key: cord-296769-xnjmk4pm authors: Valentová, Kateřina title: Cytoprotective Activity of Natural and Synthetic Antioxidants date: 2020-08-06 journal: Antioxidants (Basel) DOI: 10.3390/antiox9080713 sha: doc_id: 296769 cord_uid: xnjmk4pm Numerous chronic diseases including cancer, cardiovascular, chronic respiratory or neurodegenerative diseases, diabetes mellitus, retinal damage, and others are associated with oxidative stress [...]. mimetic, chelating agent, and intravenous magnetic resonance imaging agent mangafodipir showed preventive and protective effects against oxaliplatin-induced neurotoxicity in BALB/c mice [14] . A growing number of studies deal with the mechanism of action of cytoprotection. The cytoprotective mechanism of natural anthocyanin delphinidin against oxidative stress induced by H 2 O 2 was investigated in human chondrocytes where it inhibited reactive oxygen species (ROS)-induced apoptosis via activation of Nrf2 and nuclear factor κB (NF-κB) and activated cytoprotective autophagy showing potential in the treatment of osteoarthritis [15] . Embelin, a plant natural product from Lysimachia punctata and Embelia ribes fruit with quinone and hydroquinone functional groups plus a long hydrophobic tail completely abolished the superoxide radical generated in situ with hydrodynamic voltammetry. Moreover, it exhibited cytoprotective activity in THP-1 human leukemic monocytes and BV-2 mice microglia probably thanks to its long alkyl tail enabling its insertion in cell membranes [16] . The mechanism of anti-inflammatory and antioxidant effects of aspirin on hyperoxia-induced acute lung injury was studied in NF-κB-luciferase transgenic mice. Pretreatment with aspirin significantly reduced the protein levels of phosphorylated protein kinase B, NF-κB, and tumor necrosis factor α, indicating that aspirin reduces NF-κB activation [17] . A few publications were devoted to the effect of natural compounds in the form of complex but well-characterized extracts. Thus, the essential oil from feijoa (Acca sellowiana) fruit peal containing mostly sesquiterpenes showed strong antioxidant and free radical scavenging activity, cytoprotective activity on lymphocytes pre-treated with 100 µM tert-butylhydroperoxide (t-BOOH), as well as a decrease in intracellular ROS, induced by t-BOOH on erythrocytes and antimicrobial and antifungal activities against Staphylococcus aureus and Candida albicans, respectively [18] . Vitis vinifera var. Fetească neagră tendrils and leaves extracts, intended to be used in oral hygiene products recommended in periodontal disease, displayed a cytoprotective effect against nicotine-induced cytotoxicity and anti-inflammatory activity in human gingival fibroblasts [19] . Viburnum opulus berry phenolic extracts were able to decrease the uptake of glucose, free fatty acids, and accumulation of lipid droplets in Caco-2 cells without affecting their viability, followed by a decrease in the CD36/FAT gene expression, without influence on the GLUT2 and PPARα levels. Furthermore, the extracts revealed strong chemo-preventive activity against oxidative stress induced chemically by t-BOOH, as well as against DNA damage through the induction of DNA repair after cell exposition to methylnitronitrosoguanidine and H 2 O 2 [20] . In a subsequent study, V. opulus fruit fresh juice and a phenolic-rich fraction were able to decrease intracellular oxidative stress in mice insulinoma MIN6 cells, induced glucagon-like peptide-1 secretion in the presence of an elevated glucose concentration, and inhibited in vitro activity of the dipeptidyl peptidase-4 [21] . Several publications in this Special Issue study flavonolignans from silymarin, an extract from the fruits of Silybum marianum. Twenty-six commercially available silymarin preparations, natural silymarin from Sigma Aldrich, and a model mixture of pure flavonoid/flavonolignans mimicking the silymarin composition, all analyzed by U-HPLC-HRMS/MS, were compared using biochemical (2,2 -azino-bis-(3-ethylbenzothiazoline-6 sulfonic acid) (ABTS), oxygen radical absorption capacity (ORAC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH)) and cellular (CAA) antioxidant tests and significant differences in the antioxidant capacity of the supplements were observed [22] . Antioxidant activities of pure stereomers A and B of silybin and 2,3-dehydrosilybin, their racemic mixtures, pure silychristin A, and its derivatives (anhydrosilychristin, isosilychristin, and 2,3-dehydrosilychristin A) were investigated by using ORAC and CAA assays. Moreover, their anti-inflammatory activity was studied in macrophages and multidrug resistance modulation as inhibition of P-glycoprotein and sensitization of doxorubicin-resistant ovarian carcinoma cells overproducing P-glycoprotein was detected and the effect on related gene expression revealed a distinct mechanism of action for the individual compounds [23, 24] . Last but not least, new potential targets of silymarin constituents silybin and dehydrosilybin as dual inhibitors of BRAF and the Hedgehog pathway receptor Smoothened (SMO), two major targets in anticancer therapy, were identified in silico and confirmed in vitro [25] . The content of the Special Issue clearly shows that cytoprotection by anti-and prooxidant active molecules is still a hot topic. However, for effects demonstrated in cell cultures other than those derived from the gastrointestinal tract, the bioavailability and metabolism of the active compounds often could not be taken into consideration. Therefore, future studies should be directed towards the effects of the metabolites likely to be present in blood plasma. Antioxidant and oxidative stress: A mutual interplay in age-related diseases The Nrf2 system as a potential target for the development of indirect antioxidants The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state Direct and indirect antioxidant properties of inducers of cytoprotective proteins European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS) Oxidative stress, aging, and diseases Antioxidants: Friend or foe? Asian Pac Oxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target? Nutrients A bibliometric review of the Keap1/Nrf2 pathway and its related antioxidant compounds Potential cytoprotective activity of ozone therapy in SARS-CoV-2/COVID-19 AOP1, a new live cell assay for the direct and quantitative measure of intracellular antioxidant effects The side effects of platinum-based chemotherapy drugs: A review for chemists Quantification of berberine in Berberis vulgaris L. root extract and its curative and prophylactic role in cisplatin-induced in vivo toxicity and in vitro cytotoxicity Calmangafodipir reduces sensory alterations and prevents intraepidermal nerve fibers loss in a mouse model of oxaliplatin induced peripheral neurotoxicity Cytoprotective effects of delphinidin for human chondrocytes against oxidative stress through activation of autophagy Antioxidant properties of embelin in cell culture. Electrochemistry and theoretical mechanism of scavenging. Potential scavenging of superoxide radical through the cell membrane Anti-inflammatory and reactive oxygen species suppression through aspirin pretreatment to treat hyperoxia-induced acute lung injury in NF-κB-luciferase inducible transgenic mice Feijoa fruit peel: Micro-morphological features, evaluation of phytochemical profile, and biological properties of its essential oil Phytochemical profile and biological activities of tendrils and leaves extracts from a variety of Vitis vinifera L Viburnum opulus fruit phenolic compounds as cytoprotective agents able to decrease free fatty acids and glucose uptake by Caco-2 Cells Evaluation of Viburnum opulus L. fruit phenolics cytoprotective potential on insulinoma min6 cells relevant for diabetes mellitus and obesity Complex evaluation of antioxidant capacity of milk thistle dietary supplements Multidrug resistance modulation activity of silybin derivatives and their anti-inflammatory potential Antioxidant, anti-inflammatory, and multidrug resistance modulation activity of silychristin derivatives Dual SMO/BRAF inhibition by flavonolignans from Silybum marianum. Antioxidants 2020