Purpose To study the efficacy of Qianshan Huoxue Gao (QS) in treating acute coronary syndrome (ACS) and to explore the mechanism of action from the perspective of intestinal flora regulation. Methods Male Sprague–Dawley rats were divided into control, model, QS, and atorvastatin groups; except for the control group, rats underwent ligation of the left anterior descending branch of the coronary artery. Following treatment for 28 days, cardiac function was evaluated using an echocardiographic assay; ELISAs for serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α); assessment of cardiac enzymes and inflammatory response; hematoxylin and eosin (HE) staining for histopathological changes in the heart, skin, and viscera; 16S rRNA gene sequencing for intestinal flora diversity and structural differences analysis; and we further investigated intestinal contents using metabolomics. Results Compared with controls, CK-MB and cTnI were increased ( P <0.01); ejection factor and fractional shortening were decreased ( P <0.01); left ventricular internal end-diastolic dimension and left ventricular internal end-systolic dimension were increased ( P <0.01); and IL-2, IL-6, TNF-α, and hs-CRP were increased in the model group. Myocardial damage and inflammation were also observed by HE staining. QS improved these indexes, similar to the atorvastatin group; therefore, QS could effectively treat ACS. QS modulates the structure and abundance of the intestinal flora in ACS model rats, among which Bacteroides, Lactobacillus , and Rikenellaceae_RC9_gut_group are associated with cardiovascular disease. Metabolomics revealed that the intestinal metabolite content changed in ACS, with ethanolamine (EA) being the most relevant metabolite for ACS treatment by QS. EA was significantly positively correlated with Eubacterium xylanophilum group, Ruminococcus, unclassified f__Oscillospiraceae, Intestinimonas, Eubacterium siraeum group, Lachnospiraceae NK4A136 group , and norank f__Desulfovibrionaceae . Conclusion QS can effectively treat ACS and can restore regulation of the intestinal flora. EA may be the primary metabolite of QS, exerting a therapeutic effect in ACS.

AimsWe assessed the efficacy of the traditional Chinese medicine formulation Jia-Wei-Si-Miao-Yong-An decoction (HJ11) in the treatment of acute coronary syndrome and evaluated its impact on the intestinal microbiota and their metabolites.MethodsAn acute coronary syndrome model was established in rats, which were randomly assigned to the model, HJ11 treatment, and atorvastatin treatment groups. Rats were then administered saline solution (model and sham operation control groups) or drugs by oral gavage for 28 d. Echocardiography was performed and serum creatine kinase-MB and cardiac troponin I levels were monitored to examine the cardiac function. Inflammation was evaluated using hematoxylin and eosin staining of heart tissue, and serum interleukin-2, interleukin-6, tumor necrosis factor alpha, and high-sensitivity C-reactive protein measurements. Gut microbiota composition was analyzed via 16S rRNA gene sequencing. Metabolomics was used to determine fecal metabolites and elucidate the modes of action of HJ11 in acute coronary syndrome treatment.ResultsHJ11 improved cardiac function and attenuated inflammation in rats with acute coronary syndrome. Relative to the untreated model group, the HJ11-treated group presented normalized Firmicutes/Bacteroidetes ratio and reduced abundances of the bacterial genera norank_f__Ruminococcaceae, Desulfovibrio, Clostridium_sensu_stricto_1, Adlercreutzia, Staphylococcus, Bacteroides, Prevotella, Rikenellaceae_RC9_gut_group, unclassified_o__Bacteroidales, and Ruminococcus_gauvreauii_group. We found 23 differentially expressed intestinal metabolites, and the enriched metabolic pathways were mainly related to amino acid metabolism. We also discovered that asymmetric dimethylarginine levels were strongly associated with cardiovascular disease. Correlation analyses revealed strong associations among intestinal microflora, their metabolites, proinflammatory factors, and cardiac function. Hence, the therapeutic effects of HJ11 on acute coronary syndrome are related to specific alterations in gut microbiota and their metabolites.ConclusionThis work demonstrated that HJ11 effectively treats acute coronary syndrome. HJ11 seems to increase the abundance of beneficial bacterial taxa (Bacteroides and Rikenellaceae_RC9_gut_group), mitigate the risk factors associated with cardiovascular disease, alter bacterial metabolites, lower asymmetric dimethylarginine levels, and effectively treat acute coronary syndrome.

Metabolomics is expected to identify potential metabolites and related pathways, and further reveal the underlying mechanisms of the transition from prediabetes to diabetes. In this study, a metabolomics-based gas chromatography-mass spectrometry (GC-MS) technique was used for demonstrating the serum metabolic profiles among healthy, prediabetes, and diabetes at fasting state and 2h oral glucose tolerance test (2h OGTT) state. With Ingenuity Pathway Analysis (IPA) tool, the comparative analysis showed no significant differences in the pathway analysis (P > 0.05) between prediabetes and diabetes at either fasting state or 2h OGTT state. The self-comparative analysis demonstrated the glycine/glutathione biosynthesis in diabetes were more inhibited than that in prediabetes or healthy control at 2h OGTT state compared with fasting state (P<0.05). In addition, the protein kinase A signaling pathway in prediabetes or diabetes was significantly inhibited more than that in healthy control (P<0.05). Therefore, the glycine/glutathione biosynthesis and protein kinase A signaling could differentiate the diabetic subjects from the prediabetic and healthy control subjects, and may involve in prediabetes transition to diabetes. This study provided more metabolomics information for the transition from prediabetes to diabetes.