Cytokine and chemokine profiles in the sera of COVID-19 patients with different stages of severity.

INTRODUCTION: COVID-19 is a viral infection that disturbs the host's immune system and causes an overproduction of cytokines leading to a cytokine storm. The present study aimed to evaluate the serum levels of 27 protein biomarkers to determine their association with COVID-19 disease severity. METHODS: The serum levels of 89 patients with different degrees of COVID-19 disease severity [asymptomatic (n = 14), moderate (n = 14), severe (n = 30), and critical (n = 31)] and 14 healthy individuals were tested for a panel of 27 cytokines and chemokines using Luminex assay (27 Bio­Plex Pro Human Cytokine, Bio-rad™). RESULTS: IL-12, IL-2 and IL-13, as well as IL-17 and GM-CSF were clearly undetectable in asymptomatic patients. IL-8 levels were higher in asymptomatic compared with other groups. Very high levels of IL-6, IL-10 and the chemokines MIP-1α, MCP-1 and IP10 were associated with disease progression, while IL-4 tends to decrease with disease severity. CONCLUSION: Our study provides more evidence that excessive cytokine synthesis is linked to the disease progression.

Development and validation of the first HBV qRT-PCR assay in the Mediterranean area targeting the X region.

Hepatitis B virus (HBV) infection is a global public health burden and affects approximatively 300 million people around the world. Since, HBV population is represented with genetic diversity, having different viral effects. Development of a new prognosis method play a key role on the efficiency of the different treatment. The HBx protein of HBV has a potential role in Hepatocellular Carcinoma (HCC), which makes it a valuable target for HCC prognosis. In this context, the first quantitative real-time PCR (qRT-PCR) assay in the Mediterranean area was developed and validated. Specific primers and probes of a conserved X region across all HBV genotypes were designed and the qRT-PCR was performed with the TaqPath 1-Step Multiplex Master Mix on 441 Moroccan plasma samples in Pasteur Institute of Morocco. The assay demonstrated a linear quantification range of 1010-101 IU/reaction (R2 = 0.99) and a quantification limit of 15 IU/mL. Comparative evaluations with the COBAS Ampliprep/COBAS TaqMan (CAP/CTM) HBV, v2.0 and the artus HBV QS-RGQ assays showed strong correlations (R2 = 0.92 and R2 = 0.89, respectively). Our test is fast, highly sensitive, specific, reproducible, and labor-saving. This system will be of great advantage to Mediterranean countries in their efforts to eliminate viral hepatitis B and C by 2030, enabling precise monitoring and effective treatment of HBV infections.

New triazole-based coordination complexes as antitumor agents against triple negative breast cancer MDA-MB-468 cell line.

The present work describes the synthesis of a new triazole based ligand 3-(3,5-dimethyl-1H-pyrazol-1-yl)-1-methyl-1H-1,2,4-triazole (LM) and demonstration of its coordination diversity giving rise to a family of seven new coordination complexes, namely: [Ni(LM)3](ClO4)2·C2H6OS (5), [Co2(LM)6](ClO4)4·(C2H5)O (6), [Cd(LM)2Cl2] (7), [Cu(LM)2NO3]NO3 (8), [Fe(LM)3](BF4)2 (9), [Zn(LM)3](BF4)2 (10) and [Zn(LM)2NO3]NO3 (11), whose crystal structure was determined by single-crystal X-ray diffraction. Cytotoxic activity was evaluated against the MDA-MB-468 cancer cell line, which serves as a model for triple-negative breast cancer, and compared to the precursor molecule (L), as well as their coordination complexes (H3O){[NiL3](ClO4)3} (1), [CoL3](ClO4)2·2H2O (2), [CdL2Cl2] (3) and [CuL3](NO3)2 (4), for which the crystal structure was earlier determined. Notably, cadmium complexes 3 and 7 exhibit remarkable cytotoxicity and demonstrated a high selectivity index towards cancer cells when compared to peripheral blood mononuclear cells. Such activity highlights their potential function as anticancer agents.

In vitro evaluation of dioscin and protodioscin against ER-positive and triple-negative breast cancer.

Women's breast cancer is one of the most significant healthcare issues for the human race that demands a proactive strategy for a cure. In this study, the cytotoxic activity (MTT assay) of two natural steroidal compounds, protodioscin and dioscin, against two major subtypes of human breast cancer estrogen receptor-positive (ER-positive)/MCF-7 and triple-negative breast cancer (TNBC)/MDA-MB-468), was assessed. The clonogenic capacity was evaluated using the clonogenic assay. Oxidative stress was determined by measuring the formation of malondialdehyde and H2O2 and the assessment of total antioxidant enzyme activities (SOD, GPx, GR, and TrxR). Protodioscin and dioscin were highly cytotoxic against the tested cell lines (1.53 µM

Phytochemical profile and antioxidant capacity, α-amylase and α-glucosidase inhibitory activities of Oxalis pes-caprae extracts in alloxan-induced diabetic mice.

Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress and leading to glycation reaction with formation of advanced glycation end products. However, medicinal plants are still a source of inspiration for the discovery of new treatments of several diseases, including diabetes. The present study was aimed to evaluate the antioxidant and antidiabetic properties of Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. The phytochemical and antioxidant activities of both aqueous and methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH and ABTS+), ferrous ions (Fe2+) chelating activity and reducing power assay. Additionally, the detection of Amadori products and advanced glycation end products was used to determine the antiglycation potential. α-glucosidase and α-amylase inhibitory assessment was employed to determine the antidiabetic effect, while alloxan-induced diabetic mice were used to measure the in-vivo activities of antioxidants and carbohydrates enzymes. The effect of the methanolic extract on body weight and blood glucose level of extract-treated diabetic mice were also investigated. Among the tested extract, the methanolic extract was the richest in phenolic compounds which is directly related with their remarkable antioxidant, enzyme inhibitory and antiglycation activity. The oral administration of the two doses of Oxalis pes-caprae flowers (150 mg/kg and 250 mg/kg) daily for 3 weeks resulted in hypoglycemic effect compared to the reference drug, glibenclamide (10 mg/kg). Furthermore, the extract was shown to significantly increase the activities of antioxidants and glycolysis enzymes in the liver, kidney and spleen of diabetic mice, compared to diabetic control group. Therefore, Oxalis pes-caprae extract effectively exhibited hypoglycemic and antidiabetic effects as indicated by in-vitro and in-vivo studies, confirming the protective effects on hyperglycemia and oxidative damage.

Dittrichia viscosa L. Leaves: A Valuable Source of Bioactive Compounds with Multiple Pharmacological Effects.

This work focused on the leaves of Dittrichia viscosa, a plant used in Mediterranean folk medicine. Compared to water extract, the methanolic extract had higher antioxidant effects. Moreover, this extract showed potent in vitro inhibitory activity against α-amylase and α-glucosidase and showed an interesting antiglycation effect. Additionally, the evaluation of the cytotoxic activity of the methanolic extract against two human breast cancer cell lines, MCF-7 and MDA-MB-468, was very promising, with no cytotoxicity towards normal cells (peripheral blood mononuclear cells (PBMCs). The antibacterial effect was also assessed and showed potent inhibitory activity against Proteus mirabilis and Bacillus subtilis. On the other hand, Dittrichia viscosa leaves were rich in macro-elements containing appropriate micro-elements and high levels of phenolics and flavonoids such as caffeic acid derivatives. Taken together, the results obtained in this study indicate that Dittrichia viscosa could constitute a valuable source of bioactive molecules and could be used either on the preventive side or for therapeutic applications without toxicity.

Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes.

The complexes: [CoL2](ClO4)2 (1), [FeL2](ClO4)2 (2), [NiL2](ClO4)2 (3) and [MnLCl2] (4), with L = diethyl-1,1'-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized. Structural analysis revealed two distinct patterns influenced by the counter ions where L acts as a tridentate chelating ligand. The in vitro antitumor activity of L and L' (diethyl 2,2'-(pyridine-2,6-diylbis(5-methyl-1H-pyrazole-3,1-diyl)) diacetate) as well as their metal complexes, was tested by the measurement of their cytostatic and cytotoxic properties towards the blood cancer mastocytoma cell line P815. We have also investigated their interactions with the antioxidant enzyme system. As a result, [MnL'Cl2] (1') exhibited the strongest activity compared to reference cis-platin with no cytotoxicity towards normal cells PBMCs (Peripheral Blood Mononuclear Cells). On the other hand, the antioxidant enzyme activity showed that the efficiency of metal complex 1' against P815 tumor cells was via the rise in the SOD activity and inhibition of CAT enzyme activity. This proof of concept study allows disclosure of a new class of molecules in cancer therapeutics.

Update and New Insights on Future Cancer Drug Candidates From Plant-Based Alkaloids.

Cancer is a complex multifactorial disease that results from alterations in many physiological and biochemical functions. Over the last few decades, it has become clear that cancer cells can acquire multidrug resistance to conventional anticancer drugs, resulting in tumor relapse. Thus, there is a continuous need to discover new and effective anticancer drugs. Natural products from plants have served as a primary source of cancer drugs and continue to provide new plant-derived anticancer drugs. The present review describes plant-based alkaloids, which have been reported as active or potentially active in cancer treatment within the past 4 years (2017-2020), both in preclinical research and/or in clinical trials. In addition, recent insights into the possible molecular mechanism of action of alkaloid prodrugs naturally present in plants are also highlighted.

A Systematic Review of the Current Hepatitis B Viral Infection and Hepatocellular Carcinoma Situation in Mediterranean Countries.

Viral hepatitis B is a global public health problem affecting nearly two billion subjects; 3.3% of whom are from the WHO (World Health Organization) Eastern Mediterranean Region (EMRO). It induces both acute and chronic hepatic disorders with subsequent liver cirrhosis and hepatocellular carcinoma (HCC) in a considerable percentage of patients based on the age of exposure. In this review, hepatitis B virus (HBV) and HCC prevalence, distribution and prevalence of different genotypes, and male/female infection frequencies in relation to the vaccination status in the Mediterranean countries were reported. Study Design. This systematic review describes the prevalence of hepatitis B infection, genotype distribution of hepatitis B virus, and prevalence and incidence of hepatocellular carcinoma in Mediterranean countries belonging to three different continents: Southern Europe (Spain, France, Italy, Croatia, and Greece), North Africa (Morocco, Algeria, Tunisia, Libya, and Egypt), and the Near East region (Syria, Lebanon, Turkey, Israel, and Palestine). We tried to collect new data from electronic databases: PubMed, ScienceDirect, ResearchGate, Google Scholar, and public health reports between 1980 and 2019. For each publication, we recorded reference, publication year, study characteristics (date, locations, sample size, and study population), and participant characteristics (population group, year, age, and sex). No language limitation was imposed, and articles or reports from non-peer-reviewed sources were not considered for this analysis. The main keywords were HBV prevalence, hepatitis B infection, HBV genotype, and HCC. Inclusion and Exclusion Criteria. Healthy population-based studies included the following sample populations: (i) voluntary blood donors, (ii) pregnant women, (iii) community studies, (iv) hemodialysis patients, (v) hospitalized patients, (vi) healthcare workers, (vii) sex workers, (viii) drug abusers, and (ix) prisoners. We excluded studies from the following special groups who were assumed to be at a special high risk: patients from sexually transmitted disease clinics and thalassemia clinics and professional or paid blood donors.

Performance Comparison of the artus HBV QS-RGQ and the CAP/CTM HBV v2.0 Assays regarding Hepatitis B Virus DNA Quantification.

BACKGROUND: Over 240 million people are chronically infected with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. The quantification of the HBV DNA level is critical for monitoring the efficacy of antiviral treatment of chronic HBV patients. METHODS: In our study, we compared the performance of the artus HBV QS-RGQ assay to the CAP/CTM v2.0 test, as a reference method, on 142 Moroccan patients. The analytical performance of the artus HBV QS-RGQ assay, such as the limit of detection, quantification, precision, reproducibility, and linearity, was determined using dilution series from 10 to 0.1 log10 IU/mL. RESULTS: Detection rates and viral loads quantified by the artus HBV QS-RGQ assay were significantly lower than those from the CAP/CTM v2.0 assay (73.94% vs. 82.39%; 3.34 ± 1.94 log10 IU/mL vs. 3.91 ± 2.45 log10 IU/mL; p < 0.01). A Bland-Altman plot found a mean difference of (CAP/CTM v2.0 - artus HBV QS - RGQ) = 0.5717 log10 IU/mL, with an average range of -1.13 to 2.31 log10 IU/mL. The two methods demonstrated a high correlation (r = 0.88) for 100 positive samples, a moderate correlation for samples below 2000 IU/mL (r = 0.76), and a very high correlation for the samples above 2000 IU/mL (r = 0.95). Linearity of the artus QS-RGQ test ranged from 1.07 to 7.51 log10 IU/mL. CONCLUSION: The artus HBV QS-RGQ assay showed a strong correlation, precision, and linearity in comparison with the CAP/CTM v2.0. However, viral loads determined by the artus HBV QS-RGQ assay were lower than those determined by the CAP/CTM v2.0 assay.

Berberine Impairs the Survival of Triple Negative Breast Cancer Cells: Cellular and Molecular Analyses.

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Non-available targeted therapy for TNBC represents its biggest treatment challenge. Thus, finding new promising effective drugs is urgently needed. In the present study, we investigated how berberine, a natural isoquinoline, impairs the survival of TNBC cells in both cellular and molecular levels. Our experimental model was based on the use of eight TNBC cell lines: MDA-MB-468, MDA-MB-231, HCC70, HCC38, HCC1937, HCC1143, BT-20, and BT-549. Berberine was cytotoxic against all treated TNBC cell lines. The most sensitive cell lines were HCC70 (IC50 = 0.19 µM), BT-20 (IC50 = 0.23 µM) and MDA-MB-468 (IC50 = 0.48 µM). Using flow cytometry techniques, berberine, at 0.5 and 1 µM for 120 and 144 h, not only induced cell cycle arrest, at G1 and/or G2/M phases, but it also triggered significant apoptosis. At the molecular level, these results are consistent with the expression of their related proteins using Western blot assays. Interestingly, while berberine was cytotoxic against TNBC cells, it had no effect on the viability of normal human breast cells MCF10A cultured in a 3D matrigel model. These results suggest that berberine may be a good potential candidate for TNBC drug development.

Treatment with Lead Chloride During Pregnancy and the Postnatal Period Alters Cell Proliferation and Immune Function in Swiss Albino Mice.

In the current study, we investigated the effect of lead chloride (PbCl2) administration (50 and 100 ppm) on organ and body weight as well as its bioaccumulation during pregnancy and the postnatal period in mice. We showed that lead has no effect on the body weight of mice. However, spleen weight is affected by the two doses of PbCl2 while liver and kidney weights are altered only by the 100-ppm dose. Inductively coupled plasma atomic emission spectrometry (ICP-AES) analysis showed that lead accumulates in the blood, spleen, and thymus. Both doses of PbCl2 significantly reduced splenocyte and thymocyte cell counts after stimulation with lipopolysaccharide (LPS) and phytohemagglutinin A (PHA), respectively. On the other hand, we showed that the levels of Th1 cytokines (interleukin-2 (IL-2), interferon gamma (IFN-γ)), and tumor necrosis factor alpha (TNF-α) were reduced in the serum of mice treated with PbCl2 in a dose-dependent manner, as measured by ELISA. The levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) were very low in untreated mice and were also reduced by treatment with PbCl2. The levels of IL-2, IFN-γ, IL-4, IL-10, and TNF-α secretion differentially decreased in LPS-stimulated splenocytes in lead-treated mice. Using PHA-stimulated thymocytes, we observed a reduction in the levels of IL-2, IL-4, IL-10, and TNF-α in the PbCl2-treated groups. However, IFN-γ concentration in the supernatant of these cells was not decreased when mice were treated with 50 ppm of lead.

Reactive Oxygen Species-Mediated Apoptosis and Cytotoxicity of Newly Synthesized Pyridazin-3-Ones In P815 (Murin Mastocytoma) Cell Line.

BACKGROUND: In cancer cells, the intracellular antioxidant capacity and the redox homeostasis are mainly maintained by the glutathione- and thioredoxin-dependent systems which are considered as promising targets for anticancer drugs. Pyridazinones constitute an interesting source of heterocyclic compounds for drug discovery. The present investigation focused on studying the in-vitro antitumor activity of newly synthesized Pyridazin-3(2h)-ones derivatives against P815 (Murin mastocytoma) cell line. METHODS: The in-vitro cytotoxic activities were investigated toward the P815 cell line using tetrazolium-based MTT assay. Lipid peroxidation and the specific activities of antioxidant enzymes were also determined. RESULTS: The newly compounds had a selective dose-dependent cytotoxic effect without affecting normal cells (PBMCs). Apoptosis was further confirmed through the characteristic apoptotic morphological changes and DNA fragmentation. Two compounds (6F: and 7H: ) were highly cytotoxic and were submitted to extend biological testing to determine the likely mechanisms of their cytotoxicity. Results showed that these molecules may induce cytotoxicity via disturbing the redox homeostasis. Importantly, the anticancer activity of 6F: and 7H: could be due to the intracellular reactive oxygen species hypergeneration through significant loss of glutathione reductase and thioredoxin reductase activities. This eventually leads to oxidative stress-mediated P815 cell apoptosis. Furthermore, the co-administration of 6F: or 7H: with Methotrexate exhibited a synergistic cytotoxic effect. CONCLUSIONS: considering their significant anticancer activity and chemosensitivity, 6F: and 7H: may improve the therapeutic efficacy of the current treatment for cancer.

Phytochemical Characterization, Antioxidant and In Vitro Cytotoxic Activity Evaluation of Juniperus oxycedrus Subsp. oxycedrus Needles and Berries.

In order to evaluate the antioxidant properties of aqueous and methanol extracts of needles and berries of Juniperus oxycedrus subsp. oxycedrus (Joo) species, various antioxidant capacity assessment tests (free radical scavenging assays (DPPH• and ABTS•+ tests), ferrous ions (Fe2+) chelating activity and reducing power assay (FRAP) were conducted. In all of the tests, the extracts exhibited strong antioxidant activity. Furthermore, in-vitro cytotoxic activity assays of the methanolic extracts showed potent cytotoxic effects against two breast cancer cell lines (MDA-MB-468 and MCF-7), with no cytotoxicity towards normal cells (PBMCs). Reactive oxygen species generation was presumed to be a potential reason for the observed cytotoxic effects. According to all the above, and considering its appropriate composition of mineral elements and phenolic compounds, Joo could offer a beneficial and natural source of bioactive compounds that can be either used on the preventive side as it could potentially be used in the clinic without toxicity.

Phytochemical analysis, cytotoxic and antioxidant activities of Myrtus communis essential oil from Morocco.

Background Myrtus communis L. is an aromatic evergreen plant common in Morocco. In addition to its culinary uses, it has been used medicinally as a disinfectant, an antiseptic or as a hypoglycemic agent. However, its cytotoxic activity has not been well investigated so far. The current study describes the chemical composition, cytotoxic and antioxidant activities of Myrtus communis L essential oil obtained from different regions of Morocco. Methods Myrtus communis essential oils were obtained by hydrodistillation, and analyzed by gas chromatography coupled with mass spectrometry. Cytotoxic activity was evaluated in murine mastocytoma P815 and MCF-7 breast cancer cells, using the MTT assay. In addition, DNA fragmentation was assessed by gel electrophoresis. The antioxidant effect was determined by measuring bleaching of ß-carotene with the linoleic acid and the DPPH radical scavenging methods. Results GC-MS analysis showed high amounts of methyl eugenol (18.7%), α-terpineol (15.5%) and geranyl acetate (11.64%) in essential oil from the Benslimane region. In contrast, essential oil from Ouazzane was particularly rich in 1,8-cineole (36.3%). The cytotoxicity results showed that MCF-7 cells were more sensitive than P815 cells to the essential oils from Ouazzane and Benslimane regions with IC50 values of 4 and 6.25 µg/mL, respectively. Moreover, this cytotoxicity was partly associated with DNA fragmentation, which is one of the characteristics of apoptosis. The tested essential oils did not show strong antioxidant activity. Conclusions Myrtus communis L. essential oil exhibits a weak antioxidant effect, but induced remarkable cytotoxic activity by a mechanism related to apoptosis, suggesting a possible application of the bioactive compounds as natural anticancer compounds.

Cytotoxicity of new pyridazin-3(2H)-one derivatives orchestrating oxidative stress in human triple-negative breast cancer (MDA-MB-468).

Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H2 O2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC50 values of 3.12 and 4.9 µM, respectively. Furthermore, cells exposed to 6f showed a significant increase in H2 O2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities.

Studies on the Dual Cytotoxicity and Antioxidant Properties of Berberis vulgaris Extracts and Its Main Constituent Berberine.

The present study attempts to investigate the cytotoxic activity of ethanol and ethyl acetate extracts of the Moroccan Berberis vulgaris and its major component berberine, together with exploring their antioxidant properties. It also consists of studying the combination effect of berberine and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, against the human breast adenocarcinoma cell line (MCF-7). Using the MTT assay, we report a differential cytotoxic effect of ethanol and ethyl acetate extracts since the ethanol extract is more cytotoxic than the ethyl acetate one, with IC50 = 3.54 µg/mL and 596.71 µg/mL, respectively. Interestingly, no cytotoxic effect was observed against normal cells. Furthermore, these extracts showed a remarkable antioxidant activity as measured by the DPPH free radicals scavenging assay. In fact, the IC50 values are 69.65 µg/mL and 77.75 µg/mL for the ethanol and ethyl acetate extracts, respectively. In addition, several concentrations of berberine, when combined with the NO donor used at IC30, induced a synergistic cytotoxic activity at concentrations ranging from 8.40 µM to 33.60 µM, as revealed by the combination index values, using the Chou-Talalay method. However, at the other concentrations tested, an antagonistic effect was observed. The observed cytotoxicity was related to apoptosis induction as demonstrated by the annexin-V-streptavidin FITC-staining analysis.

More insights into the pharmacological effects of artemisinin.

Artemisinin is one of the most widely prescribed drugs against malaria and has recently received increased attention because of its other potential biological effects. The aim of this review is to summarize recent discoveries of the pharmaceutical effects of artemisinin in basic science along with its mechanistic action, as well as the intriguing results of recent clinical studies, with a focus on its antitumor activity. Scientific evidence indicates that artemisinin exerts its biological activity by generating reactive oxygen species that damage the DNA, mitochondrial depolarization, and cell death. In the present article review, scientific evidence suggests that artemisinin is a potential therapeutic agent for various diseases. Thus, this review is expected to encourage interested scientists to conduct further preclinical and clinical studies to evaluate these biological activities.

Chemical Composition and Cytotoxic and Antibacterial Activities of the Essential Oil of Aloysia citriodora Palau Grown in Morocco.

The aim of this work is to investigate the in vitro cytotoxic and antibacterial effects of the essential oils of Aloysia citriodora Palau, harvested in different regions of Morocco. The chemical profile was established using gas chromatography-mass spectrometry analysis. The cytotoxic activity against P815, MCF7, and VERO cell lines as well as the normal human peripheral blood mononuclear cells (PBMCs) was evaluated using the MTT assay. Standard, ATCC, strains of bacteria (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) were cultivated in Muller Hinton media. Then, agar disc diffusion, minimum inhibitory concentrations (MICs), and minimal bactericidal concentrations (MBCs) were determined using microdilution method. The essential oils obtained were predominantly composed of ß-spathulenol (15.61%), Ar-curcumene (14.15%), trans-caryophyllene oxide (14.14%), and neral (10.02%). The results of the assays showed that the cytotoxic effect of the essential oil of A. citriodora was high on P815 and moderate on MCF7 and on VERO cell lines. However, no cytotoxic effect was observed on PBMCs. On the other hand, essential oils showed a significant antimicrobial activity against both Gram-negative and Gram-positive bacteria. MICs ranged between 2.84 and 8.37 mg/ml. Essential oil of A. citriodora leaves possesses significant antibacterial effect and cytotoxic activity against tumor cell lines.

Differential Cytotoxic Activity of Essential Oil of Lippia citriodora from Different Regions in Morocco.

The aim of this work was to investigate the cytotoxic effect of the essential oil of dried leaves of Lippia citriodora (H.B. & K.) harvested in different regions of Morocco. This effect was evaluated against the P815 murine mastocytoma cell line using the MTT assay. Interestingly, this work demonstrated for the first time that these essential oils exhibited a strong cytotoxic activity against the P815 cell line, with IC50 values ranging from 7.75 to 13.25 µg/ml. This cytotoxicity began early and increased in a dose- and time-dependent manner. The chemical profile of these essential oils was analyzed by gas chromatography coupled to mass spectrometry. Importantly, the difference in terms of major components' contents was not significant suggesting probably that the differential cytotoxicity between these essential oils could be attributed to the difference in the content of these essential oils in minor compounds, which could interact with each other or with the main molecules. Finally, this study demonstrated for the first time that essential oils of L. citriodora from different regions in Morocco induced apoptosis against P815 tumor cell line.