Gan-Pi-Tong-Zhi Decoction Ameliorates OVA-Induced Asthma Through MAPK and Nrf2 Signaling Pathways and Regulating Gut Microbiota

Purpose: This study aims to investigate the therapeutic mechanism of Gan-Pi-Tong-Zhi Decoction (GPTZ) in asthma. Methods: The study explored the chemical components of GPTZ by using UPLC-Q-TOF-MS, and utilized the database for target identification, and predicted potential pathways using network pharmacology. The protective effects of GPTZ against asthma were assessed by measuring levels of inflammatory factors and biochemical markers related to oxidative stress. 16S rRNA gene sequencing was used to explore the underlying mechanism of GPTZ against asthma through gut-lung axis, while quantitative PCR (qPCR) analyses, Western blot, and immunohistochemistry were used to identify targets within key signaling pathways. Results: A total of 25 components in GPTZ were identified. Network pharmacology analysis revealed 150 common targets through which GPTZ may treat asthma via the gut–lung axis. Enrichment analysis indicated that the therapeutic effects of GPTZ are related to its regulation of MAPK and Nrf2 signaling pathways. These findings were further supported by experimental validation at both the gene and protein expression levels. In OVA-induced asthmatic rats, GPTZ administration alleviated asthma symptoms, reduced systemic inflammation, and mitigated pathological damage in lung and colon tissues. Treatment with GPTZ ameliorated microbial dysbiosis at both phylum and genus levels, while enhancing the functional capacity of the gut microbiota. Additionally, it markedly inhibited the release of TNF-α, IL-6, and IL-1β, elevated the activities of antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), and decreased malondialdehyde (MDA). Conclusion: GPTZ effectively alleviates asthma. The mechanism lies in inhibiting the inflammatory response mediated by MAPK signaling pathway and activating the antioxidant response mediated by Nrf2 signaling pathway. This protective effect may be potentially associated with the maintenance of gut microbiota homeostasis. Keywords: Gan-Pi-Tong-Zhi decoction, asthma, MAPK signaling pathway, Nrf2 signaling pathway, Gut microbiota