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| Traditional Chinese medicine regulates redox state to suppress viral infection and inflammatory response by the multi-target intervention of flavonoid-polyphenol antioxidants |
| Hits 288 Download times 120 Received:June 24, 2025 |
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| DOI
10.11656/j.issn.1672-1519.2025.12.12 |
| Key Words
Mahuang Decoction;multi-target antioxidant;respiratory virus infection;inflammatory response;flavonoid-polyphenol antioxidant |
| Author Name | Affiliation | E-mail | | LUO Qiwen | Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, China | | | WU Meiling | Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, China
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China | | | ZHANG Chunwang | Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, China | | | HUO Lingjie | Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, China | | | ZHANG Fulin | Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, China | | | ZHAO Jia | School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China | | | ZHANG Han | State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | WANG Yuyan | Department of Medical Mircobiology and Parasitology, School of Basic Medical Science, Fudan University, Shanghai 200032, China | | | SHI Dongyun | Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, China
Free Radical Regulation and Application Research Center, Fudan University, Shanghai 200032, China | dyshi@fudan.edu.cn | | LIU Shanlin | Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Fudan University, Shanghai 200032, China
Free Radical Regulation and Application Research Center, Fudan University, Shanghai 200032, China | slliu@shmu.edu.cn |
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| Abstract
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| [Objective] To investigate the redox mechanism of the flavonoid-polyphenol antioxidants in the four herbs of Mahuang Decoction to inhibit SARS-CoV-2 infection and reduce inflammatory injury of lung tissue. [Methods] The antioxidant properties of the components in Mahuang Decoction were assessed using the free radical medical detection technique，including scavenging abilities of superoxide anion，hydroxyl radical，and DPPH radical，as well as the total antioxidant capacity and total polyphenol content. We used herbs and antioxidant monomers from Mahuang Decoction to intervene in virus-infected cells and assayed to analyze changes in intracellular O2·- and the viral core protein level. In vivo experiment was performed using the Lipopolysaccharide（LPS）-induced mouse model. The mice were examined for the levels of tumor necrosis factor-α（TNF-α） and interleukin-6（IL-6），changes of macrophages in spleen and changes of inflammation and redox indexes of nuclear factor erythroid 2-related factor 2（NRF2）， thioredoxin-1（TRX1）， malondialdehyde（MDA），and 3-nitrotyrosine（3NT） in lung tissue. [Results] The results showed that among Mahuang，Guizhi，Zhigancao and Xingren，Mahuang exhibited the strongest scavenging abilities of hydroxyl and DPPH radicals and the strongest total antioxidant capacity，as well as the highest polyphenol content. Guizhi had the strongest scavenging ability of superoxide anion，while the antioxidant capacity of Zhigancao and Xingren was relatively weaker. The intervention of virus-infected cells using Guizhi was found to inhibit the replication of SARS-CoV-2 and Delta variant. Guizhi inhibited ROS signaling and suppressed the inflammatory response by upregulating the NRF2-TRX1 antioxidant pathway. In addition，quercetin，a flavonoid monomer in Mahuang Decoction exhibited strong scavenging abilities of superoxide anion and hydroxyl radicals，and was able to inhibit viral replication obviously. [Conclusion] The flavonoid-polyphenol antioxidants represented by Mahuang and Guizhi could play a multi-targeted role in redox regulation and exert different roles in different stages of viral infection，so as to realize effective and precise intervention. By revealing the mechanism of action of flavonoid-polyphenol antioxidants in antiviral infections and inhibition of inflammatory responses，these results would help to guide the rational compatibility of traditional Chinese medicine ingredients to achieve precise intervention during the treatment of different clinical courses of illnesses. The results of this study also suggested that the antioxidant intervention of traditional Chinese medicine could be used to control respiratory viral infections and prevent new pandemic disasters in a broad-spectrum manner，and provide new ideas for exploring the combination of antioxidant strategies and traditional Chinese medicine. |
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