Editing Aldose reductase inhibitor

'''Aldose reductase inhibitors''' are a class of [[medication|drugs]] being studied as a way to prevent [[Human eye|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 [[polyol pathway|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 [[lens (anatomy)|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==
<gallery class="center">
File:Alrestatin.svg|[[Alrestatin]]
File:Epalrestat.svg|[[Epalrestat]]
File:Fidarestat structure.svg|[[Fidarestat]]
File:Imirestat.svg|[[Imirestat]]
File:Lidorestat.svg|[[Lidorestat]]
File:Minalrestat.svg|[[Minalrestat]]
File:Ponalrestat.svg|[[Ponalrestat]]
File:Ranirestat.svg|[[Ranirestat]]<ref name="pmid17593238">{{cite journal | vauthors = Várkonyi T, Kempler P | title = Diabetic neuropathy: new strategies for treatment | journal = Diabetes, Obesity & Metabolism | volume = 10 | issue = 2 | pages = 99–108 | date = February 2008 | pmid = 17593238 | doi = 10.1111/j.1463-1326.2007.00741.x | s2cid = 13025417 }}</ref>
File:Salfredin B11.svg|[[Crucibulum (fungus)#Bioactive compounds|Salfredin B<sub>11</sub>]]
File:Sorbinil.svg|[[Sorbinil]]
File:Tolrestat structure.svg|[[Tolrestat]]
File:Zenarestat structure.svg|[[Zenarestat]]
File:Zopolrestat.svg|[[Zopolrestat]]
</gallery>

Natural sources reported to inhibit aldose reductase include [[indian gooseberry]], [[spinach]], [[cumin]] seeds, [[fennel]] seeds, [[basil]] leaves, [[lemon]], [[black pepper]], [[Orange (fruit)|orange]], [[Curry tree|curry]] leaves, [[cannabis]],<ref name="pmid29427593">{{cite journal | vauthors = Smeriglio A, Giofrè SV, Galati EM, Monforte MT, Cicero N, D'Angelo V, Grassi G, Circosta C | title = Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol | journal = Fitoterapia | volume = 127 | pages = 101–108 | date = June 2018 | pmid = 29427593 | doi = 10.1016/j.fitote.2018.02.002 }}</ref> [[cinnamon]]<ref name="pmid19114390">{{cite journal | vauthors = Saraswat M, Muthenna P, Suryanarayana P, Petrash JM, Reddy GB | title = Dietary sources of aldose reductase inhibitors: prospects for alleviating diabetic complications | journal = Asia Pac J Clin Nutr | volume = 17 | issue = 4 | pages = 558–65 | date = 2008 | pmid = 19114390 }}</ref> and [[lichen]].<ref name="pmid24735436">{{cite journal | vauthors = Raj PS, Prathapan A, Sebastian J, Antony AK, Riya MP, Rani MR, Biju H, Priya S, Raghu KG | title = Parmotrema tinctorum exhibits antioxidant, antiglycation and inhibitory activities against aldose reductase and carbohydrate digestive enzymes: an in vitro study | journal = Nat. Prod. Res. | volume = 28 | issue = 18 | pages = 1480–4 | date = 2014 | pmid = 24735436 | doi = 10.1080/14786419.2014.909420 | s2cid = 19749777 }}</ref><ref>{{Cite journal|last1=Sebastian|first1=Jomon|last2=A|first2=Prathapan|last3=Sulochana|first3=Priya|last4=KG|first4=Raghu|date=2014-08-01|title=Kinetic and docking studies reveal aldose reductase inhibition potential of edible lichen Parmotrema tinctorum|url=http://www.thepharmajournal.com/archives/?year=2014&vol=3&issue=6&part=A&ArticleId=375|journal=The Pharma Innovation Journal|language=en|volume=3|issue=6}}</ref> [[Luteolin]], a type of [[flavonoid]] found mostly in leaves, and their synthetic derivatives are potential inhibitors of aldose reductase.<ref name="pmid27396410">{{cite journal | vauthors = Sebastian J | title = Structure-Activity Relationship Study Reveals Benzazepine Derivatives of Luteolin as New Aldose Reductase Inhibitors for Diabetic Cataract | journal = Curr Drug Discov Technol | volume = 13 | issue = 3 | pages = 152–163 | date = 2016 | doi = 10.2174/1570163813666160701023100 | pmid = 27396410 }}</ref>       
Other ARIs: 
*[[Risarestat]]
*[[Exisulind]]
*[[Govorestat]]: CNS-penetrant ARI
*[[Caficrestat]]: [[AT001]]
*[[AT003]]

==Diabetic cataract==
Diabetic [[cataract]] formation follows an increase in sugars in the [[lens (anatomy)|lens]]. The excess sugar within the lens is reduced by [[aldose reductase]] to its [[Alcohol (chemistry)|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.<ref>{{cite book | vauthors = Newell FW | title = Ophthalmology: Principles and Concepts | edition = Fifth | location = London | publisher = The CV Mosby Company | year = 1982 | page = 332 }}</ref>

==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 [[mucus|mucous]] secretion associated with these.<ref name="pmid21203431">{{cite journal | vauthors = Yadav UC, Aguilera-Aguirre L, Ramana KV, Boldogh I, Srivastava SK | title = Aldose reductase inhibition prevents metaplasia of airway epithelial cells | journal = PLOS ONE | volume = 5 | issue = 12 | pages = e14440 | year = 2010 | pmid = 21203431 | pmc = 3010981 | doi = 10.1371/journal.pone.0014440 | bibcode = 2010PLoSO...514440Y | doi-access = free }}</ref>

== References ==
{{Reflist|33em}}

{{Enzyme inhibition}}

[[Category:Aldose reductase inhibitors| ]]