GC-MS Based Metabolomics Reveals the Synergistic Mechanism of Gardeniae Fructus-Forsythiae Fructus Herb Pair in Lipopolysaccharide-Induced Acute Lung Injury Mouse Model

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.

Changes in fecal metabolic and lipidomic features by anti-TNF treatment and prediction of clinical remission in patients with ulcerative colitis

“…3-Hydroxybutyric acid was found to attenuate stress-induced inflammatory responses and increase SCFA production in an in vitro colonic microbial model. 24,25 In RM, a decrease in fecal 3-hydroxybutyric acid levels to the normal range noted in HC was observed after 56 weeks of treatment in our study. It is presumed that 3-hydroxybutyric acid might be actively utilized in the body system, including colon tissues in RM, resulting in a decreased level of 3-hydroxybutyric acid in fecal samples.…”

Amplifying protection against acute lung injury: Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

“…The amplified protection effect of herb pairs against ALI has recently been demonstrated. Wu et al discovered that Forsythiae Fructus (FF, Lianqiao in Chinese) and Gardeniae Fructus (FG, Zhizi in Chinese) can ameliorate lung damage caused by lipopolysaccharides (LPS) and decrease inflammatory factors in bronchoalveolar lavage fluid (BALF) through a synergistic restoration of fatty acid metabolic pathways ( Wu et al, 2021 ). Furthermore, Paeoniflorin-luteolin has the binding affinity to Nuclear factor-kappa B (NF-κB), affects the signal transduction of the Mitogen activated protein kinase (MAPK) pathway, thereby reduces the secretion of tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) in BALF induced by LPS ( Liu et al, 2024 ).…”