Context Since methods utilised in the treatment of glioblastoma multiforme (GBM) are inadequate and have too many side effects, usage of herbal products in the treatment process comes into prominence. Lichens are symbiotic organisms used for medicinal purposes for many years. There are various anticancer treatments about components of two lichen species used in the present study. Objective Antitumor potential of three lichen secondary metabolites including olivetoric acid (OLA) and physodic acid (PHA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) and psoromic acid (PSA) isolated from Rhizoplaca melanophthalma (DC.) Leuckert (Lecanoraceae) were investigated on human U87MG-GBM cell lines and primary rat cerebral cortex (PRCC) cells for the first time. Materials and methods PRCC cells used as healthy brain cells were obtained from SpragueDawley rats. The treatments were carried out on the cells cultured for 48 h. Cytotoxic effects of different concentrations (2.5, 5, 10, 20 and 40 mg/L) of metabolites on the cells were determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. Total antioxidant capacity (TAC) and total oxidant status (TOS) parameters were used for assessing oxidative alterations. Oxidative DNA damage potentials of metabolites were investigated via evaluating 8-hydroxy-2 0 -deoxyguanosine (8-OH-dG) levels. Results Median inhibitory concentration (IC 50 ) values of OLA, PHA and PSA were 125.71, 698.19 and 79.40 mg/L for PRCC cells and 17.55, 410.72 and 56.22 mg/L for U87MG cells, respectively. It was revealed that cytotoxic effects of these metabolites showed positive correlation with concentration, LDH activity and oxidative DNA damage. Discussion and conclusion The present findings obtained in this study revealed that primarily OLA and then PSA had high potential for use in the treatment of GBM. ARTICLE HISTORY

Background:Mushrooms have been valued for their nutritive content and as traditional medicines; several important medicinal properties of mushrooms have been recognized worldwide.Objective:The purpose of this study was to elucidate the cell growth inhibitory potential of four edible mushrooms; Coprinus comatus (O.F. Mull.) Pers. (Agaricaceae), Tricholoma fracticum (Britzelm.) Kreisel (Tricholomataceae), Rhizopogon luteolus Fr. and Nordholm (Rhizopogonaceae), Lentinus tigrinus (Bull.) Fr. (Polyporaceae) on hepatocellular carcinoma (HepG2) cells in conjunction with their antioxidant and antibacterial capacities.Materials and Methods:Five different extracts of edible mushrooms were obtained using water, methanol, acetone, n-hexane and chloroform as solvent systems for cytotoxic, antioxidant and antibacterial properties.Results:C. comatus showed substantial in vitro cytotoxic activity against HepG2 cell lines with all extracts especially with chloroform 50% inhibition (IC50 value of 0.086 mg/ml) and acetone (IC50 value of 0.420 mg/ml). Chloroform extract of C. comatus had maximum amount of β-carotene (25.94 μg/mg), total phenolic content (76.32 μg/mg) and lycopene (12.00 μg/mg), and n-hexane extract of L. tigrinus had maximum amount of flavonoid (3.67 μg/mg). While chloroform extract of C. comatus showed the highest 2, 2-diphenyl-1-picrylhydrazyl (DPPH) capturing activity (1.579 mg/ml), the best result for metal chelating activity was obtained from methanolic extract (0.842 mg/ml). Moreover, all tested mushrooms demonstrated antibacterial activity and n-hexane extract of L. tigrinus and acetone extracts of T. fracticum were the most active against tested microorganism.Conclusion:These results indicate that different extracts of investigated mushroom have considerable cytotoxic, antioxidant and antibacterial properties and may be utilized as a promising source of therapeutics.

Overall, obtained data indicated that LA was highly toxic on GBM and PRCC cells. However, DA and then UA had high anti-oxidant capacity on PRCC cells. These results suggest that further studies that will be held on LA may play a critical role in GBM treatment.

Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure and neurotoxic and hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds are used in a broad mix of industries, from cosmetics and pharmaceuticals to agriculture. They affect critical biological functions in cellular events and enzymatic reactions, as well as endocrinal and mineral metabolisms. There are limited dose-related data about boric acid (BA) and other boron compounds, including colemanite (Col), ulexite (UX) and borax (BX), which have commercial prominence. In this study, we evaluate boron compounds’ genetic, cytological, biochemical and pathological effects against aluminum chloride (AlCl3)-induced hematotoxicity and neurotoxicity on different cell and animal model systems. First, we perform genotoxicity studies on in vivo rat bone marrow cells and peripheric human blood cultures. To analyze DNA and chromosome damage, we use single cell gel electrophoresis (SCGE or comet assay) and micronucleus (MN) and chromosome aberration (CA) assays. The nuclear division index (NDI) is used to monitor cytostasis. Second, we examine the biochemical parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidative status (TOS)) to determine oxidative changes in blood and brain. Next, we assess the histopathological alterations by using light and electron microscopes. Our results show that Al increases oxidative stress and genetic damage in blood and brain in vivo and in vitro studies. Al also led to severe histopathological and ultrastructural alterations in the brain. However, the boron compounds alone did not cause adverse changes based on the above-studied parameters. Moreover, these compounds exhibit different levels of beneficial effects by removing the harmful impact of Al. The antioxidant, antigenotoxic and cytoprotective effects of boron compounds against Al-induced damage indicate that boron may have a high potential for use in medical purposes in humans. In conclusion, our analysis suggests that boron compounds (especially BA, BX and UX) can be administered to subjects to prevent neurodegenerative and hematological disorders at determined doses.

Herbal medicines are efficient to reduce side effects in the fight against glioblastoma, which plays a critical role within brain cancer species. The recent studies designated for testing the effects of lichens that have shown numerous anticancer activities on glioblastoma so far. In the present study, different concentrations of water extract obtained from Usnea longissima Ach. were used in order to determine cytotoxic (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase tests), antioxidant (via total antioxidant capacity test), pro-oxidant (via total oxidant status test) and genotoxic (via 8-hydroxy-2′-deoxyguanosine test) effects of them on human U87MG-glioblastoma cancer cell lines. Primary mixed glial-neuronal non-cancerous cells from Sprague-Dawley rats were also utilized to measure the effects of treatments on non-cancerous cells. Based on median inhibitory concentration values, the data belonged to non-cancerous cells (2486.71 mg/l) showed distinct towering compared to U87MG (80.93 mg/L) cells. The viability of non-cancerous and U87MG cells exposed to extract is decreased in a dose dependent manner. It was also showed that low concentrations of extract notably increased total antioxidant capacity on non-cancerous cells. In addition, various phenolic compounds in extract were detected through high-performance liquid chromatography. The recent results encourage that extract will be able to have therapeutic potential against glioblastoma.

It is known that lichens are utilized for the treatment of many diseases including ulcer, diabetes, and cancer for many years. Secondary metabolites in the structure of the lichens provide various activity properties for them. In the present study, cytotoxic and oxidative effects of main constituents of Pseudevernia furfuracea (L.) Zopf (Parmeliaceae), olivetoric acid (OA), and physodic acid (PA) were investigated on cultured human amnion fibroblasts (HAFs). OA and PA were isolated from P. furfuracea using column chromatography and their structures were determined by proton nuclear magnetic resonance and carbon-13 nuclear magnetic resonance. HAFs were incubated during 48 h in the presence of OA and PA, at different concentrations from 6.25 mg/L to 200 mg/L. OA showed higher cytotoxicity than PA. In fact, median inhibitory concentration values of OA and PA were 571.27 and 3373.69 mg/L, respectively. The lower concentrations (<50 mg/L) of OA and PA did not cause oxidative stress and genotoxicity; furthermore, they supported anti-oxidative capacity of HAFs. Therefore, all these data suggested that both tested metabolites, especially PA might be developed as natural health medicine to protect human body against oxidative stress and genotoxicity. As far as we know, this is the first report on the cytotoxic and anti-oxidative activities of OA and PA on HAFs.

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The present study aims at assessing the efficacies of olivetoric acid (OA) and physodic acid (PA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) in human lymphocytes (HLs) in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to establish cytotoxicity in HLs. Besides, oxidative stress and genotoxicity were monitored by estimating the changes of total oxidative stress (TOS) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, respectively, in HLs. At the same time, OA- and PA-induced total antioxidant capacity (TAC) levels in HLs were determined. Although especially low concentrations of OA (IC50=109.94 mg/L) and PA (IC50=665.49 mg/L) did not show cytotoxic effect at high levels in HLs, it was revealed that cytotoxicity was significantly (p<0.05) associated with oxidative stress and genotoxicity via correlation analysis. While TOS level in HLs did not statistically (p>0.05) increase in the presence of all treatments (0.5-100 mg/L) of PA, TAC level was increased by PA applications in certain concentrations (0.5-10 mg/L). Overall, the obtained data indicate that OA and especially PA as lichen compounds that do not cause oxidative stress can be a new resource of therapeutics as recognized in the present study with their high antioxidant features.