Litsea japonicaExtract Inhibits Aldose Reductase Activity and Hyperglycemia-Induced Lenticular Sorbitol Accumulation in db/db Mice

Abstract

Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway. AR-dependent synthesis of excess polyols leads to lens opacification in diabetic cataract. The purpose of this study is to investigate the protective effect of Litsea japonica extract (LJE) on diabetes-induced lens opacification and its protective mechanism in db/db mice. Seven-week-old male db/db mice were treated with LJE (100 and 250 mg/kg body weight) once a day orally for 12 weeks. LJE dose dependently inhibited rat lens aldose reductase activity in vitro (IC50 = 13.53 ± 0.74 µg/mL). In db/db mice, lens was slightly opacified, and lens fiber cells were swollen and ruptured. In addition, lenticular sorbitol accumulation was increased in db/db mice. However, the administration of LJE inhibited these lenticular sorbitol accumulation and lens architectural changes in db/db mice. Our results suggest that LJE might be beneficial for the treatment of diabetes-induced lens opacification. The ability of LJE to suppress lenticular sorbitol accumulation may be mediated by the inhibition of AR activity.

Flavonoids from Litsea japonica Inhibit AGEs Formation and Rat Lense Aldose Reductase In Vitro and Vessel Dilation in Zebrafish

“…Recently, it was reported that a crude extract from the leaves of L. japonica induced apoptosis of HL-60 leukemia cells [15] and significantly inhibited complement activity in vitro [16]. In our ongoing efforts to identify effective, naturally sourced therapeutic agents for diabetic complications, we found that an extract from L. japonica reduced the development of diabetic nephropathy via the inhibition of AGEs formation in db/db mice [17] and prevented diabetes-induced lens opacification via the inhibition of AR activity [18]. However, the active compounds underlying these effects of L. japonica remain unknown.…”

Resveratrol protects against high glucose‑induced oxidative damage in human lens epithelial cells by activating autophagy

“…For instance, accumulation of sorbitol produced as a result of enzymatic reduction of glucose by aldose reductase, has been established as an initiating factor for diabetic cataract pathogenesis ( 7 , 8 ). Specifically, the intracellular deposition of the polyol sorbitol causes significant osmotic changes in lens tissues, resulting in lens fiber degeneration and liquefaction, eventually inducing sugar cataract formation, lens swelling and opacities ( 4 , 9 ). In addition, the apoptosis of lens epithelial cells (LECs) is also enhanced by the osmotic stress induced by abnormal sorbitol accumulation in the lens, which is also involved in diabetic cataract formation ( 10 , 11 ).…”

Investigation of synergistic mechanism and identification of interaction site of aldose reductase with the combination of gigantol and syringic acid for prevention of diabetic cataract

“…The lens homogenate from each of the five groups (groups I to V) was prepared in PBS (pH 7.4). Sorbitol levels in the lens were measured as previously described [ 52 , 53 ]. Briefly, a total of 1 mL of extract from each lens was mixed with 2 mL glycine buffer (0.05 M, pH 9.4) containing 2 mM NAD (Nicotinamide adenine dinucleotide) and 0.05 mL sorbitol dehydrogenase (25.6 U/mL) and incubated at room temperature for 60 min.…”