Abstract
Aim:
To investigate the protective effects of Ginkgo biloba extract (GBE) on high glucose-induced apoptosis of human lens epithelial cells (HLEC) and the possible molecular mechanisms.
Methods:
The cultured HLEC were allotted into 6 groups: normal group, high glucose group, low-, moderate-, and highdose GBE group, and the bendazac lysine group. Cell viability, cell apoptosis, the activities of cell antioxidases, aldose reductase, caspase-3, the levels of cell antioxidants, and the expressions of Bcl-2 and Bax were assessed by different methods.
Results:
After being incubated with high glucose for 24 h, HLEC underwent apoptosis and exhibited significant oxidative stress. In the presence of GBE at different doses, the rate of HLEC apoptosis was lower and the oxidative stress state was significantly ameliorated. The increased ratio of Bax to Bcl-2 was significantly reduced and the activation of caspase-3 was suppressed by GBE in a dose-dependent manner.
Conclusion:
GBE prevents HLEC from high glucose-induced apoptosis through inhibiting oxidative stress, reducing the ratio of Bax to Bcl-2, and decreasing the activity of caspase-3. Therefore, GBE has a potential protective effect against diabetic cataract formation.
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Leske MC, Wu SY, Hennis A, Connell AM, Hyman L, Schachat A . Diabetes, hypertension, and central obesity as cataract risk factors in a black population. The Barbados Eye Study. Ophthalmology 1999; 106: 35–41.
Klein BE, Klein R, Lee KE . Diabetes, cardiovascular disease, selected cardiovascular disease risk factors, and the 5-year incidence of age-related cataract and progression of lens opacities: the Beaver Dam Eye Study. Am J Ophthalmol 1998; 126: 782–90.
Oishi N, Morikubo S, Takamura Y, Kubo E, Tsuzuki S, Tanimoto T, et al. Correlation between adult diabetic cataracts and red blood cell aldose reductase levels. Invest Ophthalmol Vis Sci 2006; 47: 2061–4.
Li WC, Kuszak JR, Dunn K, Wang RR, Ma W, Wang GM, et al. Lens epithelial cell apoptosis appears to be a common cellular basis for non-congenital cataract development in humans and animals. J Cell Biol 1995; 130: 169–81.
Pladzyk A, Ramana KV, Ansari NH, Srivastava SK . Aldose reductase prevents aldehyde toxicity in cultured human lens epithelial cells. Exp Eye Res 2006; 83: 408–16.
Carambula SF, Matikainen T, Lynch MP, Flavell RA, Goncalves PB, Tilly JL, et al. Caspase-3 is a pivotal mediator of apoptosis during regression of the ovarian corpus luteum. Endocrinology 2002; 143: 1495–501.
Qi JP, Wu AP, Wang DS, Wang LF, Li SX, Xu FL . Correlation between neuronal injury and caspase-3 after focal ischemia in human hippocampus. Chin Med J (Engl) 2004; 117: 1507–12.
Siegel G, Schafer P, Winkler K, Malmsten M . Ginkgo biloba (EGb 761) in arteriosclerosis prophylaxis. Wien Med Wochenschr 2007; 157: 288–94.
Zou W, Kim BO, Zhou BY, Liu Y, Messing A, He JJ . Protection against human immunodeficiency virus type 1 Tat neurotoxicity by Ginkgo biloba extract EGb 761 involving glial fibrillary acidic protein. Am J Pathol 2007; 171: 1923–35.
Lu Q, Yin XX, Wang JY, Gao YY, Pan YM . Effects of Ginkgo biloba on prevention of development of experimental diabetic nephropathy in rats. Acta Pharmacol Sin 2007; 28: 818–28.
Wang JY, Yin XX, Wu YM, Tang DQ, Gao YY, Wan MR, et al. Ginkgo biloba extract suppresses hypertrophy and extracellular matrix accumulation in rat mesangial cells. Acta Pharmacol Sin 2006; 27: 1222–30.
Head KA . Natural therapies for ocular disorders, part two: cataracts and glaucoma. Altern Med Rev 2001; 6: 141–66.
Thiagarajan G, Chandani S, Harinarayana Rao S, Samuni AM, Chan-drasekaran K, Balasubramanian D . Molecular and cellular assessment of Ginkgo biloba extract as a possible ophthalmic drug. Exp Eye Res 2002; 75: 421–30.
Srivastava S, Tammali R, Chandra D, Greer DA, Ramana KV, Bhat-nagar A, et al. Regulation of lens aldose reductase activity by nitric oxide. Exp Eye Res 2005; 81: 664–72.
Preet A, Siddiqui MR, Taha A, Badhai J, Hussain ME, Yadava PK, et al. Long-term effect of Trigonella foenum graecum and its combination with sodium orthovanadate in preventing histopathological and biochemical abnormalities in diabetic rat ocular tissues. Mol Cell Biochem 2006; 289: 137–47.
Seo HG, Nishinaka T, Yabe-Nishimura C . Nitric oxide up-regulates aldose reductase expression in rat vascular smooth muscle cells: a potential role for aldose reductase in vascular remodeling. Mol Pharmacol 2000; 57: 709–17.
Srivastava SK, Bhatnagar A, Friedrich B, Ramana KV . NADPH oxi-dase and aldose reductase inhibition attenuates high glucose-induced NF-kappaB activation and apoptosis of human lens epithelial cells. Invest Ophthalmol Vis Sci 2004; 45: 1698.
Ramana KV, Friedrich B, Bhatnagar A, Srivastava SK . Aldose reductase mediates cytotoxic signals of hyperglycemia and TNF-alpha in human lens epithelial cells. FASEB J 2003; 17: 315–7.
Mohanty I, Joshi S, Trivedi D, Srivastava S, Gupta SK . Lycopene prevents sugar-induced morphological changes and modulates an-tioxidant status of human lens epithelial cells. Br J Nutr 2002; 88: 347–54.
Mulhern ML, Madson CJ, Danford A, Ikesugi K, Kador PF, Shino-hara T . The unfolded protein response in lens epithelial cells from galactosemic rat lenses. Invest Ophthalmol Vis Sci 2006; 47: 3951–9.
Biswas S, Harris F, Singh J, Phoenix D . Role of calpains in diabetes mellitus-induced cataractogenesis: a mini review. Mol Cell Biochem 2004; 261: 151–9.
Hegde KR, Varma SD . Cataracts in experimentally diabetic mouse: morphological and apoptotic changes. Diabetes Obes Metab 2005; 7: 200–4.
Allen DA, Yaqoob MM, Harwood SM . Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications. J Nutr Biochem 2005; 16: 705–13.
Kyselova Z, Stefek M, Bauer V Pharmacological prevention of diabetic cataract. J Diabetes Complications 2004; 18: 129–40.
Kojima M, Sun L, Hata I, Sakamoto Y, Sasaki H, Sasaki K . Efficacy of alpha-lipoic acid against diabetic cataract in rat. Jpn J Ophthalmol 2007; 51: 10–3.
Lee AY, Chung SS . Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 1999; 13: 23–30.
Yin XX, Zhang YD, Liu X . The inhibitory effects of Ginkgo biloba extract and Astragalus saponin I on aldose reductase extracted from bovine lens. Acta Acad Med Xuzhou 2006; 26: 478–81.
Chung SS, Ho EC, Lam KS, Chung SK . Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol 2003; 14: S233–6.
Desagher S, Martinou JC . Mitochondria as the central control point of apoptosis. Trends Cell Biol 2000; 10: 369–77.
Verzola D, Bertolotto MB, Villaggio B, Ottonello L, Dallegri F, Frumento G, et al. Taurine prevents apoptosis induced by high ambient glucose in human tubule renal cells. J Investig Med 2002; 50: 443–51.
Evans JL, Goldfine ID, Maddux BA, Grodsky GM . Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002; 23: 599–622.
Budihardjo I, Oliver H, Lutter M, Luo X, Wang X . Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol 1999; 15: 269–90.
Green DR, Reed JC . Mitochondria and apoptosis. Science 1998; 281: 1309–12.
Gulbins E, Dreschers S, Bock J . Role of mitochondria in apoptosis. Exp Physiol 2003; 88: 85–90.
Vousden KH . Outcomes of p53 activation—spoilt for choice. J Cell Sci 2006; 119: 5015–20.
Gross A, McDonnell JM, Korsmeyer SJ . BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999; 13: 1899–911.
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Project supported by College Natural Science Research Foundation of Jiangsu Province (No 03KJ13360143).
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Wu, Zm., Yin, Xx., Ji, L. et al. Ginkgo biloba extract prevents against apoptosis induced by high glucose in human lens epithelial cells. Acta Pharmacol Sin 29, 1042–1050 (2008). https://doi.org/10.1111/j.1745-7254.2008.00837.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00837.x
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