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The aim of this study was to examine the chemical composition and antioxidant activities of the essential oils and anthocyanin ofBorago officinalisflowers. At the flowering stage, the essential oil yield in Korba (0.95 ± 0.03%) was higher than that in Beja (0.29 ± 0.03%, w/w). The essential oil composition was characterized by high proportions of (E,E)-decadienal, the main compound of monoterpene aldehydes class. The reverse phase–high-performance liquid chromatography–mass spectrometry analysis indicated that flower anthocyanins were extracted and analysed for the first time and petunidin 3,5 diglucoside (58.8% in Korba and 54.93% in Beja) was the major anthocyanin followed by delphinidin 3,5 diglucoside (36.45% in Korba and 44.45% in Beja). During the development of borage flower, anthocyanin yield increased significantly (P < 0.05) from budding to full flowering stages in the two studied regions. Antioxidant activity of anthocyanin extracts and essential oil followed the same trend as anthocyanin and essential oil yields in Korba and Beja regions. In all tests, anthocyanin extracts of borage flowers showed better antioxidant activity than essential oils. A notable variability was found among the anthocyanin and essential oil concentrations and their antioxidant activities between the two studied regions, indicating a strong influence of the degree of maturity on metabolite production. [ABSTRACT FROM AUTHOR]

In the present study, we assessed the antioxidant and antileishmanial potential from fresh leaves of Ballota (B.) hirsuta essential oil (EO). The GC-MS analysis of B. hirsuta EO revealed that spathulenol and germacrene D were the main components accounting for 26.03% and 19.64% of the total EO, respectively. B. hirsuta EO possesses moderate antioxidant activity, both in neutralizing DPPH radicals and in inhibiting β-carotene bleaching. In addition, it exhibits both high antileishmanial activity and selectivity towards the promastigote and amastigote forms. Specifically, B. hirsuta EO showed an IC 50 value of 20.78 µg/mL and 23.62 µg/mL, against the promastigote and amastigote forms of L. infantum, respectively. It also demonstrated an IC 50 value of 22.39 and 25.76 µg/mL, against the promastigote and amastigote forms of L. major, respectively. However, it exhibited moderate cytotoxicity, with a selectivity index below 10. The investigation of the molecular mechanism of action revealed that B. hirsuta EO inhibited only the sterol pathway, including CYP51 gene expression. Additionally, in silico analysis indicated that the main compounds of B. hirsuta EO, germacrene and spathulenol, exhibited excellent affinity energy against Leishmania enzymes trypanothione reductase (TryR) and trypanothione synthase (TryS). This denotes the potential of these compounds as promising agents to control leishmaniasis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Combination therapy at appropriately suitable doses presents a promising alternative to monotherapeutic drugs. In this study, Cinnamomum verum and Syzygium aromaticum essential oils and their major compounds have exhibited substantial leishmaniacidal potential against both promastigote and amastigote forms of Leishmania (L.) major . However, they displayed high cytotoxicity against Raw264.7 macrophage cells. Interestingly, when combined with each other or with amphotericin B, they demonstrated a synergistic effect (FIC<0.5) with low cytotoxicity. These combinations are able to modulate the production of nitric oxide (NO) by macrophages. Notably, the combination of S. aromaticum Essential oil with amphotericin B stimulates macrophage cells by increasing NO production to eliminate leishmanial parasites. Furthermore, investigation of the molecular mechanism of action of these synergistic combinations reveals potent inhibition of the sterol pathway through the inhibition of the CYP51 gene expression. The findings suggest that combination therapy may offer significant therapeutic benefits in both food and pharmaceutical fields.

Antibiotic resistance of the Gram-negative bacterium Pseudomonas aeruginosa and its ability to form biofilm through the Quorum Sensing (QS) mechanism are important challenges in the control of infections caused by this pathogen. The extract of Myrtus communis (myrtle) showed strong anti-QS effect on C hromobacterium . violaceum 6267 by inhibiting 80 % of the production of violacein pigment at a sub-MIC concentration of 1/8 (31.25 μg/mL). In addition, the extract exhibited an inhibitory effect on virulence factors of P. aeruginosa PAO1 at half MIC (125 μg/mL), significantly reducing the formation of biofilms (72.02 %), the swarming activity (75 %), and the production of protease (61.83 %) and pyocyanin (97 %). The active fraction also downregulated the expression of selected regulatory genes involved in the biofilm formation and QS in the P. aeruginosa PAO1 strain. These genes included the autoinducer synthase genes ( lasI and rhlI ), the genes involved in the expression of their corresponding receptors ( lasR and rhlR ), and the pqsA genes. The analysis of the active fraction by HPLC/UV/MS and NMR allowed the identification of three phenolic compounds, 3,5-di- O -galloylquinic acid, myricetin 3- O -α-l-rhamnopyranoside (myricitrin), and myricetin 3- O -(2″- O -galloyl)-ß-d-galactopyranoside. In silico studies showed that 3,5-di- O -galloylquinic acid, with an affinity score of -9.20 kcal/mol, had the highest affinity to the active site of the CviR protein (3QP8), a QS receptor from C. violaceum . Additionally, myricetin 3- O -α-l-rhamnopyranoside (myricitrin) and myricetin 3- O -(2″- O -galloyl)-ß-d-galactopyranoside interact to a lesser extent with 3QP8. In conclusion, this study contributed significantly to the discovery of new QS inhibitors from M. communis leaves against resistant Gram-negative pathogens., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Carlos Jiméenez reports financial support was provided by Spanish State Agency for Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The present study aimed to evaluate the leishmanicidal potential of the essential oil (EO) of Micromeria ( M. ) nervosa and to investigate its molecular mechanism of action by qPCR. Furthermore, in silicointeraction study of the major M. nervosa EO compounds with the enzyme cytochrome P450 sterol 14α-demethylase (CYP51) was also performed. M. nervosa EO was analyzed by gas chromatography-mass spectrometry (GC-MS). Results showed that α-pinene (26.44%), t -cadinol (26.27%), caryophyllene Oxide (7.73 ± 1.04%), and α-Cadinene (3.79 ± 0.12%) are the major compounds of M. nervosa EO. However, limited antioxidant activity was observed, as this EO was ineffective in neutralizing DPPH free radicals and in inhibiting β-carotene bleaching. Interestingly, it displayed effective leishmanicidal potential against promastigote (IC 50 of 6.79 and 5.25 μg/mL) and amastigote (IC 50 of 8.04 and 7.32 μg/mL) forms of leishmania (L.) infantum and L. major , respectively. Molecular mechanism investigation showed that M. nervosa EO displayed potent inhibition on the thiol regulatory pathway. Furthermore, a docking study of the main components of the EO with cytochrome P450 sterol 14α-demethylase (CYP51) enzyme revealed that t -cadinol exhibited the best binding energy values (-7.5 kcal/mol), followed by α-cadinene (-7.3 kcal/mol) and caryophyllene oxide (-7 kcal/mol). These values were notably higher than that of the conventional drug fluconazole showing weaker binding energy (-6.9 kcal/mol). These results suggest that M. nervosa EO could serve as a potent and promising candidate for the development of alternative antileishmanial agent in the treatment of leishmaniasis.

Chlorpyrifos (CPF) poisoning is a public health problem for which there is not currently any effective prophylaxis. In this study, we investigated the protective effect of grape seed extract (GSE) against CPF-induced hepatotoxicity. Rats were daily treated either with CPF (2 mg/kg) or CPF and GSE (20 mg/kg) for 1 week, sacrificed, and their livers dissected for biochemical, molecular, and histopathological analyses. CPF generated liver dysfunction by altering carbohydrate, lipid, amino acid, ammonia and urea metabolism, and provoked mitochondrial impairment through disturbing tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and mitochondrial viability. CPF also induced cholinergic excitotoxicity along with oxidative stress and histopathological alterations. Interestingly, treatment with GSE prevented all the detrimental effects of CPF through the regulation of cytochrome P450 (CYP450) gene expression. Molecular docking analysis indicated that GSE-containing polyphenols acted as epigenetic modulators through inhibiting DNA (cytosine-5)-methyltransferase 1 (DNMT1), thus favoring the CYP2C6 detoxification pathway. Thereby, GSE might be a promising strategy in the protection of the liver against CPF toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aerial parts of cypress ( Cupressus sempervirens L.) of three collect regions (Bizerte, Ben-Arous and Nabeul) were reported for their essential oil (EO) compositions, antioxidant, antimicrobial and insecticidal activities. Results showed that the higher EO yields were observed in Bizerte and Ben Arous (0.56%), followed by Nabeul (0.49%). The EO composition showed the predominance of α-pinene with 36.72% in Bizerte, 30.22% in Nabeul and 30% in Ben-Arous. Cypress EO of Bizerte showed higher antiradical capacity (IC 50  = 55 µg/mL) than Ben-Arous (IC 50  = 97.50 µg/mL) and Nabeul (IC 50  = 155 µg/mL). E. faecalis was the most sensitive strain to cypress EO of Bizerte with the largest inhibition zone (IZ = 65 mm). Regarding the insecticidal activity, cypress EO of Bizerte had the highest mortality of Tribolium castaneum with a lethal concentration of LC 50  = 164.3 µL/L air after 24 h exposure.

The organic solvent extracts (hexane, chloroform, acetone, methanol and water) of coriander fruits were reported for their antioxidant and repellent activities. The methanol and acetone extracts revealed the highest antiradical activity as compared to the other solvent extracts. HPLC analysis revealed that phenolic acids were the major compounds in chloroform and acetone extracts, whereas flavonoids in methanol and water extracts. The methanol extract of coriander fruits exhibited the highest repellent effect against coleopteran insects. Additionally, the hexane extract of coriander fruits also exhibited potent repellent and toxic activities against rice weevil. It appeared that coriander fruit extract obtained with the apolar solvent had more repellent potential against Sitophilus oryzae as compared to Tribolium castaneum . For Lasioderma serricorne , the methanol extract of coriander fruits reduced in a very significant way the adults followed by the chloroform and hexane extracts.

The phytochemical composition of Laurus nobilis essential oil and their anticholinesterase, antioxidant, and insecticidal potential were studied. Also, the oil volatile fraction was compared in semolina at the beginning and after storage periods. For that, a headspace solid-phase-microextraction analysis (HS-SPME) coupled with gas chromatography and mass spectrometry was undertaken. Significant quantitative and qualitative differences of the oil volatile fraction were detected according to storage periods and occupation space ratios. Additionally, anti-acetylcholinesterase activity of L. nobilis oil against T. castaneum adults was evaluated. Results revealed that insecticide activity varied according to storage duration and occupation space. Besides, the oil acts on acetylcholine hydrolysis by inhibiting the activity of acetylcholinesterase. These results highlighted that L. nobilis essential oil may be recommended as an eco-friendly alternative for preserving semolina during storage.

Current study aims to evaluate the effect of essential oil on the conservation of chicken fillets. Following a screening, Tetraclinis articulata was selected for its antimicrobial ( Enterococcus feacalis ATCC 29212, MIC < 0.031 mg/mL) and antioxidant (IC 50  = 1000 µg/mL) potentials with no cytotoxicity effect towards murine macrophage cells. The treatment of chicken fillets, especially with 200 ppm of T. articulata essential oil per 100 g of product reduced significantly ( p   <   0.05 ) lipid oxidation during 12 days of refrigerated storage. Microbial flora charges decreased significantly ( p   <   0.05 ) with a rate of 50.31% for 200 ppm of essential oil from the 6 th day of storage. The acidity of treated fillets was lower than control samples (1.3 g/kg) from the 3 rd day of storage. In addition, a clear effect was recorded by reducing water losses during cooking under the tested doses of essential oil. Withall, findings encouraged the use of T. articulata to extend poultry meat product shelf life.

Objective: The aim of the present study was to investigate the effects of Grape seed extract (GSE) and exercise training on Doxorubicin (Doxo)-induced cardio, hepato and myo toxicities in healthy rats., Methods: Thirty male Wistar rats were randomly divided into five groups and daily treated by intraperitoneal route during two months either with ethanol 10% (Control); Doxo (1.5 mg/kg); Doxo + exercise (1.5 mg/kg + swimming exercise for 30 min twice a week); Doxo + GSE (1.5 mg/kg + GSE 2.5 g/kg); Doxo + GSE + exercise (1.5 mg/kg + GSE 2.5 g/kg + swimming exercise for 30 min twice a week). At the end of the treatment, tissues were collected and processed for the determination of oxidative stress (OS), intracellular mediators, energy fuelling biomarkers, carbohydrate metabolism parameters and muscle histopathology., Results: Doxo provoked OS characterised by an increased lipoperoxidation (LPO) and protein carbonylation and decreased antioxidant enzyme activities. Doxo also affected intracellular mediators, disturbed carbohydrate metabolism and energy fuelling in skeletal muscle as assessed by down-regulated Electron Transport Chain (ETC) complex activities leading in fine to altered skeletal muscle structure and function., Conclusion: Almost all Doxo-induced disturbances were partially corrected with GSE and exercise on their own and more efficiently with the combined treatment (GSE + exercise).

Nanoencapsulation is widely considered as a highly effective strategy to enhance essential oils' (EO) stability by protecting them from oxidative deterioration and evaporation. The present study aims to optimize and characterize an efficient technique for encapsulating Cinnamomum (C.) verum essential oil into chitosan nanoparticles using response surface methodology (RSM). Moreover, the optimized C. verum EO nanoparticle was investigated for its antibacterial (against Gram-positive and Gram-negative bacteria), antifungal (against Candida albicans ), and antiparasitic activity (against Leishmania parasites). Five parameters were investigated using a Plackett-Burman and Box-Behnken statistical design: the chitosan molecular weight, TPP concentration, C. verum EO/chitosan ratio, mixing method, and the duration of the reaction. Encapsulation efficiency and anti-candida activity were considered as responses. The antibacterial, anticandidal, and anti-leishmanial activities were also assessed using a standard micro-broth dilution assay and the cytotoxicity assay was assessed against the macrophage cell line RAW 264.7. The optimized nanoparticles were characterized using Fourier transform infrared spectroscopy, Zeta potential, and scanning electron microscopy. The study results indicated that under optimal conditions, the nanoencapsulation of C. verum EO into chitosan nanoparticles resulted in an encapsulation efficiency of 92.58%, with a regular distribution, a nanoparticle size of 480 ± 14.55 nm, and a favorable Zeta potential of 35.64 ± 1.37 mV. The optimized C. verum EO/chitosan nanoparticles showed strong antifungal activity against C. albicans pathogens (CMI = 125 µg mL -1 ), notable antibacterial activity against both Gram-positive and Gram-negative bacteria (ranging from 125 to 250 µg mL -1 ), high leishmanicidal potential against the promastigotes form of L. tropica and L. major (IC50 = 10.47 and 15.09 µg mL -1 , respectively), and a four-fold cytotoxicity reduction compared to non-encapsulated essential oil. These results suggest that C. verum EO-loaded chitosan nanoparticles could be a promising delivery system for the treatment of cutaneous Candida albicans infections.

The present study investigated the antioxidant, antibacterial, antiviral and anti-inflammatory activities of different aerial parts (flowers, leaves and seeds) of Datura stramonium . The plant material was extracted with 80% methanol for about 24 h. The sensitivity to microorganisms analysis was performed by the microdilution technique. Antioxidant tests were performed by scavenging the DPPH and ABTS radicals, and by FRAP assay. Anti-inflammatory activity was evaluated through the inhibition of nitric oxide production in activated macrophage RAW 264.7 cells. Cell viability was assessed with an MTT assay. Results show that the flower extract revealed a powerful antimicrobial capacity against Gram-positive bacteria and strong antioxidant and anti-inflammatory activities. No significant cytotoxicity to activated macrophages was recorded. High resolution electrospray ionization mass spectrometry and nuclear magnetic resonance analysis identified two molecules with important anti-inflammatory effects: 12α-hydroxydaturametelin B and daturametelin B. Molecular docking analysis with both pro-inflammatory agents tumor necrosis factor alpha and interleukin-6 revealed that both compounds showed good binding features with the selected target proteins. Our results suggest that D. stramonium flower is a promising source of compounds with potential antioxidant, antibacterial, and anti-inflammatory activities. Isolated withanolide steroidal lactones from D. stramonium flower extract with promising anti-inflammatory activity have therapeutic potential against inflammatory disorders.

Aims: This study aimed to determine the antibacterial and antileishmanial potential of Micromeria nervosa extracts. The identification of the antileishmanial compound and the study of its molecular mechanism of action have also been undertaken., Methods and Results: Ethanol extract showed high polyphenol content and diethyl ether extract exhibited high DPPH scavenging and low beta-carotene bleaching activity (IC50 = 13.04 ± 0.99 and 200.18 ± 3.32 μg mL-1, respectively). However, diethyl ether extract displayed high antibacterial activity against Gram-positive strains including methicillin-resistant Staphylococcus aureus (MIC = 31.25 μg mL-1), Staph. aureus ATCC6538 (MIC = 62.5 μg mL-1), and Listeria monocytogenes ATCC 19115 (MIC = 125 μg mL-1), as well as high antileishmanial activity against the promastigote forms of L. infantum and L. major (IC50 = 11.45 and 14.53 μg mL-1, respectively). The active compound was purified using bioassay-guided fractionation and thin layer chromatography, and identified as ursolic acid using high-performance liquid chromatography coupled with a photodiode array and mass spectrometry. The purified compound was strongly inhibitory against the promastigote and amastigote forms of L. infantum and L. major (IC50 = 5.87 and 6.95 μg mL-1 versus 9.56 and 10. 68 μg mL-1, respectively) without overt cytotoxicity against Raw 264.7 macrophage cells (SI = 13.53 and 11.43, respectively). The commercial compound (ursolic acid) showed similar activity against amastigotes and promastigotes forms of L. infantum and L. major. Moreover, its molecular mode of action against leishmaniasis seems to involve the expression of the ODC and SPS genes involved in thiol pathway., Conclusion: Extracts of M. nervosa can be considered as a potential alternative to antimicrobial and antileishmanial drugs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Introduction: Chronic kidney disease (CKD) is a worldwide public health concern characterised by a progressive alteration of renal function, and obesity, diabetes and hypertension are major risk factors. Oxidative stress is commonly observed in CKD patients resulting from an imbalance between overproduction of reactive oxygen species (ROS) and impairment of defense mechanisms. Therefore, strategies that alleviate oxidative stress may have major clinical implications towards improving vascular health and reducing the burden of CKD. Also, CKD worsens the quality of life of patients, therefore it is fundamental to implement new therapeutic strategies aimed at slowing down its progression., Materials and Methods: This interventional study is a randomised placebo-controlled clinical trial consisting at the daily oral supplementation with high dosing grape seed flour (GSF ≈ 1 g/kg) for experimental (n = 30) or starch for placebo (n = 10) to patients suffering from CKD of various stages and aetiologies. Blood and urine samples were collected at baseline and after a six-month-long supplementation period to follow up the disease evolution through the determination of renal function biomarkers, as well as antioxidant, anti-inflammatory and blood parameters., Results: Supplementation with high dosing GSF was safe and well tolerated during the entire period of investigation. GSF clearly improved the main renal function biomarkers as GFR, proteinuria, blood pressure, oxidative stress and inflammation as well as the overall patient welfare as indicated by several blood parameters., Conclusion: Most importantly high dosing GSF specifically halted and even reversed the progression of diabetic nephropathy a major cause of CKD and end stage renal disease.

Context: The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. Lithium (Li) used as drug for many neurological disorders such as bipolar disorders., Objective: This study aims to assess lithium toxicity and to evaluate the hepatic-protective properties of a grape skin seed and extract (GSSE)., Materials and Methods: Twenty-four male Wistar rats were exposed for 30 days to either various lithium concentrations, GSSE alone, or lithium supplemented with GSSE. The proteomic analysis revealed alterations of liver protein profiles after lithium treatments that were successfully identified by mass spectrometry., Results: Lithium treatment induced an oxidative damage by the alteration of antioxidant enzymes activities such as superoxide dismutase, CAT, and Gpx. The regulated proteins are mainly involved in the respiratory electron transport chain, detoxification processes, ribosomal stress pathway, glycolysis, and cytoskeleton. Proteins were differentially expressed in a dose-dependent manner. Interestingly, GSSE reversed the situation and restored the level of liver proteins whose abundance was modified after lithium treatment, arguing for its protective activity., Conclusion: Our data demonstrated the ability of proteomic analysis to underline the toxicity mechanisms of lithium in animal models. Based on these results, GSSE may be envisaged as a nutritional supplement to weaken the liver toxicity of lithium., (© The Author(s) 2022.)

Introduction: Bleomycin is an effective chemotherapeutic agent with main side effects including lung fibrosis which limited its clinical use. The aim of this study is to evaluate the protective effect of grape seed and skin extract (GSSE) against bleomycin-induced oxidative damage and inflammation in rat lung, by assessing respiratory index (RI), oxidative and nitrosative stress (SOD and XO activity, NO), fibrotic mediators (hydroxyproline and collagen), apoptosis (cytochrome C and LDH), inflammation (IL-6, TNF-α and TGF-β1), and histological disturbances., Methods: Rats were pre-treated during three weeks with vehicle [ethanol 10% control] or GSSE (4 g/kg) and then administered with a single dose of bleo (15 mg/kg bw) at the 7th day. Results: Bleo disturbed lung function through the accumulation of hydroxyproline and collagen, decreased SOD activity but increased XO activity as well as GSH and NO levels. Bleo also increased the pro-inflammatory cytokines IL-6, TNF-α, and TGF-β1, and pro-apoptotic cytochrome C factor and induced severe histological alterations of lung parenchyma. Interestingly GSSE pre-treatment efficiently counteracted most of the bleo-induced lung tissue damages., Conclusion: Data suggest that GSSE exerts anti-oxidant, ant-inflammatory, and anti-fibrosis properties that could find potential application in the protection against bleo-induced lung fibrosis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Obesity is a worldwide health problem and a significant risk factor for diabetes and cardiovascular diseases. Gut microbiota (GM) plays an essential role in obesity, and prebiotics such as polyphenols could be one way to improve microbial dysbiosis-induced obesity., Objective: This study was designed to assess the effectiveness of grape seed and skin extract (GSSE), and/or orlistat on obese rats fed with high fat diet by targeting GM modulations. The impact of treatments was also studied in non-obese rats., Material and Methods: Rats were rendered obese or kept with a standard diet for three months. Then they were treated either with GSSE or orlistat or with the combined treatment (GSOR) during three months and then sacrificed. Adipose tissues, blood and faeces were collected and analyzed., Results: In obese rats and to a lesser extent in non-obese rats, treatments decreased the weight of various adipose tissues and the serum levels of cholesterol, LDL, triglycerides, lipase, and CRP and increased HDL and adiponectin. GSOR treatment was even more efficient that orlistat. Obese rats had less GM diversity than non-obese rats and orlistat reduced it even more. However, diversity was restored with GSSE and GSOR treatments. Potential pathogenic Streptococcus alactolyticus/gallolyticus species were greatly increased in obese rats and drastically reduced with the treatments, as wells as other potential pathobionts., Conclusions: GSSE exerts beneficial effects in obese rats and restores, at least partially, the observed dysbiosis. GSOR induced the highest beneficial effect. Moreover, the various treatments could also enhance physiological and GM modifications in non obese rats., (© 2022. The Author(s).)