限的益处。中草药Pogostemonis Herba为Pogostemon Cablin (Blanco) Benth.的地上部分，具有有效的抗病毒、抗菌、抗炎、抗癌作用。它被广泛用于治疗各种咽喉和呼吸系统疾病，包括 COVID-19、病毒感染、咳嗽、过敏性哮喘、急性肺损伤和肺癌。感染 CoV-2 的 hACE2 过表达小鼠巨噬细胞 RAW264.7 细胞和 hACE2 转基因小鼠。将 hACE2 过表达 RAW264.7 细胞暴露于 SARS-CoV-2。采用CCK8法检测细胞活力，流式细胞术检测细胞凋亡率。 qPCR检测巨噬细胞M1表型标志物（TNF-α和IL-6）和M2标志物（IL-10和Arg-1）的表达以及病毒载量。小鼠鼻内接种 SARS-CoV-2 omicron 变体以诱导病毒性肺炎。通过全谱流式细胞术分析感染小鼠肺组织中巨噬细胞、中性粒细胞和 T 细胞的水平。通过蛋白质印迹法检测关键蛋白的表达。Diosmetin-7-O-β-D-吡喃葡萄糖苷（DG）表现出最强的抗SARS-CoV-2活性。 1.25-50 μM浓度的DG干预不仅减少了SARS-CoV-2感染的RAW264.7细胞中的病毒复制、细胞凋亡和炎性细胞因子（IL-6和TNF-α）的产生，而且还将巨噬细胞极性从 M1 表型逆转为 M2 表型。此外，DG (25-100 mg/kg) 治疗可减轻 SARS-COV-2 感染小鼠的急性肺损伤，并减少巨噬细胞浸润。从机制上讲，DG通过靶向YTHDF1抑制SARS-COV-2基因表达和HK3翻译，导致糖酵解介导的NF-κB通路失活。DG发挥有效的抗病毒和抗炎活性。它通过抑制病毒复制并通过靶向 YTHDF1 加速 M2 巨噬细胞极化来减少 SARS-COV-2 感染小鼠的肺炎，表明其治疗 COVID-19 的潜力。版权所有 © 2024。由 Elsevier B.V 出版。

Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer.To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice.The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by western blot assay.Diosmetin-7-O-β-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 1.25-50 μM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway.DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.Copyright © 2024. Published by Elsevier B.V.