ArticlePloS one2016
Bioactivity-Guided Identification of Botanical Inhibitors of Ketohexokinase.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Morin as a Modulator of Hepatic Glucose Fluxes: A Balance Between Antihyperglycemic Potential and Mitochondrial Toxicity.Journal of biochemical and molecular toxicology · 2025Article
- Examining Prenylated Xanthones as Potential Inhibitors Against Ketohexokinase C Isoform for the Treatment of Fructose-Driven Metabolic Disorders: An Integrated Computational Approach.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pharmacophore-based virtual screening andFrontiers in pharmacology · 2025Article
- Hereditary fructose intolerance: A comprehensive review.World journal of clinical pediatrics · 2022Review
- Molecular aspects of fructose metabolism and metabolic disease.Cell metabolism · 2021Review
- Osthol Ameliorates Kidney Damage and Metabolic Syndrome Induced by a High-Fat/High-Sugar Diet.International journal of molecular sciences · 2021Article
- The Contribution of Dietary Fructose to Non-alcoholic Fatty Liver Disease.Frontiers in pharmacology · 2021Review
- Recent advances in the pathogenesis of hereditary fructose intolerance: implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease.Cellular and molecular life sciences : CMLS · 2020Review
- Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease.European heart journal · 2018Review
- Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice.The Journal of clinical investigation · 2018Article
- Traditional Persian Medicine and management of metabolic dysfunction in polycystic ovary syndrome.Journal of traditional and complementary medicine · 2018Review
- Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice.Nature communications · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveIn developed countries with westernized diets, the excessive consumption of added sugar in beverages and highly refined and processed foods is associated with increased risk for obesity, diabetes, and cardiovascular diseases. As a major constituent of added sugars, fructose has been shown to cause a variety of adverse metabolic effects, such as impaired insulin sensitivity, hypertriglyceridemia, and oxidative stress. Recent studies have shown that ketohexokinase isoform C is the key enzyme responsible in fructose metabolism that drive's fructose's adverse effects. The objective of this study was to identify botanical ingredients with potential for inhibitory activity against ketohexokinase-C and fructose-induced metabolic effects by using a series of in vitro model systems.
methodsExtracts from 406 botanicals and 1200 purified phytochemicals were screened (initial concentration of 50 μg/mL and 50 μM, respectively) for their inhibitory activity using a cell free, recombinant human ketohexokinase-C assay. Dose response evaluations were conducted on botanical extracts and phytochemicals that inhibited ketohexokinase-C by > 30% and > 40%, respectively. Two different extract lots of the top botanical candidates were further evaluated in lysates of HepG2 cells overexpressing ketohexokinase-C for inhibition of fructose-induced ATP depletion. In addition, extracts were evaluated in intact Hep G2 cells for inhibition of fructose-induced elevation of triglyceride and uric acid production.
resultsAmong the botanical extracts, phloretin (Malus domestica) extracts were the most potent (IC50: 8.9-9.2 μg/mL) followed by extracts of Angelica archangelica (IC50: 22.6 μg/mL-57.3 μg/mL). Among the purified phytochemicals, methoxy-isobavachalcone (Psoralea corylifolia, IC50 = 0.2 μM) exhibited the highest potency against ketohexokinase isoform C activity followed by osthole (Angelica archangelica, IC50 = 0.7 μM), cratoxyarborenone E (Cratoxylum prunifolium, IC50 = 1.0 μM), and α-/γ-mangostin (Cratoxylum prunifolium, IC50 = 1.5 μM). Extracts of Angelica archangelica, Garcinia mangostana, Petroselinum crispum, and Scutellaria baicalensis exhibited ketohexokinase inhibitory activity and blocked fructose-induced ATP depletion and fructose-induced elevation in triglyerides and uric acid.
conclusionsAngelica archangelica, Garcinia mangostana, Petroselinum crispum, and Scutellaria baicalensis were the top four botanical candidiates identified with inhibitory activity against ketohexokinase-C. Future studies are needed to show proof of mechanism and the efficacy of these botanical extracts in humans to blunt the negative metabolic effects of fructose-containing added sugars.
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