Simultaneous Exposure to Noise and Toluene Induces Oxidative and Inflammatory Damage in the Heart of Wistar Rats: Therapeutic Potential of Olea europaea L. Leaf Extract.

Workers in occupational settings often face simultaneous exposure to multiple risk factors, including noise and chemicals. This study aimed to investigate the effects of combined exposure to noise and toluene on the cardiac health of rats, with a focus on assessing the potential mitigating effects of Olea europaea L. (OLE) leaf extract (40 mg/kg/day). The evaluation involved scrutinizing biochemical and hematological markers, quantifying oxidative stress levels, determining proinflammatory cytokines in the serum, and conducting an in silico Docking studies. Forty-two male Wistar rats were divided into eight groups-(n = 6/group):-Control-group-(C),-OLE-group-(Rats administered OLE), NT-group (rats co-exposed to noise and toluene), NT-4 group-(rats co-exposed to noise and toluene four weeks after the exposure period), NT + OLE1-group (rats co-exposed to noise and toluene treated with OLE for one week), NT + OLE2-group-(rats co-exposed to noise and toluene treated with OLE for two weeks), NT + OLE3-group-(rats co-exposed to noise and toluene treated with OLE for three weeks), and NT + OLE4-group (rats co-exposed to noise and toluene treated with OLE for four weeks). The results revealed that combined exposure to noise and toluene led to oxidative damage and increased serum levels of proinflammatory cytokines. However, OLE treatment attenuated these effects by reducing lipid peroxidation and enhancing catalase and superoxide dismutase activities. Additionally, OLE treatment significantly decreased proinflammatory cytokine levels compared to the noise and toluene co-exposed group. The study highlighted the potential of OLE to attenuate the adverse effects of combined exposure to noise and toluene, attributed to its anti-inflammatory and antioxidant properties.

Olea europaea L. leaf extract mitigates pulmonary inflammation and tissue destruction in Wistar rats induced by concurrent exposure to noise and toluene.

This study aimed to investigate the effects of combined exposure to noise (85 dB(A)) and inhaled Toluene (300 ± 10 ppm) on rat lung health. It also aimed to assess the potential therapeutic effects of Olea europaea L. leaves extract (OLE) (40 mg/kg/day) using biochemical, histopathological, and immunohistochemical (IHC) analyses, as well as determination of pro-inflammatory cytokines (TNF-α and IL-1ß), and in silico Docking studies. The experiment involved forty-two male Wistar rats divided into seven groups, each exposed to a 6-week/6-hour/day regimen of noise and Toluene. The groups included a control group, rats co-exposed to noise and Toluene, and rats co-exposed to noise and Toluene treated with OLE for different durations. The results indicated that noise and Toluene exposure led to structural damage in lung tissue, oxidative harm, and increased levels of pro-inflammatory cytokines (TNF-α and IL-1ß). However, the administration of OLE extract demonstrated positive effects in mitigating these adverse outcomes. OLE treatment reduced lipid peroxidation and enhanced the activities of catalase and superoxide dismutase, indicating its anti-oxidant properties. Furthermore, OLE significantly decreased the levels of pro-inflammatory cytokines compared to the groups exposed to noise and Toluene without OLE treatment. Moreover, the in silico investigation substantiated a robust affinity between COX-2 and OLE components, affirming the anti-inflammatory activity. Overall, our findings suggest that OLE possesses anti-inflammatory and anti-oxidative properties that mitigate the adverse effects of concurrent exposure to noise and Toluene.

Ozone therapy (O2-O3) alleviates the progression of early intervertebral disc degeneration via the inhibition of oxidative stress and the interception of the PI3K/Akt/NF-κB signaling pathway.

Intervertebral disc degeneration (IDD) stands for the most frequent cause of low back pain. Finding a cure for this disease is an important challenge as current conservative treatments and surgical interventions fail to bring a solution to this disease. Ozone therapy (O2-O3) has yielded outstanding outcomes in intervertebral disc pathology. The ozone's efficacy in the treatment of IDD remains unconfirmed. This study aimed to assess the effectiveness of intradiscal ozone injection on IDD induced in a rat. Effects of ozone therapy on the viability of nucleus pulposus cells were evaluated by CCK-8 assays. Macrophage immunoreactivity was detected by immunohistochemical, the expression of collagen type II was evaluated by western blot, and measurement of oxidative stress parameters was realized. Molecular docking studies were carried out in order to predict the interaction formed between O3 and the target enzymes, on the one hand, O3 with PI3K and, on the other hand, O3 with COX-2. IRM, X-ray, hematoxylin-eosin, and bleu alcian staining were realized to assess the therapeutic impacts of ozone in the puncture-induced rat model of IDD. In vivo, O3 ameliorated the IDD in the early stage of this disease. It was also displayed in molecular docking that O3 might bind to PI3K to suppress the PI3K/Akt/NF-κB signaling pathway. This study's results show that the O3 should be administered at the low grade of IDD and at an early stage because it cannot restore the advanced inflammatory alteration of the IVD. Our results corroborated also that O3 inhibits the progression of IDD via the PI3K/Akt/NF-κB signaling pathway, which supports O3 as an effective therapeutic option for treating IDD.

Semi-synthesis, α-amylase inhibition, and kinetic and molecular docking studies of arylidene-based sesquiterpene coumarins isolated from Ferula tunetana Pomel ex Batt.

Despite all the significant progresses made to enhance the efficacy of the existing bank of drugs used to manage and cure type II diabetes mellitus, there is still a need to search and develop novel bioactive compounds with superior efficacy and minimal adverse effects. This study describes the valorization of the natural bioactive sesquiterpene coumarin via the semi-synthesis of new analogs and the study of their α-amylase inhibition activity. The sesquiterpene coumarin named coladonin (1) was quantitatively isolated from the chloroform extract of endemic Ferula tunetana roots. Subsequently, the oxidation of 1via the Jones oxidation reaction, used as a key reaction, afforded precursor 2. The condensation of oxidized coladonin (2) with various aryl aldehydes provided a series of new arylidene-based sesquiterpene coumarin derivatives (3a-m), which were characterized by NMR and ESI-HRMS experiments. All derivatives evaluated in vitro for their α-amylase inhibitory potential showed interesting α-amylase inhibition with IC50 values ranging from 7.24 to 28.98 µM. Notably, compounds 3k and 3m exhibited lower IC50 values (7.24 µM and 8.38 µM, respectively) compared to the standard (acarbose: IC50 = 9.83 µM). In addition, the structure-activity relationship (SAR) for all the compounds was studied. The most active compounds were found to be mixed-type inhibitors, which was revealed by kinetic studies. Furthermore, molecular in silico docking studies were established for all synthesized analogs with the binding site for the α-amylase enzyme.

Anthraquinones from Rhamnus alaternus L.: A Phytocosmetic Ingredient with Photoprotective and Antimelanogenesis Properties.

The purpose of the present work was to develop a phytocosmetic sunscreen emulsion with antioxidant activity and an anti-melanogenic effect, containing an anthraquinone-enriched extract of Rhamnus alaternus (A.E.). Our findings demonstrated that A.E. decreased the levels of reactive oxygen species, DNA damage, and malondialdehyde induced by UVA in human keratinocytes and melanocytes. Furthermore, the calculated SPF value in vitro of the cream containing A.E. was 14.26±0.152. Later, it was shown that A.E. extract had an inhibitory effect on the amount of melanin. This extract could also reduce B16F10 intracellular tyrosinase activity. Besides, docking studies were carried out to provide a logical justification for the anti-tyrosinase potential. The findings showed that, A.E. may provide protection against UVA-induced oxidative stress and could be thought of as a viable treatment for hyperpigmentation disorders.

A molecular chemodosimeter to probe "closed shell" ions in kidney cells.

Two quinidine-functionalized coumarin molecular probes have been synthesized and have been found to bind metal cations (Cd2+, Co2+, Cu2+, Fe2+, Hg2+, Ni2+, and Zn2+) with high affinity in organic-aqueous media (DMSO-HEPES). The chemodosimeters coordinate with the Zn2+ ions in a two-to-one ratio (molecular probe : Zn2+) with a log ß of 10.0 M-2. Upon the addition of the closed-shell metal ions studied, a fluorescence turn-on via an excimer formation is seen at 542 nm due to the quinaldine moiety adopting a syn arrangement when coordinated to the metal Zn2+ ions. Confocal microscopy monitored free Zn2+ ions in the Human Embryonic Kidney cell line HEK293 by coordinating with the chemodosimter.

Chemical composition, antioxidant and anti-tyrosinase potentials of Acacia cyclops trunk bark using in vitro and in silico approaches.

The purpose of this paper was to evaluate the phytochemical profile of Acacia cyclops trunk bark methanol extract using LC-MS/MS, as well as to assess its antioxidant and anti-tyrosinase activities. Thus, total phenolic and flavonoid contents of the studied extract were established and 19 compounds were detected and quantified. In addition of their antioxidant potential against DPPH and ABTS assays, in vitro and in silico studies were adopted to evaluate tyrosinase inhibitory property of A. cyclops extract. Methanol trunk bark extract showed significant total phenolic content, antioxidant potential in terms of free radical scavenging, as well as an interesting tyrosinase inhibitory action (IC50= 05.12 ± 0.41 µg/mL). The molecular docking analysis and the drug-likeness prediction of the major selected compounds supported the significant anti-tyrosinase activity of the studied extract. The obtained results suggest that A. cyclops extract could be a promising candidate in the treatment of skin hyperpigmentation disorders.

Novel Oleanolic Acid-Phtalimidines Tethered 1,2,3 Triazole Hybrids as Promising Antibacterial Agents: Design, Synthesis, In Vitro Experiments and In Silico Docking Studies.

As part of the valorization of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3ß-hydroxyolean-12-en-28-oic acid, OA-1)-phtalimidines (isoindolinones) conjugates 18a-u bearing 1,2,3-triazole moieties were designed and synthesized by treating an azide 4 previously prepared from OA-1 isolated from olive pomace (Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues, 18a-u, were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes, and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa. Attractive results were obtained, notably against L. monocytogenes. Compounds 18d, 18g, and 18h exhibited the highest antibacterial activity when compared with OA-1 and other compounds in the series against tested pathogenic bacterial strains. A molecular docking study was performed to explore the binding mode of the most active derivatives into the active site of the ABC substrate-binding protein Lmo0181 from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor of the experimental data.

Chemical Composition, Toxicity and Repellency of Inula graveolens Essential Oils from Roots and Aerial Parts against Stored-Product Beetle Tribolium castaneum (Herbst).

In this work, essential oils extracted from roots and aerial parts of Inula graveolens by hydrodistillation and their fractions obtained by chromatographic simplification were first investigated for their chemical composition by GC/MS and then evaluated for the first time for their repellency and contact toxicity properties against Tribolium castaneumadults. Twenty-eight compounds were identified in roots essential oil (REO), which accounted for 97.9 % of the total oil composition, with modhephen-8-ß-ol (24.7 %), cis-arteannuic alcohol (14.8 %), neryl isovalerate (10.6 %) and thymol isobutyrate (8.5 %) as major constituents. Twenty-two compounds were found in the essential oil from aerial parts (APEO), which accounted for 93.9 % of the total oil, with borneol (28.8 %), caryophylla-4(14),8(15)-dien-6-ol (11.5 %), caryophyllene oxide (10.9 %), τ-cadinol (10.5 %) and bornyl acetate (9.4 %) as main compounds.REO and APEO displayed stronger repellency after 2 h of exposure (80.0 and 90.0 %, respectively) against T. castaneum at the concentration of 0.12 µL/cm2 . After fractionation, fractions R4 and R5 exhibited greater effects (83.3 % and 93.3 %, respectively) than the roots essential oil. Furthermore, the fractions AP2 and AP3 showed higher repellency (93.3 and 96.6 %, respectively) than the aerial parts oil. The LD50 values of oils from roots and aerial parts topically applied were 7.44 % and 4.88 %, respectively. Results from contact toxicity assay showed that fraction R4 was more effective than the roots oil with LD50 value of 6.65 %. These results suggests that essential oils of roots and aerial parts from I. graveolens may be explored as potential natural repellent and contact insecticides against T. castaneum in stored products.

Chemical Profile of the Pits Oil from the Tunisian 'Alig' Cultivar of Phoenix dactylifera L.: In Vivo Wound Healing Potential Evaluation of a Cream Formulated from the Extracted Oil and Insights from Molecular Docking and SAR Analysis.

Since ancient times the oil from date palm pits (Phoenix dactylifera L.) has been used to heal wounds. In order to prove this traditional usage of the pits, this oil was extracted from the pits of the Tunisian cultivar 'Alig' and its physico-chemical properties and the chemical composition were evaluated. The fatty acid profile, evidenced by GC, allowed to classify this oil as an oleic-myristic acid oil with a clear abundance of oleic acid (53.66 %). 1 H and 13 C-NMR as well as FT-IR analyses confirmed the presence of fatty acids in triglyceride forms. Furthermore, in vivo wound healing activity of a cream formulated from the extracted oil was performed, for the first time, using a rat model and was compared to placebo cream and a commercial formulation, MEBO®. This study showed that the test cream promoted the healing of pressure ulcers better than the placebo cream and the MEBO® ointment. The results showed that this vegetable oil is able to improve the healing of infected wounds in rats, thus supporting its traditional use. The contribution of the main oleic, linoleic and myristic acids that can be derived from enzymatic hydrolysis to the healing activity of the whole pits oil was predicted by in silico study and the calculated pharmacokinetics parameters.

Synthesis and In Silico Docking Study towards M-Pro of Novel Heterocyclic Compounds Derived from Pyrazolopyrimidinone as Putative SARS-CoV-2 Inhibitors.

In addition to vaccines, antiviral drugs are essential in order to suppress COVID-19. Although some inhibitor candidates have been determined to target the SARS-CoV-2 protein, there is still an urgent need to continue researching novel inhibitors of the SARS-CoV-2 main protease 'Omicron P132H', a protein that has recently been discovered. In the present study, in the search for therapeutic alternatives to treat COVID-19 and its recent variants, we conducted a structure-based virtual screening using docking studies for a new series of pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives 5-13, which were synthesized from the condensation reaction of pyrazolopyrimidinone-hydrazide (4) with a series of electrophiles. Some significant ADMET predictions-in addition to the docking results-were obtained based on the types of interactions formed and the binding energy values were compared to the reference anti- SARS-CoV-2 redocked drug nirmatrelvir.

Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis.

In the present study, we assess tyrosol derivatives bearing 3,5-disubstituted isoxazoles and 1,4-disubstituted triazoles for their ability to inhibit the proliferation of K562 cells derived from leukemia as well as primary chronic myeloid leukemia (CML) cells obtained from the peripheral blood of 15 CML patients including 10 patients with untreated chronic phase and 5 patients with resistance against imatinib or multiple TKI. Our results showed that most derivatives displayed significant anti-proliferative activity against K562 cells in a dose-dependent manner. Among them, compounds 3d and 4a exhibited greater potent anticancer activity with respective IC50 values of 16 and 18 µg/mL (45 µM and 61 µM). Interestingly, compound 3d inhibited CML cell proliferation not only in newly diagnosed but also in imatinib-resistant patients. We demonstrated that the anti-proliferative effect of this compound is mediated by a pro-apoptotic activity by promoting oxidative stress and modulating the activity of the Akt, p38 MAPK and Erk 1/2 pathways. In conclusion, our data highlight the potential of this class of derivative as a novel promising therapeutic agent for CML therapy.

Chitosan-CdS Quantum Dots Biohybrid for Highly Selective Interaction with Copper(II) Ions.

Cadmium sulfide (CdS) quantum dots (QDs) were homogeneously embedded into chitosan (CTS), denoted as CdS@CTS, via an in situ hydrothermal method. The intact structure of the synthesized materials was preserved using freeze-drying. The materials were characterized using X-ray diffraction (XRD), X-ray photoelectron spectroscopy, transmission electron microscopy, high-resolution TEM, scanning TEM, dispersive energy X-ray (EDX) for elemental analysis and mapping, Fourier transform infrared spectroscopy, nitrogen adsorption-desorption isotherms, thermogravimetric analysis, UV-vis spectroscopy, and diffuse reflectance spectroscopy (DRS). The synthesis procedure offered CdS QDs of 1-7 nm (average particle size of 3.2 nm). The functional groups of CTS modulate the in situ growth of CdS QDs and prevent the agglomeration of CdS QDs, offering homogenous distribution inside CTS. CdS@CTS QDs can also be used for naked-eye detection of heavy metals with high selectivity toward copper (Cu2+) ions. The mechanism of interactions between Cu2+ ions and CdS@CTS QDs were further studied.

Synthesis and In Silico Docking of New Pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine-based Cytotoxic Agents.

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV-Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC50 values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.

Design, Microwave-Assisted Synthesis and In Silico Prediction Study of Novel Isoxazole Linked Pyranopyrimidinone Conjugates as New Targets for Searching Potential Anti-SARS-CoV-2 Agents.

A series of novel naphthopyrano[2,3-d]pyrimidin-11(12H)-one containing isoxazole nucleus 4 was synthesized under microwave irradiation and classical conditions in moderate to excellent yields upon 1,3-dipolar cycloaddition reaction using various arylnitrile oxides under copper(I) catalyst. A one-pot, three-component reaction, N-propargylation and Dimroth rearrangement were used as the key steps for the preparation of the dipolarophiles3. The structures of the synthesized compounds were established by 1H NMR, 13C NMR and HRMS-ES means. The present study aims to also predict the theoretical assembly of the COVID-19 protease (SARS-CoV-2 Mpro) and to discover in advance whether this protein can be targeted by the compounds 4a-1 and thus be synthesized. The docking scores of these compounds were compared to those of the co-crystallized native ligand inhibitor (N3) which was used as a reference standard. The results showed that all the synthesized compounds (4a-l) gave interesting binding scores compared to those of N3 inhibitor. It was found that compounds 4a, 4e and 4i achieved greatly similar binding scores and modes of interaction than N3, indicating promising affinity towards SARS-CoV-2 Mpro. On the other hand, the derivatives 4k, 4h and 4j showed binding energy scores (-8.9, -8.5 and -8.4 kcal/mol, respectively) higher than the Mpro N3 inhibitor (-7.0 kcal/mol), revealing, in their turn, a strong interaction with the target protease, although their interactions were not entirely comparable to that of the reference N3.

Trifluoromethylated Flavonoid-Based Isoxazoles as Antidiabetic and Anti-Obesity Agents: Synthesis, In Vitro α-Amylase Inhibitory Activity, Molecular Docking and Structure-Activity Relationship Analysis.

Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by 1H NMR, 13C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 µM, and with IC50 values of 12.6 ± 0.2 µM-27.6 ± 1.1 µM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 µM), with a potency (IC50 = 12.6 ± 0.2 µM) similar to that of the positive control acarbose (IC50 = 12.4 ± 0.1 µM). The study of the structure-activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.

Glioblastoma-specific anticancer activity of newly synthetized 3,5-disubstituted isoxazole and 1,4-disubstituted triazole-linked tyrosol conjugates.

Two series of 3,5-disubstituted isoxazoles (6a-e) and 1,4-disubstituted triazoles (8a-e) derivatives have been synthesized from tyrosol (1), a natural phenolic compound, detected in several natural sources such as olive oil, and well-known by its wide spectrum of biological activities. Copper-catalyzed microwave-assisted 1,3-dipolar cycloaddition reactions between tyrosol-alkyne derivative 2 and two series of aryl nitrile oxides (5a-e) and azides (7a-e) regiospecifically afforded 3,5-disubstituted isoxazoles (6a-e) and 1,4-triazole derivatives (8a-e), respectively in quantitative yields. Synthesized compounds were purified and characterized by spectroscopic means including 1D and 2D NMR techniques and HRMS analysis. The newly prepared hybrid molecules have been evaluated for their anticancer and hemolytic activities. Results showed that most derivatives displayed significant antiproliferative activity against human glioblastoma cancer cells (U87) in a dose-dependent manner. Compounds 6d (IC50 = 15.2 ± 1.0 µg/mL) and 8e (IC50 = 21.0 ± 0.9 µg/mL) exhibited more potent anticancer activity. Moreover, most derivatives displayed low hemolytic activity, even at higher concentrations which suggested that these classes of compounds are suitable candidates for further in vivo investigations. The obtained results allow us to consider the newly synthesized isoxazole- and triazole-linked tyrosol derivatives as promising scaffolds for the development of effective anticancer agents.

Chemical Composition and Cytotoxic Activity of the Fractionated Trunk Bark Essential Oil from Tetraclinis articulata (Vahl) Mast. Growing in Tunisia.

The aim of the present research was to determine the chemical composition and the cytotoxic effects of Tetraclinis articulata trunk bark essential oil (HEE) obtained by steam distillation and five fractions obtained by normal phase silica chromatographic separation. Chemical analysis allowed the identification of 54 known compounds. Relatively high amounts of oxygenated sesquiterpenes (44.4-70.2%) were detected, mainly consisting of caryophyllene oxide (13.1-26.6%), carotol (9.2-21.2%),14-hydroxy-9-epi-(E)-caryophyllene (3.2-15.5%) and humulene epoxide II (2.6-7.2%). The cytotoxic activity against human mammary carcinoma cell lines (MDA-MB-231) and colorectal carcinoma cell lines (SW620) of the essential oil and its fractions were assessed. All the samples displayed moderate to weak activity compared to 5-fluorouracil. The colorectal carcinoma cell line was relatively more sensitive to the essential oil and its fractions compared to the breast cancer cell line, showing IC50 values from 25.7 to 96.5 µg/mL. In addition, the essential oil and its fraction E.2 revealed a cytotoxic activity against colorectal carcinoma cell line, with IC50 values lower than 30 µg/mL. This is the first report on the chemical composition and cytotoxic activity of the trunk bark essential oil of T. articulata.

Anti-tyrosinase, anti-cholinesterase and cytotoxic activities of extracts and phytochemicals from the Tunisian Citharexylum spinosum L.: Molecular docking and SAR analysis.

Previously phytochemical investigations carried out on the flowers and trunk bark extracts of Citharexylum spinosum L. tree, allowed the isolation of twenty molecules belonging to several families of natural substances [triterpene acids, iridoid glycosides, phenylethanoid glycosides, 8,3'-neolignan glycosides, together with other phenolic compounds]. In the present work, a biological evaluation (anti-tyrosinase, anticholinesterase and cytotoxic activities) was performed on the prepared extracts and the isolated secondary metabolites. The results showed that the EtOAc extract of the trunk bark displayed the highest anti-tyrosinase effect with a percent inhibition of 55.0 ± 1.8% at a concentration of 100 µg/mL. The highest anticholinesterase activity was presented by the same extract with an IC50 value of 99.97 ± 3.01 µg/mL. The EtOAc extract of flowers and that of the trunk bark displayed the best cytotoxic property with IC50 values of 96.00 ± 2.85 and 88.75 ± 2.00 µg/mL, respectively, against the human cervical cancer cell line (HeLa), and IC50 values of 188.23 ± 3.88 and 197.00 ± 4.25 µg/mL, respectively, against the human lung cancer (A549) cell lines. Biological investigation of the pure compounds showed that the two 8,3'-neolignan glycosides, plucheosides D1-D2, generate the highest anti-tyrosinase potency with a percent inhibition of 61.4 ± 2.0 and 79.5 ± 2.3%, respectively, at a concentration of 100 µM. The iridoid glycosides exhibited a significant anticholinesterase activity with IC50 values ranging from 17.19 ± 1.02 to 52.24 ± 2.50 µM. Triterpene pentacyclic acids and iridoid glycosides exerted encouraging cytotoxic effects against HeLa with IC50 values ranging from 9.00 ± 1.10 to 25.00 ± 1.00 µM. The study of the structure-activity relationship (SAR) has been sufficiently and widely discussed. The natural compounds that exhibited the significant bioactivities were docked.

Effect of oleuropein on oxidative stress, inflammation and apoptosis induced by ischemia-reperfusion injury in rat kidney.

AIMS: This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism. MAIN METHODS: Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot. KEY FINDINGS: Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys. SIGNIFICANCE: In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties.