Papers by Abdelhakim BOUYAHYA
Molecules
Medicinal plants are rich sources of bioactive compounds widely used as medicaments, food additiv... more Medicinal plants are rich sources of bioactive compounds widely used as medicaments, food additives, perfumes, and agrochemicals. These secondary compounds are produced under stress conditions to carry out physiological tasks in plants. Secondary metabolites have a complex chemical structure with pharmacological properties. The widespread use of these metabolites in a lot of industrial sectors has raised the need to increase the production of secondary metabolites. Biotechnological methods of cell culture allow the conservation of plants, as well as the improvement of metabolite biosynthesis and the possibility to modify the synthesis pathways. The objective of this review is to outline the applications of different in vitro culture systems with previously reported relevant examples for the optimal production of plant-derived secondary metabolites.

Cancers
The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, w... more The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Even though mTOR signaling plays a critical role in promoting mitochondria-related protein synthesis, suppressing the catabolic process of autophagy, contributing to lipid metabolism, engaging in ribosome formation, and acting as a critical regulator of mRNA translation, it remains one of the significant signaling systems involved in the tumor process, particularly in apoptosis, cell cycle, and cancer cell proliferation. Therefore, the mTOR signaling system could be suggested as a cancer biomarker, and its targeting is important in anti-tumor therapy research. Indeed, its dysregulation is involved in differ...

Molecules
Walnut oil, like all vegetable oils, is chemically unstable because of the sensitivity of its uns... more Walnut oil, like all vegetable oils, is chemically unstable because of the sensitivity of its unsaturated fatty acids to the oxidation phenomenon. This phenomenon is based on a succession of chemical reactions, under the influence of temperature or storage conditions, that always lead to a considerable change in the quality of the oil by promoting the oxidation of unsaturated fatty acids through the degradation of their C–C double bonds, leading to the formation of secondary oxidation products that reduce the nutritional values of the oil. This research examines the oxidative stability of roasted and unroasted cold-pressed walnut oils under accelerated storage conditions. The oxidative stability of both oils was evaluated using physicochemical parameters: chemical composition (fatty acids, phytosterols, and tocopherols), pigment content (chlorophyll and carotenoids), specific extinction coefficients (K232 and K270), and quality indicators (acid and peroxide value) as well as the eva...

Molecules
This study aimed to evaluate the effects of peanut varieties cultivated in Morocco (Virginia and ... more This study aimed to evaluate the effects of peanut varieties cultivated in Morocco (Virginia and Valencia) and extraction methods (cold press, CP; Soxhlet, Sox and maceration, and Mac) on the fatty acid profile, phytosterol, and tocopherol contents, quality characteristics, and antioxidant potential of peanut seed oil. The DPPH method was used to determine the antioxidant activity of the oils. The results revealed that fatty acid content was slightly affected by the extraction technique. However, the CP method was shown to be an excellent approach for extracting oil with desirable quality features compared to the Sox and Mac methods. Furthermore, the peanut oil extracted via CP carried a higher amount of bioactive compounds and exhibited remarkable antioxidant activities. The findings also revealed higher oleic acid levels from the Virginia oil, ranging from 56.46% to 56.99%. Besides, a higher total phytosterol and tocopherol content and DPPH scavenging capacity were obtained from t...

Molecules
The present study investigated and compared the quality and chemical composition of Moroccan waln... more The present study investigated and compared the quality and chemical composition of Moroccan walnut (Juglans regia L.) oil. This study used three extraction techniques: cold pressing (CP), soxhlet extraction (SE), and ultrasonic extraction (UE). The findings showed that soxhlet extraction gave a significantly higher oil yield compared to the other techniques used in this work (65.10% with p < 0.05), while cold pressing and ultrasonic extraction gave similar yields: 54.51% and 56.66%, respectively (p > 0.05). Chemical composition analysis was carried out by GC–MS and allowed 11 compounds to be identified, of which the major compound was linoleic acid (C18:2), with a similar percentage (between 57.08% and 57.84%) for the three extractions (p > 0.05). Regarding the carotenoid pigment, the extraction technique significantly affected its content (p < 0.05) with values between 10.11 mg/kg and 14.83 mg/kg. The chlorophyll pigment presented a similar content in both oils extract...

Current Pharmaceutical Design
: Plants are a source of diverse classes of secondary metabolites with anticancer properties. Pac... more : Plants are a source of diverse classes of secondary metabolites with anticancer properties. Paclitaxel (Taxol) is an anticancer drug isolated from various Taxus species and is used as a chemotherapeutic agent against various cancers. The biosynthesis of paclitaxel is a complex pathway, making its total chemical synthesis commercially non-viable; hence, alternative novel sources – like plant cell culture and heterologous expression systems, are being investigated to overcome this issue. Advancements in the field of genetic engineering, microbial fermentation engineering, and recombinant techniques have significantly increased the achievable yields of paclitaxel. Indeed, paclitaxel selectively targets microtubules and causes cell cycle arrest in the G2/M phase, inducing a cytotoxic effect in a concentration and time-dependent manner. Innovative drug delivery formulations, like the development of albumin-bound nanoparticles, nano-emulsions, nano-suspensions, liposomes, and polymeric micelles, have been applied to enhance the delivery of paclitaxel to tumor cells. This review focuses on the production, biosynthesis, mechanism of action, and anticancer effects of paclitaxel.

Toxins
The present study aimed to evaluate the acute and subacute toxicity profiles of Erodium guttatum ... more The present study aimed to evaluate the acute and subacute toxicity profiles of Erodium guttatum extracts in mice using the methods described in the guidelines of the OECD. In the acute toxicity study, the LD50 value was greater than 2000 mg/kg. The subacute toxicity study of E. guttatum extracts showed no significant changes in body or organ weights. The administration of E. guttatum extracts to mice at a dose of 200 mg/kg led to an increase in white blood cells, platelets and hemoglobin. Moreover, the aqueous extract of E. guttatum only decreased liver aspartate aminotransferase (ASAT) levels at a dose of 200 mg/kg, and creatinine and urea levels did not show any significant alterations compared to the control group. Our results showed that the extracts of E. guttatum caused a slight increase in alanine aminotransferase (ALAT) and triglycerides. The histological study showed that mice treated with E. guttatum extracts experienced some histopathological changes in the liver, partic...

Foods
Oil oxidation is the main factor limiting vegetable oils’ quality during storage, as it leads to ... more Oil oxidation is the main factor limiting vegetable oils’ quality during storage, as it leads to the deterioration of oil’s nutritional quality and gives rise to disagreeable flavors. These changes make fat-containing foods less acceptable to consumers. To deal with this problem and to meet consumer demand for natural foods, vegetable oil fabricators and the food industry are looking for alternatives to synthetic antioxidants to protect oils from oxidation. In this context, natural antioxidant compounds extracted from different parts (leaves, roots, flowers, and seeds) of medicinal and aromatic plants (MAPs) could be used as a promising and sustainable solution to protect consumers’ health. The objective of this review was to compile published literature regarding the extraction of bioactive compounds from MAPs as well as different methods of vegetable oils enrichment. In fact, this review uses a multidisciplinary approach and offers an updated overview of the technological, sustain...

Oxidative Medicine and Cellular Longevity, 2022
Crocus species are mainly distributed in North Africa, Southern and Central Europe, and Western A... more Crocus species are mainly distributed in North Africa, Southern and Central Europe, and Western Asia, used in gardens and parks as ornamental plants, while Crocus sativus L. (saffron) is the only species that is cultivated for edible purpose. The use of saffron is very ancient; besides the use as a spice, saffron has long been known also for its medical and coloring qualities. Due to its distinctive flavor and color, it is used as a spice, which imparts food preservative activity owing to its antimicrobial and antioxidant activity. This updated review discusses the biological properties of Crocus sativus L. and its phytoconstituents, their pharmacological activities, signaling pathways, and molecular targets, therefore highlighting it as a potential herbal medicine. Clinical studies regarding its pharmacologic potential in clinical therapeutics and toxicity studies were also reviewed. For this updated review, a search was performed in the PubMed, Science, and Google Scholar database...

Food Research International, 2022
Chenopodium album L., is a medicinal plant widely cultivated in Europe, North America, Iran, Sout... more Chenopodium album L., is a medicinal plant widely cultivated in Europe, North America, Iran, South Africa, Australia, South America, and Asia. This species is commonly used in folk medicine to treat many diseases such as cancer, viral infections, parasitic diseases, gastrointestinal disorders, as well as bacterial and fungal infections. The present review was carried out to highlight previous studies on C. album, including its botanical description, geographical distribution, genetic diversity, ecological variability, ethnomedicinal use, bioactive compounds, pharmacological properties, and toxicology. The data collected on C. album was generated using various scientific research databases such as SciFinder, PubMed, Google Scholar, SpringerLink, ScienceDirect, Web of Science, Scopus, and Wiley Online. In this review, the data presented focus on C. album to elucidate its ethnomedicinal use, pharmacological activities, and chemical composition in order to investigate the possible therapeutic pathways of the plant. Analysis of the findings showed that C. album has a capital power in various therapeutic uses such as antibacterial, antifungal, antiviral, antiparasitic, antipruritic, anticancer, antiulcer, antirheumatic, antidiabetic, antihyperlipidemic, antioxidant, and anti-inflammatory as well as other biological functions. Indeed, data on the chemical composition of the extracts and essential oils of this plant revealed its richness in secondary metabolites. The results of this paper prove that the pharmacological properties of C. album confirm its traditional importance in the international traditional pharmacopeia. This species notably exhibits various biological activities; antibacterial, antifungal, and antioxidant effects. However, toxicological investigations and pharmacokinetic validation are necessary in order to identify a possible toxicity of this plant for future clinical trials and to validate its bioavailability.
L e role essentiel de l’alimentation est de fournir des substances nutritives necessaires pour co... more L e role essentiel de l’alimentation est de fournir des substances nutritives necessaires pour couvrir les besoins nutritionnels d’un individu. Cependant, plusieurs scientifiques soutiennent l’hypothese que quelques produits alimentaires et composants de l’aliment ont des effets physiologiques et psychologiques benefiques, en plus de leur role d’apport de molecules de base, c’est de Nutritherapie (Roberfroid, 2000; Ashwell, 2002; Ven kleef et al . 2005). Aujourd’hui, la recherche sur des composants biologiquement actifs dans les produits alimentaires devient un axe de recherche tres attirant, essentiellement dans les industries agroalimentaires.
Biointerface Research in Applied Chemistry, 2020
Recently, a new coronavirus, named Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) h... more Recently, a new coronavirus, named Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has emerged in Wuhan, Hubei province, China. SARS-CoV-2 caused a global epidemic (COVID-19), which continues to kill thousands of people around the world today. With an exclusively interhuman transmission mode, in the absence of a vaccine, the spreading of this new coronavirus is accelerating remarkably. With the studies of the molecular biology of the virus, molecular and serological diagnostic tests are implemented. However, the pathophysiology is not well understood and variable, which gives different symptoms, with a significant mortality rate. Indeed, several organs such as the lungs, brain, kidneys, immune system, and heart are affected directly and/or indirectly.
Journal of Environmental Chemical Engineering, 2018
Highlights Cu II-β-chitin/calcium phosphate hybrid was prepared using ultrasound assisted metho... more Highlights Cu II-β-chitin/calcium phosphate hybrid was prepared using ultrasound assisted method Cu(NPs) loaded onto β-chitin/calcium phosphate was obtained by chemical reduction β-chitin acts as an anchoring agent for Cu(NPs) without the use surfactants Copper materials show a high sensitivity against Gram (positive and negative) strains Cu(NPs) exhibits the best antibacterial activity toward gram-positive bacteria

Pan African Medical Journal, 2022
Introduction rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting the j... more Introduction rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting the joints. Arthritic disorders are associated with mutations of the Mediterranean fever (MEFV) gene. The aim of this study is to show whether MEFV mutations will be involved in the pathogenesis of RA, to explore the frequency of these mutations and to study the genotype-phenotype correlation between mutations in this gene and a cohort of Moroccan patients with rheumatoid arthritis (RA). Methods the present study included 100 patients with RA and 200 control group (CG) who were unrelated individuals from the same ethnic. All patients were tested for auto-antibodies: cyclic citrullinated peptide (ACPA/anti-CCP2), rheumatoid factor (RF) and were analyzed by Sanger Sequencing of the 2 and 10 exons of MEFV gene (hot-spot according to the literature). Results we detected 13 missense variants already MEFV gene mutation reported in the literature (S154T, G222A, G230L, L611H, L695A, M694V, I720M, A737L, P758S, L709A, T732A, G687A and P743L). Carrier rates of MEFV gene mutations were 24/100 (24%) for the RA group and 4/200 (4%) for CG. In the RA group, we observed that no man has presented with MEFV mutation. In the RA group, while gender, BMI, RF and ACPA were significantly higher in the mutation carrier group than those of the non-carrier group (p<0.01). The level of C-reactive protein and HAQ were slightly elevated in the carrier group but not significant. No other significant differences were observed between patients with MEFV mutations and those without MEFV mutations. Conclusion the results of this study suggest that MEFV gene mutations appear to be an aggravating factor severity of RA and consequently, patients with RA might be screened for MEFV gene mutations in countries where FMF is frequent. We report also that our study is the first one in our country Morocco.

Foods
Throughout history, honey has been used to treat various diseases. The present work examined and ... more Throughout history, honey has been used to treat various diseases. The present work examined and assessed the in vivo anti-inflammatory potential of Moroccan thyme honey and its association with essential oils from three selected plants: Origanum vulgare L.; Mentha spicata L.; Eucalyptus globulus L. The chemical composition of the essential oils was studied, and preliminary toxicity, in vitro anti-inflammatory, and antibacterial tests were conducted. Then the anti-inflammatory effect was determined by applying carrageenan and an experimental trauma-induced paw edema test in rats. The essential oils were rich in phytochemicals and showed significant antibacterial activity against four selected ATCC bacterial strains. The results revealed the significant anti-inflammatory potential of honey and mixtures with essential oils and indicated higher efficiency of mixtures compared to honey alone. It can be concluded that the mixtures of honey and essential oils have advantageous anti-inflam...

Pharmaceuticals
Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metaboli... more Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many in vitro and in vivo investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell t...

Heliyon
Among the different metal oxide nanoparticles, zinc oxide nanoparticles have gained significant i... more Among the different metal oxide nanoparticles, zinc oxide nanoparticles have gained significant importance due to their antibacterial properties against clinically pathogenic bacteria during the organal development. In the present study, biogenic zinc oxide nanoparticles were synthesized using seed extract of Citrus limon by a simple, cost-effective, and green chemistry approach. The synthesized ZnO NPs were characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, Dynamic Light Scattering, and Scanning Electron Microscopy. Next, the antimicrobial activity of ZnO NPs was tested against clinically pathogenic bacteria, i.e., Pseudomonas fluorescens, Escherichia coli, Enterobacter aerogenes, and Bacillus subtilis. Followed by, ZnO NPs were evaluated for the development of caudal fin in Zebrafish. The UV-Vis spectram result showed a band at 380 nm and FTIR results confirmed the ZnO NPs. The average crystallite size of the ZnO NPs was 52.65 AE 0.5 nm by the Debye Scherrer equation and SEM showed spherical-shaped particles. A zone of inhibition around ZnO NPs applied to P. fluorescens indicates sensitive to ZnO NPs followed by B. subtilis. Among the four different bacterial pathogens, E. aerogenes was the most susceptible compared to the other three pathogens. The calculated sub-lethal concentration of ZnO NPs at 96 h was 153.8 mg/L with a 95% confidence limit ranging from 70.62 to 214.18 mg/L, which was used with partially amputated zebrafish caudal fin growth. A significant (p < 0.5) development (95%) in the amputated caudal fin was detected at 12 days post-amputation. Low concentrated ZnO NPs can reduce developmental malformation. Collectively, suggested results strongly proved that lemon seed-mediated synthesized ZnO NPs had a good pathogenic barrier for bacterial infection during the external organal development for the first time.

Antioxidants
Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It ... more Stigmasterol is an unsaturated phytosterol belonging to the class of tetracyclic triterpenes. It is one of the most common plant sterols, found in a variety of natural sources, including vegetable fats or oils from many plants. Currently, stigmasterol has been examined via in vitro and in vivo assays and molecular docking for its various biological activities on different metabolic disorders. The findings indicate potent pharmacological effects such as anticancer, anti-osteoarthritis, anti-inflammatory, anti-diabetic, immunomodulatory, antiparasitic, antifungal, antibacterial, antioxidant, and neuroprotective properties. Indeed, stigmasterol from plants and algae is a promising molecule in the development of drugs for cancer therapy by triggering intracellular signaling pathways in numerous cancers. It acts on the Akt/mTOR and JAK/STAT pathways in ovarian and gastric cancers. In addition, stigmasterol markedly disrupted angiogenesis in human cholangiocarcinoma by tumor necrosis fact...

International Journal of Food Microbiology
The present work was carried out to understand the occurrence and antimicrobial susceptibility of... more The present work was carried out to understand the occurrence and antimicrobial susceptibility of Campylobacter spp., in various samples in Northern of Morocco. For this purpose, a random sampling was undertaken from butcher shops, traditional markets, and slaughterhouse. First, the research of Campylobacter was performed according to the Moroccan standard NM ISO: 10272-1 (2008). Second, the isolates were identified by biochemical tests and real time PCR. After the biochemical and molecular identification of suspected colonies, a disk diffusion method was executed to determine the sensitivity of Campylobacter spp. against 18 antibiotics. The results showed a moderate prevalence of Campylobacter species (130/466) recovered mainly on the Campylobacter blood base agar, where C. coli (108/130) were more prevalent comparable to C. jejuni (22/130) in poultry and cattle meat, raw milk, cloacal and surface swabs, and stool of patient suffering from diarrhea. The findings supported also the sensitivity of multiplex qPCR to detect Campylobacter strains compared to Moroccan standard NM ISO: 10272-1 (2008). Among our isolates, C. jejuni were the most susceptible strain toward colistin, florfenicol, gentamicin, streptomycin, and erythromycin. Nonetheless, the presence of multidrug Campylobacter resistant strains was highly observed in C. jejuni isolated, particularly, from broiler chickens toward the antibiotic classes of cephalosporin, penicillin, monobactam, quinolone, fluoroquinolone, sulfamide, as well as tetracycline. This may be due to common use of these drugs in veterinary medicine and farms as growth factor, which limits the usefulness of these molecules. Hence, the study highlights the importance of resistance profile monitoring of these pathogens in Northern of Morocco, in order to develop appropriate control measures and to reduce the emergence of multidrug-resistant strains.

Pharmaceuticals
A flavone, chrysoeriol is synthetized in several plant species. It comes from several natural sou... more A flavone, chrysoeriol is synthetized in several plant species. It comes from several natural sources, especially medicinal plants. The identification and isolation of this compound has been carried out and verified by several research teams using different spectral methods. It seems that the concentration of this molecule is variable and fluctuating depending on the source, the part extracted, the region, and the methods of extraction and characterization. The aim of this paper is to highlight the in vitro and in vivo pharmacological properties of chrysoeriol and to provide insight into its pharmacokinetics. Anticancer, anti-inflammatory, antibacterial, antifungal, anti-osteoporosis, anti-insecticide, and neuroprotective actions have been shown in a number of studies on this chemical. Different mechanisms in theses pharmacological effects include subcellular, cellular, and molecular targets. In vivo pharmacokinetic analysis has proved the good stability of this molecule, showing it...
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Papers by Abdelhakim BOUYAHYA