Iridoids and lignans from Valeriana officinalis and their bioactivities.

Seven undescribed iridoids, identified as valeriridoids A-E (compounds 1, 5, 18, 19a, 19b, 20a, and 20b), were isolated from the roots and rhizomes of Valeriana officinalis L., along with sixteen known iridoids and nine known lignans. The structures were elucidated using NMR and MS spectroscopy, and the absolute configurations of the undescribed iridoids were determined through ECD calculations. Valeriridoids D and E were found to be epimeric and scalemic mixtures, which were successfully resolved through a chiral column. These isolated iridoids were evaluated for their antiproliferative activities, with valeriridoid A, jatamanvaltrates P, and Q showing significant effects against human non-small cell lung cancer cells, with IC50 values of 14.68, 8.77, and 10.07 µM, respectively. Furthermore, the antihyperglycemic properties of the compounds were investigated in insulin-resistant human hepatoblastoma cells induced by palmitic acid treatment, revealing that valeriridoid A, jatamanvaltrates P, and Q at a concentration of 10 µM led to a notable increase in glucose consumption.

Bioactive phytocompounds profiling and the evaluation of analgesic, anti-inflammatory, and antihyperglycemic potential of Argyreia capitiformis (Poir.) Ooststr.: A combined in vitro, in vivo, and computational investigations.

ETHNOPHARMACOLOGICAL RELEVANCE: Argyreia capitiformis (Poir.) Ooststr. (Convolvulaceae) is traditionally used by the Chakma community in the hilly region of Bangladesh to treat minor disorders such as pain. AIM OF THE STUDY: This study intended to determine the secondary metabolites to identify bioactive compounds and evaluate antioxidant potential, in vitro anti-inflammatory and in vivo analgesic, anti-inflammatory, and antihyperglycemic activities of A. capitiformis along with in silico investigations. MATERIALS AND METHODS: Chemical profiling was carried out using HPLC and GC-MS analysis. The analgesic effect was measured employing tail immersion and acetic acid-induced writhing methods. Following protein denaturation and formalin-induced paw edema, anti-inflammatory activity was studied. The antihyperglycemic potential was assessed using an oral glucose tolerance test (OGTT), while further mechanistic investigation was conducted using an alpha-glucosidase enzyme inhibitory assay. Simulations and molecular docking analyses were performed to ascertain the stability and binding affinities of the drug-protein complex. RESULTS: A. capitiformis ethanolic extract confirmed the presence of phenolics, alkaloids, flavonoids, terpenoids, tannins, gums, steroids, and reducing sugars. HPLC analysis revealed the presence of eight polyphenolic compounds, the most abundant of which was myricetin (64.10 ± 0.14 mg per 100 g dry extract). Moreover, the GC-MS analysis revealed twenty-four molecules, the most important of which was 2,4-bis (dimethylbenzyl)-6-t-butylphenol (9.19%). The concentrations of total flavonoids, total terpenoids, total phenolics, and total tannins were ascertained to be 142.48 mg QE/g, 173.1 mg UAE/g, 19.35 mg GAE/g, and 13.05 mg GAE/g, respectively. Furthermore, the plant extract had a total antioxidant capacity of 388 mg AAE/g. In the writhing assay, the plant extract suppressed writhing by 59.73% and 76.99% at the doses of 250 and 500 mg/kg, respectively, compared to the standard diclofenac Na 87.17%, and in the tail immersion assay, the plant extract displayed a maximum average reaction time of 1.94 and 2.40 s at the doses of 250 and 500 mg/kg, respectively as compared to the control tramadol 2.84 s at 60 min. In an in vitro anti-inflammatory assay, the plant extract possessed an IC50 of 95.51 µg/ml while diclofenac Na (standard drug) was found to be 69.50 µg/ml. Afterward, in vivo anti-inflammatory activity was observed in mice over a period, particularly after 3 h, the plant extract exerted maximum percent inflammation inhibitions of 36.36% and 45.45% at the doses of 250 and 500 mg/kg, respectively whereas ibuprofen the standard drug (100 mg/kg) exhibited 61.82%. The plant extract demonstrated antihyperglycemic activity, lowering blood sugar levels to 5.7 and 4.62 mM at doses of 250 and 500 mg/kg, respectively, as opposed to 8.58 mM in the control group. Meanwhile, the standard drug glibenclamide (5 mg/kg) dropped blood glucose levels to 2.38 mM in 60 min after glucose administration. Molecular docking (MD) and molecular dynamics simulation (MDS) studies support the stability of the protein complex responsible for exerting pharmacological activities. CONCLUSION: A. capitiformis extract exhibited strong medicinal values supporting its traditional uses.

Antihyperglycemic activity of a novel polyherbal formula (HF344), a mixture of fifteen herb extracts, for the management of type 2 diabetes: Evidence from in vitro, ex vivo, and in vivo studies.

Antihyperglycemic effects of a novel polyherbal formula (HF344), comprising fifteen Thai herbal extracts, were elucidated for pharmacological mechanisms and potential for managing type 2 diabetes mellitus, by employing in vitro, ex vivo, and in vivo approaches. LC/MS analysis of HF344 extract revealed several phytoconstituents, with piperine identified as the major active compound. HF344 extract significantly enhanced insulin secretion in RINm5F cells in vitro and inhibited glucose uptake into the everted sacs of the mouse small intestine ex vivo in a concentration-dependent manner compared to the control (p < 0.05). It exhibited potent α-glucosidase inhibition in vitro, with an IC50 of 96.74 µg/mL. Moreover, HF344 extract upregulated mRNA levels of GLUT1 in L6 skeletal myoblasts, suggesting increased glucose uptake into skeletal muscle. In addition, in vivo antihyperglycemic effects were assessed in streptozotocin (STZ)-nicotinamide (NA)-induced diabetic mice. Acute oral toxicity testing confirmed the HF344 extract's safety, with an LD50 exceeding 2000 mg/kg. Oral administration of HF344 extract (500 and 1000 mg/kg) in STZ-NA-induced diabetic mice significantly reduced the area under the fasting blood glucose (FBG)-time curve (AUC) in the oral glucose tolerance test (OGTT) model and treatment for 28-day reduced the FBG levels as compared with control (p < 0.05). This was accompanied by increased serum insulin levels and improved insulin resistance. HF344 extract also demonstrated a concentration-dependent inhibitory effect on malondialdehyde (MDA) production in vitro, with an IC50 of 7.24 µg/mL. Oral treatment with HF344 extract decreased MDA production in the homogenized muscle ex vivo collected from STZ-NA-induced mice. Furthermore, pretreatment with HF344 extract effectively restored the survival of RINm5F cells from STZ-induced damage. These findings suggest that HF344 is a promising polyherbal formula for managing blood glucose levels, enhancing insulin production, and providing antioxidant benefits in T2DM. Further research is required to evaluate the clinical efficacy and safety profiles of HF344.

Potential synergistic antihyperglycemic effects of co-supplemental Amla and Olive extracts in hyperlipidemic adults with prediabetes and type 2 diabetes: results from a real-life clinical study.

Background: Hyperglycemia and type 2 diabetes mellitus (T2DM) pose a significant risk for cardiovascular diseases and associated complications in individuals with hyperlipidemia. Statin therapy, effective in reducing cholesterol and cardiovascular risks, paradoxically increases incident T2DM risk due to its adverse impact on glucose homeostasis. Therefore, there is a pressing need for safe, and effective adjunctive or alternative therapies to manage hyperglycemia in hyperlipidemic individuals. There is growing body of pharmacological evidence suggesting that Amla and Olive extract supplementation can be beneficial in managing hyperglycemia in individuals with hyperlipidemia. Objective: The present study aimed to assess for the first time the potential synergistic antihyperglycemic effects of a daily co-supplementation of 1,000 mg Amla fruit and 50 mg Olive fruit standardized extracts (Cholesfytol NG®) over a 2-months period in hyperlipidemic adults with T2DM or prediabetes. Methods: This retrospective cross-sectional observational study analyzed treatment outcomes in 191 hyperlipidemic adults under the care of their physicians at 57 General Practitioner clinics in Belgium during real-life clinical practice between March 19, 2020, and January 31, 2022. These participants received Cholesfytol NG® as supplementary therapy to improve their metabolic health. The supplement was prescribed in an open-label, non-randomized manner, tailored to each participant's need. Results: After 2-months of Cholesfytol NG® supplementation, participants showed significant reductions in glycemia levels: in the T2DM group, levels decreased by 42.7 ± 17.9 mg/dL (27.9%, p < 0.0001), and in the prediabetic group, by 2.26 ± 11.5 mg/dL (4.7%, p = 0.0020). Conversely, no significant change was observed in participants with normal baseline glycemia (1.55 ± 10.3 mg/dL, p = 0.088). Overall, glycemia levels decreased from 96.4 ± 18.2 mg/dL to 94.0 ± 13.5 mg/dL (mean decrease of 2.4 ± 14.5 mg/dL, p < 0.0001). The supplement was well tolerated and no side-effects, serious adverse events, or treatment-emergent effects were reported. Conclusion: The findings of this real-life clinical study highlight the potential synergistic antihyperglycemic effects of co-supplementation with Amla and Olive fruit extracts in managing hyperglycemia, particularly in individuals with hyperlipidemia. These results suggest that this botanical combination may help mitigate risks associated with hyperglycemia and cardiovascular disease in hyperlipidemic population. Clinical trial registration: ClinicalTrials.gov, NCT06187298.

Variation in the Phenolic Profile and Antioxidant, Antihyperglycemic, and Anti-Inflammatory Activity in Leaves of Cotoneaster zabelii during Growing Season.

Cotoneaster zabelii is a medicinal plant that is beneficial due to its polyphenol-rich leaves. In the course of optimizing the harvest time for C. zabelii cultivated in Poland, the leaf samples were collected monthly during the annual plant vegetation season, and the hydromethanolic leaf extracts were evaluated for their phenolic composition and model biological activities, including antioxidant, antihyperglycemic, and anti-inflammatory effects in vitro. The phenolic profiles were analyzed using UHPLC-PDA-ESI-MS3, HPLC-PDA, and spectrophotometric methods (total phenolic content, TPC) to understand their seasonal variability and its correlation with bioactive properties. The identified phenolic compounds included caffeic acid derivatives, flavan-3-ols (especially (-)-epicatechin and procyanidins B-type), and flavonoids like quercetin mono- and diglycosides. Leaves harvested in July and October contained the highest polyphenolic levels and demonstrated significant antioxidant activity in most tests. The leaves harvested in July, September, and October showed optimal anti-inflammatory effects, whereas the highest antihyperglycemic activity was observed in the leaves collected from June to July. Regarding polyphenolic levels and bioactivity, the summer and autumn months appear to be the most advantageous for harvesting leaf material of optimal quality for phytotherapy.

Bioaccessibility and Antidiabetic Potential of xique-xique and mandacaru Fruits in a Simulated Gastrointestinal Tract Model.

This study evaluated the influence of gastrointestinal digestion on the bioaccessibility and antidiabetic potential of xique-xique (Pilosocereus gounellei) and mandacaru (Cereus jamacaru) fruits. After digestion, the content of total phenolics and flavonoids reduced by 58.3 and 73.51% in xique-xique and 48.33 and 88.43% in mandacaru. In addition, compounds such as rutin, ρ-coumaric acid, catechin and epicatechin reduced during digestion for both fruits. The antioxidant potential by the ABTS assay increased by 153.3% for xique-xique and 273.46% for mandacaru in the intestinal phase. However, using the ORAC assay, the antioxidant potential of xique-xique reduced from 255.42 to 112.17 µmol TE g-1. The capacity of xique-xique fruit to reduce α-amylase activity reduced 23.71-fold after digestion, but the potential to inhibit α-glucosidase increased 17.8-fold. The antiglycation potential reduced in both fruits after the in vitro gastrointestinal digestion. Thus, the bioaccessibility of the phenolic compounds from the fruits, as well as their functional potential, were influenced by the digestive process, as well as by the sample evaluated.

Anti-Hyperglycemic Effects of Thai Herbal Medicines.

This study aims to investigate selected medicinal plants' anti-oxidative and antihyperglycemic activities to develop an effective remedy for lowering blood glucose levels and/or reducing diabetes complications. Thai medicinal plants, reported to have blood sugar-lowering effects, were selected for the study: Coccinia grandis, Gymnema inodorum, Gynostemma pentaphyllum, Hibiscus sabdariffa, Momordica charantia, Morus alba, and Zingiber officinale. Each species was extracted by Soxhlet's extraction using ethanol as solvent. The ethanolic crude extract of each species was then evaluated for its phytochemicals, anti-oxidant, and antihyperglycemic activities. The results showed that the extract of Z. officinale gave the highest values of total phenolic and total flavonoid content (167.95 mg gallic acid equivalents (GAE)/g and 81.70 mg CE/g, respectively). Anti-oxidant activity was determined using DPPH and ABTS radical scavenging activity. Among the ethanolic extracts, Z. officinale exhibited the highest anti-oxidant activity with IC50 values of 19.16 and 8.53 µg/mL, respectively. The antihyperglycemic activity was assessed using α-glucosidase inhibitory and glucose consumption activities. M. alba and G. pentaphyllum demonstrated the highest α-glucosidase inhibitory activity among the ethanolic extracts, with IC50 values of 134.40 and 329.97 µg/mL, respectively. Z. officinale and H. sabdariffa showed the highest percentage of glucose consumption activity in induced insulin-resistant HepG2 cells at a concentration of 50 µg/mL with 145.16 and 107.03%, respectively. The results from α-glucosidase inhibitory and glucose consumption activities were developed as an effective antihyperglycemic remedy. Among the remedies tested, the R1 remedy exhibited the highest potential for reducing blood glucose levels, with an IC50 value of 122.10 µg/mL. Therefore, the R1 remedy should be further studied for its effects on animals.

Anti-Hyperglycemic Medication Management in the Perioperative Setting: A Review and Illustrative Case of an Adverse Effect of GLP-1 Receptor Agonist.

A host of anti-hyperglycemic agents are currently available and widely prescribed for diabetes and weight loss management. In patients undergoing surgery, use of these agents poses a clinical challenge to surgeons, anesthesiologists, and other perioperative care providers with regard to optimal timing of discontinuation and resumption of use, as well as possible effects of these agents on physiology and risk of postoperative complications. Here, we provide a comprehensive review of anti-hyperglycemic medications' effects on physiology, risks/benefits, and best practice management in the perioperative setting. Additionally, we report an illustrative case of small bowel obstruction in a patient taking semaglutide for 6 months prior to an otherwise uncomplicated laparoscopic hysterectomy and bilateral salpingo-oophorectomy. This review is meant to serve not as a replacement of, but rather as a consolidated complement to, various society guidelines regarding perioperative anti-hyperglycemic agent management.

In Vitro Alpha-Glucosidase Inhibitory Effect of Etlingera Elatior Ethanol Extract Growing in Gayo Highland, Aceh Province, Indonesia.

Background: The prevalence of diabetes mellitus (DM) is increasing overtime, potentially leading to various severe health complications and mortality. Despite therapeutic agents have currently been developed, unexpected adverse effects are inevitable. Hence, safe and effective medications such as those of plant origin are critical to prevent unexpected complication in DM sufferers. Etlingera elatior has been widely used as spice and traditional medicine to treat diabetes in Aceh Province, Indonesia. However, study regarding α-glucosidase inhibitory effect of E. elatior growing in Gayo highlands, Aceh, Indonesia, is completely lacking. The aim of this study was to evaluate in vitro α-glucosidase inhibitory effect of E. elatior ethanol extracts (EEEE) growing in Gayo highlands, Aceh Province, Indonesia. Methods: Antioxidant activity was determined using DPPH procedure, whereas α-glucosidase inhibition assay was carried out using spectrophotometric method. Data analysis was performed using One-Way Analysis of Variance (ANOVA), followed by Duncan's multiple range test at α=0.05. Results: Phytochemical analysis revealed the presence of total phenolic (TPC), total flavonoid (TFC), and total tannin (TTC) content in all E. elatior plant parts, in which the highest TPC was found in the stem (158.38 GAE/g), whereas the highest TFC and TTC was obtained in the rhizome extracts. The extract of fruit showed the strongest antioxidant activities, followed by the stem and leaf, with IC 50 of 2.381 µg/mL, 6.966 µg/mL, and 19.365 µg/mL, respectively. All E. elatior extracts revealed a significant inhibitory activity against α-glucosidase at the concentration of 500 µg/mL, in which the stem extract showed the most effective α-glucosidase inhibitory effect with IC 50 value of 5.15 µg/mL, suggesting its promising potential as antidiabetic agent. Conclusions: This study highlights E. elatior potency as a novel source of antioxidant and natural antidiabetic compounds that are useful for the prevention and treatment of diabetes.

Antihyperglycemic, Antiaging, and L. brevis Growth-Promoting Activities of an Exopolysaccharide from Agrobacterium sp. FN01 (Galacan) Evaluated in a Zebrafish (Danio rerio) Model.

Agrobacterium sp. are notable for their ability to produce substantial amounts of exopolysaccharides. Our study identified an exopolysaccharide (Galacan, 4982.327 kDa) from Agrobacterium sp. FN01. Galacan is a heteropolysaccharide primarily composed of glucose and galactose at a molar ratio of 25:1. The FT-IR results suggested that Galacan had typical absorption peaks of polysaccharide. The results of periodate oxidation, Smith degradation, and NMR confirmed the presence of structural units, such as ß-D-Galp(→, →3)ß-D-Galp(1→, →2,3)ß-D-Glcp(1→, ß-D-Glcp(1→, and →2)ß-D-Glcp(1→. Galacan demonstrated significant biological activities. In experiments conducted with zebrafish, it facilitated the proliferation of Lactobacillus brevis in the intestinal tract, suggesting potential prebiotic properties. Moreover, in vivo studies revealed its antihyperglycemic effects, as evidenced by significant reductions in blood glucose levels and enhanced fluorescence intensity of pancreatic ß cells in a streptozotocin (STZ)-induced hyperglycemic zebrafish model. Additionally, antiaging assays demonstrated Galacan's ability to inhibit ß-galactosidase activity and enhance telomerase activity in a hydrogen peroxide (HP)-induced aging zebrafish model. These findings emphasized the potential of Galacan as a natural prebiotic with promising applications in diabetes prevention and antiaging interventions.

Risk of bladder cancer in patients with type 2 diabetes mellitus: a retrospective population-based cohort study in Lithuania.

PURPOSE: The objective of our study was to evaluate bladder cancer risk among Lithuanian type 2 diabetes mellitus (T2DM) patients and the effect of antihyperglycemic therapy on bladder cancer risk. METHODS: We analyzed bladder cancer risk in a cohort of patients who were diagnosed with T2DM between 2001 and 2012 in Lithuania. Bladder cancer risk in four groups of antihyperglycemic medication users (insulin-only, metformin-only, sulfonylurea-only, and pioglitazone ± any other drug) was also assessed. Standardized incidence ratios for bladder cancer were calculated. RESULTS: A total of 76,818 patients (28,762 males and 48,056 females) with T2DM were included in the final cohort. In the whole cohort of diabetic patients, 277 bladder cancer cases were observed, compared to 232.75 expected cases, according to bladder cancer rates in the general population (Standardized Incidence Ratio 1.19; 95% Confidence Interval: 1.06-1.34). Higher risk of bladder cancer was found in both men and women; however, in women the risk increase was not statistically significant. We found higher risk of bladder cancer in patients of both sexes diagnosed with T2DM at the age of 50-79 years and also in all groups of different antihyperglycemic medication users. CONCLUSION: T2DM was associated with increased risk of bladder cancer.

Antioxidants from Rubus idaeus leaves: LC-MS/MS chemical profiling, in vitro antiglycation, α-glucosidase and α-amylase inhibitory activities.

The present study evaluated a range of biological activities of Rubus idaeus leaves, often considered as by-products, in relation to hyperglycemia. The antiglycation potential of this plant has not been previously reported. In this research, the methanolic leaf extract of R. idaeus was assessed for its antioxidant, enzyme inhibitory and antiglycation activities. The bioactive compounds present in the extract were screened using LC-MS/MS. Enzyme inhibitory activities were tested on α-glucosidase and α-amylase, and the antiglycation effect was investigated using BSA-fructose model. The methanolic extract showed a high polyphenolic contents (176.26 ± 2.26 mg GAE/g) and important IC50 values for DPPH (34.79 ± 2.40 µg/mL) and ABTS radical scavenging activities (49.75 ± 2.47 µg/mL). In addition, the plant leaf extract significantly inhibited hyperglycemia-related enzymes in a dose-dependent manner and demonstrated a reduction in fluorescent AGEs, fructosamine, and dicarbonyl compounds. Therefore, R. idaeus cv Maravilla could be an effective source of therapeutics for improving the healthcare outcomes of diabetic patients.

Epicatechin and ß-Glucan from Whole Highland Barley Grain Synergistic Benefit on Attenuating Hyperglycemia via Improving Hepatic Glucose Metabolism in Diabetic C57BL/6J Mice.

Our previous study proved that epicatechin (EC) and ß-glucan (BG) from whole-grain highland barley synergistically modulate glucose metabolism in insulin-resistant HepG2 cells. However, the main target and the mechanism underlying the modulation of glucose metabolism in vivo remain largely unknown. In this study, cell transfection assay and microscale thermophoresis analysis revealed that EC and BG could directly bind to the insulin receptor (IR) and mammalian receptor for rapamycin (mTOR), respectively. Molecular dynamic analysis indicated that the key amino acids of binding sites were Asp, Met, Val, Lys, Ser, and Tys. EC supplementation upregulated the IRS-1/PI3K/Akt pathway, while BG upregulated the mTOR/Akt pathway. Notably, supplementation with EC + BG significantly increased Akt and glucose transporter type 4 (GLUT4) protein expressions, while decreasing glycogen synthase kinase 3ß (GSK-3ß) expression in liver cells as compared to the individual effects of EC and BG, indicating their synergistic effect on improving hepatic glucose uptake and glycogen synthesis. Consistently, supplementation with EC + BG significantly decreased blood glucose levels and improved oral glucose tolerance compared to EC and BG. Therefore, combined supplementation with EC and BG may bind to corresponding receptors, targeting synergistic activation of Akt expression, leading to the improvement of hepatic glucose metabolism and thereby ameliorating hyperglycemia in vivo.

Effects of Purified Vitexin and Iso-Vitexin from Mung Bean Seed Coat on Antihyperglycemic Activity and Gut Microbiota in Overweight Individuals' Modulation.

Exceeding a healthy weight significantly elevates the likelihood of developing type 2 diabetes (T2DM). A commercially available singular constituent, available as either purified vitexin or iso-vitexin, has been associated with a decreased risk of T2DM, but its synergistic effect has not been reported yet. Vitexin and iso-vitexin were extracted using an ethanol-based solvent from mung bean seed coat (MBCE) and subsequently purified using preparative liquid chromatography (Prep-LC). Eleven mixture ratios of vitexin and/or iso-vitexin were determined for their antioxidant and antihyperglycemic activities. The 1:1.5 ratio of vitexin to iso-vitexin from MBCE demonstrated the most synergistic effects for enzyme inhibition and glucose uptake in HepG2 cells within an insulin-resistant system, while these ratios exhibited a significantly lower antioxidant capacity than that of each individual component. In a gut model system, the ratio of 1:1.5 (vitexin and iso-vitexin) regulated the gut microbiota composition in overweight individuals by decreasing the growth of Enterobacteriaceae and Enterococcaceae, while increasing in Ruminococcaceae and Lachnospiraceae. The application of vitexin/iso-vitexin for 24 h fermentation enhanced a high variety of abundances of 21 genera resulting in five genera of Parabacteroides, Ruminococcus, Roseburia, Enterocloster, and Peptacetobacter, which belonged to the phylum Firmicutes, exhibiting high abundant changes of more than 5%. Only two genera of Proteus and Butyricicoccus belonging to Proteobacteria and Firmicutes decreased. The findings suggest that these phytochemicals interactions could have synergistic effects in regulating glycemia, through changes in antihyperglycemic activity and in the gut microbiota in overweight individuals. This optimal ratio can be utilized by industries to formulate more potent functional ingredients for functional foods and to create nutraceutical supplements aimed at reducing the risk of T2DM in overweight individuals.

From sugar binders to diabetes fighters: the lectin saga of antihyperglycemic activity through systematic review and meta-analysis.

Introduction: Lectins are carbohydrate-binding proteins that are extremely selective for sugar groups in the other molecules. As a result, they perform a variety of roles in biological processes involving cell, carbohydrate, and protein recognition at the cellular and molecular levels. Because lectins can bind to carbohydrates, they may play a role in determining the rate of carbohydrate digestion. They also bind to some proteins involved in diabetes mellitus (DM) pathophysiology. The present review aims to summarize the efficiency of lectins from different sources as potential antihyperglycemic agents. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were employed for the drafting. In this regard, published scientific articles on the effects of different lectins on blood glucose (BG), glucose tolerance, hormonal effects, carbohydrate-digesting enzymes, oxidative stress, and insulin production process were collected from reputed journals using electronic databases. Furthermore, the toxicity effects of lectins from different sources were collected. A specific keyword search was completed to collect numerous articles with unique experimental designs and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles. Results and Discussion: Of 13 identified studies, 11 studies were considered after double screening based on the inclusion criteria. All 11 pharmacological investigations were considered for review. Subsequent studies reflected on the pharmacological properties of lectins on the levels of BG, oxidative stress, ß-cell proliferation, insulin resistance, inhibition of carbohydrate digesting enzymes, body weight, food and water intake, lipid profile, and other parameters. This review highlights lectins as potential anti-diabetic agents. Conclusion: However, due to limited research, systematic evaluation is recommended for their development and promotion as effective potential antihyperglycemic agents. The clinical efficacy and safety of lectins against diabetes mellitus must also be evaluated.

Glycemic Variability in Pancreatogenic Diabetes Mellitus: characteristics, Risks, Potential Mechanisms, and Treatment Possibilities.

In recent years, pancreatogenic diabetes mellitus has garnered significant attention due to its high incidence, complications, and mortality rates. Glycemic variability (GV) can increase the risk of pancreatogenic diabetes mellitus and its associated complications; however, the precise mechanism remains unclear. The effective control of GV is crucial for preventing the onset of pancreatic diabetes mellitus and improving prognosis. Both diet and antidiabetic medications have substantial effects on GV. However, many patients are prescribed suboptimal or even harmful drugs. Therefore, to provide a comprehensive treatment basis for clinicians to prevent and treat pancreatogenic diabetes mellitus, this study aimed to elucidate the relationship between GV and pancreatogenic diabetes mellitus; investigate the potential mechanisms (such as oxidative stress, inflammatory response, insulin resistance, and lipid metabolism disorders); provide lifestyle guidance; and recommend drug selections to reduce the GV in patients with pancreatogenic diabetes mellitus.

Metformin and Atrial Fibrillation: A Systematic Review of Their Association.

Atrial fibrillation (AF) is a common cardiac arrhythmia with a significant impact on patient outcomes and healthcare systems. Given the rising incidence of AF with age and its association with conditions, such as diabetes, there is growing interest in exploring pharmacological interventions that might mitigate AF risk. Metformin, a widely prescribed antihyperglycemic agent for type 2 diabetes mellitus (T2DM), has demonstrated various cardiovascular benefits, including anti-inflammatory and antioxidative properties, leading to speculations about its potential role in AF prevention. This systematic review synthesizes findings from five studies examining the association between metformin use and AF risk in patients with T2DM. The review included a dynamic cohort study, three retrospective cohort studies, and a case report, all sourced from databases, such as PubMed, Embase, and the Cochrane Library. The results are mixed; while some studies suggest that metformin use is linked to a reduced incidence of AF, others report no significant association, particularly in postoperative settings. The largest cohort study highlighted a dose-response relationship, suggesting prolonged metformin use correlates with lower AF risk. Conversely, a case report raised concerns about metformin-induced lactic acidosis potentially triggering AF episodes. The review underscores the heterogeneity in study designs and outcomes, pointing to the need for more robust research to establish causality and clarify underlying mechanisms. Future studies should prioritize prospective designs and explore the pleiotropic effects of metformin on atrial remodeling and electrophysiology to better understand its potential role in AF prevention.

Phyto-pharmacological and computational profiling of Bombax ceiba Linn. Leaves revealed pharmacological properties against oxidation, hyperglycemia, pain, and diarrhea.

The present study aimed to conduct phytochemical and pharmacological profiling of methanolic crude extract of leaves of Bombax ceiba Linn. via experimental and computational approaches. Six secondary metabolites were isolated chromatographically, and the structures were elucidated by extensive analyses of high-resolution 1H and 13C NMR data. The separated compounds were characterized as ß-sitosterol (1), ß-amyrin (2), ß-amyrin acetate (3), ß-amyrin palmitate (4), ß-amyrone (5), and isoscopoletin (6). DPPH free radical scavenging assay, tail-tipping method, writhing assay, and castor oil-induced diarrheal mice methods, respectively, were used to assess the antioxidant, hypoglycemic, analgesic, and anti-diarrheal activities of the leaf extract of B. ceiba plant species. The study observed significant reductions (p < 0.05) in the level of blood glucose at 30, 60, 120, and 180 min following the administration of the crude extracts (200 mg/kg body weight (bw) and 400 mg/kg bw). These reductions occurred in a time-dependent manner. Additionally, both doses of the investigated extracts exhibited significant (p < 0.05) central and peripheral analgesic effects compared to morphine (2 mg/kg bw) and diclofenac sodium (50 mg/kg bw), respectively. Furthermore, the 400 mg/kg bw extract demonstrated anti-diarrheal activity, reducing 54.17 % of diarrheal episodes in mice compared to loperamide with 70.83 % inhibition. The computational investigations yielded results consistent with existing in vivo findings. The results obtained from molecular docking showed that the isolated compounds had a better or comparable binding affinity to the active binding sites of the glutathione reductase enzyme, mu-opioid receptor, cyclooxygenase 2 (COX-2), glucose transporter 3 (GLUT 3), and kappa opioid receptor. These findings may indicate that the compounds isolated from the B. ceiba plant species have antioxidant, analgesic, hypoglycemic, and anti-diarrheal, properties. Consequently, it was inferred that the plant B. ceiba might be beneficial in dealing with oxidation, diarrhea, hyperglycemia, and pain. Nonetheless, further investigations are necessary to perform thorough phytochemical profiling and elucidate the exact mechanistic ways of the crude extract and the isolated phytoconstituents.

SGLT2 inhibitors for the treatment of diabetes: a patent review (2019-23).

INTRODUCTION: The sodium-glucose co-transporter 2 (SGLT2) inhibitors are FDA-approved class of drugs for diabetes management. They improve glycemic control by inducing glucosuria. Notwithstanding with potent anti-hyperglycemic activity, SGLT2 inhibitors are emerging as drugs with multifaceted therapeutic potential, evidenced for cardioprotective, renoprotective, antihypertensive, and neuroprotective activities. Continuous attempts are being accomplished through structural modification, development of new formulation, or combination with other drugs, to enhance the bioactivity spectrum of SGLT2 inhibitors for better management of diabetes and related complications. AREAS COVERED: This review comprises a summary of patent applications, acquired using the Espacenet Patent Search database, concerning SGLT2 inhibitors from 2019 to 2023, with focus on improving therapeutic potentials in management of diabetes and metabolic complications. EXPERT OPINION: SGLT2 inhibitors have provided an exciting treatment option for diabetes. Originally developed as anti-hyperglycemic agents, SGLT2 inhibitors exert pleiotropic metabolic responses and have emerged as promising antidiabetic agents with cardio-protective and reno-protective activities. Given their distinct therapeutic profile, SGLT2 inhibitors have revolutionized the management of diabetes and associated complications. Emerging evidences on their therapeutic potential against cancer, male reproductive dysfunctions, and neurodegenerative diseases indicate that further research in this field may unfold novel prospective on their plausible use in the management of other chronic conditions.

Nutraceutical Properties of the Hydroalcoholic Extract and Phenolic Compounds from Yucca aloifolia Edible Flowers.

The flowers of Yucca aloifolia ("flor de izote") are considered a millenary food in the Northeastern Highlands of Puebla, Mexico. The present investigation reports on the chemical and biological activities of the hydroalcoholic extract (YAHF) obtained from this edible source. HPLC-MS profiling revealed twenty bioactive phenolic compounds with chlorogenic acid (16.5 mg g-1 DW), quercetin (9.5 mg g-1 FW), and their glycosides (rutin and quercitrin), as well as caffeic acid (8.4 mg g-1 DW) and ferulic acid (7.9 mg g-1 DW) as major compounds dissolved in YAHF. Six metabolites had potent anti-lipase (IC50<100 µg mL-1) and anti-ornithine decarboxylase activity (IC50<100 µg mL-1), whereas thirteen exerted strong anti-alpha-glucosidase properties (IC50<100 µg mL-1). The evaluation of YAHF in mice subjected to standard oral glucose tolerance tests and prolonged administration of hypercaloric/atherogenic diet (30 days), unraveled their ability to improve glucose and lipid profiles. YAHF and six phenolic compounds significantly reduced DLD-1 cell viability (IC50, 117.9 µg mL-1) and avoided polyamine accumulation linked to anti-ornithine decarboxylase activity. YAHF and its twenty constituents exerted low toxicity in probiotics (>1000 µg mL-1) and 3T3 fibroblasts (>2.5 mg-mL-1), sustaining their safeness for human consumption.