Open research questions in Natural Antidiabetic Agents Studies
389 gap statements mined from Natural Antidiabetic Agents Studies papers in our 7.9M-paper local library, which holds 1,630 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
The pharmacological activity of the extract is therefore more likely to result from additive or synergistic interactions among multiple constituents than from a single dominant compound, although the contribution of individual metabolites remains to be experimentally established.
Antinociceptive Activity of Petiveria alliacea L. Extract via GABAergic and Serotonergic Pathways in Diabetic Neuropathy Model · 2026 · DOIThere is a need to investigate the effect of β-carotene on fenugreek under drought stress conditions. The study aims to fill this gap by examining the impact of β-carotene on antioxidant defense and redox homeostasis in fenugreek.
β-carotene enhances drought tolerance in fenugreek by modulating antioxidant defense and redox homeostasis · 2026 · DOIThe need for new natural sources with antidiabetic potential. The lack of summary and analysis of studies on the antidiabetic activity of mangrove plants.
Antidiabetic potential from mangrove plants: A review of phytochemical profile and biological activities · 2026 · DOIFurther research with adequate, randomized, and controlled clinical trials should be performed to explore this compound’s therapeutic importance, safety, and efficacy against human pathogenesis.
Future research should concentrate on the development of innovative forms of QE administration that will enhance its stability and biological efficacy. Examples of such solutions include the formation of quercetin complexes with macromolecules, the use of nanoemulsion technology, microencapsulation, or combining QE with other bioactive compounds for synergistic effects.
To date, there are relatively few studies on the potential interactions of quercetin with drugs. The lack of standardization and precise dosing guidelines hampers their use in medicine.
The Effects of Quercetin on Vascular Endothelium, Inflammation, Cardiovascular Disease and Lipid Metabolism—A Review · 2025 · DOIWith further research regarding the hypoglycemic mechanism of flavonoids, the synergistic effects between flavonoids have also received widespread attention; however, the exploration of this aspect is relatively fractional and lacks further investigation and validation regarding the mechanism of the synergistic action between related targets.
Research Progress on Hypoglycemic Effects and Molecular Mechanisms of Flavonoids: A Review · 2025 · DOIFuture research should focus on conducting rigorous clinical trials to verify the benefits of these supplements in humans, while also investigating their interactions with metabolism and the gut microbiota. This gap is largely due to variability in bioactive compound content and the lack of standardized dosing.
Dietary Supplements Derived from Food By-Products for the Management of Diabetes Mellitus · 2025 · DOIThe acute intake of the CCB by subjects with T2D showed modest although significant results, which need to be validated in a long-term randomised controlled trial.
Cocoa–carob blend acute intake modifies miRNAs related to insulin sensitivity in type 2 diabetic subjects: a randomised controlled nutritional trial · 2025 · DOIThe bioaccessibility of polyphenols after digestion should also be studied and possibly transferred in vivo and to clinical trials. The sustainability of the plant system should be taken into consideration. The massive demand for plant production can lead to a harmful environmental impact. Plant diversity should be carefully monitored as invasive varieties may overtake the land.
More research is needed to identify the antidiabetic potential of the plants selected in this review in patients with diabetes. Furthermore, more research is needed to better understand the identity and mechanism of action of the active phytoconstituents at the molecular level.
Plant-Based Diets and Phytochemicals in the Management of Diabetes Mellitus and Prevention of Its Complications: A Review · 2024 · DOIOne of the challenges is the lack of standardization in the use of nutraceuticals for treating diabetes and prediabetes. Another challenge is the need for more research on the mechanisms of action of nutraceuticals and their potential interactions with other medications.
The lack of studies on the efficacy and tolerability of food supplements for maintaining normal carbohydrate metabolism. The need for alternative treatments for metabolic syndrome.
Efficacy and Tolerability of a Food Supplement Based on Zea mays L., Gymnema sylvestre (Retz.) R.br.ex Sm, Zinc and Chromium for the Maintenance of Normal Carbohydrate Metabolism: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial · 2024 · DOILimited knowledge on fenugreek genotypes' performance under different conditions. Technical challenges in analyzing the antioxidant activities and trigonelline content of fenugreek genotypes.
Comparison of Twenty Selected Fenugreek Genotypes Grown under Irrigated and Dryland Conditions: Morphology, Yield, Quality Properties and Antioxidant Activities · 2024 · DOILimited knowledge on fenugreek genotypes' performance under different conditions. Need to identify genotypes with high adaptability to changing climatic conditions. Gap in understanding the potential of fenugreek as a high-quality forage legume and its medicinal, pharmaceutical, and nutraceutical properties.
Comparison of Twenty Selected Fenugreek Genotypes Grown under Irrigated and Dryland Conditions: Morphology, Yield, Quality Properties and Antioxidant Activities · 2024 · DOIWhile the present study establishes a robust computational foundation, subsequent wet-lab in vitro and in vivo functional assays are warranted in future investigations to definitively validate its enzyme inhibitory kinetics.
A New Flavonoid Glycoside from the Stem Bark of Albizia saponaria: Isolation, Structural Elucidation, and In Silico Evaluation as a Potent α-Glucosidase Inhibitor · 2026 · DOIWhile the respective mechanisms remain to be elucidated, our results show that both compounds 1 and 2 have biological effects beyond the inhibition of carbohydrate-digesting enzymes.
Dual antidiabetic potential of arjunglucoside I and arjunetin from Terminalia chebula via modulation of insulin- and gluconeogenesis-related responses · 2026 · DOICurrent evidence is therefore sufficient to support the preclinical potential of phlorizin but remains insufficient to establish broad clinical efficacy of phlorizin-based nutraceuticals, functional foods, or advanced delivery systems in humans.
However, NAG, a critical bioactive derivative of glucose, remains relatively underexplored in this context.
Synthesis, Biological Evaluation, and Computational Studies of Phenolic N-Acetylglucosamine Glycosides as α-Glucosidase Inhibitors · 2026 · DOIFuture research should focus on long-term clinical validation and regulatory standardization to enable the safe and effective implementation of antioxidant therapies in diverse populations.
Functional and Therapeutic Roles of Plant-Derived Antioxidants in Type 2 Diabetes Mellitus: Mechanisms, Challenges, and Considerations for Special Populations · 2025 · DOIHowever, the prevention and treatment of AD by regulating the calcium-mediated mitochondrial apoptosis pathway remains unclear.
Cyanidin-3-O-Glucoside Mitigates Amyloid-Beta (1–42)-Induced Apoptosis in SH-SY5Y Cells by Regulating Ca2+ Homeostasis and Inhibiting Mitochondrial Dysfunction · 2025 · DOIThe need to identify potential anti-obesity mechanisms of plant extracts.
Phytochemical Characterization and Antioxidant Activity Evaluation for Some Plant Extracts in Conjunction with Pharmacological Mechanism Prediction: Insights into Potential Therapeutic Applications in Dyslipidemia and Obesity · 2024 · DOIIn this review, however, an HFD was used before the injection of STZ, and the duration of consumption varied widely from 14 to 84 days. There is no standardization in the literature on the glycemia cut-off points to determine DM2 in animal models; however, it is recommended to consider animals that present glucose values greater than 150 mg/kg in the fasting state and above 200 mg/kg in the fed state.
Experimental Models of Type 2 Diabetes Mellitus Induced by Combining Hyperlipidemic Diet (HFD) and Streptozotocin Administration in Rats: An Integrative Review · 2025 · DOIThe use of nutraceuticals in type 2 diabetes prevention and treatment, - The mechanisms of action of nutraceuticals in regulating metabolism and enhancing insulin sensitivity, - The best evidence regarding the impacts and possible functions of nutraceuticals in glycemic…
The study did not investigate the in vivo effects of the plant extracts, - The study used a limited number of plant extracts, - The computational studies were based on in silico…
Phytochemical Characterization and Antioxidant Activity Evaluation for Some Plant Extracts in Conjunction with Pharmacological Mechanism Prediction: Insights into Potential Therapeutic Applications in Dyslipidemia and Obesity · 2024 · DOI
Most-cited papers in Natural Antidiabetic Agents Studies
- USE OF GLUCOSE OXIDASE, PEROXIDASE, AND O-DIANISIDINE IN DETERMINATION OF BLOOD AND URINARY GLUCOSE · The Lancet · 1957 · 1,246 citations
- Oral Antidiabetic Agents · Drugs · 2005 · 971 citations
- Diagnosis and management of diabetic autonomic neuropathy. · BMJ · 1982 · 941 citations
- A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes · Phytochemistry Reviews · 2021 · 534 citations
- Inhibitors of α‐amylase and α‐glucosidase: Potential linkage for whole cereal foods on prevention of hyperglycemia · Food Science & Nutrition · 2020 · 409 citations
- Inhibition mechanism of ferulic acid against α-amylase and α-glucosidase · Food Chemistry · 2020 · 397 citations
- Quercetin and metabolic syndrome: A review · Phytotherapy Research · 2021 · 373 citations
- Alpha‐amylase as molecular target for treatment of diabetes mellitus: A comprehensive review · Chemical Biology & Drug Design · 2021 · 336 citations
- Antidiabetic Phytochemicals From Medicinal Plants: Prospective Candidates for New Drug Discovery and Development · Frontiers in Endocrinology · 2022 · 310 citations
- Mechanistic Insight into Oxidative Stress-Triggered Signaling Pathways and Type 2 Diabetes · Molecules · 2022 · 296 citations
Most recent work
- Salvadora persica Fruit Methanolic Extract, Nutritional Profiling, Therapeutic Potential in High‐Fat Diet‐Induced Hyperlipidemic Rats: In Vivo, In Vitro, and In Silico Approaches · Food Science & Nutrition · 2026
- Novel pyridazinone-based N-phenylacetamides as α-glucosidase-selective and dual α-glucosidase/aldose reductase inhibitors: Synthesis, SAR analysis, and cytotoxicity evaluation · Bioorganic Chemistry · 2026
- Dietary phytochemicals as multitarget strategies against metabolic syndrome: Mechanistic basis and translational outlook · Food Chemistry Advances · 2026
- GC-MS Guided Phytochemical Fingerprinting and Multi-Target Therapeutic Evaluation of Ixora chinensis Lam. Leaves: Insights into Its Hypoglycemic and Analgesic Activities · Biology · 2026
- Discovery of garlic-derived peptides as natural DPP4 inhibitors: An integrated computational, network pharmacology, and in situ evaluation approach · Bioorganic Chemistry · 2026
- Phytochemical profiling, in silico analysis and in vitro assessment of antioxidant and anticancer activities of methanolic extracts from Momordica cochinchinensis (Lour.) Spreng. leaf and fruit · Applied Food Research · 2026
- Synthesis, Biological Evaluation, and Computational Studies of Phenolic N-Acetylglucosamine Glycosides as α-Glucosidase Inhibitors · Marine Drugs · 2026
- Chemical characterization, phytochemical profiling, antioxidant and antidiabetic properties of Halopithys incurva (Hudson) Batters, 1902: In vitro and in silico approaches · Algal Research · 2026
- Enzyme kinetics-guided evaluation of thiazine hybrids targeting α-amylase and α-glucosidase with in vivo validation · Chemico-Biological Interactions · 2026
- A Novel Edible Eutectogel Containing Baicalein and 1‐Deoxynojirimycin Alleviates Type 2 Diabetes Mellitus · Journal of Food Science · 2026
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