Reduced Fasting Blood Glucose Levels Research Articles

A Potential Diabetic-Friendly Food Material: Optimization, Nutritional Quality, Structural Characteristics, and Functional Properties of Oat and Purple Potato Fermented by Ganoderma lucidum Mycelium

Dietary intervention is the basis for the treatment of diabetes mellitus. This study employed Ganoderma lucidum (GL) mycelium to ferment a compound medium of oat and purple potato (OPP), optimized fermentation conditions to increase the triterpene content in the resulting product (F-OPPF), and systematically investigated the impact of fermentation on the nutritional quality, structural characteristics, and functional properties of OPP. The results indicated that the triterpene content in F-OPPF significantly increased from 8.53 mg/g to 17.23 mg/g under optimal conditions (temperature: 28 °C, inoculum size: 10%, material quantity: 36 g/250 mL, and fermentation time: day 13). Fermentation resulted in enhanced nutritional quality, with increased contents of protein, soluble protein, crude fiber, ash, mineral elements, essential amino acids, polysaccharides, flavonoids, and total phenols. Mycelium not only enveloped the OPP surface but also penetrated its interior, forming a porous honeycomb-like structure. The types of reactive groups and crystals (C + V-type) were not changed after fermentation, while the crystallinity increased. F-OPPF exhibited positive changes in thermogravimetric properties, antioxidant and hypoglycemic activities, and adsorption capacity of insoluble dietary fiber. Additionally, incorporating F-OPPF into the diet markedly reduced fasting blood glucose levels and promoted weight gain in T2DM rats induced by a high-fat diet and streptozotocin. The fermented groups exhibited improvements in glyco- and lipo-metabolism, oxidative stress, and the function and pathological morphology of the pancreas, liver, and kidneys compared to the unfermented group. Collectively, these findings suggested that GL mycelium fermentation enhanced the nutritional and functional values of OPP, and F-OPPF holds potential as a raw material for developing diabetic-friendly foods.

Double-blind Randomized placebo-controlled Trials on controlling blood glucose level using the extract from <i>Opuntia ficus-indica</i> var. saboten

Objectives: The aim of this study was to evaluate the effects of Opuntia ficus-indica var. saboten extract on blood glucose regulation in both healthy individuals and those with impaired fasting glucose (IFG). Additionally, the study assessed the safety of <i>Opuntia</i> extract regarding liver and kidney function over a 12-week period.Methods: A double-blind, randomized, placebo-controlled clinical trial was conducted with 85 participants, including 47 healthy individuals and 38 individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IFG). Participants were randomly assigned to receive either Opuntia extract or a placebo for 12 weeks. Blood glucose control was evaluated using fasting blood glucose (FBS), oral glucose tolerance tests (OGTT), HbA1c, insulin, and C-peptide levels. Safety assessments included liver function tests (AST, ALT, <i>γ</i>-GTP, ALP) and kidney function tests (BUN, creatinine). Data were analyzed using independent and paired t-tests, with a significance level of p<0.05.Results: A total of 85 participants were initially enrolled, and after excluding 13 participants due to dropout, consent withdrawal, or protocol violations, the final statistical analysis was conducted with 72 participants. In the IFG group, Opuntia extract significantly reduced fasting blood glucose levels compared to the placebo group (p=0.010). Additionally, Opuntia extract reduced postprandial blood glucose levels at 120 minutes during the OGTT in healthy participants (p=0.047). No significant changes were observed in HbA1c, insulin, or C-peptide levels. Importantly, no adverse effects on liver or kidney function were detected in either group during the 12-week intervention.Conclusions: The administration of <i>Opuntia ficus-indica var. saboten</i> extract for 12 weeks demonstrated significant blood glucose-lowering effects in individuals with impaired glucose tolerance, without causing any liver or kidney toxicity. These findings suggest that <i>Opuntia</i> extract may be a safe and effective natural option for blood glucose regulation, particularly in pre-diabetic individuals. Further large-scale studies are recommended to confirm these results and explore its potential clinical applications.

Antidiabetic activity of Inonotus obliquus water extract in alloxan-induced diabetic mice.

The Inonotus obliquus is a medicinal mushroom that grows on mature birch trees and is commonly used in traditional medicine for various ailments. The current study aimed to explore the hypoglycemic, hypolipidemic, and pancreatic protective effects of the water extract of Mongolian natural Inonotus obliquus on alloxan-induced diabetic mice. Alloxan monohydrate (200 mg/kg) was intraperitoneally single injected into C57BL/6 mice to induce diabetes. Alloxan-induced diabetic mice were orally given the water extract of inonotus obliquus (WEIO) at doses of 500 mg/kg and subcutaneously administered with insulatard 0.6 IU for 4weeks. Subsequently, the levels of factors related to blood glucose, insulin and lipids were assessed. WEIO significantly restored body weight, reduced fasting blood glucose levels, improved glucose tolerance ability, and increased insulin levels compared to the control diabetic mice. WEIO also enhanced cholesterol transportation in the liver, correlated with increased HDL-C levels and decreased TC, TG and LDL-C levels. Histologic examinations revealed that WEIO alleviated alloxan-induced pancreatic tissue damage. Natural Mongolian I. Obliquus water extracts have an antihyperglycemic effect and enhance islet cell function in alloxan-induced diabetic mice. It is a good candidate for a hypoglycemic functional food or medicine.

Effects of Ficus exasperata on neurotransmission and expression of BDNF, tau, ACHE and BACE in diabetic rats

Diabetes mellitus, a chronic metabolic disorder, has significant global health implications, particularly due to its neurological complications, such as diabetic neuropathy. This condition increases the risk of neurodegenerative diseases by affecting peripheral nerves and cognition. Ficus exasperata, known for its neuroprotective properties, shows promise as a therapeutic option for addressing these complications. This study evaluates the effects of methanol extract of Ficus exasperata (MEFE) on neurotransmission and the expression of Tau, brain-derived neurotrophic factor (BDNF), acetylcholinesterase (ACHE), and Beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) in alloxan-induced diabetic Wistar rats. The controlled experimental design involved 20 Wistar rats divided into four groups (n = 5): control, diabetic untreated, diabetes + MEFE (200 mg/kg), and diabetes + insulin (0.3 IU). The methanol extract was prepared using cold maceration, and an aliquot was subjected to gas chromatography-mass spectrometry. Constituents of MEFE were docked with neurologic receptors. Blood glucose levels were measured using the glucose oxidase method, and neurotransmitter levels, antioxidants, oxidative stress markers, and the expression of Tau, BDNF, ACHE, and BACE were assessed using standard procedures and qRT-PCR. Data were analyzed using one-way ANOVA at P < 0.05. Results indicated that MEFE significantly reduced fasting blood glucose levels compared to untreated diabetic rats. In silico docking identified kaur-16-ene, a constituent of MEFE, as having the highest binding affinity for NMDA, TrkB, mAchR and nAchR receptors, indicating its neuroprotective potential. MEFE also enhanced antioxidant enzyme levels (SOD, GPx, catalase) while reducing oxidative stress markers (MDA, 8-OHdG). Gene expression analysis revealed that MEFE modulates the expression of Tau, BDNF, ACHE, and BACE, suggesting its potential to influence neurodegenerative pathways associated with diabetic neuropathy. Ficus exasperata demonstrates significant therapeutic potential in managing diabetic neuropathy and related cognitive impairments by modulating neurotransmission, protein expression, and antioxidant defenses.

1,3,4-Oxadiazole Scaffold in Antidiabetic Drug Discovery: An Overview.

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research. Oxadiazole is a five-membered heterocyclic organic compound containing two nitrogen atoms and one oxygen atom in its ring. Oxadiazole hybrids have shown the ability to improve glucose tolerance, enhance insulin sensitivity, and reduce fasting blood glucose levels. The mechanisms underlying the antidiabetic effects of oxadiazole involve the modulation of molecular targets such as peroxisome proliferator-activated receptor gamma (PPARγ), α-glucosidase, α-amylase and GSK-3β which regulate glucose metabolism and insulin secretion. The present review article describes the chemical structure and properties of oxadiazoles and highlights the antidiabetic activity through action on different targets. The SAR for the oxadiazole hybrids has been discussed in this article, which will pave the way for the design and development of new 1,3,4-oxadiazole derivatives as promising antidiabetic agents in the future. We expect that this article will provide comprehensive knowledge and current innovation on oxadiazole derivatives with antidiabetic potential and will fulfil the needs of the scientific community in designing and developing efficacious antidiabetic agents.

Lycium barbarum leaf flavonoids ameliorate high fructose induced insulin resistance in mice by regulating blood glucose and gut microbiota composition

Insulin resistance is an increasingly severe public health issue worldwide, affecting millions and significantly raising the risk of diabetes and cardiovascular diseases. Despite this, current treatment options remain limited, which has heightened interest in exploring interventions based on natural compounds. This study investigates the potential of Lycium barbarum leaf flavonoids (LBLF) to improve insulin resistance induced by high fructose in mice, with a focus on the mechanisms related to blood glucose regulation and gut microbiota composition. Research results show that, compared to the high fructose model group, treatment with metformin hydrochloride and rutin reduced fasting blood glucose levels by 32.06% and 18.94%, respectively. LBLF treatment at various doses decreased fasting blood glucose levels by 12.29%, 19.02%, and 32.98%, and insulin levels by 26.50%, 11.04%, and 28.23%, respectively, demonstrating its effective ability to regulate blood glucose levels. It was also found that LBLF effectively regulated lipid disorders, significantly reduced oxidative stress in the liver, and protected liver function. Liver transcriptomic analysis suggests that LBLF may improve insulin resistance by regulating gene expression in the MAPK and retinol metabolism signaling pathways. Additionally, gut microbiota diversity analysis revealed that LBLF treatment reduced the Firmicutes/Bacteroidetes (F/B) ratio, which is associated with obesity and metabolic disorders, thereby optimizing the gut microbiota structure disrupted by high fructose intake. These results highlight the therapeutic potential of LBLF in managing insulin resistance and associated metabolic disorders, providing a theoretical basis for further research into its broader applications.

A Neutral Polysaccharide from Medicago Sativa L.: Structural Properties and Hypoglycemic Activity In Vitro and In Vivo.

Medicago sativa polysaccharides (MSPs) are beneficial compounds extracted from Medicago sativa L. that exhibit multiple medicinal activities. However, little is known about their hypoglycemic effects. In this study, MSP-II-a, a neutral polysaccharide with an Mw of 4.3×104 Da, was isolated and purified from M. sativa L. Monosaccharide composition analysis determined that MSP-II-a was composed of arabinose, glucose, galactose, mannose, rhamnose, and xylose in a molar ratio of 2.1 : 4.0 : 1.1:0.4 : 1.4 : 1.1. Structural characterization of MSP-II was performed using a combination of methylation analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that MSP-II-a was mainly comprised of 1,4-p-Glc, 1,3,4-Rha, and 1,3-p-Gal glycosidic linkages, revealing a mesh-like texture with irregular blade shapes. In vitro assays demonstrated that MSP-II-a, at concentrations of 200 and 400 μg/mL, promoted glucose uptake in insulin-resistant 3T3-L1 adipocytes. In vivo studies have shown that MSP-II-a significantly alleviates insulin resistance by reducing fasting blood glucose levels and increasing hepatic glycogen synthesis in HFD/STZ-induced diabetic mice. These findings revealed that MSP-II-a is a promising source of bioactive polysaccharides with potential hypoglycemic activity.

Antidiabetic Effect of Bifidobacterium animalis TISTR 2591 in a Rat Model of Type 2 Diabetes.

This study investigated the beneficial effects of probiotic Bifidobacterium animalis TISTR 2591 on the regulation of blood glucose and its possible mechanisms in a rat model of type 2 diabetes. The type 2 diabetic-Sprague Dawley rats were established by the combination of a high-fat diet and a low dose of streptozotocin. After 4weeks of treatment with 2 × 108CFU/ml of B. animalis TISTR 2591, fasting blood glucose (FBG), oral glucose tolerance, serum insulin, and pancreatic and hepatic histopathology were determined. Liver lipid accumulation, glycogen content, and gluconeogenic protein expression were evaluated. Oxidative stress and inflammatory status were determined. B. animalis TISTR 2591 significantly reduced FBG levels and improved glucose tolerance and serum insulin in the diabetic rats. Structural damage of the pancreas and liver was ameliorated in the B. animalis TISTR 2591-treated diabetic rats. In addition, significant decreases in hepatic fat accumulation, glycogen content, and phosphoenolpyruvate carboxykinase-1 protein expression were found in the diabetic rats treated with B. animalis TISTR 2591. The diabetic rats showed a significant reduction of inflammation following B. animalis TISTR 2591 supplementation, as demonstrated by decreasing hepatic NF-κB protein expression and serum and liver TNF-α levels. The B. animalis TISTR 2591 significantly decreased MDA levels and increased antioxidant SOD and GPx activities in the diabetic rats. In conclusion, B. animalis TISTR 2591 was shown to be effective in controlling glucose homeostasis and improving glucose tolerance in the diabetic rats. These beneficial activities were attributed to reducing oxidative and inflammatory status and modulating hepatic glucose metabolism.

Carthamus tinctorius L. (Safflower) Flower Extract Attenuates Hepatic Injury and Steatosis in a Rat Model of Type 2 Diabetes Mellitus via Nrf2-Dependent Hypoglycemic, Antioxidant, and Hypolipidemic Effects.

This study aimed to examine the hepatic and anti-steatotic protective effects of methanolic extract from Carthamus tinctorius (safflower) flowers (SFFE), using a rat model of type 2 diabetes mellitus (T2DM), and to examine the molecular mechanisms underlying these effects. Adult male Wistar rats were used for this study. First, T2DM was induced in some rats by feeding them a high-fat diet (HFD) for 4 weeks, followed by a single dose of streptozotocin (STZ) (35 mg/kg, i.p.). Experimental groups included the following five groups (n = 8 in each): control, control + SFFE, T2DM, T2DM + SFFE, and T2DM + SFFE + brusatol (an Nrf2 inhibitor, 2 mg/kg, i.p.). SFFE was administered at a concentration of 300 mg/kg, and all experiments concluded after 8 weeks. Treatments with SFFE significantly reduced fasting blood glucose levels, free fatty acids (FFAs), cholesterol, triglycerides, and low-density lipoprotein cholesterol in both the control and T2DM rats, but they failed to reduce fasting insulin levels in these groups. SFFE treatments also improved the liver structure and reduced hepatocyte vacuolization and hepatic levels of triglycerides and cholesterol in T2DM rats, in addition to increasing the hepatic mRNA levels of keap1 and the cytoplasmic levels and nuclear activities of Nrf2 in both the control and T2DM rats. SFFE also stimulated the expression levels of PPARα and CPT-1 but reduced the malondialdehyde (MDA), mRNA levels of SREBP1, fatty acid synthase, and acetyl CoA carboxylase in both the control and T2DM rats; meanwhile, it reduced hepatic mRNA and the nuclear activities of NF-κB and increased levels of glutathione, superoxide dismutase, and heme oxygenase-1 in the livers of both groups of treated rats. Furthermore, SFFE suppressed the levels of caspase-3, Bax, tumor necrosis factor-α, and interleukin-6 in the T2DM rats. Treatment with brusatol prevented all of these effects of SFFE. In conclusion, SFFE suppresses liver damage and hepatic steatosis in T2DM through Nrf2-dependent hypoglycemic, antioxidant, anti-inflammatory, and hypolipidemic effects.

MiRNA-133a-3p Attenuates Renal Tubular Epithelial Cell Injury via Targeting MALM1 and Suppressing the Notch Signaling Pathway in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes characterized by structural and functional changes of kidneys. Human renal tubular epithelial (HK-2) cells are important for kidney recovery post injury and usually used for establishment of DN cell models. The study explored the role of microRNA (miR)-133a-3p in DN cell model and animal model. A cell model for DN was established via high glucose (HG) stimulation to HK-2 cells. Cell viability and apoptotic rate were measured by cell counting kit 8 and flow cytometry. Polymerase chain reaction was performed to quantify levels of miR-133a-3p and targets. Luciferase reporter assay was conducted to verify the binding of miR-133a-3p and MAML1. After establishment of a mouse model of DN, levels of renal function indicators were measured by biochemical analysis. Hematoxylin-eosin and periodic acid-schiff staining of kidney samples were performed to analyze histological changes. Western blotting was conducted to quantify levels of apoptotic markers, MAML1, and factors related to Notch signaling. Results showed that HG induced HK-2 cell apoptosis and the reduction of cell viability. MiR-133a-3p was lowly expressed in HG-stimulated HK-2 cells. Overexpressed miR-133a-3p improved HK-2 cell injury by increasing cell viability and hampering apoptosis under HG condition. In addition, miR-133a-3p directly targets MAML1 3'-untranslated region. MAML1 overexpression countervailed the repressive impact of miR-133a-3p on cell apoptosis in the context of HG. Moreover, miR-133a-3p inhibited the activity of Notch pathway by downregulating MAML1. MiR-133a-3p inhibits DN progression in mice, as evidenced by reduced fasting blood glucose level, improved levels of renal function parameters, and alleviation of kidney atrophy. In conclusion, miR-133a-3p improves HG-induced HK-2 cell injury and inhibits DN progression by targeting MAML1 and inactivating Notch signaling.

Carboxymethylation of paramylon derived from Euglena gracilis and its hypoglycemic mechanism in diabetic mice

Paramylon is a polysaccharide primarily composed of β-1,3-glucan, characterized by its high crystallinity and insolubility in water. Enhancing its water solubility through structural modifications presents an effective strategy to unlock its biological activity. In this study, carboxymethylation was employed to produce carboxymethylated paramylon (CEP) with varying carboxyl concentrations. The successful introduction of carboxyl groups led to a notable improvement in water solubility. In vivo experiments demonstrated that CEP reduced fasting blood glucose levels by 24.42 %, improved oral glucose tolerance, and enhanced insulin sensitivity in diabetic mice. Additionally, CEP regulated lipid homeostasis and ameliorated liver damage. Through modulation of the adenosine monophosphate-activated protein kinase/phosphoinositide 3-kinase/protein kinase B pathway and the glucose-6-phosphatase/phosphoenolpyruvate carboxykinase pathway, CEP effectively regulated hepatic glucose absorption and production. Furthermore, CEP mitigated diabetes-induced lipid metabolism disorders. These findings suggest that CEP holds significant promise in ameliorating glucose metabolism disorder, indicating its potential as a novel hypoglycemic functional food.

Evaluating the Efficacy of Metformin and Camel Milk on Streptozotocin-nicotinamide Induced Diabetic Albino Rats

Background: This study was intended to evaluate the anti-diabetic activity of metformin and camel milk solely or in combination in streptozotocin- nicotinamide induced type II diabetic albino Wistar rats. Methods: Thirty albino Wistar rats were induced with type II diabetes through streptozotocin (60 mg/kg), followed by the administration of nicotinamide (120 mg/kg) after 15 min. The rats were randomly divided into control, diabetic control, metformin-treated (100 mg/kg), camel milk-treated (50 ml/rat/day) and metformin + camel milk-treated groups for 30 days. For this study, rats with blood glucose levels higher than 250 mg/dL were included. Blood glucose levels and body weight were measured at the beginning of the study and at regular intervals throughout the experiment.Furthermore, histopathological examination of liver, kidney and pancreatic tissue was conducted to determine the effects of metformin and camel milk on these organs. Result: The results showed that treatment with metformin, camel milk, or a combination of both significantly reduced fasting blood glucose levels and improved body weight compared to the diabetic control group. Morphological improvements were also observed in the histopathological examination of liver, kidney and pancreatic tissue. The results of this study are consistent with previous research showing the anti-diabetic effects of metformin and support the emerging role of alternative therapies such as camel milk. However, further research is needed to explore the potential mechanisms underlying the observed effects.

Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism.

The incidence rate of gestational diabetes mellitus (GDM) remains high among pregnant women in the second trimester of pregnancy. However, the main clinical approach to alleviate the symptoms of GDM is to control the diet. Our study explored the therapeutic effects of omega-3 fatty acids (ω-3 FAs) on GDM at the cellular and animal levels. We found that ω-3 FAs can promote the transformation of M0 macrophages into anti-inflammatory M2 macrophages. The transformed M2 macrophages promoted β-oxidation and reduced hepatocyte lipid synthesis (P < 0.05), thereby promoting hepatic function and preventing the excessive accumulation of lipid droplets in the hepatocyte cell line HepG2. Supplementation of ω-3 FAs in pregnant GDM mice significantly reduced fasting blood glucose levels, glucose tolerance test, and insulin tolerance test indices, and lipid accumulation in the liver and effectively prevented the occurrence of liver fibrosis (P < 0.05). These therapeutic effects may be mediated through the anti-inflammatory effects of ω-3 FAs (P < 0.05). ω-3 FAs also had positive effects on the offspring of pregnant GDM mice, as demonstrated by reduced birth mortality and improved glycemic stabilization (P < 0.05). In conclusion, this study provides a possible translational medicine strategy for the treatment of GDM.

Enhancing Type 2 Diabetes Management: The Role of Pharmacist-Led Education and Booklets

Type 2 diabetes mellitus (T2DM) is a global health concern, necessitating effective management to prevent complications. Pharmacists, as accessible healthcare professionals, can play a pivotal role in patient education and self-management support. This study aimed to evaluate the impact of pharmacist-led education and booklets on glycemic control and self-management behaviors in patients with T2DM. A quasi-experimental study was conducted at a hospital in Central Java, Indonesia. Patients diagnosed with T2DM for at least six months were recruited. The intervention group received pharmacist-led education and a booklet, while the control group received standard care. Fasting blood glucose (FBG) and self-management behaviors were assessed at baseline and after three months. The intervention group demonstrated a significant reduction in FBG levels compared to the control group (p &lt; 0.05). Additionally, the intervention group showed improvements in self-management behaviors, including medication adherence, dietary control, and physical activity. Pharmacist-led education and booklets are effective in improving glycemic control and self-management behaviors in patients with T2DM. This intervention can be integrated into routine diabetes care to enhance patient outcomes.

Combination of Metformin and Epigallocatechin-3-Gallate Lowers Cortisol, 11β-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes.

The combined effects of metformin and epigallocatechin-3-gallate (EGCG) on cortisol, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), and blood glucose levels have not been investigated. This study evaluated the effectiveness of combining EGCG with metformin in regulating those levels in a rat model of diet-induced diabetes and obesity. Thirty diabetic and obese rats on a high-fat diet were treated daily for 28 days with EGCG (100 mg/kg of body weight/day), metformin (200 mg/kg of body weight/day), or both. Control groups comprised lean rats, untreated obese diabetic rats, and metformin-only-treated rats. Blood samples were collected to measure cortisol and fasting blood glucose (FBG) levels and liver tissue samples were examined for 11β-HSD1 levels. Rats receiving combination therapy had significantly reduced cortisol levels (from 36.70±15.13 to 31.25±7.10 ng/mL) compared with the untreated obese diabetic rats but not the rats receiving monotherapy. Rats receiving combination therapy and EGCG monotherapy had significantly lower 11β-HSD1 levels compared with the untreated obese diabetic rats (92.68±10.82 and 93.74±18.11 ng/L vs. 120.66±14.00 ng/L). Combination therapy and metformin monotherapy significantly reduced FBG levels (440.83±133.30 to 140.50±7.36 mg/dL and 480.67±86.32 to 214.17±102.78 mg/dL, respectively) by approximately 68.1% and 55.4% compared with rats receiving EGCG monotherapy and untreated obese diabetic rats. Combining EGCG with metformin exhibited synergistic effects compared with monotherapy for managing diabetes, leading to improved outcomes in reduction of baseline cortisol levels along with reduction in 11β-HSD1 and blood glucose levels.

Efficacy and safety of combined Chinese and western medicine in the treatment of metabolic syndrome: A network meta-analysis of randomized controlled trials

ObjectivesTo comprehensively analyze the randomized controlled clinical trials of integrated traditional Chinese medicine (TCM) and western medicine in the treatment of metabolic syndrome (MetS), and to explore the clinical efficacy and safety of different TCM combined with western medicine for MetS. The purpose of this study is to provide specific suggestions for clinical guidance in the treatment of MetS. MethodsA comprehensive literature review was conducted across several databases, including China Knowledge Network, Wanfang Data, VIP Information, China Biomedical Literature Service System, Embase, PubMed, and Web of Science, up to October 2023. The scope of this review was confined to RCTs focusing on the treatment of metabolic syndrome through an integrated approach of TCM and Western medicine. The primary efficacy endpoints analyzed were clinical efficacy, fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein (HDL). Data synthesis and analysis were performed using Stata 16 and RevMan 5.4 for both traditional and network meta-analyses. ResultsThe findings from both traditional and network meta-analyses reveal that the combination of JiangZhiHuoXue pills (JZHX) + Conventional Western Medicine (CWM) significantly reduces FBG levels. Similarly, the AnShenNingXin capsules (ASNX) + CWM combination markedly lowers TG levels, while the FuFangQiMa capsules (FFQM) + CWM combination shows enhanced efficacy in elevating HDL levels. Notably, the combination of KangNing capsules (KNJN) + CWM demonstrates a more pronounced clinical effect compared to CWM/placebo alone. ConclusionsThe study concludes that the synergistic combination of TCM and Western medicine exhibits superior therapeutic benefits in treating MetS compared to CWM/Placebo treatments alone. The combinations of JZHX, AXNX, FFQM, and KNJN with CWM emerge as potentially effective treatments.

Novel thiosemicarbazide-based β-carboline derivatives as α-glucosidase inhibitors: Synthesis and biological evaluation

In the quest for potent α-glucosidase inhibitors to combat diabetes, a series of novel thiosemicarbazide-based β-carboline derivatives (CTL1∼36) were synthesized and evaluated. CTL1∼36 exhibited remarkable inhibitory effects against α-glucosidase, with IC50 values ranging from 2.81 to 12.40 μM, significantly surpassing the positive control acarbose (IC50 = 564.28 μM). Notably, CTL26 demonstrated the most potent inhibition (IC50 = 2.81 μM) and was characterized as a non-competitive inhibitor. Through a combination assay with fluorescence quenching, 3D fluorescence spectra, CD spectra, and molecular docking, we elucidated that CTL26 formed a complex with α-glucosidase via hydrogen bondings and hydrophobic interactions, leading to α-glucosidase conformation changes that impaired enzymatic activity. In vivo studies revealed that oral administration of CTL26 (25 and 50 mg/kg/d) reduced fasting blood glucose levels, enhanced glucose tolerance, and ameliorated lipid abnormalities in diabetic mice. These findings positioned CTL26 as a promising candidate for the development of α-glucosidase inhibitors with anti-diabetic potential.

The enduring metabolic improvement of combining dual amylin and calcitonin receptor agonist and semaglutide treatments in a rat model of obesity and diabetes.

Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on body weight, glucose control, and insulin action. However, how the metabolic benefits are maintained after long-lasting treatment is unknown. This study investigates the long-term anti-obesity and anti-diabetic treatment efficacy of the DACRA KBP-336 alone and combined with the GLP-1 analog semaglutide. Zucker diabetic Sprague Dawley (ZDSD) rats with obesity and diabetes received KBP-336 (4.5 nmol/kg Q3D), semaglutide (50 nmol/kg Q3D), or the combination for 7 mo, and the treatment impact on body weight, food intake, glucose control, and insulin action was evaluated. Furthermore, serum levels of the cardiac fibrosis biomarker endotrophin were evaluated. KBP-336, semaglutide, and the combination lowered body weight significantly compared with the vehicle, with the combination inducing a larger and more sustained weight loss than either monotherapy. All treatments resulted in reduced fasting blood glucose levels and HbA1c levels and improved glucose tolerance compared with vehicle-treated rats. Furthermore, all treatments protected against lost insulin secretory capacity and improved insulin action. Serum levels of endotrophin were significantly lowered by KBP-336 compared with vehicle. This study shows the benefit of combining KBP-336 and semaglutide to obtain significant and sustained weight loss, as well as improved glucose control. Furthermore, KBP-336-driven reductions in circulating endotrophin indicate a clear reduction in the risk of complications. Altogether, KBP-336 is a promising candidate for the treatment of obesity and type 2 diabetes both alone and in combination with GLP-1 analogs.NEW & NOTEWORTHY These studies describe the benefit of combining dual amylin and calcitonin receptor agonists (DACRA) with semaglutide for long-term treatment of obesity and type 2 diabetes. Combination treatment induced sustained weight loss and improved glucose control. A DACRA-driven reduction in a serological biomarker of cardiac fibrosis indicated a reduced risk of complications. These results highlight DACRAs as a promising candidate for combination treatment of obesity and type 2 diabetes and related long-term complications.

EFEK EKSTRAK BAYAM MERAH VARIETAS MIRA TERHADAP GLUKOSA DARAH PUASA DAN MALONDIALDEHID TIKUS MODEL DMT2

Persistent hyperglycemia in type 2 diabetes mellitus (T2DM) increases the risk of lipid peroxidation that produces malondialdehyde (MDA). Red spinach mira extract (RSME) contains anthocyanins and beta carotene, both of which have the potential as antioxidants in reducing fasting blood glucose (FBG) and MDA levels. The purpose of the study was to determine the effect of RSME administration on FBG and MDA levels in T2DM. The research method was true-experimental with pretest-posttest. The study used 30 male Wistar rats, and divided into 5 groups, namely the normal group and given standard diet, K- T2DM rats and given a standard diet, K+ T2DM rats and given acarbose drug therapy 1.8 mg/200g/day, P1 T2DM rats and given a dose of RSME 688 mg/200g Body weight (BW) and P2 T2DM rats and given a dose of RSME 1376 mg/200g BW for 14 days. Statistical analysis of FBG and MDA using One Way Anova test and continued with Post Hoc test to determine the difference between groups, while to determine the effect using Paired t-test. The results of the study after intervention for 14 days, all groups given RSME experienced a decrease in FBG levels P1 by 158.60 mg/dl (p=0.000), KP2 by 180 mg/dl (p=0.000) and MDA KP1 decreased by 6.01 nmol/mL (p=0.000) and KP2 by 7.75 nmol/mL (p=0.000) and there was significant value (p&lt;0.05). The study concluded that the best dose is KP2, which reduces FBG levels by 180.84 mg/dl and MDA by 7.75 nmol/ml, the highest decrease compared to the other doses.

Integrated network pharmacology and pharmacological investigations to discover the active compounds of Toona sinensis pericarps against diabetic nephropathy

Ethnopharmacological relevanceToona sinensis (A. Juss.) Roem. Is a deciduous woody plant native to Eastern and Southeastern Asia. Different parts of this plant have a long history of being applied as traditional medicines to treat various diseases. The fruits have been used for antidiabetic, antidiabetic nephropathy (anti-DN), antioxidant, anti-inflammatory, and other activities. Aim of the studyThe purpose of this study was to investigate the effects of EtOAc (PEAE) and n-BuOH extracts (PNBE) from T. sinensis pericarps (TSP) on kidney injury in high-fat and high-glucose diet (HFD)/streptozotocin (STZ)-induced DN mice by network pharmacology and pharmacological investigations, as well as to further discover active compounds that could ameliorate oxidative stress and inflammation, thereby delaying DN progression by regulating the Nrf2/NF-κB pathway in high glucose (HG)-induced glomerular mesangial cells (GMCs). Materials and methodsThe targets of TSP 1–16 with DN were analyzed by network pharmacology. HFD/STZ-induced DN mouse models were established to evaluate the effects of PEAE and PNBE. Six groups were divided into normal, model, PEAE100, PEAE400, PNBE100, and PNBE400 groups. Fasting blood glucose (FBG) levels, organ indices, plasma MDA, SOD, TNF-α, and IL-6 levels, as well as renal tissue Nrf2, HO-1, NF-κB, TNF-α, and TGF-β1 levels were determined, along with hematoxylin-eosin (H&E) and immunohistochemical (IHC) analysis of kidney sections. Furthermore, GMC activity screening combined with molecular docking was utilized to discover active compounds targeting HO-1, TNF-α, and IL-6. Moreover, western blotting assays were performed to validate the mechanism of Nrf2 and NF-κB in HG-induced GMCs. ResultsNetwork pharmacology predicted that the main targets of PEAE and PNBE in the treatment of DN include IL-6, INS, TNF, ALB, GAPDH, IL-1β, TP53, EGFR, and CASP3. Additionally, major pathways include AGE-RAGE and IL-17. In vivo experiments, treatment with PEAE and PNBE effectively reduced FBG levels and organ indices, while plasma MDA, SOD, TNF-α, and IL-6 levels, renal tissue Nrf2, HO-1, NF-κB, TNF-α, and TGF-β1 levels, and renal function were significantly improved. PEAE and PNBE significantly improved glomerular and tubule injury, and inhibited the development of DN by regulating the levels of oxidative stress and inflammation-related factors. In vitro experiments, compound 11 strongly activated HO-1 and inhibited TNF-α and IL-6. The molecular docking results revealed that compound 11 exhibited a high binding affinity towards the targets HO-1, TNF-α, and IL-6 (<−6 kcal/mol). Western blotting results showed compound 11 effectively regulated Nrf2 and NF-κB p65 protein levels, and significantly improved oxidative stress damage and inflammatory responses in HG-induced GMCs. ConclusionPEAE, PNBE, and their compounds, especially compound 11, may have the potential to prevent and treat DN, and are promising natural nephroprotective agents.