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Cardiovascular Risk Factors
Published in Nicole M. Farmer, Andres Victor Ardisson Korat, Cooking for Health and Disease Prevention, 2022
AGEs can also form non-Maillard reactions. The second formation pathway occurs from the autooxidation of glucose and the peroxidation of lipids, known an α-oxaldehydes (Figure 5.3). And the third pathway for formation of AGEs involves the polyol pathway, where glucose is converted to sorbitol by the enzyme aldose reductase and then to fructose through enzymatic action of sorbitol dehydrogenase (Figure 5.3). Fructose metabolites (as fructose 3-phosphate) then are converted into α-oxaldehydes and interact with monoacids to form AGEs. The formation of AGEs leads to several biomarkers for in vivo formation. The most widely known AGEs are carboxymethyl-lysine (CML) (found in Maillard reactions), pentosidine and pyrraline (found in Maillard reactions), and methylglyoxal (an α-oxaldehyde).
Plantago ovata (Isabgol) and Rauvolfia serpentina (Indian Snakeroot)
Published in Azamal Husen, Herbs, Shrubs, and Trees of Potential Medicinal Benefits, 2022
Ankur Anavkar, Nimisha Patel, Ahmad Ali, Hina Alim
Aldose reductase is a possible target for treatment of diabetes because of being associated with secondary complications in diabetes. Using the SerpentinaDB database 2, plant-derived molecule (PDM) leads, i.e., indobine and indobinine were identified as potential inhibitors of aldose reductase. Further, through structural analogs, 16 leads were determined from the ZINC database. All the leads thus could help in the design of potential drugs that would act as aldose reductase inhibitors with minimal side effects (Pathania et al., 2013).
Recent Advancements of Curcumin Analogs and Curcumin Formulations in Context to Modern Pharmacotherapeutics Perspectives
Published in Debarshi Kar Mahapatra, Cristóbal Noé Aguilar, A. K. Haghi, Applied Pharmaceutical Practice and Nutraceuticals, 2021
Animeshchandra G. M. Haldar, Kanhaiya M. Dadure, Debarshi Kar Mahapatra
Kondhare et al.55 have developed novel aldose reductase inhibitors (ARIs) of therapeutic significance. The nanodispersion of curcumin THERACURMIN tested for better ARI activity and evaluated the product for aldose reductase inhibition. Aldose Reductase, the key enzyme involved in the first and rate-limiting step of polyol pathway has been implicated in the development of late microvascular complications such as nerve-damaging due to diabetic, cataract, nephropathy, etc. As a consequence, the inhibition of this enzyme is of therapeutic significance to reduce the seriousness of chronic diabetic complications. It is evident from studies that THERACURMIN as expected exhibited excellent ARI activity in 20–30 μM range with IC50 of 3 μM. This is remarkable as the product contains only 15% curcuminoids in the total dispersion and curcumin itself displays potent aldose reductase inhibition activity.
Biomarkers in diabetic neuropathy
Published in Archives of Physiology and Biochemistry, 2023
Kaveri M. Adki, Yogesh A. Kulkarni
Hyperglycaemia activates the polyol pathway. Aldose reductase utilises excess glucose and converts into sorbitol. Similarly, sorbitol dehydrogenase converts sorbitol into fructose. This cellular mechanism depletes nicotinamide adenine dinucleotide phosphate (NADPH), which causes the generation of glutathione. Glutathione is the primary antioxidant in nerve tissue. The depletion of glutathione leads to oxidative stress and slows down nerve conduction. A study by Varkonyi et al. showed that AGEs play a prime role in the progression of various diabetic complications such as duplication of basal lamina around endothelial cells results in thickening of walls of small blood vessels (Várkonyi et al. 2017). The AGEs result in excess glucose and protein complex formation. These AGEs form a complex network with collagen and harm nerves (Grisold et al. 2017).
Potential molecular mechanism of action of sodium-glucose co-transporter 2 inhibitors in the prevention and management of diabetic retinopathy
Published in Expert Review of Ophthalmology, 2022
Lia Meuthia Zaini, Arief S Kartasasmita, Tjahjono D Gondhowiardjo, Maimun Syukri, Ronny Lesmana
The polyol pathway plays a significant role in the development of diabetic complications, including retinopathy (Figure 4). Chronic hyperglycemia causes the hexokinase enzyme to become saturated, diverting the excess glucose from the glycolysis pathway. As a result, an increased flux of blood glucose (~30%) enters the polyol pathway, producing a large amount of sorbitol catalyzed by the enzyme aldose reductase. The expression of aldose reductase mRNA is high in the primary target organs of diabetic complications, including the lens, retina, and sciatic nerve. Pericyte degradation, a hallmark of DR, has also been linked to the increased aldose reductase activity in the retinal capillary [53]. The upregulation of the polyol pathway also increases cell susceptibility to oxidative stress. In the polyol pathway, the depletion of nicotinamide adenine dinucleotide phosphate (NADPH) by aldose reductase leads to failure in regenerating glutathione, a critical intracellular antioxidant, hampering the antioxidant mechanism [54].
Diabetic eye: associated diseases, drugs in clinic, and role of self-assembled carriers in topical treatment
Published in Expert Opinion on Drug Delivery, 2021
Axel Kattar, Angel Concheiro, Carmen Alvarez-Lorenzo
Hyperglycemia is also responsible for triggering the polyol pathway. Under normoglycemic conditions, the Embden–Meyerhof–Parnas catabolism route that transforms glucose into pyruvate, NADH, and ATP becomes saturated. Consequently, the polyol pathway, which commonly transforms 3% glucose, enters into action with the participation of two enzymes: (i) aldose reductase that transforms glucose into sorbitol with the consumption of NADPH and (ii) sorbitol dehydrogenase that slowly converts sorbitol into fructose while consuming NAD+. The polyol pathway, which is very active in retina and lens, metabolizes more than 30% glucose under diabetic conditions [73]. Accumulation of sorbitol causes osmotic stress, triggers leukocyte accumulation, disrupts blood-retinal barrier, favors cells apoptosis, and starts a cascade of oxidative stress-mediated reactions [74]. The excess of fructose acts as precursor of advanced glycation-end products (AGEs). In this context, aldose reductase inhibitors are gaining increased attention, and epalrestat is approved in some countries for oral administration. As an alternative, drugs that accelerate the metabolic rate of sorbitol dehydrogenase and, thus, decrease the levels of sorbitol are being tested [73].