DNA Protective Properties Research Articles

Chemical characterization, computational analysis and biological views on Daphne gnidioides Jaub. & Spach extracts: Can a new raw material be provided for biopharmaceutical applications?

The scientific world tends to turn to natural products such as medicinal and aromatic plants because of the inadequacy of commercially available synthetic drugs as antibiotics or anticancer, and their adverse effects on healthy tissues. One of these plants is Daphne gnidioides Jaub. & Spach, which belongs to the Thymelaeaceae family, and there is no data in the literature on its biological activity. This study is aimed to elucidate the chemical profiles and in vitro anticancer, antibacterial and DNA protection and enzyme inhibitory properties of methanol extracts of root, stem, and leaf of D. gnidioides Jaub. & Spach. Polyphenolic components of the extracts were characterized by HPLC-MS/MS. The highest phenolic content was detected in the leaf extract (TIPC = 43.5 ± 0.5 mg/g DE), followed by stem (TIPC = 27.3 ± 0.7 mg/g DE) and root (TIPC = 18.3 ± 0.2 mg/g DE) extracts. Vicenin-2 and 3-O-p-coumaroyl-5-O-caffeoylquinic acid were the main identified compounds in leaf and both root and stem extracts, respectively. The extracts did not show any protective effect on DNA against experimental Fenton’s reagent. The minimum inhibitory concentration and the minimum bactericidal concentration values for the root and leaf extracts against tested bacterial strains ranged from 31.25 to 500 μg/mL. After 48 h interaction of the cancer cell lines with the extracts, only the stem extract had significant cytotoxicity on HeLa cells (IC50 = 86.16 μg/mL). No remarkable activity of the extracts, which was tested against MDA-MB-231, was detected (IC50 > 1000 μg/mL). These data showed that D. gnidioides Jaub. & Spach stem extract inhibited the survival of HeLa cells in a time-dependent manner. After the treatment of IC50 concentration of stem extract with HeLa cells, an increase in LC3-II autophagic gene expression was detected. Also, the extracts exhibited significant tyrosinase inhibitory effects which were confirmed by molecular docking. To sum up, the tested extracts could be used as a starting point for the development of new multifunctional drugs.

Eulophia Nuda: A Review of Its Traditional Uses, Phytochemistry and Pharmacology

Eulophia nuda Lindl. (Orchidaceae) is a small perennial terrestrial herb found in central and Southeast Asian regions usually known for its ethnomedicinal uses by folklore and local healers in India and different regions of the world. E. nuda tubers have been used for the treatment of tumors, scrofulous glands of neck, rheumatoid arthritis, bronchitis, blood diseases, vermifuge, etc. Phytochemical properties of this plant are not much explored. Very few compounds such as phenanthrene derivatives and benzylated phenanthrene derivatives have been isolated from this plant. Pharmacologically, this plant is active in respect of cytotoxic, antioxidant, antiglycation and DNAprotection properties. The traditional knowledge and various phytochemical and pharmacological activities of this plant have been at the focus of research. The aim of present review is to systematically appraise about the literature available till date on this plant about its traditional uses, phytochemistry and pharmacology of its crude extract and isolated compounds.

A Study on Redox Potential of Phytochemicals and their Impact on DNA

The phytochemicals are endowed with antioxidant activities because of the presence of plentiful polyphenols and many other phytochemicals. However, some recent reports have suggested that phytochemicals from certain plant species exhibit DNA damaging properties mainly due to presence of alkaloids. In the present study, pBR322, Salmonella typhi DNA, insect DNA and human DNA were treated with hexanolic extract of Argemone mexicana and Thevesia peruviana leaves to assess their DNA damaging abilities. Another set of experiments was carried out using the methanolic extracts of Citrus lemon leaves to assess their DNA protecting abilities from damage of DNA by extracts of A. mexicana and T. peruviana at 150000 ppm for all DNAs used. The results indicated that the leaves extract of A. mexicanaand T. peruviana demonstrated significant DNA damaging potential at higher concentrations. In contrast, the extracts from C. limonat 15000 ppm showed maximum DNA protective properties for all DNAs used.

Antioxidant, antimicrobial and DNA protection activities of phenolic content of Tricholoma virgatum (Fr.) P.Kumm.

Tricholoma is one of the famous genera of Basidiomycota division. Although some species of this genus have been used as culinary mushrooms, very negligible investigations have been conducted on Tricholoma genus phenolic contents and their biological activities. In the present study, the antioxidant, antimicrobial, and DNA protection properties of total phenolic contents of Tricholoma virgatum (Fr.) P. Kumm. (54% methanolic extract) were assessed. T. virgatum phenolic content was determined by an analytic high-performance liquid chromatography (HPLC) method based on compression with standard phenolic compounds including gallic acid, catechin, chlorogenic acid, epicatechin, and coumaric acid. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were determined using Rel Assay kits. For DNA protective potential assay, pBR322 supercoiled DNA method was used. The antimicrobial activity assay was done based on the agar dilution method on six different microorganisms include Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida tropicalis. The total phenolic contents of this mushroom lied within range of 2.02-56.85 ppm based on coumaric acid and chlorogenic acid as standards. TAS, TOS, and OSI values were determined as 3.754±0.088 mmol/L, 8.362 ±0.085 μmol/L, and 0.223 ±0.007, respectively. T. virgatum methanol extract could exhibit a protective effect on DNA against the hydroxyl radical at 100 μg/mL concentration. Although T. virgatum is not recommended as an edible mushroom, according to our results, this mushroom could be considered as valuable source for phenolic compounds with significant antioxidant/antimicrobial effects.

Inhibitory Effects of Ceramide From the Seeds of Brassica napus L. on the Atopic Function via the Regulation of Human Kallikrein 5 and 7 Protease

The stratum corneum tryptic enzyme kallikrein 5 (KLK5) is a serine protease that is involved in the cell renewal and maintenance of the skin barrier functions. The excessive activation of KLK5 causes an exacerbation of dermatoses, such as rosacea and atopic dermatitis. Brassica napus play a well-known role in the treatment of canola oil through their anti-oxidative and DNA protective properties. We aimed to investigate whether the bioactive ceramide modulate the KLK5 protease. The ceramides were evaluated using an enzymatic assay to measure the anti-KLK5 activity. Our study revealed that the ceramides modulate the KLK5 and 7 protease activity. Ceramides may affect the skin barrier and atopic function via the regulation of proteases.

Investigation of chemical profile, biological properties of Lotus corniculatus L. extracts and their apoptotic-autophagic effects on breast cancer cells

This study aimed to reveal chemical profiles and biological activities of ethyl acetate (EA), methanol (MeOH), and water extracts of Lotus corniculatus. Ethnobotanical reports have indicated the importance of phytochemical properties of the genus Lotus. In this study, the effects of medicinal plant extracts on antioxidant (DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal chelating assays), enzyme inhibitory (on cholinesterase, tyrosinase, a-amylase and a-glucosidase), DNA protection and anticancer properties (including anti-proliferative, cell death and telomerase activity marker gene analysis, apoptotic DNA fragmentation analysis, cell migration test) were evaluated.According to chemical analysis, quercetin derivatives geraldol, isorhamnetin and kaempferol-O-coumaroylhexoside-O-deoxyhexoside isomers were dominant in the extracts. MeOH extracts showed the highest total flavonoids capacity with 21.13 mg RE/g. EA extract showed the strongest anti-amylase activity among the tested extracts. Water extract had the most protective activity against plasmid DNA. To indicate cell survival, MTT test was performed against human MCF-7 and MDA-MB-231 breast cancer cells. Half-maximal inhibitory concentration for cells were calculated and used for detection of mechanisms behind the cancer cell death. EA extract showed up-regulation of Bax proapoptotic gene and apoptotic DNA fragmentation activity on highly invasive MDA-MB-231 cells. Beclin-1 and LC3-II autophagy genes were higly expressed after treatment of MCF-7 cells with EA extracts. EA and MeOH extracts inhibited cell migration ability of both cancer cells. Linoleamide, was dominant component in EA extract and caused apoptosis on MDA-MB-231 breast cancer cells via increasing intranuclear Ca²+.The detailed mechanism behind the anticancer properties should be further investigated.

Protective Effects of C24 Ceramide From the Seeds of Brassica napus L. Against Ultraviolet B-Induced Photoaging in Normal Human Dermal Fibroblasts

Ultraviolet (UV) radiation induces skin photoaging, which is associated with the elevation of matrix metalloproteinase-1 (MMP-1) and the decrease of collagen. Brassica napus plays a well-known role in the treatment of canola oil through their anti-oxidative and DNA protective properties. However, their skin protective activity toward UVB-induced damage remains unclear. In the present study, we investigated the protective effect of C24 ceramide from B. napus on UVB-irradiated normal human dermal fibroblasts. Our results show that C24 ceramide enhanced NHDFs cell migration. The UVB-induced increase in MMP-1 and decrease in type I procollagen were ameliorated by C24 ceramide treatment. Taken together, our data strongly suggest that C24 ceramide from B. napus could reduce UVB-induced photoaging.

Investigation of the Antioxidant, α-Glucosidase Inhibitory, Anti-inflammatory, and DNA Protective Properties of Vaccinium arctostaphylos L.

The scope of this study was to investigate the total phenolic, anthocyanin, and flavonoid contents and the biological properties of ethanol extract (EE), methanol extract (ME), and aqueous extract (AE) from Vaccinium arctostaphylos L. EE, ME, and AE of V. arctostaphylos were prepared. Various biological activities such as total phenolic, anthocyanin, and flavonoid contents, and antioxidant (2,2'-diphenyl-1-picrylhydrazyl ferrous ion-chelating, and ferric reducing antioxidant power assays), α-glucosidase inhibitory, anti-inflammatory, and DNA protective properties of these extracts were studied. EE exhibited the highest total phenolic, anthocyanin, and flavonoid contents with 44.42±1.22 mg gallic acid equivalents/g dry weight, 8.46±0.49 mg/Cyaniding-3-glucoside equivalents/g dry weight, and 9.22±0.92 mg quercetin equivalents/g dry weight, respectively. The antioxidant activities of the extracts followed the order: EE>ME>AE. EE and ME inhibited α-glucosidase enzyme and their IC50 values were 0.301±0.002 mg/mL and 0.477±0.003 mg/mL, respectively. In addition, EE and ME were determined as noncompetitive inhibitors with inhibitory constant (Ki ) values of 0.48±0.02 mg/mL and 0.46±0.01 mg/mL, respectively. EE in 100 and 300 mg/kg doses caused a significant reduction in formalin-induced edema in mice, demonstrating the anti-inflammatory effect of EE. In DNA protective studies, all of the extracts protected supercoiled plasmid pBR322 DNA against damage caused by Fenton's reagents due to their radical scavenging activities. Our results demonstrated that EE of V. arctostaphylos L. had strong antioxidant, anti-inflammatory, α-glucosidase inhibitory, and DNA protective effects, suggesting that it might be an effective medical plant to prevent or treat diseases associated with oxidative damage and inflammation.

Investigation of antioxidant, α-glucosidase inhibitory, anti-inflammatory and DNA protective properties of Vaccinium arctostaphylos L.

Investigation of antioxidant, α-glucosidase inhibitory, anti-inflammatory and DNA protective properties of Vaccinium arctostaphylos L.

Some nutraceutical properties of fenugreek seeds and shoots ( Trigonella foenum-graecum L .) from the high Himalayan region

Abstract The antioxidant activity of fenugreek seeds and shoots of the fenugreek plant were compared in three different solvents (methanol, diethyl ether and water) using a cold extraction and soxhlet extraction. Various antioxidant assays i.e., DPPH• scavenging activity, FRAP, reducing power and lipid peroxidation were done. Samples were further studied for total phenolics, flavonoids and proanthocyanidins. Soxhlet extraction was more effective than cold extraction and hence soxhlet extracts of both shoots and seeds were further analyzed for DNA damage and antibacterial properties. Diethyl ether extracts of both seeds and shoots showed high DNA protective properties. Methanolic extracts of the shoots showed the highest antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa with maximum zones of inhibition of 15 and 14 mm, respectively, at 500 mg/ml. In all of the assays the fenugreek shoot extracts showed higher antioxidant, antimicrobial and DNA protective properties than fenugreek seeds, suggesting that the fenugreek shoots are the better source of antioxidant compounds than fenugreek seeds.

Novel vanillin derivatives: Synthesis, anti-oxidant, DNA and cellular protection properties

Antioxidants have been the subject of intense research interest mainly due to their beneficial properties associated with human health and wellbeing. Phenolic molecules, such as naturally occurring Resveratrol and Vanillin, are well known for their anti-oxidant properties, providing a starting point for the development of new antioxidants. Here we report, for the first time, the synthesis of a number of new vanillin through the reductive amination reaction between vanillin and a selection of amines. All the compounds synthesised, exhibited strong antioxidant properties in DPPH, FRAP and ORAC assays, with compounds 1b and 2c being the most active. The latter also demonstrated the ability to protect plasmid DNA from oxidative damage in the presence of the radical initiator AAPH. At cellular level, neuroblastoma SH-SY5Y cells were protected from oxidative damage (H2O2, 400 μM) with both 1b and 2c. The presence of a tertiary amino group, along with the number of vanillin moieties in the molecule contribute for the antioxidant activity. Furthermore, the delocalization of the electron pair of the nitrogen and the presence of an electron donating substituent to enhance the antioxidant properties of this new class of compounds. In our opinion, vanillin derivatives 1b and 2c described in this work can provide a viable platform for the development of antioxidant based therapeutics.

IMPACT OF ACTIVE COMPOUNDS ISOLATED FROM BANANA (MUSA SP. VAR. NANJANGUD RASABALE) FLOWER AND PSEUDOSTEM TOWARDS CYTOPROTECTIVE AND DNA PROTECTION ACTIVITIES

Objective: The present study was designed to evaluate for cytoprotective and DNA protective properties of the compounds isolated from ethanol extract of banana flower (EF) and ethanol extract of banana pseudostem (EE).Methods: The four active compounds viz., umbelliferone (C1) andlupeol (C2) from EF and stigmasterol (C3) and β-sitosterol (C4) from EE were isolated by activity-guided repeated fractionation through silica gel column chromatography. The isolated compounds were evaluated for cytoprotective on erythrocytes and pTZ57R/T plasmid DNA protection against hydroxyl radicals.Results: The study revealed that the compounds (C1-C4) at a concentration of 1 mg/ml exhibited 90% protection on erythrocytes membrane oxidation and also protect the pTZ57R/T plasmid DNA damage induced by hydroxyl radicals.Conclusion: These results endorse an insight for a strong chemical basis to the alleged beneficial role of EF and EE in reducing oxidative stress conditions.

O18 Revalorisation of rapeseed pomace (RSP): A study into antioxidant and DNA protective properties (in vitro) of a RSP extract and its effects on neurodegenerative disease C. elegans models

For a number of years there has been intense interest in phytochemicals due to their potential health benefits. One readily available and rich source of phytochemicals is Rapeseed pomace (RSP), a waste product obtained after edible oil production from Brassica napus . In this work, we analysed the ubiquitous secondary metabolites in RSP (harvest 2014, North East of Scotland) after soxhhlet ethanol/water (95:5) extraction. LC-MS/MS data of the extract revealed several secondary metabolites, with sinapic acid being the most abundant. The presence of a high level of phenolics in the extract was confirmed with the folin ciocalteu assay. Strong antioxidant activities of the extract was determined by using common antioxidant assays (FRAP, DPPH and ORAC). In addition, the extract (13.9 μg/mL) provided complete pBR322 plasmid DNA protection, from oxidative stress induced by AAPH (3.5 mM). Interestingly, in vitro analysis showed that the RSP extract exhibited acetylcholinesterase inhibition activity in a time and concentration dependant manner. Furthermore, cellular studies showed that incubation of neuroblastoma cells (SH Sy-5Y) with RSP extract protected cell metabolism from reactive oxygen species produced by H 2 O 2 (1 mM). We are currently undertaking in vivo studies using the model organism C. elegans . Preliminary results showed that RSP extract is non-toxic (up to 5 mg/mL) and has neuroprotective properties in C. elegans models of neurodegenerative diseases (work in progress). The positive properties associated with the RSP extract in this study warrants further investigation for the revalorisation of rapeseed pomace in the health/food industry.

Revalorisation of rapeseed pomace extracts: An in vitro study into its anti-oxidant and DNA protective properties

Rapeseed pomace (RSP) is a waste product obtained after edible oil production from Brassica napus. Analysis of ubiquitous secondary metabolites in RSP samples (two breeds, harvested in 2012/2014 respectively from North East of Scotland) and their ethanol/water (95:5) Soxhlet extracts were carried out. Soxhlet extraction of the RSP (petroleum ether followed by 95% ethanol) gave a solid extract. LC-MS/MS data of the extracts revealed several secondary metabolites, with Sinapic acid being the most abundant. Strong antioxidant activities of the Soxhlet extracts were confirmed from the results obtained in the FRAP, DPPH and ORAC assays. Furthermore, for the very first time, RSP extracts (13.9µg/ml) provided complete DNA protection, from oxidative stress induced by AAPH (3.5mM). Therefore the strong antioxidant and DNA protecting properties demonstrated by the RSP extracts in this study warrants further investigation for their revalorisation and potential use as reliable source of antioxidants in different food applications.

Unexpected effect of dry olive leaf extract on the level of DNA damage in lymphocytes of lead intoxicated workers, before and after CaNa2EDTA chelation therapy

The CaNa2EDTA chelation therapy is often practiced with antioxidant supplementation. Dry olive leaf extract (DOLE) is natural product with antioxidant and DNA protective properties. The effects of DOLE on the levels of DNA damage were investigated ex vivo in peripheral blood lymphocytes (PBLs) of 19 workers occupationally exposed to lead (Pb), before and after CaNa2EDTA chelation therapy.DOLE demonstrated pronounced radical scavenging activity in concentrations ≥1 mg/mL, and showed no genotoxicity per se, in concentrations 0.125–1 mg/mL. The level of DNA damage in PBLs of workers before chelation therapy was elevated (24.21 ± 14.26) compared to controls (6.0 ± 3.37). The incubation of PBLs before chelation therapy with selected concentration of DOLE lead to a severe increase of DNA damage (64.03 ± 20.96), exhibiting prooxidant rather than antioxidant effect. After the five-day CaNa2EDTA chelation regimen, DNA damage in PBLs of workers decreased (8.26 ± 4.62) significantly compared to baseline. Treatment of PBLs with DOLE after chelation, again produced high level of damage (41.82 ± 23.17) and the acute prooxidant effects of DOLE remained, but, DNA damage was less severe than before chelation. The DOLE exhibits prooxidant effect in presence of Pb in lymphocytes of exposed workers, and its effect is less pronounced following the removal of Pb after standard chelation therapy.

Antioxidant Machinery Related to Decreased MDA Generation by Thymus Algeriensis Essential Oil-induced Liver and Kidney Regeneration

ObjectiveThis study was conducted to determine the histopathological and biochemical effects of Thymus algeriensis essential oil (TEO) on hydrogen peroxide (H2O2)-induced oxidative stress in liver and kidney tissues of rats. MethodsRats were treated in six groups and were exposed for 2 weeks to low (LD; 100 µmol/L) and high doses (HD; 1 mmol/L) of H2O2 in the presence or absence of TEO (180 mg/kg). Liver and kidney atrophy was measured by using biochemical and histopathological assays. ResultsOur study demonstrated that H2O2 induced liver and kidney atrophy, as evidenced by the significant elevation of serum aminotransferase, urea, and creatinine levels compared with those in the control rats. Urea levels were estimated by evaluating the activity of serum urease that hydrolyzes urea into CO2 and ammonia. However, TEO treatment significantly alleviated oxidative stress in the H2O2-induced liver and kidney toxicity model by reducing the levels of malondialdehyde concomitantly with marked elevations in superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase, as well as decrease in glutathione activity. ConclusionOur data demonstrated that TEO protected against H2O2 toxicity by decreasing oxidant levels and DNA damage, as well as increasing antioxidant levels, indicating that TEO has a spectrum of antioxidant and DNA-protective properties.

Oxyresveratrol: Structural Modification and Evaluation of Biological Activities.

Oxyresveratrol (2,4,3′,5′-tetrahydroxystilbene, 1), a phytoalexin present in large amounts in the heartwood of Artocarpus lacucha Buch.-Ham., has been reported to possess a wide variety of biological activities. As part of our continuing studies on the structural modification of oxyresveratrol, a library of twenty-six compounds was prepared via O-alkylation, aromatic halogenation, and electrophilic aromatic substitution. The two aromatic rings of the stilbene system of 1 can be chemically modulated by exploiting different protecting groups. Such a strategy allows for selective and exclusive modifications on either ring A or ring B. All compounds were evaluated in vitro for a panel of biological activities, including free radical scavenging activity, DNA protective properties, antiherpetic activity, inhibition of α-glucosidase and neuraminidase, and cytotoxicity against some cancer cell lines. Several derivatives were comparably active or even more potent than the parent oxyresveratrol and/or the appropriate positive controls. The partially etherified analogs 5′-hydroxy-2,3′,4-trimethoxystilbene and 3′,5′-dihydroxy-2,4-dimethoxystilbene demonstrated promising anti-herpetic and DNA protective activities, offering new leads for neuropreventive agent research, whereas 5′-hydroxy-2,3′,4,-triisopropoxystilbene displayed anti-α-glucosidase effects, providing a new lead molecule for anti-diabetic drug development. 3′,5′-Diacetoxy-2,4-diisopropoxystilbene showed potent and selective cytotoxicity against HeLa cancer cells, but the compound still needs further in vivo investigation to verify its anticancer potential.

Impact of xanthohumol (a prenylated flavonoid from hops) on DNA stability and other health-related biochemical parameters: Results of human intervention trials.

Xanthohumol (XN) is a hop flavonoid found in beers and refreshment drinks. Results of in vitro and animal studies indicate that it causes beneficial health effects due to DNA protective, anti-inflammatory, antioxidant, and phytoestrogenic properties. Aim of the present study was to find out if XN causes alterations of health-related parameters in humans. The effects of the flavonoid were investigated in a randomized crossover intervention trial (n = 22) in which the participants consumed a XN drink (12 mg XN/P/day). We monitored alterations of the DNA stability in single cell gel electrophoresis assays in lymphocytes and of several health-related biomarkers. A decrease of oxidatively damaged purines and protection toward reactive oxygen species induced DNA damage was found after the consumption of the beverage; also the excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-guanosine in urine was reduced. The assumption that the flavonoid causes DNA protection was confirmed in a randomized follow-up study with pure XN (n = 10) with a parallel design. Other biochemical parameters reflecting the redox- and hormonal status and lipid- and glucose metabolism were not altered after the intervention. Taken together, our data indicate that low doses of XN protect humans against oxidative DNA damage.

New insight into multifunctional role of peroxiredoxin family protein: Determination of DNA protection properties of bacterioferritin comigratory protein under hyperthermal and oxidative stresses

Bacterioferritin comigratory protein (BCP) is a monomeric conformer acting as a putative thiol-dependent bacterial peroxidase, however molecular basis of DNA-protection via DNA-binding has not been clearly understood. In this study, we characterized the DNA binding properties of BCP using various lengths and differently shaped architectures of DNA. An electrophoretic mobility shift assay and electron microscopy analysis showed that recombinant TkBCP bound to DNA of a circular shape (double-stranded DNA and single-stranded DNA) and a linear shape (16–1000 bp) as well as various architectures of DNA. In addition, DNA protection experiments indicated that TkBCP can protect DNA against hyperthermal and oxidative stress by removing highly reactive oxygen species (ROS) or by protecting DNA from thermal degradation. Based on these results, we suggest that TkBCP is a multi-functional DNA-binding protein which has DNA chaperon and antioxidant functions.

DNA protection, antioxidant, antibacterial and enzyme inhibition activities of heartwood and sapwood extracts from juniper and olive woods

In this study, DNA protective, antioxidant, antibacterial and enzyme inhibiting properties of methanol extracts obtained from juniper and olive heartwood and sapwood were determined.