Introduction: Ping An Fang Yu Yin (PAFYY) is a traditional Chinese herbal tea formula commonly used to treat respiratory infections, including COVID-19. Previous research indicates potential antiinflammatory activities; however, the underlying mechanisms remain unclear. This study aimed to investigate the mechanisms underlying the therapeutic effects of PAFYY, specifically its electron-transport and bioenergetic properties, through network pharmacology, electrochemical analysis, and Microbial Fuel Cell (MFC) assessments. Methods: Active compounds and their respective targets were identified via database searches. Proteinprotein interaction networks were constructed using the STRING database and further analyzed using Cytoscape and MCODE software. Molecular docking was employed to assess the binding affinity between identified key compounds and their targets. Cyclic voltammetry (CV) and MFC assays evaluated the electrontransport characteristics of PAFYY water and ethanol extracts. Results: The analysis identified 298 active compounds associated with 1,940 biological targets, highlighting key targets including EP300, CREBBP, ESR1, AKT1, MAPK3, MAPK1, and STAT3. GO and KEGG pathway enrichment analyses revealed that PAFYY significantly influences immune system processes and neuronal signaling pathways. Molecular docking confirmed the anti-inflammatory and antiviral potential of the identified active compounds. Additionally, electrochemical studies demonstrated that PAFYY contains electroactive substances mediating electron-driven redox reactions. Discussion: Recent studies have demonstrated that traditional Chinese herbal teas contain electron shuttles capable of mediating electron transfer in electrogenic bacteria. Emerging evidence further indicates that electroactive plant polyphenols can modulate microbial ecology through redox-mediated mechanisms. Our findings suggest that PAFYY may act on the microbiota-immune axis, with its electron-shuttling constituents contributing not only to direct cellular effects and antioxidant activity but also to modulation of the gut microbiome in ways that support antiviral immunity and attenuate inflammation. These results may inform future research into the mechanistic basis of medicinal herbs, while highlighting the potential of MFCs as a functional screening platform for identifying bioactive redox compounds. Conclusion: The anti-COVID-19 properties of PAFYY may be largely attributed to its electron-transport capabilities, mediated through electroactive compounds. These findings provide novel insights into the mechanistic basis of traditional Chinese medicine prescriptions, potentially enhancing their therapeutic application.
Mailem et al. (Tue,) studied this question.