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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    • "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.
    PLoS ONE 10/2013; 8(10):e78217. DOI:10.1371/journal.pone.0078217 · 3.23 Impact Factor
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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.
    PLoS ONE 06/2013; 8(6):e67126. DOI:10.1371/journal.pone.0067126 · 3.23 Impact Factor
    • "In another study, an aqueous extract of cumin prevented in vitro glycation of total soluble protein, α-crystallin, and delayed the progression and maturation of STZ-induced cataract in rats. Cumin prevented loss of chaperone activity in diabetic rats and also attenuated the structural changes of α-crystallin in lens, which is a long-lived protein and is susceptible to several post-translational modifications in certain diabetic conditions.[113] Eight-week sub-acute administration of cumin to STZ-diabetic rats reduced hyperglycemia and glucosuria accompanied by an improvement in body weight, blood urea and reduced excretion of urea and creatinine.[114] "
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    ABSTRACT: Cuminum cyminum and Carum carvi are the sources of cumin and caraway seeds respectively, which have been used since antiquity for the treatment of various indications in traditional healing systems in wide geographical areas. Cumin and caraway seeds are rich sources of essential oils and have been actively researched for their chemical composition and biological activities. In recent times (especially during the last 3 years) considerable progress has been made regarding validation of their acclaimed medicinal attributes by extensive experimental studies. In this attempt many novel bioactivities have been revealed. This review highlights the significance of cumin and caraway as potential source of diverse natural products and their medicinal applications.
    Pharmacognosy Reviews 03/2011; 5(9):63-72. DOI:10.4103/0973-7847.79101
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