Effects of Gossypetin on Glucose Homeostasis in Diet-Induced Pre-Diabetic Rats.

Natural flavonoids exert many potential health benefits, including anti-hyperglycaemic effects. However, the effects of gossypetin (GTIN) on glucose homeostasis in pre-diabetes have not yet been investigated. This study examined the effects of GTIN on key markers of glucose homeostasis in a diet-induced pre-diabetic rat model. Pre-diabetes was induced by allowing the animals to feed on a high-fat high-carbohydrate (HFHC) diet supplemented with 15% fructose water for 20 weeks. Following pre-diabetes induction, the pre-diabetic animals were sub-divided into five groups (n = 6), where they were either orally treated with GTIN (15 mg/kg) or metformin (MET) (500 mg/kg), both with and without dietary intervention, over a 12-week period. The results demonstrated that animals in the untreated pre-diabetic (PD) control group exhibited significantly higher fasting and postprandial blood glucose levels, as well as elevated plasma insulin concentrations and increased homeostatic model assessment for insulin resistance (HOMA2-IR) index, relative to the non-pre-diabetic (NPD) group. Similarly, increased caloric intake, body weight and plasma ghrelin levels were observed in the PD control group. Notably, these parameters were significantly reduced in the PD animals receiving GTIN treatment. Additionally, glycogen levels in the liver and skeletal muscle, which were disturbed in the PD control group, showed significant improvement in both GTIN-treated groups. These findings may suggest that GTIN administration, with or without dietary modifications, may offer therapeutic benefits in ameliorating glucose homeostasis disturbances associated with the PD state.

Exploring the Biological Effects of Anti-Diabetic Vanadium Compounds in the Liver, Heart and Brain.

The prevalence of diabetes mellitus and diabetes-related complications is rapidly increasing worldwide, placing a substantial financial burden on healthcare systems. Approximately 537 million adults are currently diagnosed with type 1 or type 2 diabetes globally. However, interestingly, the increasing morbidity rate is primarily influenced by the effects of long-term hyperglycemia on vital organs such as the brain, the liver and the heart rather than the ability of the body to use glucose effectively. This can be attributed to the summation of the detrimental effects of excessive glucose on major vascular systems and the harmful side effects attributed to the current treatment associated with managing the disease. These drugs have been implicated in the onset and progression of cardiovascular disease, hepatocyte injury and cognitive dysfunction, thereby warranting extensive research into alternative treatment strategies. Literature has shown significant progress in utilizing metal-based compounds, specifically those containing transition metals such as zinc, magnesium and vanadium, in managing hyperglycaemia. Amongst these metals, research carried out on vanadium reflected the most promising anti-diabetic efficacy in cell culture and animal studies. This was attributed to the ability to improve glucose management in the bloodstream by enhancing its uptake and metabolism in the kidney, brain, skeletal muscle, heart and liver. Despite this, organic vanadium was considered toxic due to its accumulative characteristics. To alleviate vanadium's toxic nature while subsequently manipulating its therapeutic properties, vanadium complexes were synthesized using either vanadate or vanadyl as a base compound. This review attempts to evaluate organic vanadium salts' therapeutic and toxic effects, highlight vanadium complexes' research and provide insight into the novel dioxidovanadium complex synthesized in our laboratory to alleviate hyperglycaemia-associated macrovascular complications in the brain, heart and liver.

Anti-amyloid aggregation and anti-hyperglycemic activities of novel ruthenium uracil Schiff base compounds.

The formation and characterization of new diamagnetic ruthenium uracil mono-imine compounds: [(η6-p-cymene)RuII(L)Cl][BF4] (L = H2urpda = 5-((pyridin-2-yl)methyleneamino)-6-aminouracil) for 1, urdpy = 6-amino-1,3-dimethyl-5-((pyridin-2-ylmethylene)amino)uracil) for 2 or urqda = 5-((quinolin-2-yl)methyleneamino)-6-aminouracil) for 3); cis-[RuII(L)(bipy)2] (L =  urpy = 5-((pyridin-2-yl)methyleneamino)uracil) for 4 and H2dadp = 5,6-diaminouracil for 5) are described. A paramagnetic ruthenium uracil Schiff base compound,  trans-[RuIV(L)(PPh3)Cl2] (L = H2urpda for 6) was also formed. Various physicochemical techniques were utilized to characterize the novel ruthenium compounds. Similarly, the stabilities of 1 - 3 and 6 monitored in chloro-containing and the non-coordinating solvent, dichloromethane show that they are kinetically inert, whereas, in a high nucleophilic environment, the chloride co-ligands of these ruthenium complexes were rapidly substituted by DMSO. In contrast, the substitution of the labile co-ligands for these ruthenium complexes by DMSO molecules in a high chloride content was suppressed. Solution chemical reactivities of the different ruthenium complexes were rationalized by density functional theory computations. Furthermore, the binding affinities and strengths between BSA and the respective ruthenium complexes were monitored using fluorescence spectroscopy. In addition, the in vitro anti-diabetic activities of the novel metal complexes were assessed in selected skeletal muscle and liver cell lines.

Therapeutic Potential of Various Intermittent Fasting Regimens in Alleviating Type 2 Diabetes Mellitus and Prediabetes: A Narrative Review.

Intermittent fasting has drawn significant interest in the clinical research community due to its potential to address metabolic complications such as obesity and type 2 diabetes mellitus. Various intermittent fasting regimens include alternate-day fasting (24 h of fasting followed by 24 h of eating), time-restricted fasting (fasting for 14 h and eating within a 10 h window), and the 5:2 diet (fasting for two days and eating normally for the other five days). Intermittent fasting is associated with a reduced risk of type 2 diabetes mellitus-related complications and can slow their progression. The increasing global prevalence of type 2 diabetes mellitus highlights the importance of early management. Since prediabetes is a precursor to type 2 diabetes mellitus, understanding its progression is essential. However, the long-term effects of intermittent fasting on prediabetes are not yet well understood. Therefore, this review aims to comprehensively compile existing knowledge on the therapeutic effects of intermittent fasting in managing type 2 diabetes mellitus and prediabetes.

Evaluating the impact of type 2 diabetes mellitus on pulmonary vascular function and the development of pulmonary fibrosis.

The increasing prevalence of type 2 diabetes mellitus (T2DM) is a significant worldwide health concern caused by sedentary lifestyles and unhealthy diets. Beyond glycemic control, T2DM impacts multiple organ systems, leading to various complications. While traditionally associated with cardiovascular and microvascular complications, emerging evidence indicates significant effects on pulmonary health. Pulmonary vascular dysfunction and fibrosis, characterized by alterations in vascular tone and excessive extracellular matrix deposition, are increasingly recognized in individuals with T2DM. The onset of T2DM is often preceded by prediabetes, an intermediate hyperglycemic state that is associated with increased diabetes and cardiovascular disease risk. This review explores the relationship between T2DM, pulmonary vascular dysfunction and pulmonary fibrosis, with a focus on potential links with prediabetes. Pulmonary vascular function, including the roles of nitric oxide (NO), prostacyclin (PGI2), endothelin-1 (ET-1), thromboxane A2 (TxA2) and thrombospondin-1 (THBS1), is discussed in the context of T2DM and prediabetes. Mechanisms linking T2DM to pulmonary fibrosis, such as oxidative stress, dysregulated fibrotic signaling, and chronic inflammation, are explained. The impact of prediabetes on pulmonary health, including endothelial dysfunction, oxidative stress, and dysregulated vasoactive mediators, is highlighted. Early detection and intervention during the prediabetic stage may reduce respiratory complications associated with T2DM, emphasizing the importance of management strategies targeting blood glucose regulation and vascular health. More research that looks into the mechanisms underlying pulmonary complications in T2DM and prediabetes is needed.

Maternal prediabetes as a risk factor of preeclampsia and placental dysfunction in pregnant female Sprague-Dawley rats.

BACKGROUND: Prediabetes (PD) is associated with intermediate hyperglycaemia, dyslipidaemia, reduced nitric oxide (NO) bioavailability and moderate hypertension. All these factors are risk factor for preeclampsia (PE). However, the effects of the PD on placental function have not been shown. Accordingly, this study sought to investigate a possible link between maternal PD and the risk of developing PE. METHODS: Pregnant female Sprague-Dawley rats (N = 18) were divided into normal, preeclamptic and prediabetic groups (n = 6 in each group) to study the effects of maternal PD on placenta function over the period of 19 days. Blood glucose and blood pressure were measured on gestational day (GND) 0, 9 and 18. Placental vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) mRNA expression were measured terminally. Data were analysed using ANOVA followed by the Tukey-Kramer post hoc test. Values of p < .05 were used to indicate statistical significance. RESULTS: Maternal PD and PE significantly increased blood glucose, decrease NO concentration and increase in MAP by comparison to the normal pregnant control group. Maternal PD significantly decreased VEGF, PlGF mRNA expression with a slight increase in sFlt-1 mRNA expression comparison to the normal pregnant control group. CONCLUSIONS: Maternal PD is associated with placental dysfunction due to impaired glucose handling, endothelial dysfunction and an imbalance in angiogenic and antiangiogenic factors. Therefore, maternal PD is a risk factor of PE.

People with prediabetes (PD) are at risk of developing type 2 diabetes. Studies have shown that PD can cause blood vessel problems in both men and women. However, there have not been any studies on prediabetic pregnant women, so we do not know much about the pregnancy problems they might face. Looking into new factors related to blood vessel growth and health in PD could help us understand how to diagnose and manage PD during pregnancy. This could reduce the risk of problems similar to pre-eclampsia. Research in this area will help mothers and their doctors be more aware of the complications PD can cause during pregnancy. This could lead to fewer health problems and deaths for both mothers and babies linked to type 2 diabetes.

Improved Gut Health May Be a Potential Therapeutic Approach for Managing Prediabetes: A Literature Review.

Given the growing global threat and rising prevalence of type 2 diabetes mellitus (T2DM), addressing this metabolic disease is imperative. T2DM is preceded by prediabetes (PD), an intermediate hyperglycaemia that goes unnoticed for years in patients. Several studies have shown that gut microbial diversity and glucose homeostasis in PD or T2DM patients are affected. Therefore, this review aims to synthesize the existing literature to elucidate the association between high-calorie diets, intestinal permeability and their correlation with PD or T2DM. Moreover, it discusses the beneficial effects of different dietary interventions on improving gut health and glucose metabolism. The primary factor contributing to complications seen in PD or T2DM patients is the chronic consumption of high-calorie diets, which alters the gut microbial composition and increases the translocation of toxic substances from the intestinal lumen into the bloodstream. This causes an increase in inflammatory response that further impairs glucose regulation. Several dietary approaches or interventions have been implemented. However, only a few are currently in use and have shown promising results in improving beneficial microbiomes and glucose metabolism. Therefore, additional well-designed studies are still necessary to thoroughly investigate whether improving gut health using other types of dietary interventions can potentially manage or reverse PD, thereby preventing the onset of T2DM.

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes.

Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes.

Pregestational Prediabetes Induces Maternal Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation and Results in Adverse Foetal Outcomes.

Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.

The relationship between adipose tissue RAAS activity and the risk factors of prediabetes in different ethnicities: A protocol for a systematic review and meta-analysis.

BACKGROUND: The incidence and prevalence of prediabetes has become a global concern. The risk factors of prediabetes, such as insulin resistance, adiposity, lipotoxicity and obesity, in conjunction with the alteration of the renin-angiotensin-aldosterone system (RAAS), have been positively correlated with the high morbidity and mortality rate. Thus, this systematic review seeks to establish the relationship between the risk factors of prediabetes, namely insulin resistance adiposity, lipotoxicity, obesity and the RAAS. Therefore, a synthesis of these risk factors, their clinical indicators and the RAAS components will be compiled in order to establish the association between the RAAS alteration and obesity in prediabetic patients. METHODS: This protocol for a systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) standards. This will be accomplished by searching clinical Medical Subject Headings categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers will examine all of the findings and select the studies that meet the qualifying criteria. To check for bias, the Downs and Black Checklist will be used, followed by a Review Manager v5. A Forrest plot will be used for the meta-analysis and sensitivity analysis. Furthermore, the strength of the evidence will be assessed utilizing the Grading of Recommendations Assessment, Development, and Evaluation procedure (GRADE). The protocol has been registered with PROSPERO CRD42022320252. This systematic review and meta-analysis will include published randomized clinical trials, observational studies and case-control studies from the years 2000 to 2022.

Investigating the Effects of Diet-Induced Prediabetes on Skeletal Muscle Strength in Male Sprague Dawley Rats.

Type 2 diabetes mellitus, a condition preceded by prediabetes, is documented to compromise skeletal muscle health, consequently affecting skeletal muscle structure, strength, and glucose homeostasis. A disturbance in skeletal muscle functional capacity has been demonstrated to induce insulin resistance and hyperglycemia. However, the modifications in skeletal muscle function in the prediabetic state are not well elucidated. Hence, this study investigated the effects of diet-induced prediabetes on skeletal muscle strength in a prediabetic model. Male Sprague Dawley rats were randomly assigned to one of the two groups (n = 6 per group; six prediabetic (PD) and six non-pre-diabetic (NPD)). The PD group (n = 6) was induced with prediabetes for 20 weeks. The diet that was used to induce prediabetes consisted of fats (30% Kcal/g), proteins (15% Kcal/g), and carbohydrates (55% Kcal/g). In addition to the diet, the experimental animals (n = 6) were supplied with drinking water that was supplemented with 15% fructose. The control group (n = 6) was allowed access to normal rat chow, consisting of 35% carbohydrates, 30% protein, 15% fats, and 20% other components, as well as ordinary tap water. At the end of week 20, the experimental animals were diagnosed with prediabetes using the American Diabetes Association (ADA) prediabetes impaired fasting blood glucose criteria (5.6-6.9 mmol/L). Upon prediabetes diagnosis, the animals were subjected to a four-limb grip strength test to assess skeletal muscle strength at week 20. After the grip strength test was conducted, the animals were euthanized for blood and tissue collection to analyze glycated hemoglobin (HbA1c), plasma insulin, and insulin resistance using the homeostatic model of insulin resistance (HOMA-IR) index and malondialdehyde (MDA) concentration. Correlation analysis was performed to examine the associations of skeletal muscle strength with HOMA-IR, plasma glucose, HbA1c, and MDA concentration. The results demonstrated increased HbA1c, FBG, insulin, HOMA-IR, and MDA concentrations in the PD group compared to the NPD group. Grip strength was reduced in the PD group compared to the NPD group. Grip strength was negatively correlated with HbA1c, plasma glucose, HOMA-IR, and MDA concentration in the PD group. These observations suggest that diet-induced prediabetes compromises muscle function, which may contribute to increased levels of sedentary behavior during prediabetes progression, and this may contribute to the development of hyperglycemia in T2DM.

Bovine serum albumin uptake and polypeptide disaggregation studies of hypoglycemic ruthenium(II) uracil Schiff-base complexes.

Our prior studies have illustrated that the uracil ruthenium(II) diimino complex, [Ru(H3ucp)Cl(PPh3)] (1) (H4ucp = 2,6-bis-((6-amino-1,3-dimethyluracilimino)methylene)pyridine) displayed high hypoglycemic effects in diet-induced diabetic rats. To rationalize the anti-diabetic effects of 1, three new derivatives have been prepared, cis-[Ru(bpy)2(urdp)]Cl2 (2) (urdp = 2,6-bis-((uracilimino)methylene)pyridine), trans-[RuCl2(PPh3)(urdp)] (3), and cis-[Ru(bpy)2(H4ucp)](PF6)2 (4). Various physicochemical techniques were utilized to characterize the structures of the novel ruthenium compounds. Prior to biomolecular interactions or in vitro studies, the stabilities of 1-4 were monitored in anhydrous DMSO, aqueous phosphate buffer containing 2% DMSO, and dichloromethane (DCM) via UV-Vis spectrophotometry. Time-dependent stability studies showed ligand exchange between DMSO nucleophiles and chloride co-ligands of 1 and 3, which was suppressed in the presence of an excess amount of chloride ions. In addition, the metal complexes 1 and 3 are stable in both DCM and an aqueous phosphate buffer containing 2% DMSO. In the case of compounds 2 and 4 with no chloride co-ligands within their coordination spheres, high stability in aqueous phosphate buffer containing 2% DMSO was observed. Fluorescence emission titrations of the individual ruthenium compounds with bovine serum albumin (BSA) showed that the metal compounds interact non-discriminately within the protein's hydrophobic cavities as moderate to strong binders. The metal complexes were capable of disintegrating mature amylin amyloid fibrils. In vivo glucose metabolism studies in liver (Chang) cell lines confirmed enhanced glucose metabolism as evidenced by the increased glucose utilization and glycogen synthesis in liver cell lines in the presence of complexes 2-4.

Glycaemic abnormalities induced by small molecule tryosine kinase inhibitors: a review.

In light of the expected increase in the prevalence of diabetes mellitus due to an aging population, sedentary lifestyles, an increase in obesity, and unhealthy diets, there is a need to identify potential pharmacological agents that can heighten the risk of developing diabetes. Similarly, it is equally important to also identify those agents that show blood glucose-lowering properties. Amongst these agents are tyrosine kinase inhibitors used to treat certain types of cancers. Over the last two decades, there has been an increase in the use of targeted chemotherapy for cancers such as renal cell carcinoma, chronic leukaemia, and gastrointestinal stromal tumours. Small molecule tyrosine kinase inhibitors have been at the forefront of targeted chemotherapy. Studies have shown that small molecule tyrosine kinase inhibitors can alter glycaemic control and glucose metabolism, with some demonstrating hypoglycaemic activities whilst others showing hyperglycaemic properties. The mechanism by which small molecule tyrosine kinase inhibitors cause glycaemic dysregulation is not well understood, therefore, the clinical significance of these chemotherapeutic agents on glucose handling is also poorly documented. In this review, the effort is directed at mapping mechanistic insights into the effect of various small molecule tyrosine kinase inhibitors on glycaemic dysregulation envisaged to provide a deeper understanding of these chemotherapeutic agents on glucose metabolism. Small molecule tyrosine kinase inhibitors may elicit these observed glycaemic effects through preservation of ß-cell function, improving insulin sensitivity and insulin secretion. These compounds bind to a spectrum of receptors and proteins implicated in glucose regulation for example, non-receptor tyrosine kinase SRC and ABL. Then receptor tyrosine kinase EGFR, PDGFR, and FGFR.

The Role of Pro-Opiomelanocortin Derivatives in the Development of Type 2 Diabetes-Associated Myocardial Infarction: Possible Links with Prediabetes.

Myocardial infarction is a major contributor to CVD-related mortality. T2DM is a risk factor for MI. Stress activates the HPA axis, SNS, and endogenous OPS. These POMC derivatives increase the blood glucose and cardiovascular response by inhibiting the PI3K/AkT insulin signaling pathway and increasing cardiac contraction. Opioids regulate the effect of the HPA axis and SNS and they are cardioprotective. The chronic activation of the stress response may lead to insulin resistance, cardiac dysfunction, and MI. Stress and T2DM, therefore, increase the risk of MI. T2DM is preceded by prediabetes. Studies have shown that prediabetes is associated with an increased risk of MI because of inflammation, hyperlipidemia, endothelial dysfunction, and hypertension. The HPA axis is reported to be dysregulated in prediabetes. However, the SNS and the OPS have not been explored during prediabetes. The effect of prediabetes on POMC derivatives has yet to be fully explored and understood. The impact of stress and prediabetes on the cardiovascular response needs to be investigated. This study sought to review the potential impact of prediabetes on the POMC derivatives and pathways that could lead to MI.

Review of the direct and indirect effects of hyperglycemia on the HPA axis in T2DM and the co-occurrence of depression.

Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which is further associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Several studies have shown that HPA axis hyperactivity is heightened in the chronic hyperglycemic state with severe hyperglycemic events more likely to result in a depressive disorder. The HPA axis is also regulated by the immune system. Upon stress, under homeostatic conditions, the immune system is activated via the sympatho-adrenal-medullary axis resulting in an immune response which secretes proinflammatory cytokines. These cytokines aid in the activation of the HPA axis during stress. However, in T2DM, where there is persistent hyperglycemia, the immune system is dysregulated resulting in the elevated concentrations of these cytokines. The HPA axis, already activated by the hyperglycemia, is further activated by the cytokines which all contribute to a diagnosis of depression in patients with T2DM. However, the onset of T2DM is often preceded by pre-diabetes, a reversible state of moderate hyperglycemia and insulin resistance. Complications often seen in T2DM have been reported to begin in the pre-diabetic state. While the current management strategies have been shown to ameliorate the moderate hyperglycemic state and decrease the risk of developing T2DM, research is necessary for clinical studies to profile these direct effects of moderate hyperglycemia in pre-diabetes on the HPA axis and the indirect effects moderate hyperglycemia may have on the HPA axis by investigating the components of the immune system that play a role in regulating this pathway.

Investigation into changes in inflammatory and immune cell markers in pre-diabetic patients from Durban, South Africa.

The prevalence of pre-diabetes is increasing in rapidly urbanizing cities, especially in individuals aged 25 - 45 years old. Studies also indicate that this condition is associated with aberrant immune responses that are also influenced by environmental factors. This study sought to investigate changes in the concentration of immune cells and select inflammatory markers in patients with pre-diabetes in Durban, South Africa. Blood samples collected from King Edward Hospital, after obtaining ethics approval, were divided into non-diabetic (ND), pre-diabetic (PD) and type 2 diabetic (T2D) using ADA criteria. In each sample, the concentration of immune cells and select inflammatory markers were determined. The results showed a significant increase in eosinophil and basophil levels in the PD group as compared to the ND group. Compared to ND, the PD and T2D groups had significant increases in serum TNFα, CD40L and fibrinogen concentrations. Additionally, there were decreases in serum CRP, IL-6, and P-selectin in the PD group while these markers increased in the T2D group. These findings were indicative of immune activation and highlight the impact of pre-diabetes in this population. More studies are recommended with a higher number of samples that are stratified by gender and represent the gender ratio in the city.

Momordica balsamina improves glucose handling in a diet-induced prediabetic rat model.

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological treatment and dietary interventions are recommended to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Momordica balsamina (MB) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this medicinal plant in conjunction with dietary intervention on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects of MB on glucose homeostasis in a diet-induced pre-diabetes rat model in the presence and absence of dietary intervention. Pre-diabetes was induced on male Sprague Dawley rats by a high fat high carbohydrate (HFHC) diet for a period of 20 weeks. Pre-diabetic male Sprague Dawley rats were treated with MB (250 mg/kg p.o.) in both the presence and absence of dietary intervention once a day every third day for a period of 12 weeks. The administration of MB with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, with reduced plasma ghrelin concentration and glycated hemoglobin by comparison to the pre-diabetic control. MB administration also improved insulin sensitivity as evidenced by the expression of glucose transporter 4 (GLUT 4) and glycogen synthase on the prediabetic treated animals. These results suggest that MB has the potential to be used to manage pre-diabetes and prevent the progression to overt type 2 diabetes as it demonstrated the ability to restore glucose homeostasis even in the absence of dietary and lifestyle intervention.

Phytochemical constituents from the roots and lignotubers of Rhoicissus tridentata and their in vitro uterotonic activity.

Rhoicissus tridentata is one of the most frequently used plants in preparing Isihlambezo, a herbal drink consumed by many South African women to induce labour and tone the uterus in pregnancy. This study aimed to identify the uteroactive compounds in this plant. Chromatographic purification of the methanol and water extracts from the roots yielded eight compounds, i.e. morin 3-O-α-L-rhamnopyranoside, trans-resveratrol 3-O-ß-glucopyranoside, a mixture of asiatic and arjunolic acids, quercetin 3-O-rhamnopyranoside, catechin, ß-sitosterol, and linoleic acid. All compounds were evaluated for their uterotonic effects using uterine smooth muscle isolated from stilboestrol-primed Sprague-Dawley rats. The mixture of asiatic and arjunolic acids showed the highest activity with EC50 of 0.02129 µg/mL for amplitude. These results validate the use of R. tridentata in ethnomedicine to facilitate labour in childbirth. Morin 3-O-α-L-rhamnopyranoside and trans-resveratrol 3-O-ß-glucopyranoside caused a relaxation of the uterine muscle, which suggests that some compounds in R. tridentata possess opposing activities.

The Potential Role of Gossypetin in the Treatment of Diabetes Mellitus and Its Associated Complications: A Review.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder caused by insulin resistance and dysfunctional beta (ß)-cells in the pancreas. Hyperglycaemia is a characteristic of uncontrolled diabetes which eventually leads to fatal organ system damage. In T2DM, free radicals are continuously produced, causing extensive tissue damage and subsequent macro-and microvascular complications. The standard approach to managing T2DM is pharmacological treatment with anti-diabetic medications. However, patients' adherence to treatment is frequently decreased by the side effects and expense of medications, which has a detrimental impact on their health outcomes. Quercetin, a flavonoid, is a one of the most potent anti-oxidants which ameliorates T2DM. Thus, there is an increased demand to investigate quercetin and its derivatives, as it is hypothesised that similar structured compounds may exhibit similar biological activity. Gossypetin is a hexahydroxylated flavonoid found in the calyx of Hibiscus sabdariffa. Gossypetin has a similar chemical structure to quercetin with an extra hydroxyl group. Furthermore, previous literature has elucidated that gossypetin exhibits neuroprotective, hepatoprotective, reproprotective and nephroprotective properties. The mechanisms underlying gossypetin's therapeutic potential have been linked to its anti-oxidant, anti-inflammatory and immunomodulatory properties. Hence, this review highlights the potential role of gossypetin in the treatment of diabetes and its associated complications.