Delay of diabetic cataract in rats by the antiglycating potential of cumin through modulation of alpha-crystallin chaperone activity. J Nutr Biochem

National Institute of Nutrition, Hyderabad 500007, India.
The Journal of nutritional biochemistry (Impact Factor: 3.79). 10/2008; 20(7):553-62. DOI: 10.1016/j.jnutbio.2008.05.015
Source: PubMed


α-Crystallin, a molecular chaperone of the eye lens, plays an important role in maintaining the transparency of the lens by preventing the aggregation/inactivation of several proteins and enzymes in addition to its structural role. α-Crystallin is a long-lived protein and is susceptible to several posttranslational modifications during aging, more so in certain clinical conditions such as diabetes. Nonenzymatic glycation of lens proteins and decline in the chaperone-like function of α-crystallin have been reported in diabetic conditions. Therefore, inhibitors of nonenzymatic protein glycation appear to be a potential target to preserve the chaperone activity of α-crystallin and to combat cataract under hyperglycemic conditions. In this study, we investigated the antiglycating potential of cumin in vitro and its ability to modulate the chaperone-like activity of α-crystallin vis-à-vis the progression of diabetic cataract in vivo. Aqueous extract of cumin was tested for its antiglycating ability against fructose-induced glycation of goat lens total soluble protein (TSP), α-crystallin from goat lens and a nonlenticular protein bovine serum albumin (BSA). The antiglycating potential of cumin was also investigated by feeding streptozotocin (STZ)-induced diabetic rats with diet containing 0.5% cumin powder. The aqueous extract of cumin prevented in vitro glycation of TSP, α-crystallin and BSA. Slit lamp examination revealed that supplementation of cumin delayed progression and maturation of STZ-induced cataract in rats. Cumin was effective in preventing glycation of TSP and α-crystallin in diabetic lens. Interestingly, feeding of cumin to diabetic rats not only prevented loss of chaperone activity but also attenuated the structural changes of α-crystallin in lens. These results indicated that cumin has antiglycating properties that may be attributed to the modulation of chaperone activity of α-crystallin, thus delaying cataract in STZ-induced diabetic rats.

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    • "Since α-crystallin is a very stable protein, the fraction of protein that remained in the solution had no changes in the secondary structure, but the aggregates and cross-linked protein due to glycation was in the insoluble fraction and remained at the upper part of the electrophoresis (SDS PAGE). Several small molecules are reported to modulate the chaperone activity of α-crystallin under various conditions, including in vitro glycation and diabetes414243. Similar to crocin(s), most of these molecules exert their effects by inhibiting the non-enzymatic glycation and oxidative damage of α-crystallin and preserving its chaperone activity to prevent cataracts under diabetic conditions. GSH, is a reducing tripeptide, unusually found at high levels in the lens, that plays an important role in the maintenance of the reduced state of this tissue. "
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    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.
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    • "As observed in previous studies [10–13], the food intake of diabetic animals was more than the respective controls. Despite the increased food intake, the body weight of diabetic animals decreased significantly (mean ± S.E body weight at the end of experiment, 205 ± 4.35 g; p<0.001) when compared to control animals (320 ± 3.65 g) and so was the case in the treated groups, curcumin, nanocurcumin and blank particle groups [202 ± 3.15 g, p<0.001; 198±5.22 "
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    ABSTRACT: Curcumin, the active principle present in the yellow spice turmeric, has been shown to exhibit various pharmacological actions such as antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic activities. Previously we have reported that dietary curcumin delays diabetes-induced cataract in rats. However, low peroral bioavailability is a major limiting factor for the success of clinical utilization of curcumin. In this study, we have administered curcumin encapsulated nanoparticles in streptozotocin (STZ) induced diabetic cataract model. Oral administration of 2 mg/day nanocurcumin was significantly more effective than curcumin in delaying diabetic cataracts in rats. The significant delay in progression of diabetic cataract by nanocurcumin is attributed to its ability to intervene the biochemical pathways of disease progression such as protein insolubilization, polyol pathway, protein glycation, crystallin distribution and oxidative stress. The enhanced performance of nanocurcumin can be attributed probably to its improved oral bioavailability. Together, the results of the present study demonstrate the potential of nanocurcumin in managing diabetic cataract.
    Full-text · Article · Oct 2013 · PLoS ONE
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    • "Our data revealed a biphasic response of MnSOD protein expression suggesting anti-oxidant biochemical defense during the first 0–24 h which diminished thereafter suggesting exposure to high glucose for a period beyond 48 h overwhelmed the anti-oxidant capacity of the cell. Results from two independent studies have suggested use of anti-oxidants prevented the oxidative damage to lens epithelial cells and arrested the loss of chaperone-like activity of α-crystallin in rat lens [24], [35]. In agreement, we also demonstrated restoration of FoxO3a protein expression to base levels with NAC, a well-known anti-oxidant suggesting dysregulation of FoxO3a expression can be reversed with the use of anti-oxidants. "
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    ABSTRACT: Forkhead box 'O' transcription factors (FoxOs) are implicated in the pathogenesis of type2 diabetes and other metabolic diseases. Abnormal activity of FoxOs was reported in the glucose and insulin metabolism. Expression of FoxO proteins was reported in ocular tissues; however their function under hyperglycemic conditions was not examined. Human lens epithelial cell line was used to study the function of FoxO proteins. Immunofluorescence, flow cytometry and Western blotting were employed to detect the FoxO proteins under the conditions of hyperglycemia. In this study we examined the role of FoxO3a in hyperglycemia-induced oxidative stress in human lens epithelial cells. FoxO3a protein expression was elevated in a dose- and time-dependent fashion after high glucose treatment. Anti-oxidant defense mechanisms of the lens epithelial cells were diminished as evidenced from loss of mitochondrial membrane integrity and lowered MnSOD after 72 h treatment with high glucose. Taken together, FoxO3a acts as a sensitive indicator of oxidative stress and cell homeostasis in human lens epithelial cells during diabetic conditions. FoxO3a is an early stress response protein to glucose toxicity in diabetic conditions.
    Full-text · Article · Jun 2013 · PLoS ONE
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