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

  • J Ethnopharmacol. 2025 Jan 10:336:118704. doi: 10.1016/j.jep.2024.118704.
Yun-Lu Xu  1 ,  Xue-Jian Li  2 ,  Wei Cai  3 ,  Wen-Ying Yu  4 ,  Jing Chen  1 ,  Qin Lee  5 ,  Yong-Jun Choi  6 ,  Fang Wu  4 ,  Ying-Jun Lou  4 ,  Hua-Zhong Ying  4 ,  Chen-Huan Yu  7 ,  Qiao-Feng Wu  8
Affiliations
  • 1. College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • 2. Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China; Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, 310018, China.
  • 3. College of Chinese Medicine, Zhejiang Pharmaceutical University, Ningbo, 315500, China.
  • 4. Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China.
  • 5. Key Laboratory of Experimental Animal and Safety Evaluation, Hangzhou Medical College, Hangzhou, 310013, China; Department of Biochemistry, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea.
  • 6. Department of Biochemistry, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea.
  • 7. Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, 310018, China. Electronic address: [email protected].
  • 8. College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China. Electronic address: [email protected].
PMID: 39182703 DOI: 10.1016/j.jep.2024.118704
Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords
Apigenin (pubchem CID: 5280443); Apigenin-7-glucoside (pubchem CID: 5280704); Diosmetin-7-O-β-D-glucopyranoside (pubchem CID: 11016019); Glycolysis; HK3; Luteolin (pubchem CID: 5280445); Luteolin-7-glucoside (pubchem CID: 5280637); Macrophage polarization; Ombuin (pubchem CID: 5320287); Quercetin (pubchem CID: 5280343); Remdesivir (pubchem CID: 121304016); Tilianin (pubchem CID: 5321954); Velutin (pubchem CID: 5464381); Viral replication; Vitexin (pubchem CID: 5280441); YTHDF1.
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