Biology:Aldose reductase inhibitor
Aldose reductase inhibitors are a class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes.
Mechanism
Their target, aldose reductase, is an enzyme that is normally present in many other parts of the body, and catalyzes one of the steps in the sorbitol (polyol) pathway that is responsible for fructose formation from glucose. Aldose reductase activity increases as the glucose concentration rises in diabetes in those tissues that are not insulin sensitive, which include the lenses, peripheral nerves, and glomerulus. Sorbitol does not diffuse through cell membranes easily and therefore accumulates, causing osmotic damage which leads to retinopathy and neuropathy.
Examples
Imirestat
Lidorestat
Minalrestat
Ponalrestat
Zopolrestat
Natural sources reported to inhibit aldose reductase include indian gooseberry, spinach, cumin seeds, fennel seeds, basil leaves, lemon, black pepper, orange, curry leaves, cannabis,[2] cinnamon[3] and lichen.[4][5] Luteolin, a type of flavonoid found mostly in leaves, and their synthetic derivatives are potential inhibitors of aldose reductase.[6]
Diabetic cataract
Diabetic cataract formation follows an increase in sugars in the lens. The excess sugar within the lens is reduced by aldose reductase to its alcohol, but the lens capsule is relatively impermeable to sugar alcohols. Because of the excess sugar alcohol (polyol), the lens imbibes water, causing osmotic imbalance. Eventually, increased sodium and decreased potassium levels and decreased glutathione levels lead to cataract formation. Topical administration of aldose reductase inhibitors have been shown to prevent the cataract in rats.[7]
Asthma and COPD
This class of drugs is also under investigation as a possible root pathology modulating treatment for asthma and COPD since it has been shown that they inhibit goblet cell metaplasia in the respiratory epithelium, thereby reducing the copious mucous secretion associated with these.[8]
References
- ↑ "Diabetic neuropathy: new strategies for treatment". Diabetes, Obesity & Metabolism 10 (2): 99–108. February 2008. doi:10.1111/j.1463-1326.2007.00741.x. PMID 17593238.
- ↑ "Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol". Fitoterapia 127: 101–108. June 2018. doi:10.1016/j.fitote.2018.02.002. PMID 29427593.
- ↑ "Dietary sources of aldose reductase inhibitors: prospects for alleviating diabetic complications". Asia Pac J Clin Nutr 17 (4): 558–65. 2008. PMID 19114390.
- ↑ "Parmotrema tinctorum exhibits antioxidant, antiglycation and inhibitory activities against aldose reductase and carbohydrate digestive enzymes: an in vitro study". Nat. Prod. Res. 28 (18): 1480–4. 2014. doi:10.1080/14786419.2014.909420. PMID 24735436.
- ↑ Sebastian, Jomon; A, Prathapan; Sulochana, Priya; KG, Raghu (2014-08-01). "Kinetic and docking studies reveal aldose reductase inhibition potential of edible lichen Parmotrema tinctorum" (in en). The Pharma Innovation Journal 3 (6). http://www.thepharmajournal.com/archives/?year=2014&vol=3&issue=6&part=A&ArticleId=375.
- ↑ "Structure-Activity Relationship Study Reveals Benzazepine Derivatives of Luteolin as New Aldose Reductase Inhibitors for Diabetic Cataract". Curr Drug Discov Technol 13 (3): 152–163. 2016. doi:10.2174/1570163813666160701023100. PMID 27396410.
- ↑ Ophthalmology: Principles and Concepts (Fifth ed.). London: The CV Mosby Company. 1982. p. 332.
- ↑ "Aldose reductase inhibition prevents metaplasia of airway epithelial cells". PLOS ONE 5 (12): e14440. 2010. doi:10.1371/journal.pone.0014440. PMID 21203431. Bibcode: 2010PLoSO...514440Y.
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