The human gut harbors microbial ecology that is in a symbiotic relationship with its host and has a vital function in keeping host homeostasis. Inimical alterations in the composition of gut microbiota, known as gut dysbiosis, have been associated with cardiometabolic diseases. Studies have revealed the variation in gut microbiota composition in healthy individuals as compared to the composition of those with cardiometabolic diseases. Perturbation of host–microbial interaction attenuates physiological processes and may incite several cardiometabolic disease pathways. This imbalance contributes to cardiometabolic diseases via metabolism-independent and metabolite-dependent pathways. The aim of this review was to elucidate studies that have demonstrated the complex relationship between the intestinal microbiota as well as their metabolites and the development/progression of cardiometabolic diseases. Furthermore, we systematically itemized the potential therapeutic approaches for cardiometabolic diseases that target gut microbiota and/or their metabolites by following the pathophysiological pathways of disease development. These approaches include the use of diet, prebiotics, and probiotics. With the exposition of the link between gut microbiota and cardiometabolic diseases, the human gut microbiota therefore becomes a potential therapeutic target in the development of novel cardiometabolic agents.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Obesity, where there is enhancement of stored body fat in adipose tissues, is associated with cardiovascular complications that are mainly related to atherosclerosis. Time-restricted feeding (TRF) is a form of restricted eating aimed at reducing weight in obese subjects. The present study aims to investigate changes in vascular endothelial function, endothelial nitric oxide synthase (eNOS), and protein kinase B (Akt) protein expressions with TRF in obese and normal rats. Male Sprague Dawley rats were divided into two normal and three obese groups; obesity was induced in the obese groups by feeding with a high-fat diet (HFD) for six weeks. After six weeks, rats were equally divided into five groups (n = 7 per group): Normal group (NR) which continued on a standard diet for six more weeks, normal group switched to TRF with a standard diet for six weeks (NR + TRFSD), obese group (OR) which continued on HFD for six more weeks, obese group switched to TRF of HFD (OR + TRFHFD), and obese group switched to TRF of a standard diet (OR + TRFSD). TRF was practiced for six weeks, after which the rats were sacrificed. Aortic endothelium-dependent and endothelium-independent relaxations and contractions were assessed using the organ bath. Aortic eNOS and Akt protein expressions were determined using immunoblotting. Fasting blood glucose, body weight, body mass index (BMI), serum lipid profile, Lee’s index, serum insulin levels, and sensitivity (HOMA-IR) were also measured. Endothelium-dependent relaxation was significantly impaired, while endothelium-dependent contraction increased in obese rats compared to that in normal rats. Both obese groups which underwent TRF with a HFD and standard diet improved their impairments in endothelium-dependent relaxation and reduced endothelium-dependent contraction; these were associated with increased expressions of aortic eNOS and Akt protein. Both obese groups with TRF reduced body weight, BMI, Lee’s index, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and improved insulin sensitivity. TRF improved endothelium-dependent relaxation and reduced endothelium-dependent contraction, thus attenuating endothelial dysfunction in obese rats. These were associated with increased aortic eNOS and Akt protein expressions.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia and is considered a major health problem in the world. It is associated with endothelial dysfunction which causes progressive vascular damage. DM is a known risk factor for atherosclerosis and cardiovascular complications such as peripheral artery disease, coronary artery disease, and stroke. Medicinal plants may act as an alternative resource or adjunctive treatment option in the treatment of diabetes and its cardiovascular complications. Parkia speciosa (Fabaceae) is a plant found abundantly in the Southeast Asian region. Its seeds, with or without pods, and roots have long been used as a traditional medicine in this region to treat hypertension and diabetes. Studies have shown its numerous beneficial pharmacological properties. Extracts of P. speciosa, particularly from its seeds and empty pods, show the presence of polyphenols. They also exhibit potent antioxidant, hypoglycemic, anti-inflammatory, and antihypertensive properties. Its hypoglycemic properties are reported to be associated with the presence of β-sitosterol, stigmasterol, and stigmat-4-en-3-one. The current review aimed to provide an overview of the current status of P. speciosa, its pharmacological potential, and its phytochemical content in attenuating diabetic vasculopathy. Glycemic status, oxidative stress, inflammation, and hyperlipidemia are known to play pivotal roles in the initiation and severity of diabetic cardiovascular diseases; thus, targeting these factors might be beneficial for preventing and/or treating diabetic vasculopathy.

Japan's largest platform for academic e-journals: J-STAGE is a full text database for reviewed academic papers published by Japanese societies