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OBJECTIVE: The purpose of this study was to assess the impact of bitter melon extract supplementation on glycemia in individuals with prediabetes. METHODS: This was a 12-week randomized, parallel, placebo-controlled study where 75 adults with prediabetes were randomly allocated into the low-dose bitter melon (300 mg/day) (n = 26), high-dose bitter melon (600 mg/day) (n = 24), or control (n = 25) groups. RESULTS: At baseline and weeks 6 and 12, anthropometrics were measured, and fasting blood samples were obtained. The high-dose (1.05% ± 10.2%) and low-dose bitter melon (3.35% ± 13.2%) groups showed smaller increases in blood glucose levels at 12 wk, compared to the control group (11.0% ± 16.3%) (p < 0.05). A subgroup analysis of participants with age ≥ the median demonstrated a greater reduction in glycated hemoglobin at 12 wk in the high-dose bitter melon group (median change: -0.20%; IQRL: -0.20%, -0.05%) vs. the control group (median change: 0.00%; IQRL: -0.10%, 0.20%) (p = 0.017). Compliance with the interventions was >95%, and the study products were tolerated well. CONCLUSION: The bitter melon extract may help maintain a healthy level of glucose in adults with prediabetes.

INTRODUCTION: Acute pancreatitis associated with Pazopanib has been reported in the literature. Bitter Melon (Momordica Charantia) is traditionally used as a folk medicine in many regions. In this report, we describe a 65-year-old patient with a diagnosis of renal cell carcinoma, admitted to the hospital with symptoms of acute pancreatitis at the 8th year of pazopanib treatment. CASE REPORT: The patient diagnosed with renal cell carcinoma was admitted to the hospital with the complaint of abdominal pain, nausea, and vomiting in the 8th year of Pazopanib treatment. It was noticed from the patient's history that he had received Bitter Melon extract for 4 days prior to the beginning of his complaints (100-150 ml/day). Levels of serum amylase and lipase were measured as 9163 U/L and 14,206 U/L, respectively. MANAGEMENT & OUTCOME: Pazopanib drug was held. The patient was treated for acute pancreatitis. Pazopanib treatment was started again after the clinical condition of the patient had improved and levels of serum amylase and lipase had returned to normal levels. Levels of serum amylase and lipase did not increase again after re-administration of pazopanib treatment. DISCUSSION: It is thought that Bitter Melon extract and pazopanib interaction might have led to acute pancreatitis. To the best of our knowledge, this case is the first to highlight the interaction of Bitter Melon extract with pazopanib. The Drug Interaction Probability Scale indicates that there is a probable association between bitter melon and acute pancreatitis.

The pharmacology, clinical efficacy, adverse effects, drug interactions, and place in therapy of bitter melon are described. Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter melon extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches. Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.

INTRODUCTION: Momordica charantia (bitter melon) is widely used for its glucose-lowering effects. This study was conducted to assess the efficacy and safety of M. charantia as an adjuvant treatment in patients with type 2 diabetes. METHODS: We performed a randomized, placebo-controlled study. Blood glucose levels, lipid profile, and adverse events were investigated after 12 weeks of treatment. Ninety subjects were included in the final analysis for glucose lowering efficacy of bitter melon. RESULTS: There were no differences in age, sex, or glycated hemoglobin (HbA1c) levels between the bitter melon extract and placebo groups. After treatment with bitter melon extract for 12 weeks, the HbA1c levels of the bitter melon and placebo groups remained unchanged; however, the average fasting glucose level of the bitter melon group decreased (p = 0.014). No serious adverse events were reported during the treatment period. CONCLUSIONS: Our data showed that bitter melon has effects of glucose lowering in patients with type 2 diabetes.

BACKGROUND: Although extracts from medicine food homologous plants have been widely used as interventions for the prevention and treatment of Type 2 diabetes mellitus (T2DM), it remains a major public health concern. Diabetes is also known as a "thirsting disorder" because it leads to the depletion of vital biomolecules in the body regardless of food or water intake and interferes with the replenishment of fluids through drinking. We developed a novel thirst-free drink (TF601) that contains a combination of traditional Chinese medicine food homologous plants extracts of Psidium guajava, Momordica charantia, Lycii Fructus, Glycyrrhizae Radix, and Camellia sinensis. In this study, we investigated TF601's drink subchronic toxicity evaluation in mice and an exploratory, uncontrolled clinical assessment of TF601 in patients with T2DM. METHODS: Herein, for toxicity studies, mice (male and female) were divided into a TF601-treated group and a control group. The TF601 drink was orally administered for 90 days to evaluate its toxicity. The mice were monitored daily for the appearance of any clinical signs. Their food intake and body weight changes were measured every week. Hematological, biochemical, and histopathological changes were also evaluated. For the exploratory human study, 14 patients with T2DM were enrolled in an uncontrolled pilot trial and glucose levels, hemoglobin A1c percentage, oral glucose tolerance levels, and body weight were monitored from baseline to 2 months later. RESULTS: Oral administration of TF601 drink in mice did not develop any clinical signs, nor did they die due to the treatment. No changes were noted in body weight, food intake, or liver, kidney, or brain histology. However, slightly significant changes were observed in the hematological and biochemical parameters only in male mice as compared with control mice. In the human clinical trial, significant improvements were noted in T2DM patients' glucose levels, and liver and kidney functions after a 2-month treatment with TF601. Overall, our toxicity studies in animals and clinical trials in humans revealed that TF601 drink was not toxic, alleviated the blood glucose level, and maintained

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance and impaired glucose homeostasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that plays a central role in adipogenesis, glucose metabolism, and insulin sensitization, and remains a validated pharmacological target for antidiabetic therapy. Momordica charantia has long been used in traditional medicine for glycemic control; however, its precise molecular mechanisms, particularly in relation to PPARγ-centered regulation, remain incompletely defined. The present study employed an integrated network pharmacology, molecular docking, molecular dynamics (MD) simulation, and ADMET profiling workflow to investigate PPARγ-directed antidiabetic phytochemicals from M. charantia. Fifteen compounds meeting oral bioavailability and drug-likeness criteria were screened, and six bioactive phytochemicals were prioritized based on network topology and target intersection analysis. Protein-protein interaction (PPI) analysis identified PPARγ as a central hub within diabetes-associated networks. Docking studies suggested favorable predicted binding affinities of selected phytochemicals within the canonical ligand-binding domain of PPARγ. MD simulations provided preliminary insights into complex stability and residue-level flexibility. ADMET assessment indicated variable pharmacokinetic profiles, with some compounds demonstrating high gastrointestinal absorption while others exhibited lipophilicity-related limitations. This study provides a mechanistic, hypothesis-driven computational framework highlighting PPARγ-directed phytochemicals from M. charantia as candidates for further experimental validation. These findings are exploratory and warrant in vitro and in vivo studies to confirm biological activity and therapeutic relevance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00621-8. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to th

Bitter gourd (Momordica charantia L.) has turned out to be a significant source of proteins and bioactive peptides, which have prospects of finding application in functional foods and nutraceuticals. It contains a high level of proteins and phytochemicals, which offer significant health benefits. Leaves, seeds, and stems are also high sources of antioxidants and are good stores of important nutrients. It can help prevent and treat a number of lifestyle-related diseases such as diabetes mellitus, cancer, nephrolithiasis, scabies, abdominal pain, and fever. This review critically evaluates the latest developments in methods of extraction of proteins and peptides from bitter gourd and emphasizes innovative methods. Such methods have enhanced extraction efficiency and protein yield, and improved functional properties. However, there are still issues in optimizing these processes to make them bioavailable and provide stable products. Furthermore, the commercial feasibility of bitter gourd proteins is limited by cost, flexibility, and marketability. This review highlights the need for research to improve extraction methods, explore new uses, and overcome trade barriers.

BACKGROUND: The rich biodiversity of West Africa supports a vast repository of medicinal plants, with traditional medicine playing a central role in managing diseases such as diabetes. Despite their widespread use, the safety and efficacy of these herbal treatments have not been scientifically explored. This study aims to analyze the traditional uses of antidiabetic plants in Economic Community of West African States countries in relation to the available scientific evidence. METHODS: A three-step approach was used. Firstly, ethnopharmacological studies on diabetes management in West Africa were identified. Secondly, the twelve most cited plants were selected on the basis of their frequency of citation of traditional antidiabetic uses, and their citation in at least five of the countries considered. Thirdly, scientific databases were searched for available in vitro, in vivo, and clinical studies examining the antidiabetic effects, antioxidant properties, and potential toxicity of the twelve plants selected. RESULTS: This study identified 638 medicinal plants from 32 ethnopharmacological studies conducted in eight West African countries. The twelve most cited plants were Mangifera indica, Rauvolfia vomitoria, Azadirachta indica, Morinda lucida, Launea taraxacifolia, Momordica charantia, Phyllanthus amarus, Vernonia amygdalina, Carica papaya, Annona senegalensis, Allium sativum and Ocimum gratissimum. Most remedies were prepared from leaves, roots, and bark, commonly as decoctions or macerations, and demonstrated notable hypoglycemic activity. However, the mechanism of action behind the antidiabetic activity of these plants has rarely been addressed, and few of these plants have undergone clinical trials and in-depth toxicological evaluations. CONCLUSION: This review highlights a significant gap between traditional knowledge and scientific assessment. Although these traditional medicinal plants show promise for diabetes management, further scientific validation is needed to ensure their safe and effective use in modern healthcare systems. © 2026. The Author(s).

Dysglycemia represents an early and progressive stage of cardiometabolic disease, characterized by IR, metabolic inflammation, and increased cardiovascular risk. Its high prevalence and largely asymptomatic course often lead to diagnostic and therapeutic inertia, resulting in missed opportunities for early intervention. Recognizing dysglycemia as a disease continuum rather than a transitional condition supports the need for anticipatory and integrated preventive strategies. Within this framework, nutraceuticals are emerging as valuable supportive tools in the management of dysglycemia, particularly in individuals with increased metabolic risk who are not yet candidates for pharmacological therapy. Nutraceutical compounds can target key pathophysiological mechanisms underlying dysglycemia, including impaired insulin sensitivity, oxidative stress, chronic low-grade inflammation, and altered postprandial glucose metabolism. Clinical evidence supports the use of selected micronutrients, polyphenols, and standardized plant extracts in improving fasting and postprandial glycemic control. Phytocomplexes derived from plants such as Mangifera indica, Momordica charantia, and Malus domestica exert complementary and multitarget actions, including modulation of carbohydrate absorption, activation of AMPK-related pathways, enhancement of peripheral glucose uptake, stimulation of incretin secretion, and improvement of endothelial function. When integrated with lifestyle and dietary interventions, nutraceuticals may reduce glycemic variability, improve metabolic resilience, and delay progression toward type 2 diabetes. Overall, nutraceuticals represent a rational bridge between lifestyle measures and pharmacological treatment in the personalized management of dysglycemia.

Background/Objectives: Nutraceuticals, consisting of bioactive compounds or materials, are increasingly regarded as promising strategies for the prevention and management of diabetes. This study aimed to evaluate the antidiabetic potential of a nutraceutical formulation (Sugar Care, SC) composed of indigestible maltodextrin, pumpkin extract, and bitter melon extract, using a type 2 diabetic mouse model. Methods: A starch postprandial model in fasted normal mice was first used to assess postprandial glycemic response. Oral administration of SC at 820 and 1230 mg/kg was applied for two weeks prior to starch challenge. Subsequently, male db/db mice were randomly assigned to a diabetic control group or an SC-treated group (820 mg/kg; n = 8 per group) for four weeks. Glucose tolerance, fasting glucose and insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, fructosamine, and thiobarbituric acid reactive substances (TBARSs) were evaluated. Results: SC at 820 and 1230 mg/kg significantly ameliorated starch-induced postprandial hyperglycemia in normal mice (p < 0.05). In db/db mice, four-week administration of SC significantly improved glucose tolerance and reduced fasting hyperinsulinemia and HOMA-IR values (p < 0.05). SC treatment also significantly decreased plasma fructosamine and TBARS levels, as well as total cholesterol and low-density lipoprotein cholesterol concentrations (p < 0.05). Conclusions: These findings provide preclinical evidence that this multi-component nutraceutical formulation improves glucose intolerance, insulin resistance, and dyslipidemia in a genetic model of type 2 diabetes. Further mechanistic and translational studies are warranted.

BACKGROUND: Phytotherapeutic agents, including Momordica charantia, have been proposed as complementary strategies to enhance metabolic control in type 2 diabetes mellitus patients on oral antidiabetic drugs. METHODS: This was a real-world, longitudinal, comparative cohort study with treatment escalation, conducted in patients with type 2 diabetes mellitus receiving metformin therapy. All patients were initially prescribed add-on dapagliflozin at 10 mg/day and re-evaluated after 6 months. Based on glycemic response at 6 months, patients were stratified into two groups: 70 patients with persistent inadequate glycemic control received adjunctive supplementation with a standardized Momordica charantia extract for 3 months (intervention group), while 85 patients who achieved glycemic targets continued dual antidiabetic therapy alone (control group). Anthropometric, hemodynamic, and metabolic parameters were assessed at baseline, 6 months, and 9 months from baseline. RESULTS: Between-group analyses revealed divergent glycemic trajectories during the 6-9 month interval. In the intervention group, HbA1c decreased from 7.82 ± 0.58% at baseline to 6.93 ± 0.30% at 6 months and to 6.34 ± 0.42% at 9 months, while in the control group, glycemic parameters showed only modest additional changes after 6 months. The reduction in HbA1c and fasting plasma glucose between 6 and 9 months was significantly greater in patients receiving Momordica charantia compared with controls (p < 0.001). Fasting plasma glucose declined from 138.4 ± 17.5 mg/dL at baseline to 122.3 ± 13.1 mg/dL at 6 months and to 113.3 ± 12.2 mg/dL at 9 months in the intervention group. Dapagliflozin therapy was associated with significant improvements in body weight, BMI, and blood pressure at 6 months in both groups, whereas adjunctive Momordica charantia supplementation did not produce significant additional effects on anthropometric or hemodynamic parameters. CONCLUSIONS: Adjunctive Momordica charantia supplementation was associated with additional improvements in glycemic control compared with continuation of dual antidiabetic therapy alone, with the most pronounced effects observed for HbA1c and fasting plasma

The use of medicinal plants by diabetic patients dates back to ancient times. In recent years, numerous reports have been published on the efficacy and safety of many medicinal plants in the treatment of diabetes through various mechanisms. This review highlights the up-to-date proposed mechanisms of action of the most common antidiabetic herbs used in Persian medicine, comprising Cinnamomum zeylanicum, Trigonella foenum-graecum, Urtica dioica, Nigella sativa, Citrullus colocynthis, Silybum marianum, Zingiber officinale, Punica granatum, Salvia officinalis, Vaccinium arctostaphylos, and Momordica charantia, with support from clinical and experimental studies. Clinical research has shown significant reductions in blood glucose levels and insulin resistance, as well as improvements in diabetes-related symptoms, including digestive disorders and lipid dysregulation, accompanied by negligible adverse effects. Continuing to study how these plants work and how effectively they treat diabetes is important for using these natural treatments in modern medicine, offering affordable and safe options for diabetes patients.

The prevalence of prediabetes is rising globally, and if untreated, it can lead to a surge in the rate of type 2 diabetes (T2D). Altogether, these conditions are characterised by hyperglycaemia, which promotes cardiovascular complications. Although Momordica has shown promising results in preclinical studies, the existing quantitative synthesis of evidence reports contradictory findings. This study aimed to evaluate the effect of Momordica charantia on fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, homeostatic model of insulin resistance (HOMA-IR), and homeostatic model of β-cell function (HOMA-β) in individuals with prediabetes or T2D. A search for randomised controlled trials was conducted on Scopus, PubMed, and Web of Science until July 19, 2025. Keywords used included M. charantia, bitter melon, prediabetes and diabetes mellitus. The data were presented as standard mean difference (SMD) and 95 % confidence intervals. Twenty-five trials with 34 sub-studies were deemed relevant. The results showed reduced FBG [SMD = -0.46 (-0.73, - 0.18), p = 0.0012] and HbA1c [SMD = -0.57 (-0.83, -0.31), p < 0.0001]. Additionally, there was a significant reduction in the level of insulin [SMD = -0.48 (-0.83, -0.12), p = 0.0082] and HOMA-IR [SMD = -0.52 (-0.95, -0.08), p = 0.0195]. However, no effect was observed on HOMA-β (p = 0.586). The study findings suggest that M. charantia may be used to improve insulin sensitivity and reduce insulin resistance, thereby improving hyperglycaemia in patients with prediabetes and T2D. © 2025 The Authors.

BACKGROUND: Type 2 diabetes mellitus (T2DM) represents a major global health problem with significant complications and high economic and social burdens, leading many patients to explore complementary and alternative medicine (CAM) for obtaining relief. This study was conducted to explore the use of CAM by patients with T2DM and factors influencing it. METHODS: A cross-sectional study was conducted at a suburban tertiary care hospital in Sri Lanka using 280 randomly selected patients diagnosed with T2DM. Data were collected using an interviewer-administered questionnaire adapted using published instruments. The questionnaire included open-ended questions on types of CAM used, a five-point Likert scale that assessed attitudes and beliefs and questions assessing knowledge and perceptions. Ethics approval was received from the Faculty of Medicine, Wayamba University of Sri Lanka (PW/2024/02/01). The data analysis used the chi-square and independent sample t- tests at a 0.05 significance level. RESULTS: The majority were females (87.5%), and 64.6% were > 60 years of age. The prevalence of CAM use was 68.6%, and 35.5% used it as a treatment for controlling diabetes concurrently with conventional medicine, while 4.5% used CAM concurrently with conventional medicine for improving their well-being. Orally consumed herbal remedies were the commonest CAM used (30.4%), followed by spiritual healing (19.1%) and music therapy (13.1%). Some used more than one type of CAM. Bitter gourd fruit (Momordica charantia), canerreed leaves (Costus speciosus) and fenugreek seeds (Trigonella foenum) were the most common herbs used. 52.1% demonstrated a lack of specific knowledge that would be required to enquire about the safety, efficacy and possible interactions with medications used concurrently. No significant association was observed between CAM use and sociodemographic characteristics or disease-related factors. CONCLUSIONS: There was widespread use of CAM by patients with T2DM. Future research with larger and diverse populations is recommended to explore CAM usage in more depth. Controlled trials for commonly used CAM therapies with or without simultaneous use of conventional medi

Natural bioactive compounds found in Momordica charantia including polysaccharides, saponins, polyphenols, alkaloids, and notably polypeptide-p (often referred to as "plant insulin")-have shown promising potential in shaping nutritional and therapeutic strategies for managing diabetes, metabolic disorders, and other nutrition-related diseases. Both retrospective and prospective analyses of bitter gourd's functional properties such as its antioxidant, antitumor, immunomodulatory, and antibacterial effects highlight its innovative use as a food ingredient in developing targeted nutritional therapies. Assessing its applicability in the food industry, particularly through the fortification of products with bitter gourd powders, pulp, juice, or extracts, could enhance consumer acceptance and elevate the perceived quality of nutritionally superior foods. The nutrifunctional attributes revealed by its nutritional profile support the strategic integration of bitter gourd into various food formulations, contributing to a broader and more diverse range of dietary options. This diversification is especially valuable in addressing the dietary monotony often associated with diabetic nutrition plans, which continue to present significant challenges. The foundation laid by this review drawing on both theoretical insights and practical applications serves as a springboard for future research into the fortifying potential of bitter gourd-based preparations. Ultimately, such products may be recommended not only as nutritional supplements but also as part of clinical and hygienic-dietetic practices.

Plant supplements are frequently used by diabetes mellitus (DM) patients in the management of their disease. Background/Objectives: The present study aimed to identify the prevalence of plant supplement use in DM patients from Romania and to evaluate patients' practices, profiles, and beliefs regarding plant supplements and the impact of their use on glycemic control. Methods: A cross-sectional online survey was conducted among Romanian diabetic patients. Results: Out of 329 validated responses, 44.07% reported supplement use. Momordica charantia L. (35.17%) was the most used. Female patients were statistically significantly more prevalent in the plant supplement user group. Plant supplement use was associated with statistically significantly lower HbA1c (7.11% vs. 7.66%, p < 0.01) and basal glycemia (127.75 mg/dL vs. 136.08 mg/dL, p < 0.01) over the previous three months. Diabetic polyneuropathy was statistically significantly less prevalent among patients who used plant supplements (31.03% vs. 42.39%, p = 0.035). The greatest proportion of responders reported that they started to use plant supplements for improving blood glycemia (88.97%), followed by the purpose of preventing DM complications (27.59%). A significant improvement in health status was reported by 53.79% of patients using herbal supplements. Conclusions: Plant supplement use was common and associated with improved glycemic parameters and lower complication prevalence.

Diabetes mellitus is a chronic metabolic disease that has a significant impact on public health and is becoming more and more common worldwide. Although effective, conventional therapies are often limited by high cost, adverse effects, and issues with patient compliance. As a result, there is growing interest in complementary and alternative therapies. Medicinal plants have played an essential role in diabetes treatment, especially in regions such as Romania, where biodiversity is high and traditional knowledge is well preserved. The pathophysiology, risk factors, and worldwide burden of diabetes are examined in this review, with an emphasis on the traditional use of medicinal plants for glycemic control. A total of 47 plant species were identified based on ethnopharmacological records and recent biomedical research, including both native flora and widely cultivated species. The bioactive compounds identified, such as flavonoids, triterpenic saponins, polyphenols, and alkaloids, have hypoglycemic effects through diverse mechanisms, including β-cell regeneration, insulin-mimetic action, inhibition of α-glucosidase and α-amylase, and oxidative stress reduction. A systematic literature search was conducted, including in vitro, in vivo, and clinical studies relevant to antidiabetic activity. Among the species reviewed, Urtica dioica, Silybum marianum, and Momordica charantia exhibited the most promising antidiabetic activity based on both preclinical and clinical evidence. Despite promising preclinical results, clinical evidence remains limited, and variability in phytochemical content poses challenges to reproducibility. This review highlights the potential of Romanian medicinal flora as a source of adjunctive therapies in diabetes care and underscores the need for standardization and clinical validation.

Type 2 diabetes mellitus (T2DM) is a chronic condition caused by decreased insulin production and increased insulin resistance. Current treatments for T2DM include pharmacological agents and lifestyle modifications, but their clinical applications have become limited due to their side effects and high cost. Herbal remedies and natural products have become popular alternative treatments as they are associated with fewer side effects. Momordica charantia Linn. (bitter melon) is a member of the Cucurbitaceae family and has been used as a traditional anti-diabetic remedy in various countries for many years. The plant contains several biologically active compounds, including glycosides, saponins, alkaloids, triterpenes, proteins, and steroids. The hypoglycemic activity of Momordica charantia is primarily attributed to its saponins, which are collectively known as charantins and alkaloids. Through network pharmacology, molecular docking and MD simulation studies, we found underlying mechanism of karela in the treatment of T2DM. The network pharmacology study concluded the Protein kinase C delta (PRKCD) as a hub gene out of 49 probable target genes. Various published studies have also asserted the pathophysiological role of PRKCD in the development of T2DM. Molecular docking study identified the top three active phytoconstituents of karela; Momordicoside C, Momorcharaside B and Momordin I, with docking scores of - 8.0 kcal/mol, - 7.9 kcal/mol, and - 7.9 kcal/mol, respectively. MD simulation studies concluded the Momordicoside C and Momorcharaside B as promising hit candidates to experimentally validate for their in vitro activity against the Protein kinase C delta. Overall, present research work highlighted the new mechanism of action of a well-known plant, Karela, in the treatment of T2DM. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the te

Background Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a chronic metabolic disorder characterized by persistent hyperglycemia. Alpha-glucosidase inhibitors like miglitol delay carbohydrate absorption, thereby reducing postprandial glucose levels. Momordica charantia (bitter melon) has demonstrated hypoglycemic effects in various studies, yet its interactions with pharmaceutical antidiabetic agents remain poorly understood. This study investigates the molecular interactions between M. charantia phytoconstituents and miglitol's enzymatic targets using in silico methods. Methods An in silico approach was employed to assess potential herb-drug interactions between M. charantia and miglitol. Phytochemical screening identified 18 bioactive compounds from M. charantia that complied with Lipinski's Rule of Five, evaluated using SwissADME. Molecular docking was performed using AutoDock Tools (v1.5.7) to examine binding affinities between these phytoconstituents and key carbohydrate-metabolizing enzymes: lysosomal alpha-glucosidase (GAA), neutral alpha-glucosidases AB (GANAB) and C (GANC), maltase-glucoamylase (MGAM), and pancreatic alpha-amylase (AMY2A). The binding interactions were visualized using PyMOL and LigPlot+ to assess molecular stability. Results Molecular docking analysis revealed that charantin exhibited the highest binding affinity across all enzymes, particularly with neutral alpha-glucosidase AB (-12.4 kcal/mol) and maltase-glucoamylase (-12.6 kcal/mol), suggesting strong inhibitory potential. Other phytoconstituents, such as quercetin, luteolin, and kaempferol, also displayed moderate to high affinity, indicating possible synergistic effects. In contrast, compounds like cis-sabinol, myrtenol, and beta-sitosterol showed significantly weaker interactions. The binding interaction analysis confirmed stable hydrogen bonding and hydrophobic interactions between charantin and key enzymatic residues, reinforcing its role as a potent inhibitor of carbohydrate metabolism. Conclusion The study suggests that M. charantia phytoconstituents, particularly charantin, may enhance miglitol's effects by inhibiting the same carbohydrate-digesting enz

Diabetic wound healing is constrained by various factors, including chronic inflammation, sustained oxidative stress, impaired angiogenesis, and abnormal wound microenvironments. Exosomes derived from mesenchymal stem cells (MSC-exo) contain a wealth of bioactive substances that play a positive role in promoting diabetic wound healing. Plant-derived exosomes, as a novel therapeutic approach, are continuously being explored. Momordica charantia (MC) has been shown to possess blood glucose-lowering effects, and its exosomes are of significant relevance for treating diabetic wounds. However, direct application of exosomes to wounds faces challenges such as poor stability and short retention time, limiting their therapeutic effectiveness and clinical applicability. Encapsulating exosomes in hydrogels is an effective strategy to preserve their bioactivity. In this study, we fabricated a hydrogel loaded with MSC-exo and MC exosomes (MC-exo) by photopolymerization of methacrylated gelatin (GelMA) and dopamine (MEMC-Gel). The resulting MEMC-Gel exhibited favorable mechanical properties, adhesion, degradability, absorbency, and biocompatibility. In vitro, MEMC-Gel demonstrated the ability to resist inflammation, counter oxidative stress, promote fibroblast migration, support endothelial cell angiogenesis, and regulate macrophage polarization. In a diabetic mouse wound model, MEMC-Gel accelerated wound healing by inhibiting inflammation and oxidative stress, modulating macrophage immune responses and hyperglycemia within the microenvironment, promoting angiogenesis, and enhancing epithelialization. In conclusion, MEMC-Gel is an outstanding hydrogel dressing that synergistically promotes repair by loading MSC-exo and MC-exo, significantly accelerating diabetic wound healing through multiple mechanisms. This multifunctional hydrogel, based on exosomes from two different sources, provides an innovative therapeutic strategy for diabetic wound repair with broad clinical application potential. © 2025 The Authors.

Diabetes remains a global health concern, leading to interest in herbal formulations for safer, effective management. The study screens the polyherbal formulations (PHF 1-5) using Costus pictus, Gymnema sylvestre, and Momordica charantia to identify the most effective synergistic ratio and evaluate the stability and safety as per the Central Council for Research in Ayurvedic Sciences (CCRAS) and Organisation for Economic Co-operation and Development (OECD) guidelines (423 and 407). PHF-3 exhibited maximum synergistic potential by in vitro antioxidant and antidiabetic activities (α-amylase inhibition - 83.52%, IC50-366.95 μg/ml, and α-glucosidase inhibition - 83.34%, IC50-373.59 μg/ml). PHF-3 was stable in accelerated conditions (40 °C ± 2 °C, 75% ± 5% relative humidity) for 6 months. Acute toxicity evaluation (2000 mg/kg) demonstrated no toxicity (LD50 > 2000 mg/kg) and sub-acute toxicity (100, 200, and 300 mg/kg-28 days) revealed no adverse behavioural, hematological, or organ-toxicity. With confirmed safety, stability PHF-3 offers potential as a natural therapy for diabetes management.

Diabetes is a global health challenge, often managed with insulin therapy. However, the direct interactions of insulin receptor (IR)-binding macromolecules with IR remain poorly understood. In this study, we explored the hypoglycemic mechanisms of BG68, a 68-amino-acid polypeptide abundant in Momordica charantia, and its stable, gastro-resistant 9-amino-acid peptide (mcIRBP-9) in combination with insulin in a type 2 diabetes mouse model. We characterized the binding kinetics of BG68 and mcIRBP-9 to the IR/insulin complex using isothermal titration calorimetry (ITC) and hydrogen‑deuterium exchange mass spectrometry (HDX-MS). Functional assays, including Western blot and phosphoproteome analyses, were performed to assess IR phosphorylation. Our findings revealed that BG68 and mcIRBP-9 synergistically enhanced glucose clearance with insulin. HDX-MS analysis showed that mcIRBP-9 bound to IR at sites distinct from insulin, initially engaging the L1 and α-CT regions before extending to L2, FnIII-2, and FnIII-3 domains. ITC confirmed spontaneous binding to the IR/insulin complex with moderate affinity, while phosphoproteome analysis demonstrated that mcIRBP-9 significantly enhanced IR phosphorylation at Y1356 and Y1362, thereby amplifying IR kinase activity and promoting glucose clearance. In conclusion, our findings suggested that mcIRBP-9 provided a "second hit" to IR following insulin binding, further enhancing IR activation. This novel mechanism highlighted mcIRBP-9 as a promising candidate for improving the efficacy of insulin therapy and combating insulin resistance in type 2 diabetes.

Background/Objectives:Momordica charantia L. (M. charantia), a widely cultivated and frequently consumed medicinal plant, is utilized in traditional medicine. Cucurbitane-type triterpenoids, significant saponin components of M. charantia, exhibit hypoglycemic effects; however, the underlying mechanisms remain unclear. Methods: This study utilized comprehensive network pharmacology to identify potential components of M. charantia cucurbitane-type triterpenoids that may influence type 2 diabetes mellitus (T2DM). Additionally, molecular docking and molecular dynamics studies were performed to assess the stability of the interactions between the selected components and key targets. Results: In total, 22 candidate active components of M. charantia cucurbitane-type triterpenoids and 1165 disease targets for T2DM were identified through database screening. Molecular docking and molecular dynamics simulations were conducted for five key components (Kuguacin J, 25-O-methylkaravilagenin D, Momordicine I, momordic acid, and Kuguacin S) and three key targets (AKT1, IL6, and SRC), and the results demonstrated stable binding. The experimental results indicate that the interactions between momordic acid-AKT1 and momordic acid-IL6 are stable. Conclusions: Momordic acid may play a crucial role in M. charantia's regulation of T2DM, and AKT1 and IL6 seem to be key targets for the therapeutic action of M. charantia in managing T2DM.

ETHNOPHARMACOLOGICAL RELEVANCE: Bitter gourd (Momordica charantia L.) is known for its ability to reduce parameters of diabetes, but its effects on prediabetic subjects have been scarcely studied. AIM OF THE STUDY: To assess the efficacy of Momordica charantia supplementation in a prediabetic population on markers of glucose homeostasis. METHODS: Two randomized controlled studies were conducted to assess the effect of bitter gourd supplementation in a prediabetic population. Study 1 was a 4-week cross-over intervention trial (n = 30), with freeze-dried bitter gourd (BG) fruit juice (2.4 g/day) or a cucumber-based control product (CC). Study 2 was a parallel trial (n = 38) lasting 12 weeks, with freeze-dried whole fruits (3.6 g/day) or a cucumber-based matched control supplement. Effects on fasting plasma glucose (FPG), insulin, HbA1c, fructosamine, postprandial glucose after an oral glucose tolerance test, and several safety biomarkers were also analyzed in both trials before and after the interventions. RESULTS: In Study 1, no significant differences were found between the bitter gourd and placebo interventions. However, a reduction in FPG in subjects with higher baseline values were found following bitter gourd supplementation, which was not observed in the control group. However, in Study 2, we observed significant reductions of FPG (p = 0.014), fasting insulin (p = 0.007), and HOMA-IR (p = 0.003) after a 12-week intervention with the bitter gourd supplement. In addition, between treatment analysis resulted in significant effects on FPG levels (p = 0.026) and HOMA-IR (p = 0.045) with no significant effects on other biomarkers related to glucose metabolism. On average, bitter gourd intervention reduced FPG by ∼0.05 mmol/L per week, whereas FPG remained unchanged following placebo. In both studies, there were no indications of health risks or side effects from consumption of the supplements. CONCLUSION: Results suggest that supplementation with bitter gourd fruit can have positive effects on fasting plasma glucose and insulin among prediabetic subjects when provided over an extended period of at least 12 weeks.

The ketogenic diet (KD) has been suggested as a useful lifestyle intervention for metabolic syndrome; however, its long-term metabolic effects remain debated. This study evaluated the biochemical impact of supplementing KD-fed rats with a diluted aqueous extract of Bitter Melon (BM) on the regulation of hepatic gluconeogenesis. Thirty-two male rats were divided into four groups: G1 (Control), G2 (KD), G3 (BM extract, 1.5 g/kg body weight), and G4 (KD + BM extract, 1.5 g/kg body weight). Serum and liver samples were analyzed for biochemical parameters. KD reduced glucose, insulin, triglycerides (TG), Free Fatty Acids (FFA), glycogen, pyruvate carboxylase, and PEPCK, while elevating cholesterol (+34%), lactate, and ketone bodies (p < 0.05). BM supplementation partially restored glucose (+15%), insulin, TG, FFA, glycogen, and enzyme activity, while lowering cholesterol (-14%), lactate (-16%), and ketone bodies (-27%) (p < 0.05). Histological analysis confirmed improved liver architecture in BM-treated groups. BM aqueous extract counteracts KD-induced metabolic disturbances, improving glucose and lipid homeostasis and supporting its role as a safe adjunct to KD for long-term metabolic management. © 2026 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.

BACKGROUND: This study investigated the therapeutic potential of aqueous fruit and seed extract of Momordica charantia L. (MC) as an alternative treatment for PCOS. OBJECTIVES: Evaluations included ovarian histopathology, fasting blood sugar, lipid profiles, antioxidant markers and hormone levels. METHODS: Female Wistar rats induced with PCOS via a single 4.5 mg/kg dose of estradiol valerate were treated with MC extracts at 500 and 1000 mg/kg/day for 60 days. RESULTS: The results showed that treatment with MC fruit and seed extract at the dose of 500 and 1000 mg/kg/day possesses potent anti-inflammatory and antioxidant activity in in-vitro models. MC fruit and seed extract showed no cytotoxicity in HeLa cell viability in the MTT assay and the highest antioxidant activity followed by DPPH compared with ascorbic acid (p < 0.01). The fasting blood sugar serum levels, total lipid profile, LH, FSH, estradiol and antioxidant enzyme levels were significantly restored after 60 days of treatment (p < 0.01). Further, MC extract significantly reduced body weight (p < 0.01) and ovarian weight (p < 0.05), restored the normal estrous cycle, resolved cysts in the ovaries and displayed positive effects on ovarian histopathology after 60 days of treatment. CONCLUSION: MC fruit and seed extracts is considered a potential treatment for PCOS in estradiol-induced female rats.

Carbohydrates in aquaculture feeds can induce metabolic disturbance when exceeding fish utilization capacity, leading to lipid accumulation and insulin resistance. Bitter melon (BM; Momordica charantia), rich in saponins, flavonoids, and polysaccharides, shows potential as a functional feed additive for glycemic control and lipid metabolism modulation. This investigation systematically assessed the effects of BM powder (BMP) supplementation (at 0.5%, 1%, and 1.5%) in high-starch (HG) diets for Cyprinus carpio. Compared to the HG group, BMP supplementation significantly reduced serum glucose (GLU) and triglycerides (TGs), while elevating total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). The BMP group exhibited reduced malondialdehyde (MDA), enhanced antioxidation ability, and mitigated hepatopancreatic and intestinal histopathological damage from carbohydrate overload. Meanwhile, BMP restored muscle C20:3n-6 and C22:6n-3 (DHA) levels decreased by HG diets. Notably, 1.5% BMP decreased hepatopancreatic and muscular glycogen/lipid deposition, induced by a high-carbohydrate diet. Gene expression analysis revealed BMP upregulated glycolysis-related genes (glucokinase [gk], pyruvate kinase [pk], and pfk) across tissues (hepatopancreas, muscle, intestine, and adipose tissue), while suppressing glycogen synthesis (gys) and gluconeogenesis (g6pase) genes. Besides, lipid biosynthesis genes were downregulated, corroborating reduced ectopic lipid storage. Taken together, these findings demonstrate that BMP supplementation significantly improves glycemic control, lipid metabolism, and antioxidant capacity in common carp. This suggests that BMP could serve as a natural, sustainable aquafeed additive to counter metabolic syndrome in intensively farmed fish.

Momordica charantia L. (Cucurbitaceae) has been widely recognized for its pharmacological potential, although studies on its leaves remain scarce. In this study, the hydroethanolic leaf extract (MCHLE) was chemically characterized by LC-MS/MS, revealing the presence of octopamine, ferulate, vitexin-2-O-rhamnoside, and other bioactive phenolics. Toxicological evaluation in Wistar rats demonstrated that both acute (2000 mg/kg) and repeated oral administration (up to 400 mg/kg for 28 days) caused no clinical or behavioral signs of toxicity. Notably, treatment significantly reduced glucose and cholesterol levels, in addition to attenuating lipid peroxidation and enhancing antioxidant defenses. In vivo, MCHLE inhibited leukocyte and neutrophil infiltration in the LPS-induced peritonitis model, with efficacy comparable to dexamethasone. It also reduced TNF-α secretion and nitric oxide generation in peritoneal fluids. In vitro assays with LPS-stimulated RAW 264.7 macrophages confirmed these effects, showing dose-dependent inhibition of TNF-α, IL-1β, and NO production. Gene expression analysis further demonstrated downregulation of TNF-α and MAPK, with marked suppression of NF-κB transcripts. Collectively, these results suggest that MCHLE exerts anti-inflammatory activity by targeting both mediator release and upstream signaling pathways, while maintaining a favorable safety profile, supporting its potential for further investigation as a promising source of bioactive compounds.

Previous studies have shown that high fat diet (HFD) causes damage to the colonic mucus barrier, and food-derived polysaccharides can help to ameliorate this damage. The study tried to explore how Momordica Charantia L. polysaccharides (MCP) intervention affects HFD-induced colonic mucus barrier damage by regulating goblet cell differentiation and mucin secretion. We found that MCP alleviated HFD-related hyperlipidemia, glucose intolerance and colonic mucus barrier damage via regulated the colonic microbiota, thereby enhancing the thickness of the mucus layer and increasing goblet cell number. MCP increased MUC2 expression and upregulated proteins in the colon related to mucus synthesis and secretion, including AGR2, RELMβ, TFF3, ATOH1, and KLF4. Concurrently, MCP treatment induced substantial alterations in gut microbiota composition, significantly increasing the relative abundance of the bacterial genera Muribaculaceae, Ligilactobacillus, Alloprevotella, and Turicibacter. Notably, these genera exhibited a negative correlation with glycolipid metabolism parameters, while showing a positive correlation with factors related to the mucus barrier. Furthermore, MCP treatment markedly enhanced amino acid metabolism and promoted arginine biosynthesis. These results suggested that targeting the mucus layer and gut microbiota through MCP might help prevent or ameliorate HFD-associated obesity.

BACKGROUND: Ischemic stroke (IS) is a prevalent cerebrovascular disorder associated with high rates of mortality and long-term disability. Neuronal ferroptosis, characterized by lipid peroxidation, plays a pivotal role in the pathogenesis of IS-related neurological dysfunction. PURPOSE: This study aimed to elucidate the neuroprotective role and mechanisms of small extracellular vesicles (sEVs) derived from Momordica charantia (MC-sEVs) in alleviating neuronal ferroptosis after IS. METHODS: MC-sEVs were isolated using gradient centrifugation and ultracentrifugation and characterized by particle size analysis, morphology observation, and exosomal marker proteins. Small RNA sequencing and lipidomic analysis were also performed to analyze the components of MC-sEVs. Using behavioral tests and a rat model of middle cerebral artery occlusion, the neuroprotective and anti-ferroptosis role of MC-sEVs was assessed. The oxygen-glucose deprivation/reoxygenation (OGD/R) induced HT22 cell model was used to evaluate the anti-ferroptosis effect of MC-sEVs in vitro. Utilizing bioinformatics analysis and molecular docking prediction, Momordica charantia-derived miR-5813b and its downstream target gene, TRIM62, were identified, which was further confirmed using a dual-luciferase reporter gene assay. TRIM62-mediated GPX4 ubiquitination was detected by co-immunoprecipitation. The miR5813b mimic and AAV-hsyn-EGFP-miR5813b were both constructed, and their neuroprotective roles were observed in vitro and in vivo. The biosafety of intravenous injection of MC-sEVs was also evaluated. RESULTS: we characterized MC-sEVs which resemble mammalian EVs and are enriched in small non-coding RNAs and lipids. Systemic administration of MC-sEVs significantly attenuated neuronal ferroptosis and promoted neurological recovery in the rat model of transient middle cerebral artery occlusion. Mechanistically, we identified miR-5813b, a plant-specific microRNA encapsulated within MC-sEVs, as a direct regulator of TRIM62, an E3 ubiquitin ligase that predominantly facilitates K48-linked ubiquitination of GPX4. Knockdown of TRIM62 or transfection with miR-5813b mimics markedly inhibited neuronal ferroptosis i

Bitter gourd, scientifically known as Momordica charantia L. with 2n = 22, is a widely recognized medicinal vegetable, renowned for its multifaceted health benefits, primarily acclaimed for its lipid- and glucose-lowering effects. Its growing demands as a food source and for industrial applications necessitate value addition in ongoing breeding initiatives to enhance genotypic traits in multifarious ways. A thorough understanding of the underlying molecular footprint is warranted for characterization, which still remains underexplored relative to other cash crops. Though a chromosome-level genome assembly of bitter gourd is available, scattered and fragmented information becomes an obstacle for assisted breeding and gene editing. Therefore, it is crucial to further dissect structural and molecular variants, noncoding RNAs (ncRNAs), transcription factors, and transcripts from whole-genome and resequencing projects. The present study leads to the development of a comprehensive genomic resource, BgDB (Bitter Gourd Resource Database) at a single platform, vital for advanced bitter gourd breeding programmes for raising bitter gourd varieties with traits of significant social and economic value. BgDB, available at https://bgdb.daasbioinfromaticsteam.in/index.php, is a user-friendly, three-tier database that offers a comprehensive interface with detailed analysed information, including 114 598 transcripts, 4914 differentially expressed genes, 32 570 predicted simple sequence repeat markers, and 162 850 primers for downstream applications. It also catalogues extensive annotations of bitter gourd-specific single nucleotide polymorphisms/insertions and deletions, long noncoding RNAs, circular RNAs, microRNAs, 1220 transcription factors, 295 transcription regulators, and 146 quantitative trait loci (QTL) distributed throughout the chromosomes. This genomic resource is poised to significantly advance genetic diversity analyses, population and varietal differentiation, and trait optimization. It further facilitates the exploration of regulatory ncRNA elements, key transcripts, and essential transcription factors and regulators. The discovery of QTL will aid in the developmen

The exploration of plant signaling pathways is transforming the way diabetes is managed, providing new, multi-target strategies for controlling this complex metabolic disorder. Medicinal plants are rich in bioactive compounds like phytohormones, flavonoids and polyphenols, which regulate key pathways including oxidative stress, inflammation, insulin resistance, and gut microbiota modulation. Research is emerging on the therapeutic potential of Momordica charantia, Cinnamomum verum and Trigonella foenum-graecum, which enhance insulin secretion, sensitivity and glucose homeostasis. These plant derived compounds, resveratrol and plant based insulin mimetics, not only address metabolic dysfunction but also offer holistic treatment for long term complications such as neuropathy and retinopathy. The development of precision medicine advances the tailoring of plant based therapies to individual metabolic responses, increasing efficacy and decreasing reliance on synthetic drugs with adverse side effects. Despite challenges of standardization, regulatory barriers, and limited clinical trials, incorporating medicinal plants into national diabetes management guidelines represents a cost effective and accessible option, particularly in resource limited settings. In this review, we highlight the importance of collaborative work across disciplines and the use of technologies such as artificial intelligence to speed research and optimize patient specific applications. The therapeutic power of plant signaling pathways is harnessed to develop sustainable, inclusive, and effective diabetes management strategies.