Role of anthraquinones in combating insulin resistance.

Insulin resistance presents a formidable public health challenge that is intricately linked to the onset and progression of various chronic ailments, including diabetes, cardiovascular disease, hypertension, metabolic syndrome, nonalcoholic fatty liver disease, and cancer. Effectively addressing insulin resistance is paramount in preventing and managing these metabolic disorders. Natural herbal remedies show promise in combating insulin resistance, with anthraquinone extracts garnering attention for their role in enhancing insulin sensitivity and treating diabetes. Anthraquinones are believed to ameliorate insulin resistance through diverse pathways, encompassing activation of the AMP-activated protein kinase (AMPK) signaling pathway, restoration of insulin signal transduction, attenuation of inflammatory pathways, and modulation of gut microbiota. This comprehensive review aims to consolidate the potential anthraquinone compounds that exert beneficial effects on insulin resistance, elucidating the underlying mechanisms responsible for their therapeutic impact. The evidence discussed in this review points toward the potential utilization of anthraquinones as a promising therapeutic strategy to combat insulin resistance and its associated metabolic diseases.

Impacts of Plant-derived Secondary Metabolites for Improving Flora in Type 2 Diabetes.

BACKGROUND: Diabetes has become a problem that plagues public healthcare systems. Recent studies have shown that intestinal flora exerts positive therapeutic effects on metabolic diseases, and plant-derived secondary metabolites are safe, effective and easy to prepare and also have an impact on intestinal flora and diabetes; these drugs have rarely been reviewed before as a class of drugs for diabetes, especially focusing on the intestinal flora. Therefore, studying the relationship between plant-derived secondary metabolites and diabetes mellitus is crucial. OBJECTIVE: The objective of this study is to summarize and investigate the therapeutic mechanism of drugs extracted from natural plants effects on type 2 diabetes mellitus. METHODS: The relationship between flora and type 2 diabetes was investigated by reviewing the recent experimental literature, and the pathways available for natural plant-derived secondary metabolites in the treatment of type 2 diabetes were summarized. RESULTS: The therapeutic mechanisms of common plant-derived secondary metabolites for type 2 diabetes were summarized with a focus on the prebiotic efficacy of natural plant-derived secondary metabolites and the modulation of intestinal flora, and the mechanisms through which plantderived secondary metabolites treat type 2 diabetes via effects on intestinal flora are further reviewed. CONCLUSION: Common plant-derived secondary metabolites can play a role in regulating bacteria in the intestinal tract by enriching beneficial bacteria and removing harmful bacteria to achieve their therapeutic effect on type 2 diabetes. In addition, due to their excellent ability to regulate intestinal flora, plant-derived secondary metabolites may also have excellent efficacy in cancer and obesity, among other diseases.

Allicin Alleviates Diabetes Mellitus by Inhibiting the Formation of Advanced Glycation End Products.

Advanced glycation end products (AGEs) cause damage to pancreatic ß-cells and trigger oxidative stress and inflammation, which promotes the development and progression of diabetes and its complications. Therefore, it is important to inhibit the formation of AGEs as part of the treatment of diabetes. Allicin is a natural antimicrobial agent with abundant pharmacological activities, and recent studies have reported its therapeutic effects in diabetes; however, the mechanism of these therapeutic effects is still unclear. Thus, the purpose of this study was to further investigate the association between allicin treatment of diabetes and AGEs. First, we established a streptozocin (STZ)-induced diabetic rat model and treated the rats with allicin for six weeks. We measured glycolipid metabolism, AGE levels, receptor of advanced glycation end products (RAGE) levels, oxidative stress, and other related indicators. The results showed that allicin improved blood glucose and body weight, reduced lipid accumulation, and inhibited AGE formation in rats. Treatment with allicin also inhibited RAGEs and thereby prevented AGE activity, which, in turn, alleviated oxidative stress and promoted insulin secretion. To further verify the effect of allicin on AGEs, we also performed in vitro nonenzymatic glycation simulation experiments. These results showed that allicin inhibited the production of AGEs by suppressing the production of AGEs intermediates. Thus, our research suggests that allicin may alleviate diabetes by inhibiting the formation of AGEs and reducing RAGE levels to relieve oxidative stress and promote insulin secretion.

Novel advances in inhibiting advanced glycation end product formation using natural compounds.

Advanced glycation end products (AGEs) are a group of complex compounds generated by nonenzymatic interactions between proteins and reducing sugars or lipids. AGEs accumulate in vivo and activate various signaling pathways closely related to the occurrence of various chronic metabolic diseases. In this paper, we describe the process through which AGEs are formed, the classification of AGEs, and biological effects of AGEs on human health. Most importantly, we review recent progress in natural compound-based AGE formation inhibitors. Major classes of natural inhibitors, including polyphenols, polysaccharides, terpenoids, vitamins and alkaloids, have been described. Their mechanisms of action have been summarized as scavenging free radicals, chelating metal ions, capturing active carbonyl compounds, protecting protein glycation sites, and lowering blood glucose levels. Although these natural compounds have good antiglycation activity, to date, they are not widely used in the clinic, likely because of their low content levels. However, these natural compounds and their molecular frameworks will play a valuable role in inspiring drug discovery.

Variants in the RARRES2 gene are associated with serum chemerin and increase the risk of diabetic kidney disease in type 2 diabetes.

Genetic susceptibility plays an important role in the pathogenesis of diabetic kidney disease (DKD). Recent studies have suggested that chemerin (encoded by the RARRES2 gene) is a risk factor for the development of DKD. We investigate the relationship between RARRES2 single nucleotide polymorphisms (SNPs) and DKD and their correlation with serum chemerin levels in Chinese individuals with type 2 diabetes (T2D). A total of 256 individuals with T2D were enrolled in this case-control study and classified into normo-, micro- and macroalbuminuria groups according to their urinary albumin/creatinine ratio (UACR). All exons of the RARRES2 gene were sequenced by polymerase chain reaction-direct sequencing, and 7 SNPs were genotyped. We found that the minor alleles of rs1047207, rs1047575 and rs1047586 were significantly associated with macroalbuminuria. Carriers of the minor allele of rs1047575 and rs1047586 also had higher urinary albumin (U-Alb) and UACR levels under both homo- and heterozygotic conditions than carriers of the major allele under the homozygotic condition. The minor alleles of rs1047207, rs1047575 and rs1047586 were significantly associated with increased serum chemerin levels under the homozygotic condition. These SNPs in the RARRES2 gene probably affect chemerin expression and likely confer susceptibility to albuminuria in individuals with T2D.

Changes of saliva microbiota in the onset and after the treatment of diabetes in patients with periodontitis.

The relationship between type 2 diabetes mellitus (T2DM) and oral microbiota is still insufficiently recognized. In the present study, we compared the salivary microbiome of nondiabetic individuals, treatment-naïve diabetic patients, and diabetic patients treated with metformin or a combination of insulin and other drugs. The α- and ß-diversity demonstrated significant differences in the salivary microbiome between the nondiabetic people and patients with a history of diabetes, while little divergence was found among individuals with a history of diabetes. After characterizing the effects of periodontitis on the microbial composition of each group, the salivary microbiome of the treatment-naïve diabetic patient group was compared with that of nondiabetic people and the metformin/combined treatment groups. The results revealed changes in the contents of certain bacteria after both the onset and the treatment of diabetes; among these differential bacteria, Blautia_wexlerae, Lactobacillus_fermentum, Nocardia_coeliaca and Selenomonas_artemidis varied in all processes. A subsequent correlational analysis of the differential bacteria and clinical characteristics demonstrated that salivary microbes were related to drug treatment and certain pathological changes. Finally, the four common differential bacteria were employed for distinguishing the treatment-naïve diabetic patients from the nondiabetic people and the treated patients, with prediction accuracies of 83.3%, 75% and 75%, respectively.

An update on the potential role of advanced glycation end products in glycolipid metabolism.

Advanced glycation end products (AGEs) play a crucial role in many major diseases, such as diabetes and atherosclerosis. AGE accumulation in the body is generally considered a consequence of hyperglycaemia. However, recent studies have shown that AGEs may also be an important cause of the initial pathogenesis of diabetes and atherosclerosis. The objective of the present review is to provide an update on the AGE-induced mechanisms involved in the pathophysiology of glucose and lipid metabolism, even though the unique mechanisms involved in these diseases are not well understood. AGE precursors (methylglyoxal) and AGE receptors have been demonstrated in animal models to mediate insulin resistance and lipid metabolism disorders. Although we have not yet achieved a complete understanding of the role of AGEs, emerging therapeutic interventions targeting AGE reduction and AGE-RAGE signalling have yielded some beneficial clinical outcomes. Additional studies are needed to evaluate the utility and mechanism of circulating and tissue AGEs to support the identification of efficient and specific interventions.

The Potential Role of Probiotics in Controlling Overweight/Obesity and Associated Metabolic Parameters in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: The prevalence of overweight/obesity in adults is raised to 39%, which is nearly tripled more than 1975. The alteration of the gut microbiome has been widely accepted as one of the main causal factors. To find an effective strategy for the prevention and treatment of overweight/obesity, a systematic review and meta-analysis were designed. METHODS: In this study, we systematically reviewed the article published from January 2008 to July 2018 and conducted a meta-analysis to examine the effects of probiotics on body weight control, lipid profile, and glycemic control in healthy adults with overweight or obesity. The primary outcomes were body weight, body mass index (BMI), waist circumference, fat mass, fat percentages, plasma lipid profiles, and glucose metabolic parameters. RESULTS: We systematically searched PubMed, Embase, and the Web of Science and identified 1248 articles, and 7 articles which were manually searched by the references of included studies and previously systematic reviews. Twelve randomized controlled trials (RCTs), including 821 participants, were included in the meta-analysis via full-text screening. Probiotics supplementation resulted in a statistical reduction in body weight (WMD [95% CI]; -0.55 [-0.91, -0.19] kg), BMI (WMD [95% CI]; -0.30 [-0.43, -0.18] kg m-2), waist circumference (WMD [95% CI]; -1.20 [-2.21, -0.19] cm), fat mass (WMD [95% CI]; -0.91 [-1.19, -0.63] kg), and fat percentage (WMD [95% CI]; -0.92 [-1.27, -0.56] %) compared with control groups. As expected, the metabolic parameters were improved significantly, with a pooled standardized mean difference in TC (SMD [95% CI]; -0.43 [-0.80, -0.07]), LDL-C (SMD [95% CI]; -0.41 [-0.77, -0.04]), FPG (SMD [95% CI]; -0.35 [-0.67, -0.02]), insulin (SMD [95% CI]; -0.44 [-0.84, -0.03]), and HOMA-IR (SMD [95% CI]; -0.51 [-0.96, -0.05]), respectively. The changes in TG (SMD [95% CI]; 0.14 [-0.23, 0.50]), HDL-C (SMD [95% CI]; -0.31 [-0.70, 0.07]), and HbA1c (SMD [95% CI]; -0.23 [-0.46, 0.01]) were not significant. CONCLUSION: This study suggests that the probiotics supplementation could potentially reduce the weight gain and improve some of the associated metabolic parameters, which may become an effective strategy for the prevention and treatment of obesity in adult individuals.

The effect of cassia seed extract on the regulation of the LKB1-AMPK-GLUT4 signaling pathway in the skeletal muscle of diabetic rats to improve the insulin sensitivity of the skeletal muscle.

BACKGROUND: This study aimed to observe the hypoglycemic effect of cassia seed extract in rats with type-2 diabetes mellitus and its effect on reducing insulin resistance in the skeletal muscle. METHODS: 50 rats were randomly divided into the normal, model, high-dose, middle-dose, and low-dose groups of cassia seed extract (n = 10 each). A high-fat diet combined with streptozotocin administration was adopted to build type 2 diabetes models. The cassia seed extract groups were fed different concentrations cassia seed extract while the normal and model groups were fed the same volume of normal saline. The weight, FINS, GIR, insulin tolerance, blood glucose and blood lipid level, oxidative stress indices and expressions related to the LKB1-AMPK-GLUT4 pathway were detected and compared between the two groups. RESULTS: Compared with the normal group, the model group showed lower weight, glucose infusion rate and expressions related to LKB1-AMPK-GLUT4 pathway and higher FINS, insulin tolerance, blood glucose and blood lipid level and oxidative stress indices (all P < 0.05). Compared with the model group, higher weight, glucose infusion rate and expressions related to LKB1-AMPK-GLUT4 pathway and lower FINS, insulin tolerance, blood glucose and blood lipid level and oxidative stress indices were observed in all groups that were administered cassia see extract (all P < 0.05). CONCLUSION: Cassia seed extract could noticeably improve the insulin resistance of diabetic rats and enhance the insulin sensitivity of their skeletal muscles. Its mechanism may be related to damage repair of the LKB1-AMPK-GLUT4 signaling pathway and oxidative stress in the skeletal muscle.