Xiaohan Liqi Granules Alleviate Inflammation and Modulate PI3K/Akt Pathway in an Intermittent Hypoxia-Induced Rat Model of OSAHS: A Network Pharmacology and Experimental Study

Objective: To investigate the mechanism of Xiaohan Liqi granules (XHLQ) on obstructive sleep apnea-hypopnea syndrome (OSAHS) using network pharmacology and animal validation. Methods: Network pharmacology was used to demonstrate the mechanism of XHLQ in OSAHS with the use of databases and software such as The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), GeneCards, Cytoscape 3.7.2, etcetera. The intermittent hypoxia (IH)-induced rat model was established by placing the rats in an IH chamber and adjusting the oxygen concentration. Hematoxylin and Eosin (H&E) staining was performed to observe the pathological changes in the lung tissues of the rats. Immunohistochemistry (IHC) was used to determine the average optical density values of PI3K and Akt. Quantitative real-time PCR (RT-qPCR) was performed to compare the relative mRNA expression levels of PI3K and Akt in each group. And Enzyme-Linked ImmunoSorbent Assay (ELISA) was used to measure serum IL-6 and TNF-alpha in rats. Results: The core ingredients of XHLQ for OSAHS were beta-sitosterol, palmitoleic acid, alpha-linolenic acid (ALA), kaempferol and linoleic acid, and the core targets were ALB, IL6, CXCL8, HIF1A, IGF1, MMP9, TLR4, NOS3 and PPARG. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the common targets of XHLQ and OSAHS were mainly involved PI3K/Akt, HIF-1, TNF-alpha, NF-kappa B and other signaling pathways. H&E staining demonstrated that XHLQ can alleviate inflammatory infiltration in the lung tissues. ELISA indicated that XHLQ decreases the expression of IL-6 and TNF-alpha. IHC staining and RT-qPCR confirmed that XHLQ can reduce the activation of PI3K and Akt. Conclusion: XHLQ may exert therapeutic effects in OSAHS through multiple targets and pathways. Animal experiments verified that XHLQ attenuated airway inflammation and down-regulated PI3K and Akt expression in an IH rat model. Thus, XHLQ shows potential as an adjunctive treatment for OSAHS.