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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).
Apiaceae Plants Growing in the East
Published in Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa, Ethnopharmacology of Wild Plants, 2021
Sherweit El-Ahmady, Nehal Ibrahim, Nermeen Farag, Sara Gabr
C. cyminum is able to reduce blood glucose levels without initiating hypoglycaemia or β-cell burn out. This antidiabetic activity was validated in the petroleum ether fraction of C. cyminum distillate through in vitro and in vivo studies. The hypoglycaemic effect was ascribed to cuminal and cuminol in the essential oil. The latter compounds were identified as potent glucose-dependent insulinotropic agents with 3.34-and 3.85-fold increase in insulin secretion, for cuminal and cuminol, respectively, compared to the 11.8 mM glucose control. This action was mediated by blocking the ATP-sensitive K+ channels and increasing the intracellular Ca2+ concentration in cultured rat pancreatic cells. In addition, both compounds exert antioxidant protective effects on insulin-secreting β cells (Patil et al. 2013). Furthermore, cuminal has been proved to inhibit aldose reductase and α-glucosidase enzymes with IC50 values of 0.00085 mg/mL and 0.5 mg/mL, respectively (Lee 2005). Aldose reductase is a key enzyme in the onset of most of the diabetic complications. On the other hand, inhibition of α-glucosidase can delay carbohydrate digestion and decrease the absorption rate of glucose (Kalita et al. 2018).
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).
Anti-EMT and anti-fibrosis effects of protocatechuic aldehyde in renal proximal tubular cells and the unilateral ureteral obstruction animal model
Published in Pharmaceutical Biology, 2022
Yu-Teng Chang, Mu-Chi Chung, Chi-Hao Chang, Kuan-Hsun Chiu, Jeng-Jer Shieh, Ming-Ju Wu
PCA has multiple pharmacological effects, including its potential in the prevention and treatment of diabetes and its complications (retinopathy, neuropathy, or nephropathy) (Jung et al. 2005; Lee et al. 2005). Prolonged hyperglycaemia in patients with diabetes activates aldose reductase, which metabolizes glucose in the blood to sorbitol, which then accumulates in the cells, causing eye, nerve, and kidney lesions (Hotta et al. 2012). PCA also has anti-inflammatory and anti-fibrotic effects on obstructive nephropathy (Yang et al. 2021). PCA inhibits aldose reductase in the polyol pathway (Jung et al. 2005; Lee et al. 2005). Therefore, the tubulointerstitial fibrosis inhibited by PCA in the diabetic nephropathy-activated polyol pathway might be a potential therapeutic strategy. Aldose reductase inhibitors have been reported to improve pulmonary and myocardial fibrosis (Li et al. 2015; Zhang et al. 2015; Wan et al. 2019). Future studies should investigate the effects of PCA on the polyol pathway in renal fibrosis.
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].