Inhibitory Effect of Crocin(s) on Lens α-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract

Abstract

Abstract:The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and α-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded regularly every two weeks and was classified into four stages. After eight weeks, the animals were sacrificed and the parameters involved in the cataract formation were measured in the animal lenses. Some parameters were also determined in the serum and blood of the rats. In addition, the effect of crocin(s) on the structure and chaperone activity of α-crystallin in the presence of glucose was studied by different methods. Crocin(s) lowered serum glucose levels of diabetic rats and effectively maintained plasma total antioxidants, glutathione levels and catalase activity in the lens of the animals. In the in vitro study, crocin(s) inhibited α-crystallin glycation and aggregation. Advanced glycation end products fluorescence, hydrophobicity and protein cross-links were also decreased in the presence of crocin(s). In addition, the decreased chaperone activity of α-crystallin in the presence of glucose changed and became close to the native value by the addition of crocin(s) in the medium. Crocin(s) thus showed a powerful inhibitory effect on α-crystallin glycation and preserved the structure-function of this protein. Crocin(s) also showed the beneficial effects on prevention of diabetic cataract.

Ursodeoxycholic acid suppresses the formation of fructose/streptozotocin‐induced diabetic cataract in rats

“…In addition, a remarkable significant increase in the level of insoluble proteins was also detected in diabetic untreated animals. Several mechanisms have been reported to explain the decrease in total and soluble proteins in diabetic lenses, for example, protein leakage through membranes as a result of osmotic stress, protein degradation due to altered proteolysis, and protein aggregation and cross-linking due to oxidative stress and subsequent damage of critical protein sulfhydryl groups [25,39,55]. The present investigation showed that administration of UDCA, either topically or through the oral route, caused a slight but nonsignificant increase in the level of soluble and total protein; however, it prevented the increase in the level of lens insoluble proteins.…”

“…In addition, the anticataractogenic potential of the bile acids UDCA and TUDCA has been demonstrated and was ascribed to their ability to maintain antioxidant status, to suppress lens epithelial cell death through alleviating the ER stress, and to prevent protein aggregation through enhancement of α‐crystallin chaperone activity . However, most of the previous in vivo anticataract studies were focusing on inducing cataract either through using chemical toxins such as selenite or through dietary manipulations that mainly produce characteristics of type 1 diabetes with severe dysfunction of β‐cells . No previous reports have experimented the effect of UDCA against cataract induced by the low‐dose fructose/streptozotocin (FR/STZ) combined model which effectively could produce the natural history and metabolic characteristics associated with IR and the mild forms of type 2 diabetes .…”

Latest advances in the extraction and determination of saffron apocarotenoids

“…The latter is liberated from bound structures after consumption of saffron or its extracts . In particular, an increasing number of studies indicates action of these apocarotenoids against several types of cancer, cardiovascular diseases, gastric disorders, Alzheimer disease, hepatotoxicity, atherosclerosis, mild to moderate depression, and diabetic cataract . Based on all these biological actions assigned to its major apocarotenoids, Tsimidou and collaborators named saffron as a functional spice in a recent review article.…”

Revisiting amino acids and peptides as anti-glycation agents

“…Although the specific mechanisms by which glycine or taurine induced diminution of glucose levels remained to be identified, this effect was attributed to the capability of these amino acids of interacting with the insulin receptor. The formation of Schiff base through the reaction of glycine with sugars such as glucose has also been observed, 28 causing a decrease of the free glucose concentration in the medium. Glycine possibly reacts with glucose or dicarbonyl compounds via its amino group, thereby resulting in lower production of AGEs.…”