1.Effect of Asari Radix et Rhizoma-Zingiberis Rhizoma Herb Pair on Lung and Liver Lipid Metabolism in Rats with COPD Based on Metabolomics and Network Pharmacology
Ping HUANG ; Zhenxiang ZHOU ; Deshun LI ; Fang HUANG ; Jingjing LI ; Bailu DUAN ; Lintao HAN ; Yong ZHAO ; Qiong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(18):152-160
ObjectiveTo investigate the effects of Asari Radix et Rhizoma-Zingiberis Rhizoma herb pair (XGHP) on lung and liver lipid metabolism in rats with chronic obstructive pulmonary disease (COPD). MethodForty SD male rats were divided into a normal group (10 rats) and a model group (30 rats). The method of cigarette smoke + tracheal injection of lipopolysaccharide(LPS) + cold stimulation was used to replicate COPD model with the syndrome of cold phlegm obstruction in lung. A COPD group, a XGHP group (5.4 g·kg-1·d-1), and an aminophylline group (0.5 g·kg-1·d-1) were established after successfully inducing the model, with 10 rats in each group. After treatment, the serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels of rats in each group were measured. Gas chromatography-mass spectrometer (GC-MS) was used to detect the differential metabolites in the lung and liver tissues of rats in each group, and the relevant targets of the differential metabolites were predicted by network pharmacology. Molecular docking was used to verify the binding ability of key components in XGHP to the relevant targets in network pharmacology. The mRNA and protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and fatty acid binding protein 4 (FABP4) in lung and liver tissues of rats in each group were detected by real-time polymerase chain reaction (PCR) and Western blot. ResultXGHP significantly increased the levels of TG, TC, and LDL-C in serum (P<0.05), and decreased the level of HDL-C (P<0.05) in rats with COPD. GC-MS results showed that there were 8 lung differential metabolites and 17 liver differential metabolites in the COPD group and XGHP group. Network pharmacology predicted 59 common targets for the two differential metabolites, mainly enriched in the PPAR signaling pathway. Molecular docking results showed that the main components in XGHP were well combined with both PPARα and FABP4. Real-time PCR showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 mRNA (P<0.05), and Western blot showed that XGHP effectively up-regulated the expression levels of PPARα and FABP4 proteins (P<0.05) in lung and liver tissues of rats with COPD. ConclusionXGHP effectively improves the blood lipid levels of rats with COPD, which may be related to the increase of the expression levels of PPARα and FABP4 mRNA and proteins in the PPAR signaling pathway, thus regulating lung and liver lipid metabolism.