Inhibition of glycation-induced cytotoxicity, protein glycation, and activity of proteolytic enzymes by extract from Perovskia atriplicifolia Roots

Abstract

Background:Protein glycation and glycotoxicity belong to the main oxidative-stress related complications in diabetes. Perovskia species are used in Asian folk medicine as antidiabetic herbs.Objective:The aim of this study was to verify the ability of the methanolic extract from Perovskia atriplicifolia Benth. roots to diminish glycation of albumin and to prevent cell damage in vitro. Furthermore, we tested the extract for in vitro antioxidant activity and inhibition of elastase and collagenase.Material and Methods:The aqueous methanol extract was analyzed by UHPLC-MS for the content of polyphenols and terpenoids. The prevention of glycated albumin-induced cell damage was tested in four mammalian cell lines (peripheral blood mononuclear cells, human embryonic kidney cells – HEK293, normal human fibroblasts, and Chinese hamster ovary cells) with the 5-(3-carboxymethoxyphenyl)-2-(4,5-dimethylthiazoly)-3-(4-sulfophenyl) tetrazolium assay.Results:Glycated albumin is significantly more toxic than native human serum albumin (LC50 from 35.00 to 48.34 μg/mL vs. 5.47–9.10 μg/mL, respectively). The extract, rich in rosmarinic acid (344.27 mg/g dry mass), mitigated the glycated albumin toxicity, and increased glycated albumin-treated cell survival by more than 50%. The inhibition of advanced glycation endproduct formation was confirmed by monitoring conformational changes. The free radical scavenging activity was higher than Trolox and metal reducing power was one-third to half that of ascorbic acid. The activity of elastase and collagenase was inhibited by 54.75% ± 6.87% and 60.03% ± 7.22%, respectively.Conclusions:The results confirm antiglycative and antiglycotoxic potential of Perovskia root and its traditional antidiabetic use. The high activity can be attributed to rosmarinic acid abundance.SUMMARY Perovskia is a small genus of aromatic shrubby plants growing in arid regions of Central and South Asia. Different parts are used in folk medicine as antiparasitic, anti-infectious and antidiabetic remedy. Here, we have studied the extract from roots for inhibition of: glycation-induced cytotoxicity, human serum albumin glycation, inflammation-related enzymes, as well as for antioxidant activity. Result: the extract from P. atriplicifolia roots inhibited protein glycation and AGE-induced toxicity in cell cultures. The mechanism is likely to rely on the antioxidant activity of high content of rosmarinic acid. Abbreviations used: AGE: advanced glycation end-products; DPPH: 2,2-diphenyl-1-picrylhydrazyl; HSA: human serum albumin.

Biosynthesis of silver nanoparticles using Tamarix articulata leaf extract: an effective approach for attenuation of oxidative stress mediated diseases

“…[57] Moreover, inhibition of protein glycation has been suggested to understand the mechanism of protection against hyperglycemic conditions in diabetes. [58] In our investigations. BSA was used as a model protein for this experiment and the increase in browning intensity was used as a marker of glycation.…”

Toxicity of advanced glycation end products (Review)

“…The effect of glycated albumin was also analysed on other mammalian cell lines: Peripheral blood mononuclear cells, 293 cells, normal human fibroblasts and Chinese hamster ovary cells. Glycated albumin was significantly more toxic than native human serum albumin (LC 50 values between 35.00-48.34 vs. 5.47-9.10 µg/ml, respectively) ( 2 ). The addition of rosmarinic acid suppressed the cytotoxic effects and inhibited the activity of elastase and collagenase ( 2 ).…”

“…Glycated albumin was significantly more toxic than native human serum albumin (LC 50 values between 35.00-48.34 vs. 5.47-9.10 µg/ml, respectively) ( 2 ). The addition of rosmarinic acid suppressed the cytotoxic effects and inhibited the activity of elastase and collagenase ( 2 ).…”

“…In studies on AGE, two classifications for the nomenclature regarding AGEs are used, which are either focused on the structure of the AGE or instead focused on the proteins being modified. In the first classification system, the most extensively studied AGEs are N -carboxymethyllysine (CML), pentosidine, crossline, pyrraline and hydroimidazolone ( 2 ). The second group includes AGE-1 (glucose-derived AGEs), AGE-2 (glyceraldehyde-derived AGEs), AGE-3 (glycolaldehyde-derived AGEs), AGE-4 (MGO/methylglyoxal-derived AGEs), AGE-5 (glyoxal-derived AGEs), AGE-6 (3-deoxyglucosone-derived AGEs) and acetaldehyde-derived AGEs (AA-AGEs) ( 12 , 13 ).…”

Investigation of the Composition, Antimicrobial, Antioxidant, and Cytotoxicity Properties of Salvia abrotanoides Essential Oil

“…e metabolites of S. abrotanoides have been used in traditional medicine, including the improvement of fever [24], antidiabetic [25], rheumatic pain [26], chronic hepatitis B virus (HBV), and leishmaniasis [27], and also other disorders like atherosclerosis, cardiovascular illness, liver, and cardiac fibrosis [28]. Likewise, it had particular role in Iranian traditional medical activity to heal leishmaniasis and skin disorders [21].…”