Mechanism and spectrum effect relationship of Shen-Ling-Bai-Zhu-San in treating viral pneumonia via inhibiting the PI3K/AKT/NF-κB signaling pathway

Ethnopharmacological relevance

Shen-ling-bai-zhu-san (SLBZS), a well-documented and widely used traditional formula, is used to treat viral pneumonia. However, the key active ingredients and mechanism of SLBZS in treating viral pneumonia are not clear.

Aim of the study

This study aimed to investigate the effect of SLBZS on viral pneumonia, identify its bioactive components, and reveal the possible mechanism.

Materials and methods

A mouse model with viral pneumonia was established to assess SLBZS's therapeutic impact. Subsequently, this study employed UPLC-Q-TOF-MS to analyze the components of SLBZS under both in vivo and in vitro conditions. Potential pathways and targets were predicted with the assistance of network pharmacology and the GEO database. Furthermore, potential active components were identified through spectrum-effect relationship analysis, and their efficacy was validated using Partial Least Squares Regression Analysis (PLSR) and molecular docking.

Results

SLBZS treatment significantly alleviated pulmonary inflammatory injury in mice infected with H1N1 and suppressed the production of inflammatory factors induced by the virus. Biochemically, it reversed the overexpression of p-PI3K/T-PI3K, p-AKT/T-AKT, and p-NF-κB p65/NF-κB p65 in lung tissues caused by H1N1 infection. This study identified 37 in vitro components and 35 in vivo components of SLBZS, among which four were found to significantly regulate the balance between overactive immune responses and beneficial inflammatory processes. Additionally, molecular docking studies indicated that atractylodin III and platycodin D have the potential to inhibit the PI3K-AKT-NF-κB signaling pathway.

Conclusion

SLBZS effectively alleviates H1N1-induced viral pneumonia by suppressing the overactivation of the PI3K-AKT-NF-κB signaling pathway. Furthermore, this study presents an innovative approach to clarify the correlation between the chemical and pharmacological profiles of drug-containing serum and tissues. By applying this method, bioactive compounds capable of regulating the balance between overactive immune responses and inflammation have been successfully identified. Among these, atractylenolide III and platycodin D stand out as potential PI3K inhibitors, which underscores their value for further exploration. Collectively, these findings provide a robust foundation for the development of novel therapeutic strategies for viral pneumonia, leveraging SLBZS and its active constituents.