Abstract
Compatibility remains among the crucial and significant characteristics of traditional Chinese medicines. The Gardeniae Fructus (FG)-Forsythiae Fructus (FF) herb pair, an epitome of formulations for heat-clearing and detoxification, is extensively used to treat bacterial pneumonia in clinical settings. However, there are few reports on their synergistic effects. This study thus investigated their compatibility by GC-MS based metabolomics using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Differential metabolites were identified by both variable importance in the projection (VIP) > 1 in orthogonal partial least-squares discriminant analysis (OPLS-DA) mode and P < 0.05. Results of biochemistry and histopathology indicated that FG-FF herb pair exerted more promising lung protective effect than its individual decoction against the LPS-induced ALI model. From the metabolomics study, 32 differential metabolites in vehicle vs. model groups, 21 differential metabolites in FF vs. model groups, 21 differential metabolites in FG vs. model groups, and 20 differential metabolites in FG-FF herb pair vs. model groups were found. Among them, the levels of 3-hydroxybutyric acid, alanine, isophthalic acid, and terephthalic acid were restored significantly in the FF group, while silanol and cholesterol were restored significantly in the FG group. For FG-FF treatment, the amount of behenic acid, a metabolite with anti-inflammatory properties, was increased, while palmitic acid, a proinflammatory metabolite, was decreased. Meanwhile, the two biomarkers were restored more significantly than that by FG or FF treatment, which indicated that the synergistic effects by FF coupled with FG might be attributed to restoring fatty acids metabolic pathway.
Highlights
Traditional Chinese medicine (TCM) remains a viable alternative to western medicine for disease prevention and treatment [1]
Effect of FG-Forsythiae Fructus (FF) Herb Pair on Lipopolysaccharide-Induced Acute Lung Injury Mouse Model. e cytokines (TNF-α and IL-1β) and inflammatory cell counts in bronchoalveolar lavage fluid (BALF), as well as the lung histopathological scores, were all markedly elevated after LPS stimulation, but almost restored to normalcy after DXMS treatment, indicating that the LPS-induced acute lung injury (ALI) model was successfully established in the mice (Figure 1)
We found that the TNF-α and IL-1β, as well as the counts of total inflammatory cells in BALF and lung injury scores after FF, FG, and FG-FF herb pair treatment, respectively, were significantly alleviated in comparison of model groups, and the effect of combination treatment was better than that of FF or FG group (Figure 1). e biochemical and histopathological tests indicate that the treatment of LPS-induced ALI in mice after FG-FF herb pair showed a promising synergistic effect
Summary
Traditional Chinese medicine (TCM) remains a viable alternative to western medicine for disease prevention and treatment [1]. FG has been shown to exhibit diverse pharmacological effects. It is effective in the treatment or management of bacterial infections, hyperlipidemia, influenza A virus infections, diabetes aging [4], and inflammatory conditions of the liver, pancreas, and ligament [5]. Shuang-Huang-Lian (SHL), where FF is the main herb of SHL, has effectively attenuated the LPS-induced ALI [11]. Its mechanism of action remains poorly understood because the various chemical constituents of FG-FF herb pair exhibit diversity in their corresponding treatment targets. GC-MS based metabolomics was performed to clarify the anti-inflammatory effects of FG-FF herb pair in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model
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