ArticleBMC complementary and alternative medicine2016
Investigation of synergistic mechanism and identification of interaction site of aldose reductase with the combination of gigantol and syringic acid for prevention of diabetic cataract.
Article in BMC complementary and alternative medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Syringic Acid in Health and Disease: Mechanisms, Biological Activities, and Future Perspectives.International journal of molecular sciences · 2026Review
- The Combination of Pterocarpus marsupium Bark Extract, Pinus strobus Bark Extract, and Ascorbyl Tetraisopalmitate Inhibits Melanogenesis via Nicotinamide Nucleotide Transhydrogenase Activation.Journal of cosmetic dermatology · 2025Article
- Resveratrol Enhances Anticancer Effects of Silybin on HepG2 Cells and H22 Tumor-bearing Mice via Inducing G2/M Phase Arrest and Increasing Bax/Bcl-2 Ratio.Combinatorial chemistry & high throughput screening · 2025Article
- Syringic acid, a promising natural compound for the prevention and management of metabolic syndrome: A systematic review.Iranian journal of basic medical sciences · 2025Review
- Biological Nitrification Inhibitors with Antagonistic and Synergistic Effects on Growth of Ammonia Oxidisers and Soil Nitrification.Microbial ecology · 2024Article
- Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non-small cell lung cancer.Experimental and therapeutic medicine · 2021Article
- Co-targeting p53-R249S and CDK4 synergistically suppresses survival of hepatocellular carcinoma cells.Cancer biology & therapy · 2020Article
- Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein.Chinese journal of integrative medicine · 2019Article
- Protective effects of sulforaphane on diabetic retinopathy: activation of the Nrf2 pathway and inhibition of NLRP3 inflammasome formation.Experimental animals · 2019Article
- Identification Of Natural Compound Derivative For Inhibition Of XLF And Overcoming Chemoresistance In Colorectal Cancer Cells.Drug design, development and therapy · 2019Article
- Phytochemicals: Target-Based Therapeutic Strategies for Diabetic Retinopathy.Molecules (Basel, Switzerland) · 2018Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGigantol and syringic acid (SA) have been shown to synergistically prevent formation of diabetic cataract (DC). However, the exact mechanism of this effect is unknown. Here, we investigate the effect of these compounds on the activity of aldose reductase (AR) and cataract formation.
methodsWe examined the synergistic anti-cataract efficacy of gigantol and SA in the high glucose- and streptozotocin -induced DC rat model; synergism was evaluated using Jin's formula. We investigated possible mechanisms of action by measuring AR expression and activity and levels of sorbitol using enzyme kinetics, Western blot, and RT-PCR. Finally, we examined binding interaction between AR and both compounds using a combination of site-directed mutagenesis, recombinant expression of wild-type and mutant proteins, and enzyme kinetics.
resultsCombination treatment of gigantol and SA synergistically protected both HLECs(human lens epithelial cells) grown in vitro and DC formation in STZ-induced rats in vivo. Synergism was attributed to inhibition of AR activity, downregulation of AR expression via impaired transcription, and decreased sorbitol levels. Enzyme kinetics studies showed that the activity of an AR Asn160Ala mutant protein was significantly decreased compared to wild-type AR, confirming that Asn160 is a key residue for interaction between AR and both compounds.
conclusionCombined administration of gigantol and SA synergize to enhance anti-cataract efficacy. The synergistic effect is mainly attributed to disruption of the polyol pathway and inhibition of AR activity.
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