ArticlePloS one2015
Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Medicinal Plants with Multiple Effects on Diabetes Mellitus and Its Complications: a Systematic Review.Current diabetes reports · 2018Pooled it
- A comprehensive review ofBiochemistry and biophysics reports · 2026Review
- Diabetes mellitus in ECOWAS: an overview of the safety and efficacy of medicinal plants used in traditional medicine practices.Tropical medicine and health · 2026Review
- Integrative Approach to Elucidate the Antidiabetic Efficacy of Cipadessa baccifera (Roth) Miq.: A Study Based on Metabolomics, Network Pharmacology, and Animal Models.Chemistry & biodiversity · 2026Article
- Prenatal Exposure to Azadiradione Leads to Developmental Disabilities.Molecular neurobiology · 2025Article
- Gedunin MitigatesPharmaceuticals (Basel, Switzerland) · 2025Article
- Characterization of multi-targeted insulin-mimetic antidiabetic peptides using in silico approaches.PloS one · 2025Article
- Preparation and Identification of Peptides with α-Glucosidase Inhibitory Activity from Shiitake Mushroom (Foods (Basel, Switzerland) · 2023Article
- Deciphering the key pathway for triterpenoid biosynthesis inFrontiers in plant science · 2023Review
- Exploring the therapeutic potential of Neem (Annals of translational medicine · 2022Review
- Anti-hyperglycemic contours of Madhugrit are robustly translated in theFrontiers in endocrinology · 2022Article
- Article
- Azadirachta indica MicroRNAs: Genome-Wide Identification, Target Transcript Prediction, and Expression Analyses.Applied biochemistry and biotechnology · 2021Article
- Exploring the role of3 Biotech · 2021Review
- Insights into the Inhibition Mechanism of Human Pancreatic α-Amylase, a Type 2 Diabetes Target, by Dehydrodieugenol B Isolated fromACS omega · 2021Article
- The recent use ofHeliyon · 2020Review
- Biological Activities of Gedunin-A Limonoid from the Meliaceae Family.Molecules (Basel, Switzerland) · 2020Review
- Evaluation of the Effect of an Aqueous Extract ofDiabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension.BMC plant biology · 2018Article
- Antidiabetic plant-derived nutraceuticals: a critical review.European journal of nutrition · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human pancreatic α-amylase (HPA) inhibitors offer an effective strategy to lower postprandial hyperglycemia via control of starch breakdown. Limonoids from Azadirachta indica known for their therapeutic potential were screened for pancreatic α-amylase inhibition, a known anti-diabetic target. Studies were carried out to reveal their mode of action so as to justify their hypoglycemic potential. Of the nine limonoids isolated/semi-synthesized from A.indica and screened for α-amylase inhibition, azadiradione and exhibited potential inhibition with an IC50 value of 74.17 and 68.38 μM, respectively against HPA under in vitro conditions. Further screening on AR42J α-amylase secretory cell line for cytotoxicity and bioactivity revealed that azadiradione and gedunin exhibited cytotoxicity with IC50 of 11.1 and 13.4μM. Maximal secreted α-amylase inhibition of 41.8% and 53.4% was seen at 3.5 and 3.3μM, respectively. Michaelis-Menten kinetics suggested a mixed mode of inhibition with maltopentaose (Ki 42.2, 18.6 μM) and starch (Ki' 75.8, 37.4 μM) as substrate with a stiochiometry of 1:1 for both azadiradione and gedunin, respectively. The molecular docking simulation indicated plausible π-alkyl and alkyl-alkyl interactions between the aromatic amino acids and inhibitors. Fluorescence and CD confirmed the involvement of tryptophan and tyrosine in ligand binding to HPA. Thermodynamic parameters suggested that binding is enthalpically and entropically driven with ΔG° of -21.25 kJ mol-1 and -21.16 kJ mol-1 for azadiradione and gedunin, respectively. Thus, the limonoids azadiradione and gedunin could bind and inactivate HPA (anti-diabetic target) and may prove to be lead drug candidates to reduce/control post-prandial hyperglycemia.
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