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Rice bran residues are known as low economic-value and contain high protein nutritional value. This notion has caught interest of scientists to study the proteins and their hydrolysates from this bioresource. However, reports on the biological activities of rice bran residue proteins and their hydrolysates are still limited. Hench, this study aimed to fractionate 4 rice bran protein fractions including albumin (ABM), globulin (GBL), prolamin (PLM), and glutelin (GTL) from Riceberry and to investigate the chemical properties and bio-protective potentials of these proteins and their hydrolysates. Riceberry GTL presented the highest yield. Phenolic compounds including anthocyanin were higher in Riceberry bran proteins. Notably, GTL hydrolysate from the Riceberry showed the strongest antioxidant activity and the best antimutagenicity. Four promising dipeptides identified in the GTL hydrolysate were pGlu-Val, pGlu-Asp, pGlu-Asn, and pGlu-Glu. This study suggested that GTL hydrolysate from Riceberry bran proteins could be further developed as functional foods for chemoprevention.

Phenolic phytometabolites are promising bioactive compounds for management of genomic instability related diseases. Formononetin (FMN) and arbutin (ARB) are found in several plant sources. Our goal was to investigate the safety and efficacy of FMN and ARB using in vitro both standardized and alternative toxicogenetic methods. FMN and ARB were evaluated through the OECD’S guidelines No. 471 (Bacterial Reverse Mutation Test –Salmonella/microsome) and No. 487 (In vitro Mammalian Micronucleus Test – CBMN assay), accordingly to the mentioned recommendations. Also, antimutagenicity of FMN and ARB was assessed in S. Typhimurium strains TA98, TA100 and TA1535, following pre-, co- and post- treatment protocols. Liver human lineages HepG2 and F C3H were assayed for cytotoxicity after exposure to FMN and ARB (24, 48 and 72 h) using in vitro WST-1 test. ARB showed no mutagenicity in the Salmonella/microsome test under both metabolic conditions (in presence or absence of 4 % S9 mix), but FMN was cytotoxic to the TA97 and TA100 strains after metabolic activation. Under this same condition, FMN induced an increase in the mutagenic index of strain TA1535 at two of the highest tested concentrations. Even so, ARB and FMN exhibited protection against the induced alkylation of DNA in multiple action modes. In the antimutagenicity assay, FMN reached the maximum of 80 % of oxidative-provoked mutagenicity reduction in TA98 strain in co-treatment with known mutagen, besides 69 % of reduction in TA100 in the same exposure condition. ARB showed up to reduce induced mutagenicity in strains TA100 and TA1535, reaching percentages from 55 % to 100 % of antimutagenicity in all of the tested exposure models against alkylating agent. In the CBMN assay, no increase in micronuclei formation was observed. The results suggest that FMN and ARB prevent DNA from mutation using multi-targeted antimutagenic roles. Finally, our data suggests that FMN and ARB are not genotoxic and presented encouraging antimutagenicity action in vitro, being promising compounds for use in genomic instability-related diseases therapeutics.

Numerous studies derived from medicinal herbs have been conducted to explore bioactive compounds as potential alternatives to synthetic drugs, aiming to mitigate harmful side effects and alleviate economic burdens. In this study, we assessed the safety and potential biological activities of extracts from Fomes fomentarius L. (FFL). The FFL extracts were obtained through various ethanol concentrations, as follows: 0%, 30%, 50%, 70%, and 100%, respectively. All extracts did not induce mutagenicity even up to 5 mg/plate concentration. In the assessment of antioxidant activity, only the hot water extract exhibited weaker antioxidant activity than the other ethanol extracts. Notably, all extracts exhibited significant antimutagenetic effects only with a metabolically active enzyme system (S9 mix). The condition of 70% ethanol extract displayed the most robust antimutagenic activity; thus, the extract was sequentially fractionated with solvents of varying polarities to isolate inhibitory components. After the fractionization, the diethyl ether and butanol fractions effectively suppressed the growth of mutated colonies, suggesting that those such as essential oils, vitamins, alkaloids, and flavonoids can be considered major active compounds. Overall, our study demonstrated that FFL extracts induce potent antioxidant and antimutagenic effects. Further investigations are warranted to verify specific active compounds which induce an antimutagenic effect. Our findings provide valuable insights into FFL as a promising source for potential functional food development. [ABSTRACT FROM AUTHOR]

Soursop (Annona muricata) is a tropical tree whose decoction derived from bark, root, seed, or leaf has been used for medicinal uses. In addition, the fruit itself is considered a food, and the juice is utilized to treat heart and liver diseases. The aim of this study was to determine the phenolic content. In addition, a water-soluble fraction of the soursop fruit pulp (WSSP) was examined for the following properties: antioxidant, mutagenic, and antimutagenicity. UV-visible spectrophotometry determined total phenolic content by the Folin-Ciocalteu method to be 11.22 ± 0.6 mg of gallic acid equivalent per gram dried extract, and free-radical scavenging activity by the 2,2′-diphenyl-1-picryl-hydrazyl (DPPH•) showed an EC50 of 1032 µg/ml. In the Salmonella/microsome assay, no marked mutagenicity was induced following WSSP treatment, and a chemopreventive capacity was observed in the antimutagenic assay. The cytotoxicity assays were carried out using the water-soluble tetrazolium salt and lactate dehydrogenase (LDH) assays demonstrated that WSSP induced significant cytotoxicity in MCF-7 and Caco-2 cells, indicating greater effectiveness of cytotoxic action by destroying cell membrane integrity. Data suggest that WSSP may exert beneficial effects as a DNA chemopreventive and antitumor agent. [ABSTRACT FROM AUTHOR]

The antimicrobial properties and importance of Ag+ have been known since ancient times. However, resistance has started to develop against silver ions, which are used indiscriminately and in high concentrations. Therefore, it is necessary to synthesize new and different silver complexes. In this study, five new molecules were synthesized by green synthesis from amino acids. Firstly, the antimicrobial activities of these molecules were tested with agar well diffusion assay. The result of this work is that it was revealed that the amino acid-silver complexes had very high inhibitory activity against microorganisms such as S. typhimirium, S. epidermidis, P. aeruginosa, K. pneumoniae, Y. pseudotuberculosis, P. vulgaris, E. faecalis, B. subtilis, E. cloaceae, S. aureus, E. coli, L. monocytogenes, C. albicans, and C. parapsilosis. It was found that these molecules have inhibition and bactericidal activity at low concentrations. The MIC, MBC, and MFC values were determined between 1.54–46.5 µg/mL, 24.7–93.1 µg/mL, and 19.0–197.0 µg/mL, respectively. Then, to determine whether these molecules are suitable as antimicrobial agents, cytotoxic and antimutagenic activity tests were performed. The results of the cytotoxicity test showed that these molecules have no cytotoxic effect on the L929 fibroblast cells except some at higher doses (e.g. 10–100 mg/mL). In addition, cell viability stimulation was recorded at some doses below 10 mg/mL. Furthermore, these molecules showed antimutagenic activity at different concentrations 1.17–5.80 µg/mL. The use of these synthesized molecules as antimicrobial agents in many fields such as food and pharmacology seems very promising. [ABSTRACT FROM AUTHOR]

Several bioactive compounds, such as polyphenols, demonstrate low toxicity and prominent effects on cancer cells with antioxidant, anti-inflammatory, and antitumor activities. Such compounds can be found in Amazon mosses Leucobryum martianum (Hornsch.) Hampe ex Müll. Hal. (Hornsch.) and Leucobryum laevifolium (Broth). Antimutagenic assay with Salmonella enterica serovar Typhimurium and cytotoxicity with different eukaryotic cell lines were carried out to screen aqueous, hydroalcoholic, and ethanolic extracts of those Amazon mosses for anticancer potential. The results indicate the capacity of all extracts of both mosses to exert chemopreventive effects against 4-nitroquinoline- N -oxide (4NQO) and 2-aminoanthracene (2-AA), which are direct or indirect mutagens. In particular, the ethanolic and aqueous extract from L. martianum. The ethanolic extract from L. martianum induces significant cytotoxicity by mitochondrial metabolism and cell membrane disruption pathways to tumor or non-tumor cells. The aqueous extract from L. martianum showed a mainly cytotoxic response in the HepG2 cells, a human liver carcinoma, reaching ~90% cytotoxicity. The same extract did not induce significant damage to normal liver cells (F C3H cells) by membrane interaction pathway. The selective cytotoxicity in the aqueous extract of L. martianum makes it a candidate against liver cancer. Further studies, including in vivo models, are necessary to validate the efficacy and safety of the aqueous extract of L. martianum. [ABSTRACT FROM AUTHOR]

• Extracts of 16 Plectranthus species were screened for antioxidant and antigenotoxicity against AFB 1 -induced mutagenicity. • Most extracts had antimutagenic effects against AFB 1 induced mutagenicity in the Ames or vitotox assay, or both. • These extracts may contribute to liver cancer prevention and management. Dichlomethane (DCM) and 90% methanol of sixteen Plectranthus species were investigated for antioxidant activity using the DPPH (2, 2-diphenyl-1-picrylhydrazyl), ABTS (2, 2-azinobis (3-ethylbenzothiazoline 6-sulfonate)) and FRAP (ferric reducing antioxidant power) assays. The Plectranthus species were also investigated for antimutagenicity using the Ames assay and antigenotoxicity using the vitotox assay. Dichloromethane extracts of Plectranthus barbatus, P. neochilus and P. argentatus , as well as 90 % methanolic extracts of Plectranthus caninus, P. fruticosus james and P. argentatus had the highest antioxidant activity in the DPPH assay. DCM extracts of P. amboinicus, P. montanus P. neochilus and P. madagascariensis had moderate to strong antimutagenicity in the Ames test at the highest concentration tested. In the vitotox assay, dichloromethane extracts of P. caninus, P. neochilus, P. ernstii, P. verticillatus, P. madagascariensis, P. montanus and the 90 % methanol extract of P. verticillatus were cytotoxic at the highest concentration tested. Of the 32 plant extracts investigated in this study, 68% showed better antioxidant activity than ascorbic acid (vitamin C), particularly in the DPPH and ABTS assays. Additionally, most plant extracts investigated in this study had antimutagenic properties against aflatoxin B 1 - induced mutagenicity in either the Ames or vitotox assay, or both, without a clear trend or correlation between antioxidant activity and antimutagenic properties. [ABSTRACT FROM AUTHOR]

Numerous studies derived from medicinal herbs have been conducted to explore bioactive compounds as potential alternatives to synthetic drugs, aiming to mitigate harmful side effects and alleviate economic burdens. In this study, we assessed the safety and potential biological activities of extracts from Fomes fomentarius L. (FFL). The FFL extracts were obtained through various ethanol concentrations, as follows: 0%, 30%, 50%, 70%, and 100%, respectively. All extracts did not induce mutagenicity even up to 5 mg/plate concentration. In the assessment of antioxidant activity, only the hot water extract exhibited weaker antioxidant activity than the other ethanol extracts. Notably, all extracts exhibited significant antimutagenetic effects only with a metabolically active enzyme system (S9 mix). The condition of 70% ethanol extract displayed the most robust antimutagenic activity; thus, the extract was sequentially fractionated with solvents of varying polarities to isolate inhibitory components. After the fractionization, the diethyl ether and butanol fractions effectively suppressed the growth of mutated colonies, suggesting that those such as essential oils, vitamins, alkaloids, and flavonoids can be considered major active compounds. Overall, our study demonstrated that FFL extracts induce potent antioxidant and antimutagenic effects. Further investigations are warranted to verify specific active compounds which induce an antimutagenic effect. Our findings provide valuable insights into FFL as a promising source for potential functional food development.

Perilla leaves are known to be a rich source of polyphenols, which have been shown to exhibit various biological effects. This study aimed to compare the bioefficacies and bioactivities of fresh (PLEf) and dry (PLEd) Thai perilla (Nga-mon) leaf extracts. Phytochemical analysis indicated that both PLEf and PLEd were abundant in rosmarinic acid and bioactive phenolic compounds. PLEd, which had higher levels of rosmarinic acid but lower levels of ferulic acid and luteolin than PLEf, exhibited greater effectiveness in a free radical scavenging assay. Furthermore, both extracts were found to suppress intracellular ROS generation and exhibit antimutagenic activity against food-borne carcinogens in S. typhimurium. They also attenuated lipopolysaccharide-induced inflammation in RAW 264.7 cells by inhibiting the expression of nitric oxide, iNOS, COX-2, TNF-α, IL-1β, and IL-6 through the suppression of NF-κB activation and translocation. However, PLEf exhibited a higher ability to suppress cellular ROS production and higher antimutagenic and anti-inflammatory activities than PLEd, which can be attributed to its combination of phytochemical components. Overall, PLEf and PLEd have the potential to serve as natural bioactive antioxidant, antimutagenic, and anti-inflammatory agents to achieve potential health benefits. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four major soluble protein fractions from rice bran protein were fractionated and hydrolyzed. • Riceberry bran alkaline hydrolysate showed the highest antioxidant potential. • Riceberry bran alkaline and alcohol hydrolysates display antimutagenicity. • Novel cancer-preventive peptides were first time identified in the alkaline hydrolysate. Rice bran residues are known as low economic-value and contain high protein nutritional value. This notion has caught interest of scientists to study the proteins and their hydrolysates from this bioresource. However, reports on the biological activities of rice bran residue proteins and their hydrolysates are still limited. Hench, this study aimed to fractionate 4 rice bran protein fractions including albumin (ABM), globulin (GBL), prolamin (PLM), and glutelin (GTL) from Riceberry and to investigate the chemical properties and bio-protective potentials of these proteins and their hydrolysates. Riceberry GTL presented the highest yield. Phenolic compounds including anthocyanin were higher in Riceberry bran proteins. Notably, GTL hydrolysate from the Riceberry showed the strongest antioxidant activity and the best antimutagenicity. Four promising dipeptides identified in the GTL hydrolysate were pGlu-Val, pGlu-Asp, pGlu-Asn, and pGlu-Glu. This study suggested that GTL hydrolysate from Riceberry bran proteins could be further developed as functional foods for chemoprevention. [ABSTRACT FROM AUTHOR]

Phenolic phytometabolites are promising bioactive compounds for management of genomic instability related diseases. Formononetin (FMN) and arbutin (ARB) are found in several plant sources. Our goal was to investigate the safety and efficacy of FMN and ARB using in vitro both standardized and alternative toxicogenetic methods. FMN and ARB were evaluated through the OECD'S guidelines No. 471 (Bacterial Reverse Mutation Test - Salmonella /microsome) and No. 487 ( In vitro Mammalian Micronucleus Test - CBMN assay), accordingly to the mentioned recommendations. Also, antimutagenicity of FMN and ARB was assessed in S . Typhimurium strains TA98, TA100 and TA1535, following pre-, co- and post- treatment protocols. Liver human lineages HepG2 and F C3H were assayed for cytotoxicity after exposure to FMN and ARB (24, 48 and 72 h) using in vitro WST-1 test. ARB showed no mutagenicity in the Salmonella /microsome test under both metabolic conditions (in presence or absence of 4 % S9 mix), but FMN was cytotoxic to the TA97 and TA100 strains after metabolic activation. Under this same condition, FMN induced an increase in the mutagenic index of strain TA1535 at two of the highest tested concentrations. Even so, ARB and FMN exhibited protection against the induced alkylation of DNA in multiple action modes. In the antimutagenicity assay, FMN reached the maximum of 80 % of oxidative-provoked mutagenicity reduction in TA98 strain in co-treatment with known mutagen, besides 69 % of reduction in TA100 in the same exposure condition. ARB showed up to reduce induced mutagenicity in strains TA100 and TA1535, reaching percentages from 55 % to 100 % of antimutagenicity in all of the tested exposure models against alkylating agent. In the CBMN assay, no increase in micronuclei formation was observed. The results suggest that FMN and ARB prevent DNA from mutation using multi-targeted antimutagenic roles. Finally, our data suggests that FMN and ARB are not genotoxic and presented encouraging antimutagenicity action in vitro , being promising compounds for use in genomic instability-related diseases therapeutics., Competing Interests: The authors report no competing interests., (© 2024 The Authors.)

Perilla leaves are known to be a rich source of polyphenols, which have been shown to exhibit various biological effects. This study aimed to compare the bioefficacies and bioactivities of fresh (PLEf) and dry (PLEd) Thai perilla (Nga-mon) leaf extracts. Phytochemical analysis indicated that both PLEf and PLEd were abundant in rosmarinic acid and bioactive phenolic compounds. PLEd, which had higher levels of rosmarinic acid but lower levels of ferulic acid and luteolin than PLEf, exhibited greater effectiveness in a free radical scavenging assay. Furthermore, both extracts were found to suppress intracellular ROS generation and exhibit antimutagenic activity against food-borne carcinogens in S. typhimurium. They also attenuated lipopolysaccharide-induced inflammation in RAW 264.7 cells by inhibiting the expression of nitric oxide, iNOS, COX-2, TNF-α, IL-1β, and IL-6 through the suppression of NF-κB activation and translocation. However, PLEf exhibited a higher ability to suppress cellular ROS production and higher antimutagenic and anti-inflammatory activities than PLEd, which can be attributed to its combination of phytochemical components. Overall, PLEf and PLEd have the potential to serve as natural bioactive antioxidant, antimutagenic, and anti-inflammatory agents to achieve potential health benefits.

Pistacia lentiscus L. is one of the most popular medicinal plants attributed to its beneficial properties on human health. However, few toxicogenetic studies have been carried out. Therefore, the aim of this study was to examine the potential genotoxic/antigenotoxic and mutagenic/antimutagenic properties of oil, ethyl acetate and ethanolic extracts of P. lentiscus L. fruits using in vitro the Ames and Umu assays, as well as in vivo micronucleus (MN) test. Extracts did not exert any significant mutagenic/genotoxic effects but provided protection against standard mutagenic and genotoxic agents including 2 nitrofluorene (2-NF) at 2.5 and 5 µg/ml; sodium azide at 5 and 10 µg/ml; 3-methylcholanthrene (3-MC) at 25 and 50 μg/ml; cyclophosphamide (CP) at 50 and 100 μg/ml; 4-nitroquinoline 1-oxide (4-NQO) at 0.05 µg/ml and 2-amino-anthracene (AA) at 0.2 µg/ml. Further, cytotoxicity and selectivity were examined on human hepatocarcinoma (HepG2), and MCF-7 breast cancer cell lines as well as a human normal-like fibroblast cell line (TelCOFS02MA) using MTT assay. Among all extracts, PF1 (ethanolic) showed the most significant selectivity index (SI) (HepG2:11.98; MCF7:4.83), which led to further investigations using an animal model. Oral administration of PF1 (125–1000 mg/kg b.w.) significantly decreased the number of micronucleated cells in CP -initiated (50 mg/kg b.w.) mice, while the number of micronucleated reticulocytes (MNRET), micronucleated polychromatic erythrocytes (MNPCE) or mitotic index (MI) were not markedly affected. Further, PF1 significantly enhanced catalase (CAT) and superoxide dismutase (SOD) activities in the livers and kidneys of these animals. The obtained results indicated the beneficial properties of P. lentiscus L. fruits for use in therapy against harmful effects of genotoxic and mutagenic agents. However, while promising it should be noted that the obtained results are preliminary and need to be confirmed prior to therapeutic use. [ABSTRACT FROM AUTHOR]

Purple rice has gained attention for its health promoting potential due to a high content of bioactive phytochemicals. The heat generated during cooking alters the quality and quantity of nutrients and phytochemicals in food. This study aimed to investigate the phytochemical profile and chemopreventive properties of cooked glutinous purple rice using cell-based assays and a rat model. Purple rice was cooked in a rice cooker and was then further extracted with solvents to obtain dichloromethane and methanol extracts. The methanol extracts of glutinous purple rice contained great amounts of phenolics, flavonoids, and anthocyanins. Protocatechuic acid (2.26–5.40 mg/g extract) and cyanidin 3-glucoside (34.3–65.7 mg/g extract) were the major phenolic acid and anthocyanin contents, respectively. After cooking, the content of anthocyanins, γ-oryzanols, and phytosterols decreased, while the amount of some phenolic acid and tocol contents increased. Methanol extracts of glutinous purple rice inhibited reactive oxygen species production about 60% in PMA-treated peripheral blood mononuclear cells, reduced nitric oxide formation in LPS-induced RAW 264.7 cells (26–39% inhibition), and exhibited antimutagenicity against several mutagens using the Ames test, but dichloromethane extracts presented only mild anti-inflammatory activities. Although methanol extracts induced mild mutagenicity (mutagenic index 2.0–2.5), they did not induce micronucleated hepatocyte formation and certain hepatic CYP450 isozyme activities in rats. However, the mutagenicity of the methanol extract significantly declined after cooking. In summary, the methanol extract of the cooked glutinous purple rice might be a promising cancer chemopreventive fraction, which was neither genotoxic nor posing adverse effects on phytochemical–drug interaction in rats. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the antimutagenicity and anthocyanin content of extracts from “purple corn strain KPSC903”, both whole kernel (WG) and corn grit (CG), during six-month storage in nylon bags (N) or aluminum foil bags (F) under vacuum at 25ºC. Ethanol extract of WG showed 87% and 81% inhibitions of the mutagens Trp-P-1 and 2- aminoanthracene, respectively, whereas that from CG showed 84% and 64% inhibitions, respectively. Diethylether and water extracts showed less inhibition. During storage, both WG and CG decreased in antimutagenicity, while anthocyanin increased from 48.81 to 66.04 mg/100 g in WG and from 26.54 to 33.01 mg/100 g in CG. Correlation coefficients between % inhibition of Trp-P-1 and anthocyanin were -0.898, -0.869, -0.956, and -0.667 for WG in N, WG in F, CG in N, and CG in F. F retarded the loss of antimutagenicity of CG better than N.

Natural dietary products of health promoting and disease preventive functional relevance are gaining significant prominence. Current investigation was aimed to decipher the underlying molecular mechanism responsible for the antimutagenic action contributing to functional relevance of floral honey (‘Pongammia pinnata’, Karanj honey) derived abscisic acid (ABA) against ethyl methanesulfonate (EMS) induced mutagenesis. Differential expression of proteins under different treatment conditions was ascertained by 2D gel electrophoresis. Selectively up-regulated characterized using MALDI-TOF MS/MS were identified as polyribonucleotide nucleotidyl transferse (PNPase), LPS-assembly lipoprotein (LptE), Outer membrane Usher protein (HtrE), ATP-dependent DNA helicase (RecG), and Phosphomethyl pyrimidine synthase (ThiC). Antimutagenicity exerted by ABA against EMS was ∼78% in wild type E. coli MG1655 strain however, in E. coli MG1655 ΔthiC, ΔpnpA, ΔrecG, and ΔhtrE this activity was found to be ∼60, 10, 9 and 10%, respectively. Proteomic analysis and antimutagenicity studies using E. coli single gene knockout strains thus indicated about the possible role of thiC, htrE, lptE, recG and pnp in observed antimutagenicity. Cyclic voltametry as well as competition kinetics through pulse radiolysis confirmed lack of antioxidant capacity in abscisic acid apparently ruling out the possibility of scavenging of electrophilic intermediates generated by ethyl methanesulfonate. It is proposed that ABA is exerting antimutagenicity through its involvement at the cellular level leading to physiological adaptation, strengthening of cell wall proteins and up-regulation of the repair proteins. This study provides a novel dimension to the functional role of abscisic acid from its nutraceutical perspective.

Amantadine (AMA) is a useful drug in neuronal disorders, but few studies have been performed to access its toxicological profile. Conversely, doxorubicin (Dox) is a well-known antineoplastic drug that has shown neurotoxic effects leading to cognitive impairment. The aims of this study are to evaluate the cytotoxic, genotoxic, and mutagenic effects of AMA, as well as its possible protective actions against deleterious effects of Dox. The Salmonella/microsome assay was performed to assess mutagenicity while cytotoxicity and genotoxicity were evaluated in SH-SY5Y cells using MTT and comet assays. Possible modulating effects of AMA on the cytotoxicity, genotoxicity, and mutagenicity induced by Dox were evaluated through cotreatment procedures. Amantadine did not induce mutations in the Salmonella/microsome assay and decreased Dox-induced mutagenicity in the TA98 strain. AMA reduced cell viability and induced DNA damage in SH-SY5Y cells. In cotreatment with Dox, AMA attenuated the cytotoxicity of Dox and showed an antigenotoxic effect. In conclusion, AMA does not induce gene mutations, although it has shown a genotoxic effect. Furthermore, AMA decreases frameshift mutations induced by Dox as well as the cytotoxic and genotoxic effects of Dox in SH-SY5Y cells, suggesting that AMA can interfere with Dox mutagenic activity and attenuate its neurotoxic effects. • Amantadine increases strand break DNA in SH-SY5Y cells. • Frameshift mutations induced by doxorubicin are inhibited for amantadine. • The combination amantadine plus doxorubicin increases the cell viability of SH-SY5Y cells. • Amantadine decreases the genotoxicity of doxorubicin in SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

In this study bioassay-guided screening of Tecomella undulate was performed for its cytotoxic, antimutagenic and anticancer potential. The ariel parts were extracted on a polarity basis (methanol, dichloromethane and hexane). The in vivo toxicity was assessed on Caenorhabditis elegans, and its locomotion was affected by Tecomella undulata hexane (TUAH) the most. Ames test for antimutagenicity showed Tecomella undulata methanol (TUAM) exhibited against mutagen 2AA showed inhibition of 71.03% and 26.32% 2AA in TA98 while in in vitro MTT assay on carcinoma cell lines TUAM showed 68.1% cytotoxicity. Moreover, In resazurin assay on fibroblast cells African green monkey kidney VERO and on the panel of carcinoma cell lines, the most effective extract was TUAM on liver HepG-2 with CC 50 value 117.37 ± 4.73 µg/ml followed by on lungs A549 with 142.01 ± 5.3. Furthermore, for the bioassay-guided screening, the selectivity index was calculated for TUAM CC 50 ratio on HepG-2 and VERO which showed a decent 2.77 score. After column chromatography, the fraction TU-63 should remarkable cytotoxic effect in dose–response manner assay as (Hep-G2) CC 50 value 11. 67 ± 1.37 µg/ml followed by (A549) CC 50 value 17.23 ± 0.58 µg/ml. For qualitative analysis of anticancer potential LC-ESI-MS/MS the potential phytochemicals were identified. In silico molecular modelling against selected carcinogenic proteins. The results suggest Tecomella undulate the substantial anticancer potential which supports potential natural anticancer therapeutic drug candidate development for combating cancer. [ABSTRACT FROM AUTHOR]

The use of Chamomilla recutita as a tranquilizing, anti-inflammatory, and analgesic tea is based on the empirical knowledge of medicinal plants. This work aims at assessing the mutagenic and antimutagenic potential –by means of the Allium cepatest –of an infusion of dry chamomile leaves. Eleven trials were conducted, with four replicates each, as such: T1 –negative control; T2 –paracetamol, 800mg L-1(positive control); T3 –chamomile in the usual dose, 12g L-1; T4 –60g L-1of chamomile; T5 –120g L-1of chamomile;T6 –paracetamol 800mg L-1and chamomile12g L-1; T7 –paracetamol 800mg L-1and chamomile 60g L-1; T8 –paracetamol 800mg L-1and chamomile120g L-1; T9 –paracetamol 800mg L-1and, 24 hours later, chamomile 12g L-1; T10 –paracetamol 800mg L-1and, 24 hours later, chamomile 60g L-1; T11 –paracetamol 800mg L-1and,24 hours later, chamomile 120g L-1.It was found that both the 12g L-1infusion and the stronger ones significantly reduced the mitotic index. In regard to mitotic anomalies, only T11 was significantly increased relative to T1 (p=0.012). All trials increased the frequency of interphase anomalies in a significant way (p

Abstract Background An extract from Spatholobus suberectus (S. suberectus) Dunn has been reported to show potent antimutagenic effects against N-alkyl-N-nitrosoureas in umu screening. The aim of this study was to identify the antimutagenic components from extracts of S. suberectus against N-methyl-N-nitrosourea (MNU) in the Ames assay with Salmonella typhimurium strain TA1535 and to elucidate the antimutagenic mechanism of the flavonoids. Results From the ethyl acetate fraction obtained from fractionation of the methanol extract of S. suberectus Dunn, medicarpin, formononetin and isoliquiritigenin were successfully isolated through a combination of normal- and reversed-phase chromatography. Genistein and naringenin, which were already reported to be contained in S. suberectus Dunn, were also tested for their antimutagenicity towards MNU, along with formononetin, isoliquiritigenin and medicarpin. Our results demonstrated that genistein, isoliquiritigenin, medicarpin and naringenin were antimutagenic against MNU without showing cytotoxicity. MNU is reported to cause not only DNA alkylation but also induce reactive oxygen species. The hydroxyl radical scavenging capacity of the flavonoids was correlated with the antimutagenic capacity, indicating that the hydroxyl radical scavenging activity was involved in their antimutagenicity towards MNU. Conclusions It is important to prevent DNA damage by N-nitrosamines for cancer chemoprevention. Genistein, isoliquiritigenin, medicarpin and naringenin were demonstrated to possess an antigenotoxic effects against carcinogenic MNU due to their radical scavenging activity.

Cancer is one of the most diagnosed and life threatening disease throughout the world. Nevertheless present day clinical management for cancers are surgery, radiations which are insufficient to contain the disease burden. In the past two decades, more than half of chemotherapeutic drugs developed are either directly or indirectly dependent on medicinal base phytocompounds or their derivative. The present study aims to provide the base for chemotherapeutic phytochemicals. Fagonia indica showed significant antimutagenic potential with reference to control IC50 values were calculated as 146.33±5.2µg/ml, TA100 (AZS) 105.33±4.0µg/ml, TA98 (2AA) 113.6±5.2µg/ml followed and TA98 (AZS) 112.6±4.4 in Ames test. For this reason, the antiproliferation effect of extracts on cancer cell lines was studied through resazurin fluorescence. On HepG-2 cell lines 50% cytotoxic concentration (CC50) of (FIWM) was recorded as 128.3±,2.43µg/ml. On the homo sapiens epithelial cell of lung tissue (A549), the high throughput instrumental analysis of Fagonia indica depicts maximum cytotoxic effect in 30hr. The electrical impedance displays the real-time evidence about qualitative apoptosis expressed. The impedance results were supported as palmitic acid from Fagonia indica virtually that inhibits Cyclin Dependent Kinase 2 (CDKs 2) in silico molecular docking studies. Fagonia indica extract possesses substantial antimutagenic, cytotoxic and anticancer activity which supports the potential of its phytochemicals for drug development. [ABSTRACT FROM AUTHOR]

Molasses is one of the popular and traditional foods produced and consumed in Turkey for a long time. The present work aimed to evaluate the safety of molasses which is produced traditionally and industrially. Ames/Salmonella mutagenicity and the MTT cytotoxicity methods were used for the safety evaluation. The amounts of furan derivatives were comparatively determined. 5-hydroxymethylfurfural (HMF) content of some samples were above the legal limit of 70 mg/kg. Ames/Salmonella mutagenicity assay showed that molasses had no mutagenic effect. On the other hand, antimutagenic activity was observed after metabolic activation. The margins of exposure were above the value of 100, thus indicating the safety of samples regarding furan derivatives exposure. The higher HMF content and osmophilic yeast counts of traditionally produced molasses as compared to the industrially produced samples are alarming, and suggest that traditional and industrial food production may need a separate risk assessments by the national authority. [ABSTRACT FROM AUTHOR]

The mutagenicity and antimutagenicity of leaves and flower extract of Cynara syriaca Boiss were studied with Ames assay in Salmonella typhimurium TA98 and TA100 strains. While leaves extract did not show any mutagenic effects against all the tester strains with or without metabolic activation, the flower extract showed mutagenic effect against TA98 strain without metabolic activation. On the other hand, it has been observed that the extracts have antimutagenic activity against mutations induced by sodium azide and daunomycin. The antimicrobial activity of extracts was determined by disc diffusion and MIC value. Both of the extracts possess weak antimicrobial activity. Cupric reducing antioxidant capacity (CUPRAC), DPPH free radical scavenging activity, and ABTS radical cation decolorization methods were carried out to determine the antioxidant activity. Among the tested antioxidant methods, the highest antioxidant capacity was determined in ABTS radical cation decolorization assay in which both of the extracts exhibited the best effect. Flower extract exhibited higher activity also in DPPH free radical scavenging.

Recently, Morinda citrifolia Linn., popularly known in Brazil as noni, is used in folk medicine for its therapeutic properties to prevent and cure various diseases, among them cancer. The fruit has in its composition compounds with biological activities and, consequently, have chemopreventive effects. In this context, the objective of the study was to evaluate the antimutagenic/mutagenic potential of aqueous extract of the noni through the Micronucleus Test in vivo and to investigate the possible toxic effect of noni through the in vitro Cytotoxicity Test. The animals (6 animals/group) were treated for 15 consecutive days with aqueous extract (via gavage) and on day 15th were given intraperitoneally cyclophosphamide (CPA, 25 mg/Kg) and sacrificed 24 hours after treatment for evaluate of erythrocyte frequency micronucleated polychromatic (MNPCE). The chinese hamster ovary (CHO) cells were incubated with aqueous extract of noni at the concentrations of 50, 200, 1000, 2500 and 5000 μg/ml for 3 hours and Ehrlich ascitic tumor cells (TAE) using concentrations of 1.0; 0.5 and 0.25 mg/ml of the noni extract, incubated for 24 hours. After treatment, the cell viability test was performed with tripan blue, in triplicate. The results showed that pretreatment with aqueous extract of noni, under the conditions tested, significantly reduced the frequency of MNPCE (p

Purple rice has gained attention for its health promoting potential due to a high content of bioactive phytochemicals. The heat generated during cooking alters the quality and quantity of nutrients and phytochemicals in food. This study aimed to investigate the phytochemical profile and chemopreventive properties of cooked glutinous purple rice using cell-based assays and a rat model. Purple rice was cooked in a rice cooker and was then further extracted with solvents to obtain dichloromethane and methanol extracts. The methanol extracts of glutinous purple rice contained great amounts of phenolics, flavonoids, and anthocyanins. Protocatechuic acid (2.26–5.40 mg/g extract) and cyanidin 3-glucoside (34.3–65.7 mg/g extract) were the major phenolic acid and anthocyanin contents, respectively. After cooking, the content of anthocyanins, γ-oryzanols, and phytosterols decreased, while the amount of some phenolic acid and tocol contents increased. Methanol extracts of glutinous purple rice inhibited reactive oxygen species production about 60% in PMA-treated peripheral blood mononuclear cells, reduced nitric oxide formation in LPS-induced RAW 264.7 cells (26–39% inhibition), and exhibited antimutagenicity against several mutagens using the Ames test, but dichloromethane extracts presented only mild anti-inflammatory activities. Although methanol extracts induced mild mutagenicity (mutagenic index 2.0–2.5), they did not induce micronucleated hepatocyte formation and certain hepatic CYP450 isozyme activities in rats. However, the mutagenicity of the methanol extract significantly declined after cooking. In summary, the methanol extract of the cooked glutinous purple rice might be a promising cancer chemopreventive fraction, which was neither genotoxic nor posing adverse effects on phytochemical–drug interaction in rats.

In this study, the toxic effects of monosodium glutamate (MSG), which is the sodium salt of glutamic acid and used as a flavor-enhancing additive in foods, and the protective role of cape gooseberry (Physalis peruviana L.) extract against these effects were investigated using Allium cepa L. test material with physiological, cytogenetic, and biochemical parameters. In the study, physiological changes were evaluated by determining root length, weight gain, and rooting percentage; genetic changes were evaluated by chromosomal abnormalities, micronucleus (MN) formation, mitotic index ratio (MI), and DNA damage. Oxidative stress was evaluated by determining the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Further, the relationships between oxidative stress and other parameters in the study were investigated. The antimutagenic effect of P. peruviana L. extract was evaluated as inhibition caused by MSG-induced chromosomal abnormalities (CAs) and DNA damage. In the study, six groups, including one control and five applications, were formed. The bulbs of Allium cepa L. in the control group were treated with tap water; the bulbs in the administration groups treated with 1000 mg/L MSG, 125 mg/L, and 250 mg/L concentrations of P. peruviana L. extract and MSG (1000 mg/L) in combination with P. peruviana L. extracts (125 mg/L and 250 mg/L) for 72 h. At the end of the application, compared to the control group, MSG application caused decreases in rooting percentage, weight gain, root length and MI, increases in frequencies of MN formation, chromosomal abnormalities, and DNA damage. In the biochemical analysis, it was determined that there were increases in MDA, SOD, and CAT levels and a decrease in GSH level. P. peruviana L. extract ameliorated MSG toxicity by showing improvement in all these parameters depending on the application concentration. As a result, considering the toxic effects of MSG, it has been understood that the use as a food additive should be abandoned and the use of P. peruviana L. in addition to daily nutrition has been found to be a good antioxidant nutrient in reducing the effects of exposed toxic substances. [ABSTRACT FROM AUTHOR]

Flavonoids—compounds abundant in balanced daily diets—have been extensively investigated for biological activity. The pronounced antiproliferative effects of flavonoids have prompted studies to elucidate their mode of action against tumor cells. The anticancer properties of myricetin, a 3′,4′,5′-tri-hydroxylated flavonol, have been confirmed for a number of neoplasms, but myricitrin, its 3-O-rhamnoside derivative found in fruits and other parts of edible plants, has been scarcely investigated as a chemopreventive agent. This study evaluated the antiproliferative potential of myricitrin obtained from Combretum lanceolatum (Combretaceae) against MCF7 (breast), PC-3 (prostate), HT-29 (colon), 786-0 (kidney), and HL-60 (acute promyelocytic leukemia) cancer cell lines, using the sulforhodamine B and tetrazolium salt assays. Myricitrin proved most effective in inhibiting growth of HL-60 cells (GI50 = 53.4 μmol·L−1), yet showed weak antiproliferative activity against other cell lines. Possible cytotoxic mechanisms involving inhibition of topoisomerases I and IIα by myricitrin were also evaluated, revealing inhibitory activity only against topoisomerase IIα. The results suggested that topoisomerase IIα inhibition is the probable mechanism responsible for the antiproliferative activity of myricitrin. In vivo mutagenicity by myricitrin and its possible antimutagenic effect on doxorubicin-induced DNA damage were also investigated by performing the somatic mutation and recombination test (SMART) on Drosophila melanogaster. Myricitrin proved nonmutagenic to the offspring of standard (ST) and high-bioactivation (HB) crosses, while cotreatments with doxorubicin revealed the antimutagenic properties of myricitrin, even under conditions of high metabolic activation. [ABSTRACT FROM AUTHOR]

In this study, antimutagenic effects of ethanolic extracts of Stachys thirkei and Stachys annua subsp. annua belonging to Lamiaceae family that grow in Duzce of Turkey were investigated on Salmonella typhimurium TA98 and TA100 strains without metabolic activation using Salmonella/microsome test system. Three different concentrations (0.025, 0.05 and 0.1 mg/plate) of the ethanolic extracts of S. thirkei and S. annua subsp. were used as active materials in which the major components were 2-ethylhexanol (30.012%) and 2-beta-pinene (26.40%), respectively. The highest concentration (0.1 mg/plate) of S. thirkei had a moderate antimutagenic effect on the Salmonella typhimurium TA98 strain with a 26.79% inhibition rate. It was also established that the extract of S. thirkei at highest concentration (0.1 mg/plate) exhibited strong antimutagenic effect (with 44.03% maximum inhibition) on TA100 strain. Furthermore, it was found that 0.05 mg/plate ethanolic extract showed moderate antimutagenic activity with 25.55% inhibition rate. The highest concentration (0.1 mg/plate) of ethanolic extract of S. annua subsp. showed moderate antimutagenic activity on both Salmonella typhimurium TA98 and TA100 strains with inhibition rates of 20.39 and 22.13%, respectively. No antimutagenic activity on Salmonella typhimurium TA98 and TA100 strains was observed at the lowest doses of both plant species. As a result, it is concluded that S. thirkei and annua subsp. have antimutagenic activity and further studies may be recommended in terms of different parameters. [ABSTRACT FROM AUTHOR]

Background: Cleistocalyx nervosum var. paniala is a local fruit mainly cultivated in the north of Thailand. Our previous study has reported that the methanol extract of C. nervosum seed presented antimutagenicity in a Salmonella mutation assay. The present study focused on the effect of a low-polar extract of C. nervosum seed on the early stages of diethylnitrosamine (DEN)- and dimethylhydrazine (DMH)-induced carcinogenesis in rats. Methods: Dried C. nervosum seed powder was extracted using dichloromethane. To study its effect on the initiation stage of carcinogenesis of rats, they were fed with various doses of C. nervosum seed extract (CSE) for 21 days. DEN injection was used to initiate hepatocarcinogenesis and partial hepatectomy was performed to amplify mutated hepatocytes resulting in micronucleated hepatocyte formation. To study the role of CSE on the promotion stage, rats were injected with DEN and DMH to induce preneoplastic lesions and the numbers of glutathione S-transferase placental form (GST-P) positive foci in the liver and aberrant crypt foci (ACF) in the colon were measured. This was followed by CSE administration for 10 weeks. The inhibitory mechanisms of CSE on initiation and promotion stages, including xenobiotic metabolism, cell proliferation and apoptosis, were investigated. Results: The total phenolic content in CSE was 80.34 ± 2.29 mg gallic acid equivalents (GAE) per g of extract and 2,4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone was found to be a major flavonoid. The main terpenoids in CSE were β-selinene, α-selinene, γ-selinene and o-cymene while 24(Z)-methyl-25-homocholesterol was a major phytosterol. CSE significantly decreased the number of micronucleated hepatocytes in DEN-initiated rats and enhanced the activities of hepatic glutathione S-transferase and UDP-glucuronyltransferase. Furthermore, the formation of preneoplastic lesions in the liver and colon was statistically reduced by CSE. CSE also diminished cell proliferation in the liver and colon indicated by the number of PCNA positive cells. However, CSE did not alter the numbers of apoptotic hepatocytes and colonocytes in DEN- and DMH-initiated rats. Conclusions: The dichloromethane extract of C. nervosum seed demonstrated chemopreventive effects on chemically-induced carcinogenesis in both initiation and promotion stages in rats. The inhibitory mechanism might be involved in the modulation of hepatic detoxifying enzymes and suppression of hepatocyte and colonocyte proliferation.

Onosma bracteata Wall. (Boraginaceae) is a highly valuable medicinal herb that is used for the treatment of fever, bronchitis, asthma, rheumatism, stomach irritation, and other inflammatory disorders. The present study aims to explore the hepatoprotective potential of ethanolic extract (Obeth) from O. bracteata aerial parts against carbon tetrachloride (CCl4) which causes hepatic damage in the male Wistar rats. Obeth showed effective radical quenching activity with an EC50 of 115.14 and 199.33 µg/mL in superoxide radical scavenging and lipid peroxidation analyses respectively along with plasmid DNA protective potential in plasmid nicking assay. The Obeth modulated mutagenicity of 2 Aminofluorine (2AF) in the pre-incubation mode of investigation (EC50 10.48 µg/0.1 mL/plate) in TA100 strain of Salmonella typhimurium. In in vivo studies, pretreatment of Obeth (50, 100, and 200 mg/kg) had the potential to normalize the biochemical markers aggravated by CCl4 (1mL/kg b.wt.) including liver antioxidative enzymes. Histopathological analysis also revealed the restoration of CCl4-induced liver histopathological alterations. Immunohistochemical studies showed that the treatment of Obeth downregulated the expression levels of p53 and cyclin D in hepatocytes. and downregulation in the Western blotting analysis revealed the downregulation of p-NF-kB, COX-2, and p53. HPLC data analysis showed the supremacy of major compounds namely, catechin, kaempferol, epicatechin, and Onosmin A in Obeth. The present investigation establishes the hepatoprotective and chemopreventive potential of O. bracteata against CCl4-induced hepatotoxicity via antioxidant defense system and modulation of the expression of proteins associated with the process of carcinogenesis in hepatic cells.

Melissa officinalis (L) is used traditionally for different medical purposes such as tonic, antispasmodic, carminative, diaphoretic, surgical dressing for wounds, sedative hypnotic, strengthening the memory and relief of stress induced headache.The methanolic extractof Melissa officinalis (Mo-ME) was investigated for antimutagenic activity. The extraction was done by Soxhlet extraction method and the extract was evaluated for antimutagenic assay against EMS induced mice by micronucleus and chromosomal aberration assay. Briefly, mice were treated with methanolic extract of Melissa officinalis (Mo-ME) (100, 200 300 & 400 mg/kgbw) for 15 days. Without the doses of EMS, no and mutagenic effects were observed in blood and bone marrow samples of the mice. Micronucleus and chromosomal aberration test revealed the protective effects of Mo-ME when administered at high doses.The reduction profiles in the MN induction of methanolic extract of Melissa officinalis at the concentration (100, 200, 300 and 400 mg/kgbw) with EMS were estimated as 14.5%, 28.0%, 47.7% and 81.5% respectively. The methanolic extract of Melissa officinalis exhibited no cytotoxic and mutagenic effects but only have antimutagenic effects, an effect that can be attributed the presence of majorital compounds, and the antimutagenic property of Mo-ME is an indication of its medicinal relevance.

Objective: To evaluate the influence of fertilization and phenological stages on secondary metabolites production and chemoprotective effects of Coriandrum sativum (C. sativum) L. Methods: The plants were grown under organic or chemical fertilizer, collected at vegetative and flowering development stages and their hydroalcoholic extracts were analyzed by phytochemicals methods, mass spectrometry, antioxidant and antimutagenic assays. Results: All extracts exhibited metabolites such as coumarins, flavonoids and steroids, and mass spectrometry showed similar molecular peaks among the extracts evaluated, suggesting the presence of palmitic and α -linolenic acids. Vegetative C. sativum extract grown under chemical fertilizer showed better antioxidant activity, according to the DPPH assay. Vegetative C. sativum extracts grown under organic and chemical fertilizer were able to effectively reduce micronucleous frequency in the simultaneous and pre-treatment protocols, especially reaching 55.90% of damage reduction in the pre-treatment protocol. Conclusions: These findings suggest that chemical fertilization promotes an increase in the content of flavonoids in C. sativum and, consequently, leads to better antioxidant and antimutagenic activities, as well as reinforces the potential uses of this culinary plant in health promotion and disease prevention.

Palm date pits as a source of bioactive chemicals have received only a limited amount of attention. This study was conducted to determine the bioactive components of Ajwa date pits, as well as their antibacterial and antimutagenic activities. Therefore, chromatographic techniques were used to extract and isolate the phenolic compounds in date pits, which were further elucidated by using spectroscopic techniques (FTIR and NMR) for identification of most abundant bioactive metabolites. Data showed that the methanolic extract of date pits contained high levels of total phenols (17.38 mg GA/g) and flavonoids (5.324 mg QE/g). The HPLC analysis of date pits’ extract showed the presence of six phenolic compounds. Interestingly, there was a significant amount of gallic acid (11.85 mg GA/gFW), which was isolated via chromatography (thin layer chromatography) and identified by spectroscopic investigation (FTIR, MS, 1H, and 13C NMR). An inhibitory effect on Gram-positive and Gram-negative bacteria was observed for date pit gallic acid purified. S. aureus cell viability was completely inhibited at 200 µg/mL of acid for 6 h. Moreover, gallic acid was found to have a significant antimutagenic activity against Salmonella typhimurium at all tested concentrations, with a decrease in percent mutagenicity from 52 to 32 in the case of test substance TA98, and from 39 to 15 for test substance TA100 in terms of percent antimutagenicity. Gallic acid at a dose of 3000 g/plate had the greatest antimutagenic effect on S. typhimurium TA98, with the lowest toxicity. Overall, the bioactive properties of date pits’ extracts were investigated, with a particular attention to their chemical composition, biological activity, and pharmaceutical applications.

Onosma bracteata Wall. (Boraginaceae) is a highly valuable medicinal herb that is used for the treatment of fever, bronchitis, asthma, rheumatism, stomach irritation, and other inflammatory disorders. The present study aims to explore the hepatoprotective potential of ethanolic extract (Obeth) from O. bracteata aerial parts against carbon tetrachloride (CCl4) which causes hepatic damage in the male Wistar rats. Obeth showed effective radical quenching activity with an EC50 of 115.14 and 199.33 µg/mL in superoxide radical scavenging and lipid peroxidation analyses respectively along with plasmid DNA protective potential in plasmid nicking assay. The Obeth modulated mutagenicity of 2 Aminofluorine (2AF) in the pre-incubation mode of investigation (EC50 10.48 µg/0.1 mL/plate) in TA100 strain of Salmonella typhimurium. In in vivo studies, pretreatment of Obeth (50, 100, and 200 mg/kg) had the potential to normalize the biochemical markers aggravated by CCl4 (1mL/kg b.wt.) including liver antioxidative enzymes. Histopathological analysis also revealed the restoration of CCl4-induced liver histopathological alterations. Immunohistochemical studies showed that the treatment of Obeth downregulated the expression levels of p53 and cyclin D in hepatocytes. and downregulation in the Western blotting analysis revealed the downregulation of p-NF-kB, COX-2, and p53. HPLC data analysis showed the supremacy of major compounds namely, catechin, kaempferol, epicatechin, and Onosmin A in Obeth. The present investigation establishes the hepatoprotective and chemopreventive potential of O. bracteata against CCl4-induced hepatotoxicity via antioxidant defense system and modulation of the expression of proteins associated with the process of carcinogenesis in hepatic cells. [ABSTRACT FROM AUTHOR]

Rheum emodi Wall. Ex. Meissen is an important food and medicinal plant growing wild in western Himalayas. The current endeavor was undertaken to carry out bioassay guided fractionation and isolation of antimutagenic principle(s) present in the rhizomes of Rheum emodi. The antimutagenicity assay was performed to check the recuperating effect of 80% aqueous methanol extract of rhizomes of R. emodi and its fractions i.e. n-hexane, chloroform, ethyl acetate, n-butanol and water fractions, against 4-nitro-o-phenylenediamine (NPD), sodium azide, and 2AF-induced mutagenicity in TA98 and TA100 strains using the Ames Salmonella his+ reversion assay. The crude 80% aqueous methanol extract and ethyl acetate fraction exhibited strong antimutagenicity. The antimutagenic potential of the extracts and fractions was markedly enhanced when indirect acting mutagen was used in both the tester strains of Salmonella typhimurium. In an effort to identify the molecules responsible for the antimutagenic effect displayed by R. emodi, four anthraquinones i.e. aloe-emodin, chrysophanol, emodin and rhein detected in the ethyl acetate fraction by HPLC analysis were also tested for their antimutagenic potential in both the tester strains. It was found that the anthraquinones in their pure form showed lower antimutagenicity than the mother fraction from which they were isolated. The results point towards a synergistic effect of the principles present in the mother fraction. [ABSTRACT FROM AUTHOR]

Background: An extract from Spatholobus suberectus (S. suberectus) Dunn has been reported to show potent antimutagenic effects against N-alkyl-N-nitrosoureas in umu screening. The aim of this study was to identify the antimutagenic components from extracts of S. suberectus against N-methyl-N-nitrosourea (MNU) in the Ames assay with Salmonella typhimurium strain TA1535 and to elucidate the antimutagenic mechanism of the flavonoids. Results: From the ethyl acetate fraction obtained from fractionation of the methanol extract of S. suberectus Dunn, medicarpin, formononetin and isoliquiritigenin were successfully isolated through a combination of normal- and reversed-phase chromatography. Genistein and naringenin, which were already reported to be contained in S. suberectus Dunn, were also tested for their antimutagenicity towards MNU, along with formononetin, isoliquiritigenin and medicarpin. Our results demonstrated that genistein, isoliquiritigenin, medicarpin and naringenin were antimutagenic against MNU without showing cytotoxicity. MNU is reported to cause not only DNA alkylation but also induce reactive oxygen species. The hydroxyl radical scavenging capacity of the flavonoids was correlated with the antimutagenic capacity, indicating that the hydroxyl radical scavenging activity was involved in their antimutagenicity towards MNU. Conclusions: It is important to prevent DNA damage by N-nitrosamines for cancer chemoprevention. Genistein, isoliquiritigenin, medicarpin and naringenin were demonstrated to possess an antigenotoxic effects against carcinogenic MNU due to their radical scavenging activity. [ABSTRACT FROM AUTHOR]

Abstract Background Mutations play a major role in the pathogenesis and development of several chronic degenerative diseases including cancer. It follows, therefore that antimutagenic compound may inhibit the pathological process resulting from exposure to mutagens. Investigation of the antimutagenic potential of traditional medicinal plants and compounds isolated from plant extracts provides one of the tools that can be used to identify compounds with potential cancer chemopreventive properties. The aim of this study was to isolate and characterise the compounds responsible for the antimutagenic activity of Combretum microphyllum. Methods The methanol leaf extract of C. microphyllum was evaluated for antimutagenicity in the Ames/microsome assay using Salmonella typhimurium TA98. TA100 and TA102. Solvent-solvent fractionation was used to partition the extracts and by using bioassay-guided fractionation, three compounds were isolated. The antimutagenic activity of the three compounds were determined in the Ames test using Salmonella typhimurium TA98, TA100 and TA102. The antioxidant activity of the three compounds were determined by the quantitative 2,2-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging method. The cytotoxicity was determined in the MTT assay using human hepatocytes. Results A bioassay-guided fractionation of the crude extracts for antimutagenic activity led to the isolation of three compounds; n-tetracosanol, eicosanoic acid and arjunolic acid. Arjunolic acid was the most active in all three tested strains with a antimutagenicity of 42 ± 9.6%, 36 ± 1.5% and 44 ± 0.18% in S. typhimurium TA98, TA100 and TA102 respectively at the highest concentration (500 μg/ml) tested, followed by eicosanoic acid and n-tetracosanol. The antioxidant activity of the compounds were determined using the quantitative 2,2 diphenyl-1-picryhydrazyl (DPPH)-free radical scavenging method. Only arjunolic acid had pronounced antioxidant activity (measured as DPPH-free scavenging activity) with an EC50 value of 0.51 μg/ml. The cytotoxicity of the isolated compounds were determined in the MTT assay using human hepatocytes. The compounds had low cytotoxicity at the highest concentration tested with LC50 values >200 μg/ml for n-tetracosanol and eicosanoic acid and 106.39 μg/ml for arjunolic acid. Conclusions Based on findings from this study, compounds in leaf extracts of C. microphyllum protected against 4-NQO and MMC induced mutations as evident in the Ames test. The antimutagenic activity of arjunolic acid may, at least in part, be attributed to its antioxidant activity resulting in the detoxification of reactive oxygen species produced during mutagenesis.

Context: There is a growing market demand for Hypericum sp., a pharmacologically active plant that has been traditionally used to treat various ailments. However, there have been limited studies on the extract or essential oil of Hypericum lydium Boiss (Hypericaceae). Objective: This study investigates for the first time the antioxidant, mutagenic and antimutagenic activity of an ethanol extract of H. lydium. Material and methods: Ethanol extract from aerial parts of H. lydium harvested from Turkey were tested for this mutagenic and antimutagenic activities (2.0–0.002 mg/plate) using Ames Salmonella/microsome test system. 4-Nitro-o-phenylenediamine (4-NPD) (3 μg/plate) for the Salmonella typhimurium TA98 and sodium azide (NaN3) (8 μg/plate) for the S. typhimurium TA100 were used as positive controls. The antioxidant activity, total antioxidant activity and phenolic constituent of the extract (2.0–0.002 mg/mL) was determined by the inhibition of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), β-carotene-linoleic acid model and by means of Folin–Ciocalteu reagent, respectively. Results: The extract showed no sign of mutagenicity at the tested concentrations (0.002–2.0 mg/mL), and showed concentration-dependent antimutagenic activity against NaN3 and 4-NPD ranging from 26.8 to 81.5%. The extract was found to be an efficient scavenger of DPPH (IC50 0.165 ± 0.23 mg/mL) and to inhibit β-carotene-linoleic acid bleaching (IC50 0.39 ± 0.11 mg/mL). Discussion and conclusion: These findings indicate ethanol extract of H. lydium to be a safe and effective agent that may be incorporated into new strategies for the prevention of cancer and mutagenesis.

Context: Medicinal plants continue to act as a repository for novel drug leads with novel mechanisms of action. Podophyllum hexandrum Royale (Berberideceae) treats diverse conditions in folk medicine. Objective: The antimutagenic potential of P. hexandrum was evaluated against endosulfan-induced clastogenicity in a piscine model by cytogenetic endpoints. Materials and methods: Podophyllum hexandrum rhizomes were subjected to successive solvent extraction. Fish were exposed to hexane, chloroform, ethyl acetate, methanol and aqueous extracts (15 mg/L each) of plant and endosulfan (0.05 mg/L) alone followed by their combination for antimutagenicity estimates. Chromosomal aberrations (CA) were made from kidney cells and micronuclei (MN) slides from peripheral blood erythrocytes at 48, 72 and 96 h. Antioxidant activity was analyzed by the DPPH assay. Phytochemical analyses were carried out using chromatographic and spectroscopic techniques. Results: Endosulfan induced significant (p

Goji (Lycium barbarum L.) leaves are emphasized as a functional tea or as dietary supplements. The phenolic compound profile, antioxidant, enzyme inhibitory, antimicrobial, and antimutagenic activities of leaf extracts from two selected cultivars in comparison with wild-growing plants have been evaluated. HPLC-DAD/ESI-ToF-MS analysis revealed the presence of phenolic acids and flavonoids with chlorogenic acid and rutin being the dominant compounds in the cultivated plants, whereas rutin and kaempeferol-3-O-rutinoside for wild growing ones. In particular, cv. Erma contained the highest amount of chlorogenic acid and showed a strong tyrosinase-inhibitory effect. Staphylococcus aureus, Listeria monocytogenes, and Penicillium funiculosum were the most sensitive strains when exposed to extracts from cultivated plants. Antimutagenic activity was evaluated by Ames' test. The tested extracts provided high protection against mutagenicity induced by 2-anthramine (2-AA) to Salmonella typhimurium strains TA 98 and TA 100 (max. inhibition (%) 88% and 74.2%, respectively). Overall, Goji leaves are a rich source of bioactive compounds with functional properties that need further risk/benefit evaluation when used in foods or health-promoting formulations.

Ficus deltoidea var. deltoidea is used as traditional medicine for diabetes, inflammation, and nociception. However, the antimutagenic potential and cytoprotective effects of this plant remain unknown. In this study, the mutagenic and antimutagenic activities of F. deltoidea aqueous extract (FDD) on both Salmonella typhimurium TA 98 and TA 100 strains were assessed using Salmonella mutagenicity assay (Ames test). Then, the cytoprotective potential of FDD on menadione-induced oxidative stress was determined in a V79 mouse lung fibroblast cell line. The ferric-reducing antioxidant power (FRAP) assay was conducted to evaluate FDD antioxidant capacity. Results showed that FDD (up to 50 mg/mL) did not exhibit a mutagenic effect on either TA 98 or TA 100 strains. Notably, FDD decreased the revertant colony count induced by 2-aminoanthracene in both strains in the presence of metabolic activation (p < 0.05). Additionally, pretreatment of FDD (50 and 100 µg/mL) demonstrated remarkable protection against menadione-induced oxidative stress in V79 cells significantly by decreasing superoxide anion level (p < 0.05). FDD at all concentrations tested (12.5–100 µg/mL) exhibited antioxidant power, suggesting the cytoprotective effect of FDD could be partly attributed to its antioxidant properties. This report highlights that F. deltoidea may provide a chemopreventive effect on mutagenic and oxidative stress inducers.

The mutagenicity and antimutagenicity of leaves and flower extract of Cynara syriaca Boiss were studied with Ames assay in Salmonella typhimurium TA98 and TA100 strains. While leaves extract did not show any mutagenic effects against all the tester strains with or without metabolic activation, the flower extract showed mutagenic effect against TA98 strain without metabolic activation. On the other hand, it has been observed that the extracts have antimutagenic activity against mutations induced by sodium azide and daunomycin. The antimicrobial activity of extracts was determined by disc diffusion and MIC value. Both of the extracts possess weak antimicrobial activity. Cupric reducing antioxidant capacity (CUPRAC), DPPH free radical scavenging activity, and ABTS radical cation decolorization methods were carried out to determine the antioxidant activity. Among the tested antioxidant methods, the highest antioxidant capacity was determined in ABTS radical cation decolorization assay in which both of the extracts exhibited the best effect. Flower extract exhibited higher activity also in DPPH free radical scavenging. [ABSTRACT FROM AUTHOR]

Background: Honey contains several substances with antimicrobial properties that appear more recalcitrant to generating bacterial-evolved resistance than traditional antibiotics. Objectives: This study seeks to characterize the evolution of bacteria grown for successive generations in honey as an antimutagenic medium versus ampicillin. Materials and Methods: A naive strain of Staphylococcus aureus was serially cultured for 17 days in Lysogeny broth (LB) containing sublethal concentrations of medical-grade Manuka honey, polyfloral honey, and ampicillin. Glucose as an osmotic control and pure LB were included for comparison. A portion of each culture was removed every 24 h to (a) determine the amount of growth that occurred during the previous 24 h and (b) use as a genetic stock in serially transferred tubes containing the same inhibitory compound as used previously. Results: As indicated by an increase in growth over sequential 24-h period, bacteria rapidly gained resistance to ampicillin in a step-wise pattern. However, bacteria grown in Manuka and polyfloral honey never exceeded their initial growth levels. Bacteria grown in relatively high concentrations of honey for a single 24-h period consistently lost viability after one transfer, a phenomenon that has not been reported in the literature before and which indicates the inability of bacteria to adapt to honey as an antimutagenic medium. While bacteria grown in honey did not evolve the ability to grow at higher concentrations, a single isolate grown in Manuka honey gained tolerance to Manuka by successfully surviving and proliferating beyond second transfers. Bacteria that developed antibiotic resistance were found to remain sensitive to honey. Moreover, bacteria lost their resistance to ampicillin upon a single exposure to Manuka honey. [ABSTRACT FROM AUTHOR]

Abstract Leishamaniasis is a neglected disease caused by over 20 Leishmania species, occurring in more than a hundred countries. Miltefosine (hexadecylphosphocholine) is the single oral drug used in treatment for leshmaniases, including cases of infections resistant to pentavalent antimony. Our group has recently demonstrated the ability of miltefosine to cause genomic lesions by DNA oxidation. Acknowledging that antioxidant compounds can potentially modulate Reactive Oxygen Species (ROS), our study verified whether ascorbic acid reduces the genotoxic and mutagenic effects caused by miltefosine, and whether it interferes with drug efficacy. For this purpose, uninfected Swiss mice received simultaneous (single dose treatment) miltefosine and ascorbic acid (gavage and intraperitoneally), besides pre and post treatments (ascorbic acid 24 h before and after drug administration); furthermore, Balb/c mice infected with Leishmania infantum received miltefosine plus ascorbic acid (repeated doses treatment). We conducted comet assays, micronucleus tests, dosages of superoxide dismutase enzyme and parasitic burden by the limiting dilution assay. We observed that ascorbic acid administered intraperitoneally displayed a protective effect over damage caused by miltefosine. However, this effect was not not observed when the same doses were administered via gavage, possibly due to low serum levels of this antioxidant. Ascorbic acid's protective effect reinforces that miltefosine damages DNA by oxidizing its nitrogenous bases, which is reduced by ascorbic acid due to its ability of protecting genetic material from the action of ROS. Therefore, our results show that this drug is efficient in reducing parasitic burden of L. infantum. Graphical abstract Male Swiss and Balb/c mice were used to demonstrate that ascorbic acid reduces the genetic damage induced by miltefosine, without decreasing its antileishmanial activity. In addition, the results reveal that miltefosine is effective in reducing the parasitic burden of L. infantum at lower doses than others previously reported. Image 1 Highlights • The ascorbic acid reduces the genetic damage induced by miltefosine. • The ascorbic acid did not interfere in the eficacy the antileishmanial miltefosine. • The miltefosine is effective in reducing the parasitic burden of L. infantum. [ABSTRACT FROM AUTHOR]

Some plant‐derived bioactive compounds produced by fungal endophytes have been proven to have antimicrobial and antioxidant activities. In this study, endophytic fungi were isolated from 20 orchid samples collected in northern Thailand from 12 genera of orchids. In total, 97 isolates were isolated from the leaves (44.3%), stems (40.2%) and flowers (15.5%) of the orchid samples. The antifungal activity was investigated of the endophytic isolates against the plant pathogenic fungi. The results showed that 13 endophytic isolates provided antifungal activities against Fusarium sp., Colletotrichum sp. and Curvularia sp. The endophyte CK F05‐5, which was isolated from the flower part of Dendrobium lindleyi, was chosen for further testing because it the highest level of antifungal activity against Fusarium sp. The isolate CK F05‐5 was identified as Fusarium oxysporum on the basis of its ITS sequences of 5.8 s rRNA, and phytochemical analysis revealed the presence of coumarins. The ethyl acetate extract of CK F05‐5 was examined for its total phenolic content and antioxidant activity using Folin–Ciocalteu's reagent and 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay, respectively. The phenolic content was 160.51 mg of GAE/g of extract, and the free radical scavenging activity was 89.61 µg/ml at the half maximal inhibitory concentration (IC50). The antimutagenic potential of the ethyl acetate extract of CK F05‐5 against Trp‐P‐1 mutagenic substances was determined using the Ames test which revealed that the extract of CK F05‐5 at 10 mg/plate had the highest antimutagenic activity against Trp‐P‐1 (51.2%) and 39.6% for strains TA98 and TA100, respectively. The active compounds present in the acetate extract of CK F05‐5 were examined using GC‐MS analysis, which displayed the presence of gibepyrone A, pyrrolo [1, 2‐a] pyrazine‐1, 4‐dione, hexahydro‐3‐(2‐methylpropyl) and indoleacetic acid as major components. Based on the results, this endophytic fungus contains various bioactive components that have various biological activities. This useful information could help in producing potentially valuable and novel pharmaceutical products. [ABSTRACT FROM AUTHOR]

(E)-2-((4-tert-butylbenzylimino)methyl)-4-methoxyphenol is synthesized by the reaction of 4-tert-buthylbenzylamine with 5-methoxysalicylaldehyde. The structure of the Schiff base is investigated by FT-IR, UV-visible, and 1H NMR, 13C NMR, and X-ray data. Moreover, the molecular structure, molecular electrostatic potential surfaces (MEP), frontier molecular orbitals, and nonlinear optical properties (NLO) are also investigated by density functional theory (DFT) calculations. The experimental and calculated results show that the phenol-imine form of the compound is more favoured than the keto-amine form. The most energy favourable docked structures are obtained from the rigid molecular docking of the compound with DNA. The compound binds at the active site of DNA proteins by weak non-covalent interactions. UV-Vis spectroscopy studies of the interactions between the compounds and calf thymus DNA (CT-DNA) show that the compounds interact with CT-DNA via the electrostatic and intercalative binding. The compound inhibits the frameshift and base pair mutations in the absence of S9 mix with a high inhibition rate. Also, the molecular docking is made to identify the interaction between the ligand and DNA. [ABSTRACT FROM AUTHOR]

Purpose: Determination of the mutagenic potential of new biologically active compounds is of great concern for preliminary toxicity testing and drug development. Methods: The mutagenic and antimutagenic effects of some quinoline- and isoquinoline-sulfonamide analogs of aripiprazole (1-8), which display potent antidepressant, anxiolytic, and antipsychotic properties, were evaluated using the Vibrio harveyi assay and OSIRIS Property Explorer software. Additionally, the Ames test was used as the reference. Results: In silico prediction showed that compounds 5 (N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)quinoline-7-sulfonamide) and 6 (N-(4-(4-(2,3-Dichlorophenyl)piperazin-1-yl)butyl)quinoline-7-sulfonamide) trigger a mutagenic structural alert. However, this was not confirmed by in vitro assays, as none of the tested compounds displayed mutagenic activity against all tested strains of bacteria. Moreover, compounds 1-8 displayed a protective effect against the mutagenicity induced by a direct acting mutagen NQNO. The most beneficial antimutagenic properties showed compound 5 which exhibited strong antimutagenic properties in all tested V. harveyi strains. High antimutagenic potency of this compound was confirmed in the Ames TA100 assay system. Conclusion: Newly synthesized azinesulfonamide analogs of aripiprazole may be considered as genotoxically safe as they do not display mutagenic activity on the tester strains. Moreover, the tested compounds demonstrated significant antimutagenic properties that can be valuable for prevention of the NQNO genotoxicity. Additionally, it appears that the Vibrio harveyi assay can be applied for primary mutagenicity and antimutagenicity assessment of chemical substances, thus, representing a useful alternative tool for compounds safety evaluation.