Good Hypoglycemic Effect Research Articles

Chinese carrier of the HNF1A p.Gln444fs variant exhibits enhanced response to sulfonylureas

BackgroundWe assessed the response to sulfonylureas and the functional characteristics of HNF1A mutations in patients with maturity-onset diabetes of the young type 3 (MODY3). MethodsWe recruited a family with suspected MODY in this study, and gene sequencing (whole-exome sequencing) was used to screen germline mutations. Luciferase reporter assays were used to evaluate the activity of the mutated genes. ResultsHeterozygous HNF1A variant (NM_000545.8:c.1330_1331del, p.Gln444fs) was identified in the proband and was not found in his father, grandmother, and nonrelated healthy controls. The mutant protein had 552 amino acids, 110 fewer than the wild type protein. Furthermore, the amino acid sequence was completely different between the mutant protein and the wild type protein starting from the 444th amino acid. Luciferase reporter assays revealed that the variant had impaired HNF4A promoter–regulation activity. The patient did not achieve good hypoglycemic effects during long-term treatment with insulin and metformin. The effect of hypoglycemic treatment was highly significant after the addition of sulfonylurea drugs. ConclusionsThe HNF1A p.Gln444fs variant associated with MODY3, and most likely a truncated protein, impaired HNF1A transcriptional activity. The variant carrier experienced an enhanced response to sulfonylureas.

Explore the Role and Influence of Bex gliflozin (A Type of SGLT-2 Inhibitors) in Type 2 Diabetes

There are many chronic metabolic diseases in the world, and diabetes is one of them. Blood sugar control and improvement of insulin resistance are the main means of clinical treatment of type 2 diabetes (T2D). A variety of hypoglycemic drugs are now used in the clinic, but due to the different physical conditions of patients, only 50% of the drugs that may play a certain curative effect. Traditional T2D drug treatment relies on the regulation of insulin and has a variety of side effects. Bex gliflozin, as a sodium-glucose co-transporter 2 inhibitor (SGLT2i), the tubules have a reabsorption effect on glucose in the original urine, and the mechanism of action of Bex gliflozin is to inhibit this function of the kidneys, which makes part of the glucose not reabsorbed by the renal tubules and excreted with urine, thereby achieving the purpose of hypoglycemia. As an approved SGLT2i, it has shown good hypoglycemic effect and safety in the treatment of diabetes, combined with others. In addition, Bex gliflozin has a certain protective effect on the heart and kidneys, and some studies have shown that it has no significant effect on blood pressure and weight. This article summarizes the therapeutic progress and mechanism of SGLT2i and Bex gliflozin in T2D, in order to expanse of the indications for Bex gliflozin.

Mechanism of action of Huangbaichen Sanwei formulation in treating T2DM based on network pharmacology and molecular docking.

Huangbaichen Sanwei formulation (HBCS) has been reported to have a good hypoglycemic effect, but its pharmacological mechanism of action remains unclear. We used network pharmacology and molecular docking to explore the potential mechanism of action of HBCS against type-2 diabetes mellitus (T2DM). Fifty-five active components from HBCS interfered with T2DM. Twenty-five core targets, such as AKT1, INS, INSR, MAPK1 were identified. Enrichment analyses showed that HBCS was involved mainly including insulin receptor signaling pathway, extracellular region, and insulin-like growth factor receptor binding and other biological processes; common targets had roles in treating T2DM by regulating diabetic cardiomyopathy and insulin resistance. Molecular docking verified that components combined with core targets. HBCS play a part in treating T2DM through multiple components and targets at the molecular level, which lays a theoretical foundation for research using HBCS to treat T2DM. The components, predicted targets, and T2DM targets of HBCS were searched through databases, and common targets were determined. Further screening of the core targets was conducted through the establishment of a protein -protein interaction network. The core targets were analyzed by Gene Ontology (GO) annotation utilizing the DAVID platform. And the enrichment of signaling pathways was explored by employing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Cytoscape 3.9.1 was employed to construct a "TCM-components-core target-pathway" network. Autodock Vina was used to dock molecules to compare the binding activity of active molecules with targets.

Effects of Cinnamon Powder on Glucose Metabolism in Diabetic Mice and the Molecular Mechanisms.

The liver is the primary organ regulating glucose metabolism. In our recent study, cinnamon improved liver function in diabetic mice. However, it is not clear whether cinnamon can reduce the glycemia of diabetic animals by regulating liver glucose metabolism. The purpose of this study was to investigate the hypoglycemic mechanism of cinnamon powder (CP) from the perspective of regulating liver glucose metabolism. To achieve this, different doses of CP (200, 400, or 800 mg/kg body weight) were given to diabetic mice by gavage once per day for 8 weeks. These mice were compared with healthy controls, untreated diabetic mice, and diabetic mice treated with metformin (the main first-line drug for type 2 diabetes). CP treatment effectively reduced fasting blood glucose levels and food intake, improved glucose tolerance and fasting serum insulin levels, and decreased glycated serum protein levels in diabetic mice. Furthermore, treatment with CP increased liver glycogen content and reduced the level of the gluconeogenesis precursor pyruvate in the liver. Data obtained by qPCR and western blotting suggested that CP improved glucose metabolism disorders by regulating AMPKα/PGC1α-mediated hepatic gluconeogenesis and PI3K/AKT-mediated hepatic glycogen synthesis. CP exhibits good hypoglycemic effects by improving hepatic glycogen synthesis and controlling hepatic gluconeogenesis. Therefore, CP may be applied as a functional food to decrease blood glucose.

Glucose‐Responsive Microneedle Patch With Variable Crosslinking Density and Flexible Core–Shell Structure for Insulin Delivery

AbstractDeveloping glucose‐responsive microneedle patches with features of simple preparation, high insulin loading, and safety has a great contribution to the treatment of diabetic patients. In this work, a novel glucose‐responsive core–shell microneedle patch is prepared from biocompatible materials by a facile process. The exterior glucose‐responsive shell is composed of polyvinyl alcohol (PVA) and ɛ‐polylysine modified with phenylboronic acid , and the inner flexible core is prepared by pure PVA loaded with insulin. The shell shows superior glucose‐induced swelling and controlled insulin release ability due to the decomposition of borate ester bonds under the synergistic effect of glucose and water. The microneedle patch also features flexibility and high insulin loading capacity (36 IU cm−2). It shows high puncture efficiency (92%) and maintains a relatively complete morphology after being removed, enabling to reduce material residues in the skin. Moreover, the microneedle patch reveals a good hypoglycemic effect in diabetic rats, achieves a hypoglycemic rate similar to that of direct injection after swelling, and works effectively to prevent excess insulin transmission. The high glucose‐responsive ability, simple preparation, high loading capacity, rapid hypoglycemic speed, high conformability to skin, and low component dissolution make this microneedle patch a suitable candidate for diabetic treatment.

Benefit-risk assessment of incretin and other anti-diabetic agents in type 2 diabetes using a stochastic multicriteria acceptability analysis model.

Benefit-risk assessment of incretin and other anti-diabetic agents in type 2 diabetes using a stochastic multicriteria acceptability analysis model.

Root-Extracted lignanamides from Limonium gmelinii (Willd.) Kuntze with a potential PTP1B inhibitory activity by regulating PI3K/AKT signaling pathway

The phytochemical study of Limonium gmelinii roots resulted in the isolation of five lignanamides (1–5). Among them, limoniumins J, K, and M (1, 2, and 4) are undescribed compounds, limoniumin L (3) is a new naturally occurring lignanamide, and limoniumin B (5) is a known compound which showed PTP1B inhibition activity with an IC50 value of 5.05 ± 2.44 μM in our previous work. Spectroscopic data analysis, including 1D and 2D NMR and HRESIMS experiments, established the chemical structures of limoniumins J − M (1–4). Compounds 1–4 showed PTP1B inhibition activity, among which compound 3 showed the most potent PTP1B inhibition with an IC50 value of 2.07 ± 0.05 μM. Compounds 3 and 5 could significantly increase cellular glucose consumption and glucose uptake in L6 muscle cells and could synergize with insulin to promote glucose consumption and glucose uptake in a concentration-dependent manner. The treatment of compound 3 also promoted glycogen synthesis in skeletal muscle cells. Western blot analysis demonstrated that the good hypoglycemic effect of compounds 3 and 5 was achieved by activating PI3K/AKT signaling pathway to promote glucose consumption, glucose uptake, and glycogen synthesis. Furthermore, studies on molecular docking revealed the potent interactions between these bioactive substances and the PTP1B protein.

Effect of Codonopsis Radix and Polygonati Rhizoma on the regulation of the IRS1/PI3K/AKT signaling pathway in type 2 diabetic mice.

Codonopsis Radix and Polygonati Rhizoma (CRPR) has a good hypoglycemic effect. The aims of the present study were to investigate the effect of CRPR on high-fat/high-sugar diet (HFHSD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) mice as well as to investigate the involved mechanism. A T2DM mouse model was generated by combining HFHSD and STZ. After the model was established, normal and model groups received the same volume of normal saline intragastrically, and the negative control group was treated with metformin (200 mg/kg·BW). The low, medium, and high CRPR groups received four consecutive weeks of oral gavage with CRPR doses of 2.5, 5, and 10 g/kg·BW, respectively, during the course of the study. Body weight and fasting blood glucose (FBG) were measured on a weekly basis. Enzyme-linked immunosorbent assay (ELISAs) were used to evaluate the serum and liver samples. Hematoxylin and eosin (H&E) staining was utilized to observe the pathological status of the liver and pancreas. Western blot (WB) analysis was performed to evaluate the protein expression levels of PI3K, p-PI3K, AKT, and p-AKT. Compared to model mice, each treatment group had significantly elevated levels of FBG, total cholesterol (TC), and triacylglycerol (TG) (P<0.01 and P<0.05, respectively). The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced in the treatment groups compared to the model group (P<0.01). Compared to the model group, fasting insulin (FINS) levels were elevated in all groups of CRPR (P<0.05), and there were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) in both the low-dose and high-dose CRPR groups (P<0.05). H&E staining indicated that CRPR treatment reduced organ enlargement, improved liver lipid accumulation, and repaired islet injury in T2DM mice. Moreover, WB analysis demonstrated that all CRPR groups significantly upregulated the protein expression of IRS1, p-GSK3β, PI3K, p-Akt and p-FOXO1(P<0.05) as well as significantly downregulated p-IRS1 and FOXO1 protein expression (P<0.05). The present study demonstrated that CRPR effectively improves the metabolic disturbance of lipids, repairs damaged liver tissues, repairs damaged pancreatic tissues, and reduces insulin resistance (IR) in T2DM mice. The mechanism of action may be associated with upregulation of the IRS1/PI3K/AKT signaling pathway and inhibition of IRS1 phosphorylation.

Observation on clinical effect of Huoxue-Jiangtang decoction formula granules in treating prediabetes: a randomized prospective placebo-controlled double-blind trial protocol

BackgroundPrediabetes is a hypermetabolic syndrome with blood sugar levels falling between the normal and diabetes. People with prediabetes have a significantly increased chances of developing diabetes, cardiovascular and cerebrovascular diseases, tumors, dementia, and other diseases in the future when compared to the healthy population. However, prediabetes is mainly treated based on lifestyle intervention, currently without targeted drug treatment plan. Traditional Chinese medicine (TCM), which has a longstanding experience, has been shown in clinical studies to be effective for the treatment of diabetes and its related complications. Furthermore, different dosage forms such as decoction and granule have developed gradually in clinical application. Preliminary studies have found that Huoxue-Jangtang Decoction (HJD), with good hypoglycemic and lipid-regulating effects, is potentially one of the complementary and alternative treatments for prediabetes. Therefore, this project intends to perform a prospective clinical study to observe the clinical effectiveness of HJD on prediabetes and the consistency of the efficacy of formula granules and the elixation.MethodsThis is a prospective, randomized, double-blind, and placebo-controlled clinical trial. A total of 183 participants are randomly assigned to HJD Formula Granules plus lifestyle intervention, HJD Elixation plus lifestyle intervention, and placebo plus lifestyle intervention. All subjects undergo 1 day of screening before participating in the study, followed by 84 days of drug intervention and observation. During and after treatment, the main outcome measures include fasting blood glucose and 2-hour postprandial blood glucose.DiscussionThis research attempts to verify the clinical efficacy and possible mechanism of HJD in the treatment of prediabetes, and prove the consistency of HJD Formula Granules with HJD Elixation. This study also aims to provide a treatment that is both effective and safe for prediabetic patients.Trial registrationClinicalTrials.gov Identifier: ChiCTR2200060813, Registered 12 June 2022.

Development and formulation of antidiabetic property of Anarcadium occidantale-based solid lipid microparticles.

Aim Anacardium occidentale (AO) possess potent anti-diabetic properties, owing to its high phytochemicals content. This study attempted to maximize the efficacy of AO by encapsulating it in a solid lipid microparticle (SLMs) formulation. Method Leaves of AO were extracted with water and formulated into SLMs using a lipid matrix composed of P90H and Dika fat. Characterisation of the SLMs include morphology, particle size, pH, encapsulation efficiency percentage, in vitro release and anti-diabetic properties. Result SLMs were spherical with sizes ranging from 16.7 ± 0.8 µm to 40.12 ± 2.34 µm, and had a fairly stable pH over time. Highest drug entrapment was 87%. Batch A2 exhibited an even release of 89%, sustained over time, and a mean percentage reduction in glucose of 25.9% at 12 h after oral administration to study animals. Conclusion A. occidentale-loaded SLMs exhibited a good hypoglycemic effect and can be used in the management of diabetes.

Network pharmacology approach to screen hypoglycemic extracts from Coptidis rhizoma and study their targets and pathways

Purpose: To screen the hypoglycemic active ingredients of Coptidis rhizoma, and study their targets as well as signal pathways via network pharmacology.&#x0D; Methods: Fifty-nine ingredients of Coptidis rhizoma were screened. Their targets were confirmed by comparing with the hypoglycemic targets in DrugBank databases. The relationship between ingredients and targets was revealed through String database. The ingredient-target-passageway network was constructed. Coptidis rhizoma was soaked in boiling water and concentrated. Rat models were rendered diabetic by the administration of streptozotocin (STZ) intraperitoneal injection. The hyperglycemic rats received Coptidis rhizoma extract (0.40 g/kg, once a day by gavage).&#x0D; Results: After four weeks of treatment, the blood glucose levels (BG) of all treated hyperglycemic rats decreased (p &lt; 0.05). Twenty-four hypoglycemic active compounds were obtained after screening the extract of Coptidis rhizome via network pharmacology. These active compounds activated 13 targets, including D (2) dopamine receptor (DRD2), Insulin-like growth factor 1 receptor (IGF1R), 5- hydroxytryptamine receptor 2C (HTR2C), 5-hydroxytryptamine receptor 3A (HTR3A) and sodiumdependent noradrenaline transporter (SLC6A2). These targets were involved in 141 pathways, e.g., cAMP signaling pathway, chemokine signaling pathway, Rap1 signaling pathway, estrogen signaling pathway, and apelin signaling pathway.&#x0D; Conclusion: Coptidis rhizoma contains several active compounds that exhibit good hypoglycemic effects. Thus, there is a need for human studies on the hypoglycemic effects of Coptidis rhizome extracts.&#x0D; Keywords: Coptidis rhizome; Hypoglycemic effects; Network pharmacology; D (2) dopamine receptor (DRD2); Insulin-like growth factor 1 receptor

Rapid Screening of Novel Dipeptidyl Peptidase-4 Inhibitory Peptides from Pea (Pisum sativum L.) Protein Using Peptidomics and Molecular Docking.

Pea protein hydrolysates (PPHs) possess good hypoglycemic effects; however, their dipeptidyl peptidase-4 (DPP-4) inhibitory activity is poorly understood, and none of the DPP-4 inhibitory peptides have been identified from PPHs. This paper aims to rapidly screen these peptides from PPHs by combining peptidomics and molecular docking. In this study, 543 peptides were identified by peptidomics, and four peptides (IPYWTY, IPYWT, LPNYN, and LAFPGSS) with DPP-4 half-maximal inhibitory concentration (IC50) values <100 μM were screened for the first time. Significantly, peptide IPYWTY exhibited the most potent DPP-4 inhibitory activity (IC50 = 11.04 μM) mainly because it formed hydrophobic interactions with the S1 pocket in DPP-4. These results indicated that combining peptidomics and molecular docking is an effective strategy for rapidly screening DPP-4 inhibitory peptides.

Multivalent glucosidase inhibitors based on perylene bisimide and iminosugar conjugates

Although multivalent glucosidase inhibitors based on iminosugars have shown enhanced inhibition activity, an effective way to improve their hypoglycemic effect in vivo, is still in infancy and needs further development. In this paper, PBI-5DNJ and PBI-6DNJ, with three or four DNJ moieties respectively conjugated at the bay position were synthesized. PBI-6DNJ evidenced stronger π-π stacking interactions and, when self-assembled, a smaller size than that of PBI-5DNJ. It was found that PBI-6DNJ exhibited superior α-glucosidases (from mice) inhibition activity (Ki = 0.14 ± 0.007 μM) in vitro than that (Ki = 0.31 ± 0.01) of PBI-5DNJ and in vivo hypoglycemic effects in mice models. PBI-6DNJ possessed good hypoglycemic effects with the percentages of PBG levels of 40.40 ± 3.33% and 39.23 ± 4.84% at a dose of 2.0 mg/kg after 15 min and 30 min of administration, respectively. In terms of measuring percentage decrease of PBG level per DNJ unit, PBI-6DNJ displayed a 2.1-fold enhancement than miglitol, demonstrating a consistency between in vitro and in vivo experiments. This paves the way to the connection between in vivo hypoglycemic potency and in vitro glucosidase inhibition assay, leading to reliable and simplified assessment of hypoglycemic potency determination, and opening a basic understanding of the design of multivalent glucosidase inhibitors.

Protective Effect of Pueraria lobate (Willd.) Ohwi root extract on Diabetic Nephropathy via metabolomics study and mitochondrial homeostasis-involved pathways

• RP extract can regulate mitochondrial biogenesis and autophagy in DN mice. • Protective mechanism of RP on DN was explored by metabolomics and molecular biology. • 32 potential biomarkers were collected using UPLC-Q-TOF/MS. • AMPK/SIRT1/PGC-1α and PINK1/Parkin pathway are involved in the effect of RP on DN. Radix Puerariae (RP) is a kind of medical and edible material and is used to treat diabetes and diabetic nephropathy (DN). However, the protective effect of RP against DN has not been explained clearly. A DN mice model was established through the co-treatment of cadmium and high fat and sugar diet (HFSD), different doses of RP extracts were given. Biochemical parameters and histopathological observation were performed to confirm the protective effect of RP on DN mice. Moreover, metabolomics analysis and molecular verification were carried out to explore the mechanism of RP extracts on DN. The results showed that RP extracts has a good hypoglycemic effect and renal- protective effect on DN mice. RP could restore the dynamic balance of mitochondrial biosynthesis and autophagy through the regulation of AMPK/SIRT1/PGC-1α and PINK1/Parkin signaling pathway, which may provide new insight for the application of RP as functional food in the prevention of DN.

Polyphenol from Rosaroxburghii Tratt Fruit Ameliorates the Symptoms of Diabetes by Activating the P13K/AKT Insulin Pathway in db/db Mice.

About 4% of the world’s population has type 2 diabetes mellitus (T2DM), and the available hypoglycemic drugs for treating diabetes have some side effects. Therefore, research on the extraction of hypoglycemic components from plants has gradually become popular. This study aimed to investigate the hypoglycemic effects of polyphenol-rich Rosa roxburghii Tratt extract (RP) isolated from Rosa roxburghii Tratt fruit and of four constituents (IRP 1–4 ) isolated from RP on db/db mice. The results indicated that the oral administration of RP and IRP 1–4 could markedly decrease the food intake, water intake, fasting blood glucose (FBG), and serum insulin levels in the db/db mice. Glucose intolerance, insulin resistance, and oxidative stress were ameliorated in the RP and IRP 1–4 groups. Histopathological observation revealed that RP and IRP 1–4 could effectively protect the liver fat against damage and dysfunction. RP and IRP 1–4 also increased the hepatic and muscle glycogen contents by increasing the phosphorylation and reducing the expression of glycogen synthase kinase 3β (GSK3β). The activities of glucokinase (GCK), phosphoenolpyruvate carboxylase (PEPCK), and glucose-6-phosphatase (G6PC) and their respective mRNA expression levels in the liver of db/db mice were simultaneously increased and decreased in the intervention groups. RP and IRP 1–4 significantly increased the expression of phosphatidylinositol 3-kinase (P13K) and the phosphorylation of protein kinase B (AKT). These results indicate that RP and IRP 1–4 exhibit good hypoglycemic effects by activating the P13K/AKT signaling pathway and regulating the expression of FOXO1 and p-GSK3β proteins, controlling hepatic gluconeogenesis and improving hepatic glycogen storage insulin resistance. Therefore, RP and IRP 1–4 could be utilized as the hypoglycemic functional component to alleviate the symptoms of T2DM.

The Effect of Strobilanthes crispus on Blood Glucose Levels and Lipid Profile of Streptozotocin-induced Diabetic Rats

BACKGROUND: Diabetes mellitus is a metabolic disease associated with unhealthy eating patterns, a lack of physical activity, obesity, smoking habits, and family history. Strobilanthes crispus (SC) contains antioxidant compounds known to exert a hypoglycemic effect during long-term interventions in non-diabetic samples. AIM: This study sought to determine the effect of administering the extract of SC leaves on the blood glucose levels and blood serum lipid profiles of streptozotocin (STZ)-induced diabetic rats. METHODS: A total of 30 male Rattus norvegicus rats were divided into control and treatment groups. The control groups consisted of negative (normal rats) and positive controls (diabetic rats), whereas the treatment groups consisted of diabetic rats administered with 3.2% and 16.8% SC leaf extract, and glibenclamide as the drug comparison groups. Blood samples were collected from the rats’ retro-orbital vein for the purposes of glucose level and lipid profile measurement before and after the induction of diabetes with STZ as well as 14 days after the intervention. The collected data were analyzed statistically by means of a one-way analysis of variance continued with Duncan’s multiple range test. RESULTS: The results showed the rats to be hyperglycemic experienced changes in their lipid profiles following the induction of diabetes. The administration of 3.2% SC leaf extract for 14 days reduced the rats’ blood glucose levels, while the effect of the 16.8% SC leaf extract was more pronounced in terms of reducing the rats’ blood glucose levels and improving their lipid profiles (reducing the triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, while increasing the high-density lipoprotein cholesterol levels). CONCLUSIONS: This study found 16.8% SC leaf extract to exert a good hypoglycemic effect and leads to an improvement in the lipid profiles in diabetic rats.

Intestinal Microbiota Play an Important Role in the Treatment of Type I Diabetes in Mice With BefA Protein.

More and more studies have shown that the intestinal microbiota is the main factor in the pathogenesis of type 1 diabetes mellitus (T1DM). Beta cell expansion factor A (BefA) is a protein expressed by intestinal microorganisms. It has been proven to promote the proliferation of β-cells and has broad application prospects. However, as an intestinal protein, there have not been studies and reports on its application in diabetes and its mechanism of action. In this study, a T1DM model induced by multiple low-dose STZ (MLD-STZ) injections was established, and BefA protein was administered to explore its therapeutic effect in T1DM and the potential mechanism of intestinal microbiota. BefA protein significantly reduced the blood glucose, maintained the body weight, and improved the glucose tolerance of the mice. At the same time, the BefA protein significantly increased the expression of ZO-1, Occludin, and significantly reduced the expression of TLR-4, Myd88, and p-p65/p65. BefA protein significantly reduced the relative expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α. In addition, our high-throughput sequencing shows for the first time that the good hypoglycemic effect of BefA protein is strongly related to the increase in the abundance of the beneficial gut bacteria Lactobacillus, Bifidobacterium and Oscillospria and the decrease in the abundance of the opportunistic pathogen Acinetobacter. Our group used animal models to verify the hypoglycemic effect of BefA protein, and first explored the potential mechanism of intestinal microbiota in BefA protein treatment.

Identification, potency evaluation, and mechanism clarification of α-glucosidase inhibitors from tender leaves of Lithocarpus polystachyus Rehd

Lithocarpus polystachyus Rehd. known as Sweet Tea in China has attracted lots of interest for its good hypoglycemic effect and the potential as a hypoglycemic agent. Based on affinity separation-UPLC-Q-TOF-MS/MS, 54 potential α-glucosidase inhibitiors were identified and 44 were structurally determined. Out of them, 41 were identified for the first time from this plant including flavonoids, fatty acids, triterpenes, alkaloids, and coumarins. Enzyme assays revealed that flavonoids exhibited higher inhibitory activity against α-glucosidase than others with astilbin (IC50 = 6.14 μg·mL−1), morin (IC50 = 8.46 μg·mL−1), and naringenin (IC50 = 10.03 μg·mL−1) showing 2- to 4-fold higher potency than the positive control acarbose. They were proved as reversible inhibitors with mixed inhibition mechanism. Ki (Ki') values and molecular dockings strongly supported the potency order of astilbin, morin and naringenin that showed in the enzyme assays.

Hypoglycemic, Hypolipidemic and Antioxidant Activities of Ocimum gratissimum Leaf Extract on Diabetic Rats

Aims: Ocimum gratissimum is a medicinal plant that has been traditionally used in the management of many diseases including diabetes mellitus. The aim of this research was to evaluate hypoglycemic, hypolipidemic and antioxidant activities of Ocimum gratissimum leaf extracts on diabetic rats.&#x0D; Study Design: Mention the design of the study here.&#x0D; Place and Duration of Study: Department of Biochemistry, Faculty of Life Science, Kebbi State University of Science and Technology Aliero, Kebbi State, Nigeria. Between february 2021 and June 2021.&#x0D; Methodology: The phytochemical screening was carried out using standard procedures. The extract was administered orally (100, 200 and 400 mg/kg body weight, for 21 days) to alloxan-induced diabetic rats. Hypoglycemic effects, change in body weight, lipid profile and antioxidant activities of diabetic rats treated with the extract were assessed and compared with normal, diabetic control and standard drug treated rats. Histological examination of the pancreas during 21 days of treatment was also carried out.&#x0D; Results: The extract produced a significant reduction in fasting blood glucose level in alloxan-induced diabetic rats. Significant differences were also observed in body weights, serum lipid profile and levels of antioxidant vitamins and enzymes of Ocimum gratissimum methanol extract treated diabetic rats, when compared with diabetic, normal and standard drug treated rats. Histopathological studies of the pancreas showed comparable regeneration of the cells by extract which were earlier necrosed by alloxan. Methanol leaf extract of Ocimum gratissimum exhibit significant hypoglycemic, hypolipidemic and antioxidant activities in alloxan-induced diabetes in rats. The extract could be further processed towards the management of diabetes mellitus.&#x0D; Conclusion: Ocimum gratissimum extract showed a promising good hypoglycemic effect, the extracts also exhibit hypolipidemic and antioxidant activities on diabetic rats. There was regeneration of pancreatic islets of Langerhans. Therefore at acute dose the extracts can serve as an alternative in the management of diabetes mellitus.

Liubao brick tea activates the PI3K-Akt signaling pathway to lower blood glucose, metabolic disorders and insulin resistance via altering the intestinal flora

Diabetes and its related metabolic disorders are worldwide public health issues. Many studies have shown that changes in the structure and composition of the intestinal flora are closely related to the host's physiological and pathological processes. In this study, we aim to explore the effect of Liubao tea (LBT) extract on hyperglycemic mice with metabolic disorders and intestinal flora dysbiosis and to further study its regulatory effect on insulin resistance and its potential regulatory mechanism. Our results show that LBT had a good hypoglycemic effect and could significantly alleviate the metabolic disorder evoked by hyperglycemia. The gut microbial sequencing showed that LBT treatment increased the diversity of intestinal flora, increased the abundance of beneficial bacteria, and reduced the abundance of harmful or conditional pathogenic bacteria, as well as significantly altered 39 of the top 50 OTUs with abundance. Besides, LBT could activate the PI3K-Akt-PPARs-GLUT2 cascade signaling pathway to improve metabolic disorders, thereby alleviating insulin resistance. These results suggest that LBT has excellent potential to become a natural functional food for the prevention of hyperglycemia and insulin resistance.