Antigenotoxic Activity Research Articles

Vitamin B12 Protects Against Genotoxicity Induced by Cisplatin.

Cisplatin is an effective synthetic chemotherapeutic drug used for cancer treatment. Vitamin B12 has been shown to possess anti-genotoxic activity. This study aimed to investigate the effect of vitamin B12 on chromosomal damage induced by cisplatin. The level of sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) were measured in cultured human blood lymphocytes treated with cisplatin and/or vitamin B12. The results showed a significantly elevated frequency of CAs and SCEs of cisplatin-treated cultures compared to the control (P < 0.05). The CAs and SCEs induced by cisplatin were significantly lowered by pretreatment of cell cultures with vitamin B12. In addition, cisplatin caused a slight reduction in the mitotic index (MI), while vitamin B12 did not modulate the effect of cisplatin on MI. Vitamin B12 can protect human lymphocytes against genotoxicity associated with cisplatin.

Olive Mill Wastewater Extract: In Vitro Genotoxicity/Antigenotoxicity Assessment on HepaRG Cells.

Olive mill wastewater (OMWW), with its high level of phenolic compounds, simultaneously represents a serious environmental challenge and a great resource with potential nutraceutical activities. To increase the knowledge of OMWW's biological effects, with an aim to developing a food supplement, we performed a chemical characterisation of the extract using the Liquid Chromatography-Quadrupole Time-of-flight spectrometry (LC-QTOF) and an in vitro genotoxicity/antigenotoxicity assessment on HepaRG ™ cells. Chemical analysis revealed that the most abundant phenolic compound was hydroxytyrosol. Biological tests showed that the extract was not cytotoxic at the lowest tested concentrations (from 0.25 to 2.5 mg/mL), unlike the highest concentrations (from 5 to 20 mg/mL). Regarding genotoxic activity, when tested at non-cytotoxic concentrations, the extract did not display any effect. Additionally, the lowest tested OMWW concentrations showed antigenotoxic activity (J-shaped dose-response effect) against a known mutagenic substance, reducing the extent of DNA damage in the co-exposure treatment. The antigenotoxic effect was also obtained in the post-exposure procedure, although only at the extract concentrations of 0.015625 and 0.03125 mg/mL. This behaviour was not confirmed in the pre-exposure protocol. In conclusion, the present study established a maximum non-toxic OMWW extract dose for the HepaRG cell model, smoothing the path for future research.

Moderate India Pale Ale beer consumption promotes antigenotoxic and non-mutagenic effects in ex vivo and in vivo mice models.

Discussion of the benefits of moderate alcohol consumption is ongoing. Broadly, research focusing on ethanol consumption tends to report no benefits. However, studies that distinguish between different types of alcoholic beverages, particularly beers, often reveal positive effects. The present study evaluated the genotoxic and mutagenic effects of moderate chronic consumption of India Pale Ale (IPA) craft beer. Sixty-four adult male Swiss mice were used and divided into control and treatment groups receiving water, IPA beer with 55.23 g of ethanol per liter of beer, aqueous solution with 55.23 g of ethanol per liter, and hop infusion ad libitum for 30 days. After this period, the animals were genetically evaluated with a comet assay. For the ex vivo comet assay, blood was collected and exposed to hydrogen peroxide (H2O2). For the in vivo assay, the alkylating agent cyclophosphamide (CP) was administered to the groups after blood collection and sacrificed after 24 h. Brain, liver, and heart tissues were analyzed. Bone marrow was collected and submitted to the micronucleus test. The groups treated with IPA beer, ethanol, and hops did not show genotoxic and mutagenic action in the blood, brain, heart, or liver. The antigenotoxic action of IPA beer and hops was observed in both in vivo and ex vivo models, showing a similar reduction in DNA damage caused by CP. There was no significant difference between the groups with regard to the formation of micronuclei by CP. Moderate chronic consumption of IPA beer and hops infusion showed antigenotoxic effects in mice but no antimutagenic action. © 2024 Society of Chemical Industry.

Exploring the bioactive potential of Mentha longifolia from Northeast India: an inclusive study on phytochemical composition and biological activities

Mentha longifolia (Lamiaceae) is regarded as highly valuable aromatic medicinal species with wide range of pharmaceutical application. In the present work, leaf essential oil of M. longifolia was applied for the assessment of in vitro pharmacological potentials and compositional analysis. A sum of 15 compounds were detected by GC-FID and GC-MS analysis of M. longifolia essential oil with total area of 99.98% where major compounds were carvone (59.56%), D-limonene (20.81%), eucalyptol (10.08%). The anti-oxidant potency of M. longifolia was estimated using two methods viz., ABTS (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assay where M. longifolia essential oil showed moderate anti-oxidant potency. M. longifolia essential oil revealed high anti-inflammatory and tyrosinase inhibitory activity with an IC50 value 3.68 μL/mL and 1.22 μL/mL respectively compared to standard sodium diclofenac (5.33 μL/mL) and kojic acid (2.28 μL/mL). The acetylcholinesterase (AchE) inhibitory and genotoxic assay was performed, where M. longifolia essential oil revealed strong anti-acetylcholinesterase and anti-genotoxic activity. Anti-microbial potential of M. longifolia essential oil was also where strong anti-bacterial activity was shown against Salmonella typhimurium, Bacillus cereus, Staphylococcus aureus, Micrococcus luteus. For anti-fungal activity, M. longifolia essential oil showed no zone of inhibition against any used strains except Aspergillus flavus. From the present research it was established that M. longifolia essential oil possesses pharmaceutical potential with strong AchE inhibitory, anti-inflammatory, anti-microbial, anti-tyrosinase, anti-genotoxic and anti-oxidant activity which can be used for plant-based drug development in future endeavor.

Antigenotoxic Activity of Polyphenolic Composition BP-C2 in Mouse Germ Cells In Vivo.

In vivo antigenotoxic activity of BP-C2 composition (at doses of 60, 80, and 120 mg/kg) based on polyphenolic compounds derived from hydrolyzed lignin was evaluated in mouse germ cells. The BP-C2 composition dose-dependently reduced the aneugenic activity of topoisomerase II inhibitor etoposide in mouse oocytes without affecting the clastogenic activity of the genotoxicant. In mouse testicular cells, the BP-C2 composition reduced the DNA-damaging activity of the pro-oxidant genotoxicant dioxidine, but not etoposide. The cytoprotective activity of BP-C2 composition was revealed in relation to etoposide-induced cytotoxicity.

Elemental Composition, Antioxidant, Anti-inflammatory and Anti-genotoxic Properties of Nitophyllum punctatum

ObjectivesMarine algae are important sources of nutritionally and pharmacologically important products. Here in the study, nutritional composition and biological activities of a marine red algae Nitophyllum punctatum were assessed. The present study aimed to analyze the nutritional composition and biological effects of the N. punctatum. MethodsThe marine algae N. punctatum was collected, shade dried and extracted using Soxhelet apparatus. The elemental composition was estimated using Atomic Absorption Spectroscopy; the anti-inflammatory effect was determined using Raw 264.7 macrophages. Genotoxicity was assessed by standard methods using Allium cepa root model. ResultsThe elemental composition analysis revealed the presence of essential minerals such as calcium, magnesium, potassium, and iron, indicating the potential nutritional value of the algae. The extract demonstrated significant inhibition of Nitric oxide (NO) production and downregulated the expression of pro-inflammatory cytokines such as TNF-α and IL-6, suggesting its potential as an anti-inflammatory agent. Furthermore, the anti-genotoxic potential of the methanol extract was evaluated using the Allium cepa model, a well-established system for assessing genotoxicity. Onion root tips were treated with various concentrations of the extract, and the chromosomal changes were performed as indicators of genotoxicity. Results indicated a protective effect against Ethyl methyl sulfonate (EMS) induced genotoxicity in onion roots. ConclusionsThe findings suggest that the methanol extract of N. punctatum possesses potent anti-inflammatory and anti-genotoxic properties, which may be attributed to the presence of bioactive compounds. The study highlights the potential pharmacological importance of N. punctatum as a source of natural compounds with anti-inflammatory and anti-genotoxic activities.

Evaluation of potential anti-aging effects of Achillea phrygia Boiss. &amp; Balansa (Asteraceae)

This study aims to determine the anti-aging effects of Achillea phrygia, an endemic plant, by evaluating its sun protection factor (SPF) level, antioxidant activity, total phenolic content, extracellular matrix-degrading enzymes (ECM) inhibition, genotoxic/anti-genotoxic, and cytotoxic activities. The SPF level was assessed using an in vitro quantitative method, while antioxidant capacity was determined through DPPH, β-carotene, and hydroxyl-radical (H2O2) scavenging assays. The total phenolic content was quantitatively conducted using the Folin Ciocalteu reagent. The inhibition of ECM-degrading enzymes was determined using matrix metalloproteinase-1 (MMP-1), hyaluronidase, and elastase enzymes. Genotoxic/anti-genotoxic properties were assessed using the AMES Salmonella/microsome assay, and cytotoxicity effects were assessed through the MTT assay. The results indicated that A. phrygia showed moderate SPF activity (SPF = 4.013) and exhibited IC50 values of 0.183 ± 0.03, 0.079 ± 0.51, and 1.18 ± 0.35 mg/mL for DPPH, β-carotene, and hydroxyl-radicals, respectively. The total phenolic content was measured to be 23.56 ± 1.42 mg GAE/g dry extract. Furthermore, the extract demonstrated inhibition of MMP-1 (47.98%) and elastase (39.2%) activities. Importantly, it did not induce DNA damage and showed antigenotoxic activity ranging from 10% to 65.6%. The cytotoxicity assay revealed an IC50 value of 42.41±4.05 µg/mL. These findings suggest that A. phrygia could be utilized as a cosmetic ingredient in skincare products due to its ability to protect against UV radiation, exhibit antioxidant properties, prevent extracellular matrix degradation, and inhibit DNA damage.

Borago Officinalis L.: A Review Oon Extraction, Phytochemical, and Pharmacological Activities.

Borago officinalis L., an annual herb belonging to the Boraginaceae family, is used in the traditional medical practices of various countries and for multiple treatments, including respiratory disorders, colds, influenza, diarrhea, cramps, inflammation, palpitation, hypertension menopause, and post-menopausal symptoms. Its pharmacological properties and biological activities - among them antioxidant, antimicrobial, anticancer, anti-inflammatory, insecticidal, antigenotoxic, and anti-obesity activity - were demonstrated in vitro and in vivo and are related to its rich content of bioactive compounds (mainly phenolic acids, flavonoids, anthocyanins, alkaloids, and terpenes) extracted from various parts of B. officinalis including leaves, flowers, seeds, and roots. This review summarizes all updated information on applied extraction processes, phytochemistry, pharmacology, and toxicity of B. officinalis.

Toxic or medicinal? New approach to the pharmacological and toxicological properties of Echinodorus macrophyllus leaves

Echinodorus macrophyllus contains some phytochemicals that can induce toxicity but are also promising as ingredients in products to promote and maintain health, improve the immune system, and prevent diseases. In this study, the aqueous and ethanolic extracts of leaves of this species were characterized by high-performance liquid chromatography, investigated in vitro regarding their modulating action on snake venom enzymes, and evaluated in digestive enzyme inhibition assays. The extracts inhibited the phospholipase activity induced by Bothrops jararacussu and B. moojeni venoms. The hemolytic activity induced by Crotalus durissus terrificus venom was potentiated by 30-73% by the ethanolic extract at the ratios analyzed. The thrombolytic activity induced by B. moojeni venom was inhibited by 51% and 34% by the aqueous and ethanolic extracts at a ratio of 1:5 (w:w), respectively. The clotting time induced by B. moojeni and Lachesis muta muta venoms was prolonged after incubation with either extract. The extracts also exerted antigenotoxic action on DNA fragmentation induced by L. muta muta venom. Both extracts lowered the enzymatic activity of α-glucosidases, and the ethanolic extract inhibited α-amylases. The inhibition of digestive enzymes suggests the extracts could decrease calorie availability from carbohydrate intake. Results confirm the potential therapeutic use of E. macrophyllus in the prevention and treatment of hemostatic changes, since the proteins of venoms inhibited by it exhibit high homology with human proteins involved in various pathophysiological processes, such as inflammatory responses and blood coagulation.

A novel black poplar propolis extract with promising health-promoting properties: focus on its chemical composition, antioxidant, anti-inflammatory, and anti-genotoxic activities.

Propolis is a resinous mixture produced by honeybees which has been used since ancient times for its useful properties. However, its chemical composition and bioactivity may vary, depending on the geographical area of origin and the type of tree bees use for collecting pollen. In this context, this research aimed to investigate the total phenolic content (using the Folin-Ciocalteu assay) and the total antioxidant capacity (using the FRAP, DPPH, and ABTS assays) of three black poplar (Populus nigra L.) propolis (BPP) solutions (S1, S2, and S3), as well as the chemical composition (HPLC-ESI-MSn) and biological activities (effect on cell viability, genotoxic/antigenotoxic properties, and anti-inflammatory activity, and effect on ROS production) of the one which showed the highest antioxidant activity (S1). The hydroalcoholic BPP solution S1 was a prototype of an innovative, research-type product by an Italian nutraceutical manufacturer. In contrast, hydroalcoholic BPP solutions S2 and S3 were conventional products purchased from local pharmacy stores. For the three extracts, 50 phenolic compounds, encompassing phenolic acids and flavonoids, were identified. In summary, the results showed an interesting chemical profile and the remarkable antioxidant, antigenotoxic, anti-inflammatory and ROS-modulating activities of the innovative BPP extract S1, paving the way for future research. In vivo investigations will be a possible line to take, which may help corroborate the hypothesis of the potential health benefits of this product, and even stimulate further ameliorations of the new prototype.

Computational assessment and in vitro test of phytochemicals of Usnea aciculifera as potential inhibitors of Escherichia coli efflux pump AcrB

Lichens produce secondary metabolites that have many pharmaceutical activities such as antimicrobial, antioxidant, antiviral, anticancer, antigenotoxic, anti-inflammatory, analgesic and antipyretic activities. However, there is limited research on their efflux pump inhibitory activities. Twelve phytochemicals were isolated from Usnea aciculifera, and their activity of AcrAB-TolC efflux pump inhibition was evaluated. Four potential compounds, which are diffractaic acid (2), 8′ -O- methylstictic acid (5), 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2,4-dimethoxy-3,6-dimethylbenzoate (8) and 3-hydroxy-4-(methoxycarbonyl)-2,5-dimethylphenyl 2-hydroxy-4-methoxy-3,6-dimethylbenzoate (9), were found by virtual screening using pharmacophore and 2D-QSAR model. Compound 8 exhibited AcrB inhibition activity in vitro with an accumulation H33342 percentage compared with untreated control of 202% at a concentration of 50 µM and increased the antibacterial activity of levofloxacin by four-fold at a concentration of 200 µM. By molecular docking and molecular dynamics (MD) simulation, the binding affinity of depside and depsidone derivatives to AcrB was also clarified. Despite the poor docking score to the AcrB binding site, compound 8 was the most stable among the four complexes at 20 ns of MD simulation. The analysis of long MD at 100 ns indicated that compound 8 interacts strongly with the residues in the distal pocket, creating a stable complex with ΔGbind of −31.51 kcal.mol-1. According to the ADMETlab 2.0 web server’s predictions of pharmacokinetics and toxicities, compound 8 has the potential for drug development. Communicated by Ramaswamy H. Sarma

Chlorophyllin attenuates the effects of benzo[a]pyrene in human hepatoma HepG2/C3A cells

Chlorophyllin, a semisynthetic compound derived from chlorophyll, has been a focus in cancer prevention because it exerts important biological activities, such as antigenotoxic, antioxidative and anticarcinogenic activities. The aim of this study was to evaluate the effect of chlorophyllin against benzo[a]pyrene toxicity in HepG2/C3A cells. Cells were co-treated (chlorophyllin plus benzo[a]pyrene) and the cell viability, cell growth kinetics, cell cycle, and apoptosis were evaluated. The mRNA levels of cell cycle and apoptotic genes were analyzed. Our results showed that chlorophyllin reduce the antiproliferative effects of benzo[a]pyrene in a multi-specific manner, restoring the normal distribution of the cell cycle and inhibiting the cell death induced by the xenobiotic. Gene expression analysis showed that benzo[a]pyrene decreased the mRNA levels of genes involved in cell cycle control (cyclins and cyclin-dependent kinases) and apoptosis. Cells co-treated with 200 µM of chlorophyllin and benzo[a]pyrene also showed a downregulation of mRNA levels of the genes, but the expression levels of the gene that encodes to tumor protein p53 were maintained near to control. Thus, chlorophyllin is a good candidate as a chemoprotective agent that mitigates the cytotoxic effects benzo[a]pyrene and, thus, might be a promising tool to prevent liver cancer.

Cladonia rangiformis Acetone Extract— New Insight into the Chemical Composition and Biological Activity

Introduction Cladonia rangiformis, also known as reindeer lichen, has been used for various remedies in folk medicine. The rich nutritional value of this lichen is reflected in the fact that it contains atranorin, which has been proven to have numerous biological activities. Objective The chemical composition, antioxidant, anticholinesterase, and antigenotoxic activities of the C. rangiformis acetone extract were investigated. The novelty of this work is that anticholinesterase activity, protective effect on human lymphocytes, and antioxidant activity by the cupric-reducing antioxidant capacity (CUPRAC) method of C. rangiformis extract were determined for the first time, as well as gas chromatography - mass spectrometry (GC-MS) profile. Methods Chemical composition was carried out by high-performance liquid chromatography (HPLC)-diode array detector and GC-MS. Antigenotoxic effect was evaluated in human lymphocytes by cytokinesis-block micronucleus assay. Total phenolic content, DPPH and ABTS radical scavenging capacities, CUPRAC, and total reducing power were determined spectrophotometrically. Determination of acetylcholinesterase activity was performed by Ellman's colorimetry assay. The statistical analysis of variance (One-way ANOVA) was performed using Origin software package version 7.0. Results HPLC method was used to identified 3 compounds with atranorin as predominant constituent (97.2%). Fumarprotocetraric and atraric acid were represented in a much smaller mutually approximate amount, 0.3 and 0.5%, respectively. Rangiformic acid was the most abundant volatile compound. Acetone extract of C. rangiformis (2 μg/mL) decreased the frequency of micronuclei by 15.5% while the radioprotectant amifostine reduced the frequency of occurrence of micronuclei by 11.4%. On the contrary, at a concentration of 1.0 mg/mL the extract exhibited an activating effect on cholinesterase (2.0%), while at a concentration of 10.0 mg/mL it showed a weak inhibitory effect (7.3%). The total phenol content was 132.71 μg gallic acid equivalents per mg of dry extract. The IC50 value for the DPPH experiment was 16.19 mg/mL and for ABTS was 11.80 mg/mL. Cupric reducing capacity and total reducing power were 17.81 μg Trolox equivalents per mg of dry extract and 0.45 μg ascorbic acid equivalents per mg of dry extract, respectively. Conclusion In addition to previously identified compounds in the acetone extract, atraric acid was identified for the first time by using HPLC method, and orcinol, β-orcinol, lauric alcohol, atranol, and rangiformic acid by using GC-MS method. The results of biological activity proved that acetone extract had antioxidant capacity and weak anticholinesterase activity. Reduction of the number of micronuclei in human lymphocytes, classified C. rangiformis as promising substances source with beneficial effects on DNA damage.

Alizarin, an Agonist of AHR Receptor, Enhances CYP1A1 Enzyme Activity and Induces Transcriptional Changes in Hepatoma Cells

The phytopigment alizarin was previously characterized as an anti-tumor drug owing to its antioxidant or antigenotoxic activities. However, the safety of alizarin is currently still under dispute. In this study, we explored the activity of alizarin in the AHR-CYP1A1 pathway and analyzed the transcriptional changes affected by alizarin using human hepatoma cell line HepG2-based assays. The results showed that alizarin decreased HepG2 cell viability in a dose-dependent manner, with IC50 values between 160.4 and 216.8 μM. Furthermore, alizarin significantly upregulated the expression of CYP1A1 and increased the ethoxyresorufin-O-deethylase activity. Alizarin also exhibited agonistic activity toward the AHR receptor in the XRE-mediated luciferase reporter gene assay, which was further confirmed via the molecular docking assay. In addition, the transcriptional analysis indicated that alizarin may act as a potential carcinogen through significantly enriching several items related to cancer in both DO and KEGG analysis. In brief, our findings indicated that alizarin shows agonistic activities to the AHR receptor through activating the AHR-CYP1A1 signaling pathway in HepG2 cells, which may lead to the risks for cancer developing.

Cocktail of three isoquinoline alkaloids derived from Glaucium grandiflorum Boiss. & A. Huet subsp. refractum (Nábelek) Mory inhibits the production of LPS-induced ROS, pro-inflammatory cytokines, and mediators through the down-regulation of p38 MAPK in BV-2 cells

Glaucium grandiflorum extracts have traditionally been used to treat brain-related disorders. G. grandiflorum extracts also exhibited inhibitory effects on cholinesterase enzymes, as well as antigenotoxic activity. However, no research has been done on the effect of G. grandiflorum alkaloid extracts on the anti-oxidative and anti-inflammatory mechanisms. In this study we aimed to evaluate the anti-oxidative and anti-inflammatory activities of the alkaloid extract obtained from G. grandiflorum as well as the mechanisms responsible for their neuroprotective effects in neuronal damage caused by LPS in BV2 cells. We used LC-MS/MS and 1H, 13C NMR analysis to determine the presence of major alkaloids (allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide (trans-cannadine-N-oxide) in the alkaloid extracts. We used flow cytometry to study the alkaloid extracts' effects on ROS production; we also employed qRT-PCR and Western Blot to analyze the effects of oxidative stress and inflammation-related genes and proteins. ROS production within the cell was inhibited by chloroform alkaloid extract (CAE). There occurred marked CAE-induced reductions in IL-1β, Cox-2, and iNOS mRNA expressions. We also observed marked reductions in IL-6 and TNF-α mRNA expressions with methanol alkaloid extract (MAE). CAE effectively suppressed IL-1β and iNOS protein levels, especially as in qRT-PCR studies, while MAE effectively reduced IL-6 and TNF-α protein levels. Additionally, MAE was found to be prominent in suppressing the levels of Cox-2 protein, unlike qRT-PCR studies. According to our study findings, oxidative stress brought about by inflammation was suppressed by alkaloid extracts from G. grandiflorum which can be attributed to their suppressor effects on the pro-inflammatory cytokines-mediators, and p38 MAPK. As a result, a drug active substance that suppresses oxidative stress and inflammation has been brought to the neuropharmacological field.

Antigenotoxic Potential of Dayak Onion Bulb and Leaf (Eleutherine bulbosa Urb.) Ethanol Extract with Allium cepa Assay

Dayak onion (Eleutherine bulbosa Urb.) has the potential as an antigenotoxic agent capable of counteracting the effects of damage to DNA due to ROS (Reactive Oxygen Species). The bioactive compounds in Dayak onions have antiradical scavenging activity that plays a role in counteracting free radicals so that they can improve the genotoxicity that occurs. The purpose of this study was to determine the antigenotoxic potential of the ethanol extract of Dayak onion bulb and Dayak onion leaf using the Allium cepa assay. This study used a completely randomized design with various treatments of extract concentration (0.5, 1, 5, and 10 ppm) after immersion of 3% hydrogen peroxide (H2O2) with 3 replications. Chromosome observations of shallot (Allium cepa L.) roots were carried out between 09.00-10.00 am and then the mitotic index and percentage of inhibition were determined. Data were analyzed descriptively qualitatively, quantitatively, and through the ANOVA test followed by the 5% DMRT test. The ethanolic extract of 10 ppm Dayak onion bulb showed the highest antigenotoxic activity with a mitotic index reaching 6.78% and an inhibition percentage of 92.25%. The antigenotoxic activity of the ethanolic extract of Dayak onion bulb was higher than the ethanolic extract of Dayak onion leaf. These results are related to the antiradical scavenging activity of the ethanolic extract of Dayak onion bulb which is also higher than the ethanolic extract of Dayak onion leaf.

Essential oil from leaves of Croton blanchetianus Baill does not present acute oral toxicity, has antigenotoxic action and reduces neurogenic and inflammatory nociception in mice

Ethnopharmacological relevanceCroton blanchetianus Baill., popularly known as “marmeleiro preto”, is an endemic plant from Brazil, being found mainly in the Northeast region. In traditional medicine, the use of medicines based on the leaves of this plant has been reported for the treatment of inflammatory processes, pain, urethral pain, gastrointestinal disorders, rheumatism and headache.Aim of the study: The present work describes the chemical characterization, as well as toxicological evaluation and antinociceptive activity of an essential oil of C. blanchetianus leaves (EOCb). Materials and methodsThe chemical constituents of the oil were identified by gas chromatography coupled to mass spectrometry (GC-MS). In vitro hemolytic activity was tested using mouse blood. Acute toxicity in mice was assessed by the oral or intraperitoneal administration of a single dose of 2000 mg/kg b.w. EOCb (1000 and 2000 mg/kg) was also evaluated for genotoxicity and antigenotoxicity in vivo using the micronucleus test. The antinociceptive activity of EOCb (25, 50 and 100 mg/kg) was evaluated through the abdominal writhing, formalin and tail flick tests. ResultsThe chemical characterization indicated as major components α-pinene (21.23%), β-phelandrene (13.92%), terpinolene (13.01%) and germacrene D (10.89%). EOCb did not cause hemolysis and was also neither toxic nor genotoxic, while protected the animals' bone marrow cells from damage caused by cyclophosphamide in oral treatment. However, all animals died after 15 min of intraperitoneal treatment. There was a reduction in the number of abdominal contortions (69.43–89.41%) as well as in licks in the first (38.77–84.47%) and second (59.75–90.74%) phases of the formalin test. In the latter case, the effects were reduced by naloxone and glibenclamide, indicating action via the opioid system and blockage of K+ channels. The latency time in the tail flick test also increased significantly. ConclusionIn conclusion, ingestion of EOCb proved to be safe when administered orally; however, it was lethal intraperitoneally. Additionally, EOCb protected mouse blood cell DNA against the action of cyclophosphamide and showed an antinociceptive effect via the opioid system and dependent on K+ channels.

Enhancing Health Benefits through Chlorophylls and Chlorophyll-Rich Agro-Food: A Comprehensive Review.

Chlorophylls play a crucial role in photosynthesis and are abundantly found in green fruits and vegetables that form an integral part of our diet. Although limited, existing studies suggest that these photosynthetic pigments and their derivatives possess therapeutic properties. These bioactive molecules exhibit a wide range of beneficial effects, including antioxidant, antimutagenic, antigenotoxic, anti-cancer, and anti-obesogenic activities. However, it is unfortunate that leafy materials and fruit peels often go to waste in the food supply chain, contributing to the prevailing issue of food waste in modern societies. Nevertheless, these overlooked materials contain valuable bioactive compounds, including chlorophylls, which offer significant health benefits. Consequently, exploring the potential of these discarded resources, such as utilizing them as functional food ingredients, aligns with the principles of a circular economy and presents exciting opportunities for exploitation.

Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells.

Diphenyl ditelluride (DPDT) is an organotellurium (OT) compound with pharmacological properties, including antioxidant, antigenotoxic and antimutagenic activities when applied at low concentrations. However, DPDT as well as other OT compounds also show cytotoxicity against mammalian cells when treatments occur at higher drug concentrations. Considering that the underlying mechanisms of toxicity of DPDT against tumor cells have been poorly explored, the objective of our study was to investigate the effects of DPDT against both human cancer and non-tumorigenic cells. As a model, we used the colonic HCT116 cancer cells and the MRC5 fibroblasts. Our results showed that DPDT preferentially targets HCT116 cancer cells when compared to MRC5 cells with IC50 values of 2.4 and 10.1 μM, respectively. This effect was accompanied by the induction of apoptosis and a pronounced G2/M cell cycle arrest in HCT116 cells. Furthermore, DPDT induces DNA strand breaks at concentrations below 5 μM in HCT116 cells and promotes the occurrence of DNA double strand breaks mostly during S-phase as measured by γ-H2AX/EdU double staining. Finally, DPDT forms covalent complexes with DNA topoisomerase I, as observed by the TARDIS assay, with a more prominent effect observed in HCT116 than in MRC5 cells. Taken together, our results show that DPDT preferentially targets HCT116 colon cancer cells likely through DNA topoisomerase I poisoning. This makes DPDT an interesting molecule for further development as an anti-proliferative compound in the context of cancer.

The molecular mechanisms underlying anti-inflammatory effects of galangin in different diseases.

When used as an alternative source of drugs to treat inflammation-associated diseases, phytochemicals with anti-inflammatory properties provide beneficial impacts. Galangin is one of the most naturally occurring flavonoids. Galangin has many biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antimicrobial, anti-obesity, antidiabetic, and anti-genotoxic activities. We observed that galangin was well tolerated and positively impacted disease underlying inflammation for the renal, hepatic, central nervous system, cardiovascular, gastrointestinal system, skin, and respiratory disorders, as well as ulcerative colitis, acute pancreatitis, retinopathy, osteoarthritis, osteoporosis, and rheumatoid arthritis. Galangin anti-inflammatory effects are mediated mainly by suppressing p38 mitogen-activated protein kinases, nuclear factor-kappa B, and nod-like receptor protein 3 signals. These effects are confirmed and supported by molecular docking. Clinical translational research is required to accelerate the bench-to-bedside transfer and determine whether galangin can be utilised as a safe, natural source of pharmaceutical anti-inflammatory medication for humans.