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.
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 cellmetaplasia in the
respiratory epithelium, thereby reducing the copious
mucous secretion associated with these.[8]
^Smeriglio A, Giofrè SV, Galati EM, Monforte MT, Cicero N, D'Angelo V, Grassi G, Circosta C (June 2018). "Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol". Fitoterapia. 127: 101–108.
doi:
10.1016/j.fitote.2018.02.002.
PMID29427593.
^Saraswat M, Muthenna P, Suryanarayana P, Petrash JM, Reddy GB (2008). "Dietary sources of aldose reductase inhibitors: prospects for alleviating diabetic complications". Asia Pac J Clin Nutr. 17 (4): 558–65.
PMID19114390.
^Raj PS, Prathapan A, Sebastian J, Antony AK, Riya MP, Rani MR, Biju H, Priya S, Raghu KG (2014). "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.
doi:
10.1080/14786419.2014.909420.
PMID24735436.
S2CID19749777.
^Sebastian J (2016). "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.
doi:
10.2174/1570163813666160701023100.
PMID27396410.
^Newell FW (1982). Ophthalmology: Principles and Concepts (Fifth ed.). London: The CV Mosby Company. p. 332.