Artichoke leaf extract, as AKR1B1 inhibitor, decreases sorbitol level in the rat eye lenses under high glucose conditions ex vivo

Abstract

In the previous study, the artichoke leaf extract showed effective inhibition of AKR1B1, the first enzyme of polyol pathway, which reduces high level of glucose to osmotically active sorbitol, important for development of chronic diabetic complications. In the present study, the effect of artichoke leaf extract and of several participating phenols (caffeic acid, chlorogenic acid, quinic acid, and luteolin) was tested on sorbitol level in rat lenses exposed to high glucose ex vivo, on cytotoxicity as well as on oxidative stress in C2C12 muscle cell line induced by high glucose in vitro. The concentration of sorbitol was determined by enzymatic analysis, the cytotoxicity was provided by WST-1 test and intracellular content of reactive oxygen species was determined by fluorescence of 2'-7'-dichlorofluorescein probe. The extract and the compounds tested showed significant protection against toxic effects of high concentration of glucose in both models. On balance, the artichoke leaf extract thus represents a prospective preventive agent of development of chronic diabetic complications, probably due to phenols content, concerning preclinical and clinical studies.

Chemical Composition of Cynara Cardunculus L. var. altilis Heads: The Impact of Harvesting Time

“…Moreover, considering the concomitant decrease in total sugars content at late maturity stages, the increase of organic acids especially in sample Car E could be explained by the increased requirements in osmolytes as a mechanism of cardoon plants to overcome stress conditions induced by the high mean and max temperatures and the concomitant low precipitation (see Figure 2) [52,53]. Compared to other reports, cardoon heads revealed greater variety and lower abundance of organic acids than seeds [23,47], while organic acids profile was similar to aerial parts [54]. Finally, the high quinic acid in sample Car E could be valorized for its confirmed high antioxidant potential [55,56].…”

Antioxidant potential of chlorogenic acid in Age‐Related eye diseases

“…can reduce cellular ROS expression, inhibit AR activity and effectively suppress sorbitol accumulation in the diabetic lens. 46 , 47 , 48 Taken together, these results suggest the potential of CGA in the prevention and treatment of cataracts. Its therapeutic effect can be achieved by the upregulation of antioxidant enzymes, modulation of apoptosis‐related proteins, and direct inhibition of AR.…”

“…Moreover, studies have documented that several natural plant extracts with CGA as their main active ingredient (such as Artichoke leaf, Maackia amurensis , Smilax China L. Stems, etc.) can reduce cellular ROS expression, inhibit AR activity and effectively suppress sorbitol accumulation in the diabetic lens 46–48 . Taken together, these results suggest the potential of CGA in the prevention and treatment of cataracts.…”

Cemtirestat, an aldose reductase inhibitor and antioxidant compound, induces ocular defense against oxidative and inflammatory stress in rat models for glycotoxicity

“…14 Accumulating evidence suggests that metabolism-based regulation of OS and activated polyol pathway are potential targets for developing promising treatments not only for retinopathy, but for cataract and even other ocular disorders in DM. 15,16 In this respect, the beneficial effects of some redox modulatory compounds [16][17][18] and natural 19,20 or synthetic derivatives 21 of AR inhibitors (ARIs) on the diabetic eye has been reported. Cemtirestat (CMTI; 3-mercapto-5H-1,2,4-triazino [5,6-b]indole-5-acetic acid), a highly selective and efficient ARI compound endowed with antioxidant (AO) activity has been synthesized by the Slovak Academy of Sciences, 22,23 and demonstrated to exhibit neuroprotection in cell culture models for glycolipotoxicity [24][25][26] and various models for experimentally DM.…”

“…Accumulating evidence suggests that metabolism‐based regulation of OS and activated polyol pathway are potential targets for developing promising treatments not only for retinopathy, but for cataract and even other ocular disorders in DM 15,16 . In this respect, the beneficial effects of some redox modulatory compounds 16–18 and natural 19,20 or synthetic derivatives 21 of AR inhibitors (ARIs) on the diabetic eye has been reported.…”