Shengmai injection (SMI) is a classical traditional Chinese medicine (TCM) officially recorded in Pharmacopoeia of the People's Republic of China (version 2015) and has long been used to treat heart failure in China. However scientific evidence for the anti-oxidative stress potential of SMI used in traditional medicine is lacking. The present study aimed to evaluate the efficacy of SMI in alleviating H2O2‑induced Oxidative Stress the underlying mechanisms MATERIALS AND METHODS: H2O2-induced oxidative stress model of cardiomyocytes was established with primary cultured neonatal rat cardiomyocytes. CCK8 cell viability assay and lacatate dehydrogenase cytotoxicity assay were performed to ensure the safety dose and lowest effective dose for the mode employing CCK-8 cell viability assay kit and lactate dehydrogenase cytotoxicity assay kit. ROS levels were determined using CM-H2DCFDA fluorescent probe in cardiomyocytes with H2O2-induced oxidative stress. The change of NAD(P)H level in cardiomyocytes was evaluated during the process of oxidative stress. The content of myocardial cytosolic Ca2+ and Ca2+ was determined using Fura-2/AM and Rhod 2-AM fluorescent probe in mitochondrial in the process of oxidative stress. Annexin V-FITC/PI double staining was applied to examine the apoptotic cells in cardiomyocytes with oxidative stress. To identify the apoptosis after oxidative stress myocardial cells with the application of Annexin V-FITC/PI double staining apoptosis detection kit. Quantitative polymerase chain reaction (RT-PCR) was applied to measure the expression of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR). Western blot was performed to observe the phosphorylation of AKT and ERK1/2. SMI was shown to significantly attenuate oxidative stress-induced cell proliferation arrest and apoptosis in neonatal rat cardiomyocytes. In addition, SMI treatment could decrease the production of reactive oxygen species (ROS), nicotinamide adenine dinucleotide (NADH) and malondialdehyde (MDA), and reduce the overloads of cytoplasmic Ca2+ and mitochondrial Ca2+ induced by H2O2. SMI could also restore the mRNA expression and activities of SOD, GSR, and CAT suppressed by H2O2. Mechanistically, SMI upregulated intracellular AKT phosphorylation and downregulate ERK1/2 phosphorylation in H2O2-treated cardiomyocytes. Pretreatment with LY294002, an AKT phosphorylation inhibitor, suppressed the protective role of SMI in cardiomyocytes, while pretreatment with PD98059, an ERK1/2 phosphorylation inhibitor, enhanced the effect of SMI. In conclusion, SMI may attenuate oxidative stress-induced damage in cardiomyocytes potentially through the AKT and ERK1/2 pathway and can function as a promising injectable traditional Chinese medicine to treat oxidative stress-induced injury.

Vasomotor dysfunction is one of the key pathological aspects of shock and heart failure (HF). Shenfu injection (SFI) has been widely used for the treatment of shock and HF in China. Pharmacological studies have suggested that SFI can reduce peripheral circulation resistance and improve microcirculation. However, whether it has a regulatory effect on macrovascular has not been elucidated. In this study, we used thoracic aorta rings isolated from Wistar rats and the human umbilical vein cell line (EA.hy926) to explore the vasodilative activity of SFI and its potential mechanisms. The relaxation due to SFI was measured after pre-treatment with selective soluble guanylate cyclase (sGC) inhibitor or cyclooxygenase (COX) inhibitor and compared with the vasodilation effect of SFI only treated with norepinephrine (NE). The contents of NO, endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), COX-1, 6-K-PGF_1α, and caveolin-1 were evaluated respectively. Additionally, the level of eNOS mRNA and total eNOS and its phosphorylation were studied to investigate the potential mechanisms involved. Experimental results showed that SFI markedly attenuated NE-induced vasoconstriction but that this effect was significantly eliminated after pre-incubation with the selective sGC inhibitor 1-H-[1, 2, 4] oxadiazolo [4, 3-α] quinoxaline-1-one (ODQ), instead of the COX inhibitor indomethacin (INDO). SFI significantly increased the eNOS content and up-regulated the eNOS mRNA expression, while it did not affect the content of COX-1 and 6-K-PGF_1α. SFI also markedly increased NO content but significantly reduced the content of ET-1 and caveolin-1 in the cell supernatant. Furthermore, it promoted the expression of total eNOS and the phosphorylation of eNOS at serine (Ser) 1177 but inhibited the phosphorylation at threonine (Thr) 495, which was significantly reversed by PI3K-specific inhibitor LY294002. In conclusion, our study showed the vasodilation effect of SFI in thoracic aorta is mediated entirely by enhancing eNOS activity through the PI3K/Akt signaling pathway, providing novel knowledge on the effect of SFI on shock and HF for future clinical applications.

Cardiometabolic diseases (CMD) are a cluster of complex syndromes characterized by cardiovascular damage resulting from metabolic dysregulation; however, their underlying mechanisms remain unclear. Recently, CMD research has paid considerable attention to the gut microbiota, though the emphasis has been on bacterial communities, and the gut mycobiome’s role is still not well understood. Hence, this review consolidates information on the correlation between the gut mycobiome and CMD and examines how the gut mycobiome may play a role in CMD progression. Accumulating evidence indicates that gut mycobiome dysbiosis, particularly the aberrant expansion of specific fungal genera such as Candida and Saccharomyces, is closely associated with the development and progression of cardiometabolic diseases. This association is primarily mediated through multiple mechanisms. For instance, fungal metabolites (enzymatic derivatives, alcohol) enhance intestinal lipid absorption, accelerate hepatic steatosis, and trigger systemic insulin resistance. Meanwhile, dysregulated cross-kingdom interactions disrupt intestinal barrier function, leading to endotoxemia and vascular inflammation, thereby promoting atherosclerosis. Additionally, fungal pathogen-associated molecular patterns activate the immune-metabolic axis, resulting in adipose tissue inflammation and glucose dysregulation. These pathways interact synergistically, collectively exacerbating metabolic dysfunction and cardiovascular damage. We also outline strategies targeting the gut mycobiome as a potential therapeutic approach for cardiometabolic diseases. By integrating current state-of-the-art insights, this review provides a critical reference for the development of novel mycobiome-based interventions in cardiometabolic disease management.

This study reviews the correlation between the gut virome and cardiovascular diseases (CVDs) and investigates the potential role of the gut virome in CVD progression. The gut virome, which includes bacteriophages and eukaryotic viruses, interacts with the intestinal microbiota and the host immune system, and affects the overall health of the host. Previous studies have demonstrated that alterations in the gut virome are closely associated with various cardiovascular conditions, including hypertension, atherosclerosis, atrial fibrillation, heart failure, and viral myocarditis. Thus, the gut virome may contribute to CVD development by regulating intestinal microecology and immune responses, affecting intestinal barrier function and systemic inflammatory responses. However, despite advancements in gut virome research, our understanding of the specific mechanisms involved and therapeutic potential in CVDs remains limited. Future developments in virus databases and advancements in sequencing technology are expected to offer new insights and methods for the early diagnosis and accurate treatment of CVDs.

Hypertension affects approximately 1.3 billion adults worldwide, yet the control rate remains below 20%, highlighting the limitation of current therapies that primarily lower blood pressure without targeting the underlying pathophysiological mechanisms. Recent research indicates that bitter taste receptors, which are structurally distinct members of the G protein-coupled receptor superfamily, have functions that extend beyond their traditional role in oral taste perception. These receptors are extensively expressed along the gut-vascular axis, including in vascular smooth muscle, cardiac tissue, macrophages, and gastrointestinal organs, thereby positioning them as crucial nodes in the regulation of immunometabolic processes. This review systematically elucidates the complex regulatory mechanisms of gut-vascular axis TAS2Rs in the pathophysiology of hypertension and investigates TAS2R-targeting compounds, with particular emphasis on their effects in modulating blood pressure. This review consolidates evidence on TAS2R signaling across vascular, immune, and gastrointestinal interfaces to outline therapeutic implications for hypertension.