Design, synthesis, In-vitro, In-silico and DFT studies of novel functionalized isoxazoles as antibacterial and antioxidant agents.

A series of new isoxazolederivatives incorporating the sulfonate ester function has been synthesized from 2-benzylidenebenzofuran-3(2 H)-one, known as aurone. The synthesis of the target compounds was carried out following an efficient methodology that allows access to the desired products in a reproducible way and with good yield. The structures of the synthesized compounds were established using NMR (1H and 13C) spectroscopy and mass spectrometry. A theoretical study was performed to optimize the geometrical structures and to calculate the structural and electronic parameters of the synthesized compounds. The calculations were also carried out to understand the influence and the effect of substitutions on the chemical reactivity of the studied compounds. The synthesized isoxazoles were screened for their antioxidant and antibacterial activities. The findings demonstrate that the studied compounds exhibit good to moderate antibacterial activity against the tested bacteria (Staphylococcus aureus, Bacillus subtilis, and Escherichia coli). Moreover, a number of the tested isoxazole derivatives exhibit high effectiveness against DPPH free radicals. Besides that, molecular docking studies were carried out to predict binding affinity and identify the most likely binding interactions between the active molecules and the target microorganisms' proteins. A 100 ns molecular dynamics study was then conducted to examine the dynamic behavior and stability of the highly potent isoxazole 4e in complex with the target bacterial proteins. Finally, the ADMET analyses suggest that all the synthesized isoxazoles have good pharmacokinetic profiles and non-toxicity and non-carcinogenicity in biological systems.

In Vitro and In Silico Studies of Antimicrobial, and Antioxidant Activities of Chemically Characterized Essential Oil of Artemisia flahaultii L. (Asteraceae).

The present study investigated the antioxidant and antimicrobial activities as well as characterized the chemical composition of the essential oils (EO) isolated from Artemisia flahaultii (EOF). EOF was extracted using hydro-distillation, and the chemical composition of EOF was ascertained by gas chromatography coupled with mass spectrometry (GC/MS). To assess antioxidant capacity, three tests were used: the 2,2-diphenyl-1-picrylhydrazil (DPPH), the total antioxidant capacity (TAC) and the ferric-reducing antioxidant power (FRAP) test. The antimicrobial activity of EOF was investigated using the diffusion assay and minimal inhibitory concentration assays (MICs). By use of in silico structure-activity simulations, the inhibitory potency against nicotinamide adenine dinucleotide phosphate (NADPH), physicochemical characters, pharmaco-centric properties and absorption, distribution, metabolism, excretion (ADME) characteristics of EOF were determined. GC/MS analysis reveals 25 components majorly composed of D-Limonene (22.09%) followed by ß-pinene (15.22%), O-cymene (11.72%), ß-vinylnaphthalene (10.47%) and benzene 2,4-pentadiynyl (9.04%). The capacity of DPPH scavenging by EOF scored an IC50 of 16.00 ± 0.20 µg/mL. TAC revealed that the examined oils contained considerable amounts of antioxidants, which were determined to be 1094.190 ± 31.515 mg ascorbic acid equivalents (AAE)/g EO. Results of the FRAP method showed that EOF exhibited activity with EC50 = 6.20 ± 0.60 µg/mL. Values for minimal inhibitory concentration (MIC) against certain clinically important pathogenic bacteria demonstrate EOF's potent antibacterial activity. MIC values of 1.34, 1.79, and 4.47 µg/mL against E. coli, B. subtilis and S. aureus were observed respectively. EOF exhibited significant antifungal activities against two stains of fungi: F. oxysporum and C. albicans, with values of 10.70 and 2.23 µg/mL, respectively. Of the total, 25 essential oils were identified. 2,4-Di-tert-butylphenol and capillin were the most active molecules against NADPH. The ADME prediction revealed that EOF was characterized by useful physicochemical characteristics and pharmaco-centric properties. The findings of this study show that the EOF can be used as an alternative to treat microbial resistance. Based on the in silico studies, EOF can be used as an "eco-friendly" NADPH inhibitor.

Antimicrobial and Antioxidant Properties of Chemically Analyzed Essential Oil of Artemisia annua L. (Asteraceae) Native to Mediterranean Area.

Artemisia annua (AA) is an aromatic plant belonging to the Asteraceae family, which has long been known for its several medicinal virtues. In addition, essential oils (EOs) extracted from AA have a wide range of therapeutic properties. Therefore, this study aimed to investigate the phytochemical composition, anti-microbial, and anti-oxidant properties of Artemisia annua essential oil (EOAA). EO was extracted, and its chemical constituents were ascertained by the use of GC-MS analysis. EOAA shows remarkable antioxidant capacities of DPPH free radical scavenging with an IC50 value of 29 ± 5.3 µg/mL and ferric reducing antioxidant power with an EC50 value of 9.21 ± 0.3 µg/mL, and it also has a good total antioxidant capacity of 911.59 ± 115.71 milligrams of ascorbic acid equivalence per gram of EO (mg AAE/g EO). Moreover, the in vitro antimicrobial screening results indicate that EOAA has shown promising antibacterial activity, especially against the Escherichia coli strain, and it also shows significant antifungal activity against Fusarium oxysporum and Candida albicans yeasts. Taken together, our findings highlight the importance of EOAA as a source of strong antioxidant and antimicrobial agents, which could be used as an alternative form to control free radicals and combat drug-resistant microbes.

Antibacterial, Antioxidant, and in silico NADPH Oxidase Inhibition Studies of Essential Oils of Lavandula dentata against Foodborne Pathogens.

Food is always subjected to microbial infection and lipid peroxidation, which frequently leads to serious food intoxications. In the present study, essential oils (EOs) extracted from Lavandula dentata Moroccan species and its major component (linalool) were chemically characterized and their antioxidant potential and antibacterial properties against foodborne pathogenic bacteria were examined. EOs phytochemical profile was carried out using gas chromatography-mass spectrometry analysis (GC-MS). The antioxidant potential was evaluated, in vitro, by use of the ß-carotene discoloration assay and in silico vs. NADPH oxidase enzymatic complex as an antioxidant marker. The antibacterial proprieties were assessed by use of minimal inhibitory concentration (MIC) and disc diffusion methods, against Gram (-) bacteria (Pseudomonas aeruginosa, Salmonella enterica, and Escherichia coli) and Gram (+) bacteria (Bacillus subtilis and Staphylococcus aureus). Linalool (49.71%) was the major component among the eighteen components identified in Lavandula dentate EO, followed by camphor (14.36%) and borneol (8.21%). The studied EO and linalool compounds showed important antioxidant activity through the ß-carotene discoloration test with IC50 values of 35.72 ± 1.21 mg/mL and 30.32 ± 1.23 mg/mL, respectively. Among all the analyzed compounds of lavender EOs, thymol, carvacrol, and α-terpineol were the most active compounds against NADPH oxidase with a glide score of -6.483, -6.17, and -4.728 kcal/mol, respectively. 2D and 3D views showed the formation of hydrogen bonds between the most active compounds and the active site of NADPH oxidase. The antibacterial data showed a significant activity of Lavandula dentata essences against tested foodborne pathogenic bacteria, especially against S. aureus and B. subtilis. Linalool proved active toward the same bacteria and had closer activity to that of lavender essential oil. In light of the obtained findings, the essential oil of Lavandula dentata Moroccan species can be used in the packaging sector as a promising natural food conservative to limit lipid oxidation and treat foodborne infections.

Solanum elaeagnifolium Var. Obtusifolium (Dunal) Dunal: Antioxidant, Antibacterial, and Antifungal Activities of Polyphenol-Rich Extracts Chemically Characterized by Use of In Vitro and In Silico Approaches.

The present work was designed to study the chemical composition and the antioxidant and antimicrobial properties of fruits (SFr) and leaf (SF) extracts from Solanum elaeagnifolium var. obtusifolium (Dunal) Dunal (S. elaeagnifolium). The chemical composition was determined using HPLC-DAD analysis. Colorimetric methods were used to determine polyphenols and flavonoids. Antioxidant capacity was assessed with DPPH, TAC, and FRAP assays. Antimicrobial activity was assessed using disk diffusion and microdilution assays against two Gram (+) bacteria (Staphylococcus aureus ATCC-6633 and Bacillus subtilis DSM-6333) and two Gram (-) bacteria (Escherichia coli K-12 and Proteus mirabilis ATCC-29906), while the antifungal effect was tested vs. Candida albicans ATCC-1023. By use of in silico studies, the antioxidant and antimicrobial properties of the studied extracts were also investigated. HPLC analysis showed that both fruits and leaf extracts from S. elaeagnifolium were rich in luteolin, quercetin, gallic acid, and naringenin. Both SFr and SF generated good antioxidant activity, with IC50 values of 35.15 ± 6.09 µg/mL and 132.46 ± 11.73 µg/mL, respectively. The EC50 of SFr and SF was 35.15 ± 6.09 µg/mL and 132.46 ± 11.73 µg/mL, respectively. SFr and SF also showed a good total antioxidant capacity of 939.66 ± 5.01 µg AAE/and 890.1 ± 7.76 µg AAE/g, respectively. SFr had important antibacterial activity vs. all tested strains-most notably B. subtilis DSM-6333 and E. coli, with MICs values of 2.5 ± 0.00 mg/mL and 2.50 ± 0.00 mg/mL, respectively. SFr demonstrated potent antifungal activity against C. albicans, with an inhibition diameter of 9.00 ± 0.50 mm and an MIC of 0.31 ± 0.00 mg/mL. The in silico approach showed that all compounds detected in SFr and SF had high activity (between -5.368 and 8.416 kcal/mol) against the receptors studied, including NADPH oxidase, human acetylcholinesterase, and beta-ketoacyl-[acyl carrier protein] synthase.

GC-MS Profiling, In Vitro Antioxidant, Antimicrobial, and In Silico NADPH Oxidase Inhibition Studies of Essential Oil of Juniperus thurifera Bark.

Juniperus thurifera is a native species to the mountains of the western Mediterranean region. It is used in traditional medicine as a natural treatment against infections. The present study aimed to carry out the chemical analysis and evaluate the antioxidant, antimicrobial, as well as in silico inhibition studies of the essential oils from Juniperus thurifera bark (EOEJT). Chemical characterization of EOEJT was done by gas chromatography (GC-MS). We have performed three antioxidant assays (Reducing power (FRAP), 2, 2-diphenylpicrylhydrazyl (DPPH), and total antioxidant capacity (TAC)) of the EOEJT. We next evaluated the antimicrobial activity against in silico study, which was carried out to help evaluate the inhibitory effect of EOEJT against NADPH oxidase. Results of the GC/MS analysis revealed seven major compounds in EOEJT wherein muurolol (36%) and elemol (26%) were the major components. Moreover, EOEJT possessed interesting antioxidant potential with an IC50 respectively of 21.25 ± 1.02 µg/mL, 481.02 ± 5.25 µg/mL, and 271 µg EAA/mg in DPPH, FRAP, and total antioxidant capacity systems. Molecular docking of EOEJT in NADPH oxidase active site showed inhibitory activity of α-cadinol and muurolol with a glide score of -6.041 and -5.956 Kcal/mol, respectively. As regards the antibacterial and antifungal capacities, EOEJT was active against all tested bacteria and all fungi, notably, against Escherichia coli K12 with an inhibition diameter of 21 mm and a MIC value of 0.67 mg/mL, as well as against Proteus mirabilis ATCC 29906 with an inhibition diameter of 18.33 ± 1.15 mm and a MIC value of 1.34 mg/mL. A more pronounced effect was recorded for the fungal pathogens Fusarium oxysporum MTCC 9913 with inhibition of 37.44 ± 0.28% and MIC value of 6.45 mg/mL, as well as against Candida albicans ATCC 10231 with an inhibition diameter of 20.33 ± 1.15 mm and a MIC value of 0.67 ± 0.00 mg/mL. Altogether, these results highlight the importance of EOEJT as a source of natural antibacterial and antioxidant drugs to fight clinically important pathogenic strains.

Phytochemical Analysis and Antioxidant, Antibacterial, and Antifungal Effects of Essential Oil of Black Caraway (Nigella sativa L.) Seeds against Drug-Resistant Clinically Pathogenic Microorganisms.

Nigella sativa (NS) is a plant that has long been utilized in traditional medicine as a treatment for certain diseases. The aim of this work was to valorize the essential oil (EO) of this species by phytochemical analysis and antimicrobial and antioxidant evaluation. EO was extracted by hydrodistillation from the seeds of Nigella sativa (EO-NS). Phytochemical content of EO-NS was evaluated by use of gas chromatography coupled to mass spectrometry (GC-MS/MS). Antioxidant ability was in vitro determined by use of three assays: 2.2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing power (FRAP), and total antioxidant capacity (TAC) relative to two synthetic antioxidants: BHT and quercetin. Antimicrobial effect was evaluated against four clinically important bacterial strains (Staphylococcus aureus, ATCC 6633; Escherichia coli, K12; Bacillus subtilis, DSM 6333; and Proteus mirabilis, ATCC 29906) and against four fungal strains (Candida albicans, ATCC 10231; Aspergillus niger, MTCC 282; Aspergillus flavus, MTCC 9606; and Fusarium oxysporum, MTCC 9913). Fifteen constituents that accounted for the majority of the mass of the EO-NS were identified and quantified by use of GC-MSMS. The main component was O-cymene (37.82%), followed by carvacrol (17.68%), α-pinene (10.09%), trans-sabinene hydrate (9.90%), and 4-terpineol (7.15%). EO-NS exhibited significant antioxidant activity with IC50, EC50, and total antioxidant capacity (TAC) of 0.017 ± 0.0002, 0.1196 ± 0.012, and 114.059 ± 0.97 mg EAA/g, respectively. Additionally, EO-NS exhibited promising antibacterial activity on all strains under investigation, especially on E. coli K12 resulting in inhibition diameter of 38.67 ± 0.58 mm and a minimum inhibitory concentration (MIC) of 1.34 ± 0.00 µg/mL. Also, EO-NS had significant antifungal efficacy, with a percentage of inhibition of 67.45 ± 2.31% and MIC of 2.69 ± 0.00 µg/mL against F. oxysporum, MTCC 9913 and with a diameter of inhibition 42 ± 0.00 mm and MIC of 0.67 ± 0.00 µg/mL against C. albicans. To minimize development of antibiotic-resistant bacteria, EO-NS can be utilized as a natural, alternative to synthetic antibiotics and antioxidants to treat free radicals implicated in microbial infection-related inflammatory reactions.

Antioxidant, Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.

Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC50 of 1.30 ± 0.05 mg/mL in the DPPH test and an EC50 equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC50) was 7.8 ± 0.3 µL EO/L, while the effective concentration in the ingestion test (LC50) was 15.0 ± 2.1 µL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.

Brocchia cinerea (Delile) Vis. Essential Oil Antimicrobial Activity and Crop Protection against Cowpea Weevil Callosobruchus maculatus (Fab.).

Antibiotics and synthetic pesticides are now playing a role in the spread of resistant pathogens. They continue to have negative consequences for animal and plant health. The goal of this work is to identify the chemical composition of Brocchia cinerea (Delile) Vis. essential oil (EO) using GC-MS(Gas Chromatography-Mass Spectrometer), evaluate its antimicrobial properties, and investigate its insecticidal and repellent effectiveness against Callosobruchus maculatus (C. maculatus). The GC-MS indicated the presence of 21 chemicals, with thujone (24.9%), lyratyl acetate (24.32%), camphor (13.55%), and 1,8-cineole (10.81%) being the most prominent. For the antimicrobial assay, the yeast Candida albicans was very sensitive to the EO with a growth inhibition diameter of (42.33 mm), followed by Staphylococcus aureus (31.33 mm). Fusarium oxysporum is the mycelia strain that appeared to be extremely sensitive to the utilized EO (88.44%) compared to the two species of Aspergillus (A. flavus (48.44%); A. niger (36.55%)). The results obtained in the microdilution method show that Pseudomonas aeruginosa was very sensitive to the EO, inhibited by a very low dose (0.0018 mg/mL). The minimum inhibitory concentration (MIC) results were between 0.0149 and 0.06 mg/mL. B. cinerea EO also demonstrated a potent insecticidal effect and a medium repulsive effect against C. maculatus. Thus, the LC50 value in the contact test was 0.61 µL/L of air, lower than that observed in the inhalation test (0.72 µL/L of air). The present study reveals that B. cinerea EO has the potential to be an antimicrobial and insecticidal agent with a better performance against several pathogenic microorganisms.

Antioxidant and Antimicrobial Activities of Chemically-Characterized Essential Oil from Artemisia aragonensis Lam. against Drug-Resistant Microbes.

This study investigated the chemical composition, antioxidant and antimicrobial activity of essential oil extracted from Artemisia aragonensis Lam. (EOA). Hydrodistillation was employed to extract EOA. Gas chromatography with flame ionization detection (GC-FID) and gas chromatography-mass spectrometry analyses (GC-MS) were used to determine the phytochemical composition of EOA. Antioxidant potential was examined in vitro by use of three tests: 2.2-diphenyl-1-picrilhidrazil (DPPH), ferric reducing activity power (FRAP) and total antioxidant capacity assay (TAC). Agar diffusion and microdilution bioassays were used to assess antimicrobial activity. GC/MS and GC-FID detected 34 constituents in the studied EOA. The major component was Camphor (24.97%) followed by Borneol (13.20%), 1,8 Cineol (10.88%), and Artemisia alcohol (10.20%). EOA exhibited significant antioxidant activity as measured by DPPH and FRAP assays, with IC50 and EC50 values of 0.034 ± 0.004 and 0.118 ± 0.008 mg/mL, respectively. EOA exhibited total antioxidant capacity of 7.299 ± 1.774 mg EAA/g. EOA exhibited potent antibacterial activity as judged by the low minimum inhibitory concentration (MIC) values against selected clinically-important pathogenic bacteria. MIC values of 6.568 ± 1.033, 5.971 ± 1.033, 7.164 ± 0.0 and 5.375 ± 0.0 µg/mL were observed against S. aureus, B. subtills, E. coli 97 and E. coli 57, respectively. EOA displayed significant antifungal activity against four strains of fungi: F. oxysporum, C. albicans, A. flavus and A. niger with values of 21.50 ± 0.43, 5.31 ± 0.10, 21.50 ± 0.46 and 5.30 ± 0.036 µg/mL, respectively. The results of the current study highlight the importance of EOA as an alternative source of natural antioxidant and antibacterial drugs to combat antibiotic-resistant microbes and free radicals implicated in the inflammatory responses accompanying microbial infection.

Lavandula dentata L.: Phytochemical Analysis, Antioxidant, Antifungal and Insecticidal Activities of Its Essential Oil.

Antioxidant, antifungal and insecticidal activities of essential oil (EO) extracted from the Moroccan lavender (Lavandula dentata) were investigated and their chemical constituents determined. Gas chromatography with flame ionization detection (GC-FID) and gas chromatography-mass spectrometry analyses (GC-MS) were used to examine the phytochemical composition of EO. Antioxidant potential was examined in vitro by use of three tests: DPPH inhibition, reducing power (FRAP) and total antioxidant capacity (TAC). Antifungal activity was assessed by calculating inhibition of growth of Alternaria alternata, Botrytis cinerea and Fusarium oxysporum. Repellent potential and toxicity of EO by contact and inhalation were performed against Callosobruchus maculatus. Sixteen constituents were detected in the EO of Lavandula dentata. The major component was linalool (45.06%) followed by camphor (15.62%) and borneol (8.28%). EO exhibited a significant antioxidant activity, as measured by DPPH and FRAP assays, with IC50 and EC50 values of 12.95 ± 1.300 mg/mL and 11.88 ± 0.23 mg/mL, respectively. EO of lavender exhibited total antioxidant capacity of 81.28 ± 2.28 mg AAE/g EO. EO of lavender showed an inhibitory effect on mycelial growth against tested fungi and was 100% in the case of B. cinerea. EO caused total mortality of adult C. maculatus from 5 µL/L air with LC50 value of 4.01 µL/L air. Significant reduction in numbers of eggs laid (99.2%) and emergence (100%) was observed in a dose-dependent manner up to maxima of 100% and 99.2%, respectively. EO of lavender also showed a moderate potency to repel insects with a mean of 34.44%. EO of Moroccan Lavandula dentata has potential to be an effective natural agent against free radical damage and could be an environmentally friendly alternative bio-fungicide and bio-insecticide.

Promising Antioxidant and Anticorrosion Activities of Mild Steel in 1.0 M Hydrochloric Acid Solution by Withania frutescens L. Essential Oil.

The present study was conducted to evaluate the anticorrosive and antioxidant activities of essential oil from Withania frutescens L. In the present study, the extraction of Withania frutescens L. essential oil (Wf-EO) was conducted using hydrodistillation before being characterized by gas chromatographic analysis (GC/MS) and flame ionization detector (GC/FID). Four bioassays were used for antioxidant testing including 2,2-diphenyl-1-picrylhydrazyl (DPPH), total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP), and ß-carotene bleaching. The inhibiting effect of Wf-EO on the corrosion behavior of mild steel in 1.0 M HCl was conducted by using polarization curves and electrochemical impedance spectroscopy techniques. The yield of Wf-EO was 0.46% including 175 compounds identified by GC-MS. The oil was mostly constituted of camphor (37.86%), followed by thujone (26.47%), carvacrol (6.84%), eucalyptol (3.18%), and linalool (2.20%). The anti-free radical activity of Wf-EO was 34.41 ± 0.91 µg/ml (DPPH), 9.67 ± 0.15 mg/ml (FRAP), 3.78 ± 0.41 mg AAE/g (TAC), and 89.94 ± 1.44% (ß-carotene). The Wf-EO showed potent antioxidant activity in all bioassays used for testing. The anticorrosion activity, polarization curves as well as EIS diagrams indicated that the Wf-EO exhibited anticorrosive properties and reacted as a suitable corrosion inhibitor in an acidic medium.

Salvia officinalis and Lippia triphylla: Chemical characterization and evaluation of antidepressant-like activity.

Salvia officinalis (Lamiaceae) and Lippia triphylla (Verbenaceae) are two plants known for their therapeutic effects in conventional medicine for the treatment of a wide extent of diseases, including the ones on the central nervous system. In the present study, the impact of aqueous extract from the leaves of these two herbs for the treatment of depression was examined. The phytochemical profile highlighted the presence of eighteen and ten polyphenolic compounds in Salvia officinalis and Lippia triphylla, respectively. The antidepressant effects of such extracts were assessed using two tests: the forced swimming test (FST) and tail suspension test (TST) in swiss albino mice. Five mice were partitioned into each group: control (distilled water), standard (Imipramine hydrochloride, 25 mg/kg) and three test ones treated with increased doses of aqueous extracts (250-500-1000 mg/kg), orally administered for two weeks. The acute treatment of the mice with aqueous extracts of Salvia officinalis and Lippia triphylla reduced significantly the time of immobility in the forced swimming test (p < 0.001) as compared to control group, and also decreased significantly the time of immobility of mice in the tail suspension test (p < 0.001). The findings attained in this work show how both plants possess potential anti-depressant-like effects; however, the translation from the results presented in this work to a potential use as therapeutic agents would require the acquisition of a stronger scientific evidence.

Evaluation of the acute toxicity of the extracts of Anacyclus pyrethrum var. pyrethrum (L.) and Anacyclus pyrethrum var. depressus Maire in Swiss mice.

BACKGROUND AND AIM: Anacyclus pyrethrum (L.) has been used in traditional North African and Indian medicine for the treatment of several diseases such as cancer, rheumatism, epilepsy, diabetes, and Alzheimer's disease. Despite its medical benefits, few studies have examined its toxicity. The present study evaluated the acute toxicity of hydroethanolic extracts of different parts (roots, seeds, leaves, and capitula) of two varieties of A. pyrethrum (L.), namely, A. pyrethrum var. pyrethrum (L) and A. pyrethrum var. depressus (Ball) Maire, in mice. MATERIALS AND METHODS: Acute toxicity was evaluated after the oral administration of different extracts at doses of 300, 500, and 2000 mg/kg. Mortality, body weight, general behavior, and adverse effects were observed daily for 14 days. At the end of the experiment, mice were sacrificed, and biochemical parameters and histopathology of the liver, kidneys, and spleen were analyzed. RESULTS: The extracts of different parts of both plants induced no signs of toxicity or mortality during the observation period, excluding capitulum and seed extracts, which induced slight sedation at a dose of 2000 mg/kg. The LD50 of the extracts was estimated to exceed 2000 mg/kg. The administration of A. pyrethrum var. pyrethrum roots at a dose of 300 mg/kg resulted in significantly increased AST levels. However, the A. pyrethrum var. depressus root extract induced significant increases in the levels of both transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). The remaining extracts of both plants at a dose of 500 mg/kg significantly increased AST levels. Moreover, all plant extracts excluding the A. pyrethrum var. pyrethrum capitulum extract at 2000 mg/kg provoked significant increases in AST levels, and A. pyrethrum var. depressus roots provoked a significant increase of ALT levels. Meanwhile, mice treated with high doses of extracts (2000 mg/kg) displayed histopathological changes in the liver, kidneys, and spleen characterized by hepatic distress, inflammatory infiltration, focal tubular necrosis, vascular congestion, and lymphoid hyperplasia. CONCLUSION: The results of the present study indicate that the hydroethanolic extracts of different parts of two varieties of A. pyrethrum (L.) were not toxic in mice at low concentrations, whereas some toxic effects were detected in mice treated at 2000 mg/kg.

Antibacterial, antifungal and antioxidant activity of total polyphenols of Withania frutescens.L.

Our objective in this work is evaluated the antibacterial, antifungal and antioxidant activity of the phytochymic compounds of the roots and leaves of a species Withania frutescens. In the first part, the phenolic compound is determinate by the Folin-Ciocalteau reaction, the richness of the roots in polyphenols (53.33 ±â€¯1.20 mg EGA/g Extract) is six times higher than that of the leaves. The antioxidant test is evaluated by four methods: DPPH test, reducing power test (FRAP), total antioxidant capacity (CAT) and the ß-carotene discoloration test. The IC-50 values of the DPPH test of the studied parts are of the order of 0.36 µg/ml and 6.63 µg/ml, which showed a lower anti-free radical activity than that of BHT (0.12 µg/ml). The results obtained by the FRAP method revealed a low reducing power of iron for two extracts (EC-50 of 0.45%) compared to Quercetine (EC-50 of 0.03%). The compounds of root and leaf extracts have a significant total antioxidant capacity, respectively 477.65 ±â€¯37.60 and 317.03 ±â€¯46.64 mg EAA/g Extract. In the ß-carotene discoloration test, extracts from the aerial and underground parts showed antioxidant activity of 57% followed by (36%), respectively. The evaluation of the antibacterial activity of in vitro extracts against microorganisms is carried out by two methods: disc diffusion and microdilution. The results show that the extracts exert an intermediate inhibitory effect (inhibition diameter between 8 and 15 mm, the smallest MIC obtained is 2.80 mg/ml) on all strains tested. The antifungal activity was estimated by determining the growth inhibition rate of the fungus tested. Indeed, the compounds studied exhibit a good antifungal effect since the minimum inhibitory concentration (MIC) of 4.5 mg/ml for root extract and 9 mg/ml for leaf extract.