Diosmetin-7-O-β-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication

• Published in: Journal of ethnopharmacology Vol. 336; p. 118704
• Main Authors: Xu, Yun-Lu, Li, Xue-Jian, Cai, Wei, Yu, Wen-Ying, Chen, Jing, Lee, Qin, Choi, Yong-Jun, Wu, Fang, Lou, Ying-Jun, Ying, Hua-Zhong, Yu, Chen-Huan, Wu, Qiao-Feng
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10.01.2025
• Subjects: Glycolysis; HK3; Macrophage polarization; Viral replication; YTHDF1; YTHDF1; Apigenin (pubchem CID: 5280443); Macrophage polarization; Remdesivir (pubchem CID: 121304016); Luteolin (pubchem CID: 5280445); Apigenin-7-glucoside (pubchem CID: 5280704); HK3; Vitexin (pubchem CID: 5280441); Velutin (pubchem CID: 5464381); Quercetin (pubchem CID: 5280343); Diosmetin-7-O-β-D-glucopyranoside (pubchem CID: 11016019); Glycolysis; Ombuin (pubchem CID: 5320287); Tilianin (pubchem CID: 5321954); Viral replication; Luteolin-7-glucoside (pubchem CID: 5280637)
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118704

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 0.625–2.5 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. MacrophageDiosmetin-7-O-β-D-glucopyranoside derived from Pogostemonis Herba alleviated SARS-Cov-2 virus-induced pneumonia by reshaping macrophage polarization and limiting viral replication via targeting YTHDF1. [Display omitted]