Drugs For Treatment Of Diabetes Research Articles

Evaluation of the Neuroprotective Action of <i>Azadirachta indica</i> Leaves Extract in Streptozotocin-induced Diabetic Rodent Model

Among the most common and painful consequences of diabetes mellitus, Diabetic Peripheral Neuropathy (DPN) is one of the most common. For DPN management, a variety of techniques have been used, ranging from traditional medicines to alternative approaches. Natural compounds are also the focus of research to explore the possible treatment by replacing or combining with the existing therapies. Different neurological changes in diabetic neuropathy and the effect of the Azadirachta indica (neem) extract were assessed with nerve conduction velocity, and biochemical and histological analysis in Streptozotocin-induced diabetic mellitus. The therapeutic effect of the extract was evaluated with doses 100, 200 and 500mg/kg body weight for 4 weeks after induction of diabetes. The protective effect was evaluated by treating the animals with hydroalcoholic extract of neem leaves in 500mg/kg dose before the induction of diabetes and post-treatment with the standard drug Metformin (500mg/kg). Both resulted in a significant reduction in blood glucose, additionally, 500mg/kg body weight dose revealed the signs of neuroprotection in diabetic rats. Neem leaf extract appears to be promising for future investigations, which might contribute to the emergence of new drugs for diabetes treatment and diabetic neuropathy either alone or in combination with conventional therapies.

Unraveling Light-Activated Insulin Action in Regulating Blood Glucose: New Photoactivatable Insight as a Novel Modality in Diabetes Management.

Diabetes, particularly type 2 diabetes (T2D), is the main component of metabolic syndrome. It is highly prevalent and has drastically increased with sedentary lifestyles, notably behaviors linked to ease of access and minimal physical activity. Central to this condition is insulin, which plays a pivotal role in regulating glucose levels in the body by aiding glucose uptake and storage in cells, and what happens to diabetes? In diabetes, there is a disruption and malfunction in insulin regulation. Despite numerous efforts, effectively addressing diabetes remains a challenge. This article explores the potential of photoactivatable drugs in diabetes treatment, with a focus on light-activated insulin. We discuss its advantages and significant implications. This article is expected to enrich the existing literature substantially, offering a comprehensive analysis of potential strategies for improving diabetes management. With its minimal physical intrusion, light-activated insulin promises to improve patient comfort and treatment adherence. It offers precise regulation and localized impact, potentially mitigating the risks associated with conventional diabetes treatments. Additionally, light-activated insulin is capable of explicitly targeting RNA and epigenetic factors. This innovative approach may pave the way for more personalized and effective diabetes treatments, addressing not only the symptoms but also the underlying biological causes of the disease. The advancement of light-activated insulin could revolutionize diabetes management. This study represents a pioneering introduction to this novel modality for diabetes management.

Phytoconstituents of Terminalia catappa linn fruits extract exhibit promising antidiabetic activities against α-amylase and α-glucosidase in vitro and in silico

Terminalia Catappa fruits are recognized for their use in diabetes treatment, yet the mechanism by which they inhibit diabetes-related enzymes remain largely undefined. This study aimed to elucidate the therapeutic potential and interactions of T. catappa fruit extract through in vitro and in silico approaches. The compounds from T. catappa fruit were extracted using microwave-assisted extraction techniques, followed by qualitative phytochemical screening and quantitative analysis via GC-MS. The physicochemical properties were evaluated according to the Lipinski rule and ADMET criteria. Antidiabetic analyses, both in vitro and in silico, were performed on the secondary metabolites found in T. catappa fruit, targeting α-amylase and α-glucosidase enzymes. The methanol and ethyl acetate extracts of T. catappa fruit contained alkaloids, flavonoids, saponins, steroids, and terpenoids. These extracts inhibited α-glucosidase and α-amylase in a dose-dependent manner, with the methanol extract of T. catappa showing significantly higher inhibitory activity than pure acarbose (by two- and five-fold, respectively) and the ethyl acetate extract. Furthermore, the antioxidant activity of the methanolic extract was seven times greater than that of the ethyl acetate extract. Molecular docking studies supported these findings, revealing that the ΔG values of gibberellic acid, rescinnamine, and digoxin were comparable to those of acarbose. Notably, digoxin has higher ΔG values against α-amylase than acarbose, while gibberellic acid, rescinnamine, and nerolidol showed ΔG values similar to acarbose. Gibberellic acid, unique to the methanol extract, demonstrated high ΔG values, suggesting its significant role in the extract's enhanced glucosidase and amylase inhibitory activities. This study identifies specific compounds (digitoxin, rescinnamine, gibberellic acid, and nerolidol) and proposes the potential of multi-target drugs in diabetes treatment. Understanding these phytochemical constituents and their effects on diabetes-involved enzymes could benefit individuals with type 2 diabetes, particularly those at higher risk of complications.

Research Advances in Fusion Protein-Based Drugs for Diabetes Treatment.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by elevated blood glucose levels, resulting in multi-organ dysfunction and various complications. Fusion proteins can form multifunctional complexes by combining the target proteins with partner proteins. It has significant advantages in improving the performance of the target proteins, extending their biological half-life, and enhancing patient drug compliance. Fusion protein-based drugs have emerged as promising new drugs in diabetes therapeutics. However, there has not been a systematic review of fusion protein-based drugs for diabetes therapeutics. Hence, we conducted a comprehensive review of published literature on diabetic fusion protein-based drugs for diabetes, with a primary focus on immunoglobulin G (IgG) fragment crystallizable (Fc) region, albumin, and transferrin (TF). This review aims to provide a reference for the subsequent development and clinical application of fusion protein-based drugs in diabetes therapeutics.

Edukasi pengetahuan masyarakat dalam pemanfaatan daun insulin di Desa Jambi Kecil Kabupaten Muaro Jambi

The insulin plant (Tithonia diversifolia (Hemsl.) A. Gray) is a flowering plant with orange-colored flowers that belongs to the Asteraceae family. It can be cultivated as an ornamental plant in gardens or green spaces and used in traditional medicine. The benefits and potential of this plant are numerous, including its use as green manure, pest, and disease control, fodder for livestock, soil and water conservation, and its potential in traditional treatments for urinary tract infections, digestive issues, and diabetes management. This community service aims to enhance public knowledge regarding using insulin plant leaves as crude drugs for diabetes treatment. The method employed involves conducting informational sessions through lectures followed by a question-and-answer session. The results show the community learned about using insulin plants as a diabetes remedy. The community's knowledge about using insulin plants as a traditional remedy as a decoction for diabetes treatment increased to 100%.

Development and Identification of Novel α-Glucosidase Inhibitory Peptides from Mulberry Leaves.

The mulberry leaf is a botanical resource that possesses a substantial quantity of protein. In this study, alcalase hydrolysis conditions of mulberry leaf protein were optimized using the response surface method. The results showed that the optimum conditions were as follows: substrate protein concentration was 0.5% (w/v), enzymatic hydrolysis temperature was 53.0 °C, enzymatic hydrolysis time was 4.7 h, enzyme amount was 17,800 U/g, and pH was 10.5. Then mulberry leaf peptides were separated by ultrafiltration according to molecular weight. Peptides (<3 kDa) were screened and subsequently identified using LC-MS/MS after the evaluation of α-glucosidase inhibition across various fractions. Three novel potential bioactive peptides RWPFFAFM (1101.32 Da), AAGRLPGY (803.91 Da), and VVRDFHNA (957.04 Da) with the lowest average docking energy were screened for molecular dynamics simulation to examine their binding stability with enzymes in a 37 °C simulated human environment. Finally, they were prepared by solid phase synthesis for in vitro verification. The former two peptides exhibited better IC50 values (1.299 mM and 1.319 mM, respectively). These results suggest that the α-glucosidase inhibitory peptides from mulberry leaf protein are potential functional foods or drugs for diabetes treatment, but further in vivo studies are needed to identify the bioavailability and toxicity.

The Severity of COVID-19 in Diabetes Patients.

Diabetic patients are significantly stimulated by COVID-19 infection. The dreadful risk of COVID-19 mortality may be affected. In order to preserve precious lives, it is essential to comprehend how diabetes and COVID-19 are related, as well as how to manage diabetes. We aimed to focus on the mechanism, impact, and drug treatment of diabetes in COVID-19 patients. A comprehensive scrutiny of the published literature in diverse pharmaceutical and medical databases such as Google Scholar, PubMed, Science Direct, DOAJ etc., were successfully conducted and classified accordingly. We discussed the severity of COVID-19 in diabetes patients. A patient with diabetes has a higher risk of COVID-19 mortality by influencing the development and prognosis of the disease. The recommended drugs for diabetes treatment in COVID-19 may reduce COVID-19 mortality. Metabolic syndrome diabetes is a risk factor enhancing the development and diagnosis of COVID-19. In order to treat diabetic patients who have COVID-19 infection, insulin is preferable over oral hypoglycemic medications.

Risk factors for drug-treated major adverse cardio-cerebrovascular events in patients on primary preventive statin therapy: A retrospective cohort study

We aim to identify risk factors of major adverse cardio-cerebrovascular events (MACCE) using a proxy of drug treatment for a MACCE after the start of statin therapy in the primary cardiovascular prevention group, taking drug dose, persistency and adherence into account. We conducted a retrospective inception cohort study using data from the University of Groningen prescription database IADB.nl, covering patients in the Northern part of the Netherlands. We identified adult starters on primary preventive statin therapy as patients without any statin or cardiovascular drug prescription in the two years before the first statin dispensing and used a weighted Cox proportional hazard model to estimate hazard ratios (HR) with their 95 % confidence intervals (95 %CI). Among 39,487 primary preventive statin starters, 23% received drug treatment for a MACCE within a median follow-up period of four years. Increasing age, male gender and presence of diabetes drug treatment were significantly associated with the outcome (HR: 1.03; 95 %CI: 1.02–1.04; HR: 1.27; 95 %CI: 1.12–1.44 and HR: 1.39; 95 %CI: 1.24–1.56, respectively). If patients remained statin therapy persistent, adherence was no longer associated with drug treatment for a MACCE. In 23 % of the statin therapy initiators, incident drug treatment for a MACCE occurred with a median of four years. To reduce event rates in this group, older patients, males and diabetes patients should be closely monitored. Non-adherence in the early stage of treatment should be avoided to prevent non-persistence.

Insulin-loaded nanoparticles based on acetylated cashew gum/chitosan complexes for oral administration and diabetes treatment

Insulin is one of the most important drugs in the clinical treatment of diabetes. There is growing interest in oral insulin administration as it mimics the physiological pathway and potentially reduces side effects associated with subcutaneous injection. In this study, a nanoparticulate system was developed using acetylated cashew gum (ACG) and chitosan by the polyelectrolyte complexation method, for oral administration of insulin. The nanoparticles were characterized by size, zeta potential and encapsulation efficiency (EE%). And they had a particle size of 460 ± 11.0 nm, PDI of 0.2 ± 0.021, zeta potential of 30.6 ± 0.48 mV, and an EE% of 52.5 %. Cytotoxicity assays were performed for HT-29 cell lines. It was observed that ACG and nanoparticles did not have a significant effect on cell viability, verifying their biocompatibility. Hypoglycemic effects of the formulation were analyzed in vivo, noting that the nanoparticles reduced blood glucose by 51.0 % of baseline levels after 12 h, not inducing signs of toxicity or death. Biochemical and hematological profiles were not clinically modified. Histological study indicated no signs of toxicity. Results showed that the nanostructured system presented itself as a potential vehicle for oral insulin release.

Symptoms of depression, perceived social support, and medical coping modes among middle-aged and elderly patients with type 2 diabetes.

Objective: To understand the prevalence of depression in diabetes population, explore the relationship between diabetes and depression, and the impact of comprehensive psychological and behavioral intervention on depression related to diabetes and glucose metabolism. Methods: 71 middle-aged and elderly patients with type 2 diabetes were investigated and evaluated with Self Rating Depression Scale (SDS), Medical Coping Scale (MCWQ) and Social Support Scale (PSSS). Patients who met the research criteria were randomly divided into an experimental group and a control group. The number of effective cases in the two groups was 36 and 35 respectively. In addition to conventional diabetes drug treatment, the experimental group was supplemented with comprehensive psychological and behavioral intervention, while the control group was only given conventional treatment. The fasting blood glucose, 2-h postprandial blood glucose, body weight and depression index were measured before and after treatment in the two groups. Results: The prevalence of depression in patients with diabetes was as high as 60%, and that in the elderly control group was 5%; In type 2 diabetes population, depression is negatively related to the total score of social support and medical coping surface, and positively related to avoidance, blood sugar, women, course of disease, education level below junior high school, body mass index, and number of complications in medical coping; The fasting blood glucose, 2-h postprandial blood glucose, body mass index, and depression index of the two groups decreased, and the range and speed of decline in the experimental group were higher than those in the control group; There were significant differences between the two groups in fasting blood glucose, 2-h postprandial blood glucose and depression index; During the follow-up period, the blood glucose and depression index of the experimental group increased. Conclusion: Depression has a high prevalence rate in middle-aged and elderly people with type 2 diabetes, and has a negative impact on blood sugar control in diabetes patients; Psychological and behavioral comprehensive intervention can improve the glucose metabolism and depressive symptoms of middle-aged and elderly patients with type 2 diabetes.

CURRENT TRENDS AND AVAILABILITY OF INJECTABLE THERAPY IN PAKISTAN FOR MANAGEMENT OF DIABETES MELLITUS

Background: Diabetes is a metabolic disorder and is a growing healthcare problem in South Asian countries. The management guidelines provided by American Diabetes Association (ADA) have provided a thorough approach for the use of oral and injectable therapies. Current statistics indicate an increase in premature mortality, which poses a severe danger to global prosperity. Sulphonylureas, biguanides, alpha glucosidase inhibitors and thiazolidinediones are examples of recent generations of drugs that have been created as a result of scientific and technological developments and have a high efficacy in reducing hyperglycemia. Objectives: This communication aims to connote the trends and availability of injectable therapy in lower middle income countries. Methodology: We reviewed a number of studies (published between 2010-2020), a market survey for availability and the Drug Regulatory Authority of Pakistan official website for the registration status of newly registered injectable therapy for managing diabetes mellitus. Results: Novel classes of drugs that have been developed as potential targets for diabetes treatment drugs include Incretin mimics, Amylin analogues, GIP analogues, Peroxisome proliferator-activated receptors, and dipeptidyl peptidase-4 inhibitor. In Pakistan and other parts of the world, getting new insulin products in sufficient quantities has always been demanding. A list of imported insulin and GLP-1 products and their availability in lower middle income countries like Pakistan, India and Bangladesh is made so as to meet international standards. Conclusion: This short communicatiob shows the availability of Injectable therapy for management of diabetes in Pakistan.

Identification, measurement, and evaluation of blood concentrations of insulin glargine and insulin lispro by UPLC–MS–MS in a dead body suspected of insulin overdose

Insulin preparations, which are drug treatments for diabetes, cause fatal hypoglycemia when an overdose is administered. Cases of homicide and suicide using these preparations have been reported and are of great forensic interest. However, there are few reports assessing the postmortem concentration of insulin preparations, and it is often difficult to determine the cause of death. In the present study, we report a case of a suspected insulin glargine and insulin lispro overdose for suicide. A woman in her 30s had a history of mental illness and diabetes. The day before her death, she reported to her boyfriend that she had taken large doses of insulin preparations and prescription drugs. An autopsy revealed no fatal injuries or lesions. Drug screening tests revealed several prescription drugs, none of which showed toxic concentrations. Analysis using LC-MS/MS detected insulin glargine in the peripheral and cardiac blood at 429 μU/mL and 1362 μU/mL, respectively, whereas insulin lispro was detected in both the peripheral and cardiac blood at levels below the lower limit of quantification (LLOQ; <50 μU/mL). The cause of death was considered likely to be hypoglycemia caused by an overdose of insulin glargine. Insulin glargine is rapidly metabolized after subcutaneous administration and is rarely detected in the blood when used at therapeutic doses. There are no other reports on the quantification of insulin glargine parent compounds in postmortem samples, and this case provides important data on postmortem blood concentrations of insulin glargine intoxication.

Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model.

Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.

Effect of Dapagliflozin on Serum Uric Acid in Type 2 Diabetes Mellitus patients

Diabetes is one of the most common metabolic diseases, linked to hyperuricemia. Several studies have shown that high serum uric acid levels (SUA) are associated with an increased risk of diabetes. SGLT2 inhibitors (Sodium Glucose Cotransporter-2 Inhibitors) are a new drug for diabetes treatment. In addition to their ability to lower blood glucose, they have other benefits, including lowering serum uric acid levels. This study aimed to evaluate the effect of dapagliflozin, which is a selective inhibitor of SGLT2 Cotransporters present in the kidneys, on serum uric acid levels in patients with type 2 diabetes, compared with a control group. The study included 51 patients with type 2 diabetes, randomly selected from an endocrinology clinic, who started dapagliflozin treatment 5 and 10 mg at recruitment. The control group included 64 patients with type 2 diabetes treated with metformin. Patients were monitored for 3-6 months and serum uric acid levels were measured at baseline and after follow-up. 3 months after treatment, the mean concentration of uric acid in the dapagliflozin group was lower than that of the metformin group (4.58 vs. 5.24 mg/dl p = 0.0143). At 6 months follow-up, SUA levels decreased by 0.79 mg/dL and it was statistically significant (p = 0.0004), compared with control group where there was no statistically significant change in SUA levels. Statistically, there was no significant difference in uric acid levels between doses 5 and 10 mg. However, decreasing in SUA levels with dapagliflozin 5 mg was greater than that occurred with dapagliflozin 10 mg after 6 months of treatment. In conclusion, Dapagliflozin results in a decrease of SUA levels in patients with type 2 diabetes by increasing urinary excretion of uric acid induced by SGLT2 inhibitors.

Comparative effect of metformin versus sulfonylureas with dementia and Parkinson’s disease risk in US patients over 50 with type 2 diabetes mellitus

IntroductionType 2 diabetes is a risk factor for dementia and Parkinson’s disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions....

Effect of Ganoderma lucidum fermentation on the content and α-glucosidase inhibitory activity of mulberry leaves flavonoid

Diabetes is now a worldwide disease that has a negative impact on human health.As a result,the search for low-cost,safe,and effective diabetes treatment drugs derived from natural medicinal plants has become a research priority.Mulberry leaf(ML)flavonoids have been proven to be a highly effective α-glucosidase inhibitor and have a good effect on the treatment of diabetes.The solid state fermentation of Ganoderma lucidum utilizing ML as substrate was explored in this study with the goal of increasing the concentration and-glucosidase inhibitory effect of mulberry leaf flavonoid(MLF).The results indicated that fermented by G.lucidum for 8 d could increase the content of MLF from 1.596 mg/ml to 4.736 mg/ml.Meanwhile the polysaccharide in ML would be degraded and utilized as nutritions to support the cell growth of G.lucidum.The inhibitory rate of MLF on α-glucosidase was significantly enhanced by fermentation.During the concentration of 10μg/ml,the α-glucosidase inhibition rate of MLF was enhanced from 45.31±2.24%to 73.46±3.28%when fermented by G.lucidum for 8d.Moreover,it was found that the inhibition type of MLF would change from competitive inhibition to mixed-type inhibition.This study will serve as a reference for microbial fermentation and enrichment of medicinal plant active components,as well as a contribution to the high-value-added use of mulberry leaf resources.

Anti-Inflammatory Properties of Metformin During Cultivation of Primary Rat Astrocytes in a Medium with High Glucose Concentration.

Investigation of the relationship between inflammation and energy metabolism is important for understanding biology of chronic noncommunicable diseases. Use of metformin, a drug for treatment of diabetes, is considered as a promising direction for treatment of neurodegenerative diseases and other neuropathologies with an inflammatory component. Astrocytes play an important role in the regulation of energy metabolism and neuroinflammation; therefore, we studied the effect of metformin on the cellular responses of primary rat astrocytes cultured in a medium with high glucose concentration (22.5 mM, 48-h incubation). Lipopolysaccharide (LPS) was used to stimulate inflammation. The effects of metformin were assessed by monitoring changes in the expression of proinflammatory cytokines and synthesis of oxylipins, assayed with ultra-high-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). Changes at the intracellular level were assessed by analyzing phosphorylation of ERK kinase and transcription factor STAT3, as well as enzymes mediating oxylipin synthesis, cyclooxygenase 1 and 2 (COX). It was found that, independent on glucose concentration, metformin reduced the LPS-stimulated release of cytokines IL-1β and IL-6, decreased activity of the transcription factor STAT3, ERK kinase, synthesis of the derivatives of the cyclooxygenase branch of metabolism of oxylipins and anandamide, and did not affect formation of ROS. The study of energy phenotype of the cells showed that metformin activated glycolysis and inhibited mitochondrial respiration and oxidative phosphorylation, independent on LPS stimulation and cell cultivation at high glucose concentration. Thus, it has been shown that metformin exhibits anti-inflammatory effects, and its effect on the synthesis of cytokines, prostaglandins, and other lipid mediators could determine beneficial effects of metformin in models of neuropathology.

Traditional Chinese Medicine Ginseng Dingzhi Decoction Ameliorates Myocardial Fibrosis and High Glucose-Induced Cardiomyocyte Injury by Regulating Intestinal Flora and Mitochondrial Dysfunction.

Myocardial fibrosis refers to the pathological changes of heart structure and morphology caused by various reasons of myocardial damage. It has become an important challenge in the later clinical treatment of acute myocardial infarction/ischemic cardiomyopathy or diabetes complicated with heart failure. Ginseng Dingzhi Decoction (GN), a Chinese herbal medicine, can reduce heart failure and protect cardiomyocytes. We infer that this may be related to the interaction with intestinal microbiota and mitochondrial homeostasis. The regulatory mechanism of GN on gut microbiota and mitochondria has not yet been elucidated. The intestinal microbiota was analyzed by the 16S rRNA gene; the fecal samples were sequenced and statistically analyzed to determine the changes of microbiota in the phenotype of heart failure rats. In addition, GN can regulate the microbial population that increases the proportion of short-chain fatty acids and anti-inflammatory bacteria and reduces the proportion of conditional pathogens to diabetic phenotype. The results suggest that GN may improve myocardial injury by regulating intestinal flora. Our data also show that stress-type heart failure caused by TAC (transverse aortic constriction) is accompanied by severe cardiac hypertrophy, reduced cardiac function, redox imbalance, and mitochondrial dysfunction. However, the use of GN intervention can significantly reduce heart failure and myocardial hypertrophy, improve heart function and improve myocardial damage, and maintain the mitochondrial homeostasis and redox of myocardial cells under high glucose stimulation. Interestingly, through in vitro experiments after TMBIM6 siRNA treatment, the improvement effect of GN on cell damage and the regulation of mitochondrial homeostasis were eliminated. TMBIM6 can indirectly regulate mitophagy and mitochondrial homeostasis to attenuate myocardial damage and confirms the regulatory effect of GN on mitophagy and mitochondrial homeostasis. We further intervened cardiomyocytes in high glucose through metformin (MET) and GN combination therapy. Research data show that MET and GN combination therapy can improve the level of mitophagy and protect cardiomyocytes. Our findings provide novel mechanistic insights for the treatment of diabetes combined with myocardial injury (myocardial fibrosis) and provide a pharmacological basis for the study of the combination of Chinese medicine and conventional diabetes treatment drugs.

An observational study conducted prospectively in a cancer specialty hospital found that drug-related issues were common among elderly cancer patients

High glucose levels are a hallmark of the metabolic condition known as diabetes mellitus and is responsible for a higher number of deaths annually than cancer and AIDS combined. Unfortunately, currently available drugs for diabetes treatment have several drawbacks and limitations, such as hepatotoxicity and cardiovascular toxicity, which limit their use as safe drugs. Therefore, our research aims to develop synthetic compounds as potential antidiabetic agents, particularly new analogues of thiazolidine-2,4-dione (TZD), which are recognised as agonists of Peroxisome Proliferator Activated Receptor- γ (PPAR- γ) and oral insulin-sensitizing drugs that reduce insulin resistance. Materials and Methods: Our research focuses on proper substitution at the C-5 position of thiazolidine-2,4-dione to produce better and more effective antidiabetic compounds with improved pharmacological properties and reduced toxicity. We created a number of thiazolidine-2,4-dione analogues with a C-5 substitution and confirmed their structures using IR, 1H-NMR, and MASS spectroscopy. Results: Among the synthesized compounds, three analogues, namely 5-(2-pyridinylbenzylidene) thiazolidine-2,4-dione, 5-(3,4-dimethoxybenzylidene) thiazolidine-2,4-dione, and 5-(2,3,4-trifluorobenzylidene) thiazolidine-2,4-dione, exhibited significant antidiabetic activity in streptozotocin-induced diabetic mice, comparable to the drug Pioglitazone. Molecular docking studies of these compounds using a protein target showed amino acid interactions with Leu270, Gln283, and Arg288, similar to Rosiglitazone and Pioglitazone. Moreover, these compounds did not show any toxic effects in mice, even at a high dose of 2000 mg/kg, indicating their safety profile. Conclusion: The synthesis of modified and improved thiazolidine-2,4-dione-containing drugs, which are safer and more effective than currently available drugs, is of utmost importance in antidiabetic drug research. Our study's findings provide a promising foundation for the development of new TZD analogues as potential antidiabetic agents with improved pharmacological properties and reduced toxicity.

Effects of phloridzin on blood glucose and key enzyme G-6-Pase of gluconeogenesis in mice.

The effects of phloridzin (PHL), main component of Malus hupehensis (MH) tea leaves, on blood glucose (BG) and glucose-6-phosphatase (G-6-Pase) were investigated to provide a basis for finding a scheme of stabilizing BG. Glucose uptake of insulin resistant HepG2 cells was measured by glucose oxidase method. Glucose tolerance, fasting BG (FBG) and postprandial BG (PBG) were determined by BG test strips. The expression of G-6-Pase was detected by Western blot. The results showed that glucose uptake was enhanced and the expression of G-6-Pase was inhibited by PHL in insulin resistant HepG2 cells. Glucose tolerance was enhanced, FBG level was increased and PBG level was decreased by PHL in mice. The expression of G-6-Pase in the liver was enhanced under fasting state, and was inhibited by the low and medium dose under postprandial state. It indicated that PHL has a positive effect on stabilizing BG in mice, which is related to bidirectional regulation of G-6-Pase activity. PRACTICAL APPLICATIONS: Malus hupehensis, edible and medicinal plant, which has been proved by long-term application and experiments that it has a good effect on stabilizing blood glucose, preventing diabetes and adjuvant treatment. Its effect is closely related to its main component PHL. Thus, MH can be used as a dietary regulating drink for daily life to maintain blood glucose. Its main ingredient is PHL, which can be developed as a candidate drug for diabetes treatment.