Displaying publications 1 - 20 of 37 in total

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  1. Fulltext Dietary Phenolic Compounds as Anticancer Natural Drugs: Recent Update on Molecular Mechanisms and Clinical Trials
    Bakrim S, El Omari N, El Hachlafi N, Bakri Y, Lee LH, Bouyahya A
    Foods, 2022 Oct 23;11(21).
    PMID: 36359936 DOI: 10.3390/foods11213323
    Given the stochastic complexity of cancer diseases, the development of chemotherapeutic drugs is almost limited by problems of selectivity and side effects. Furthermore, an increasing number of protective approaches have been recently considered as the main way to limit these pathologies. Natural bioactive compounds, and particularly dietary phenolic compounds, showed major protective and therapeutic effects against different types of human cancers. Indeed, phenolic substances have functional groups that allow them to exert several anti-cancer mechanisms, such as the induction of apoptosis, autophagy, cell cycle arrest at different stages, and the inhibition of telomerase. In addition, in vivo studies show that these phenolic compounds also have anti-angiogenic effects via the inhibition of invasion and angiogenesis. Moreover, clinical studies have already highlighted certain phenolic compounds producing clinical effects alone, or in combination with drugs used in chemotherapy. In the present work, we present a major advance in research concerning the mechanisms of action of the different phenolic compounds that are contained in food medicinal plants, as well as evidence from the clinical trials that focus on them.
  2. Fulltext Phytochemical Compounds and Nanoparticles as Phytochemical Delivery Systems for Alzheimer's Disease Management
    Bakrim S, Aboulaghras S, El Menyiy N, El Omari N, Assaggaf H, Lee LH, et al.
    Molecules, 2022 Dec 19;27(24).
    PMID: 36558176 DOI: 10.3390/molecules27249043
    Alzheimer's disease remains one of the most widespread neurodegenerative reasons for dementia worldwide and is associated with considerable mortality and morbidity. Therefore, it has been considered a priority for research. Indeed, several risk factors are involved in the complexity of the therapeutic ways of this pathology, including age, traumatic brain injury, genetics, exposure to aluminum, infections, diabetes, vascular diseases, hypertension, dyslipidemia, and obesity. The pathophysiology of Alzheimer's disease is mostly associated with hyperphosphorylated protein in the neuronal cytoplasm and extracellular plaques of the insoluble β-amyloid peptide. Therefore, the management of this pathology needs the screening of drugs targeting different pathological levels, such as acetylcholinesterase (AchE), amyloid β formation, and lipoxygenase inhibitors. Among the pharmacological strategies used for the management of Alzheimer's disease, natural drugs are considered a promising therapeutic strategy. Indeed, bioactive compounds isolated from different natural sources exhibit important anti-Alzheimer effects by their effectiveness in promoting neuroplasticity and protecting against neurodegeneration as well as neuroinflammation and oxidative stress in the brain. These effects involve different sub-cellular, cellular, and/or molecular mechanisms, such as the inhibition of acetylcholinesterase (AchE), the modulation of signaling pathways, and the inhibition of oxidative stress. Moreover, some nanoparticles were recently used as phytochemical delivery systems to improve the effects of phytochemical compounds against Alzheimer's disease. Therefore, the present work aims to provide a comprehensive overview of the key advances concerning nano-drug delivery applications of phytochemicals for Alzheimer's disease management.
  3. Fulltext Expediting Multiple Biological Properties of Limonene and α-Pinene: Main Bioactive Compounds of Pistacia lentiscus L., Essential Oils
    El Omari N, Mrabti HN, Benali T, Ullah R, Alotaibi A, Abdullah ADI, et al.
    Front Biosci (Landmark Ed), 2023 Sep 27;28(9):229.
    PMID: 37796709 DOI: 10.31083/j.fbl2809229
    BACKGROUND: Screening new natural molecules with pharmacological and/or cosmetic properties remains a highly sought-after area of research. Moreover, essential oils and volatile compounds have recently garnered significant interest as natural substance candidates. In this study, the volatile components of Pistacia lentiscus L. essential oils (PLEOs) isolated from the fruit and its main compounds, alpha-pinene, and limonene, are investigated for antioxidant, antidiabetic, and dermatoprotective activities.

    METHODS: In vitro antioxidant activity was investigated using 2,2'-diphenyl-1-picrylhydrazyl (DPPH), fluorescence recovery after photobleaching (FRAP), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. The antidiabetic and dermatoprotective effects were studied using enzyme inhibitory activities.

    RESULTS: Antioxidant tests showed that PLEO has the best activity (ranging from 29.64 ± 3.04 to 73.80 ± 3.96 µg/mL) compared to its main selected molecules (ranging from 74 ± 3.72 to 107.23 ± 5.03 µg/mL). The α-glucosidase and α-amylase assays demonstrated that the elements tested have a promising antidiabetic potential with IC50values ranging from 78.03 ± 2.31 to 116.03 ± 7.42 µg/mL and 74.39 ± 3.08 to 112.35 ± 4.92 µg/mL for the α-glucosidase and α-amylase assays, respectively, compared to the standard drug. For the tyrosinase test, we found that the EOs (IC50 = 57.72 ± 2.86 µg/mL) followed by limonene (IC50 = 74.24 ± 2.06 µg/mL) and α-pinene (IC50 = 97.45 ± 5.22 µg/mL) all exhibited greater inhibitory effects than quercetin (IC50 = 246.90 ± 2.54 µg/mL).

    CONCLUSIONS: Our results suggest that the biological activities of PLEO, as well as its main compounds, make them promising candidates for the development of new strategies aimed at improving dermatoprotection and treating diseases associated with diabetes mellitus and oxidative stress.

  4. Fulltext Molecular mechanisms underlying the clinical efficacy of panobinostat involve Stochasticity of epigenetic signaling, sensitization to anticancer drugs, and induction of cellular cell death related to cellular stresses
    El Omari N, Bakrim S, Khalid A, Abdalla AN, Almalki WH, Lee LH, et al.
    Biomed Pharmacother, 2023 Aug;164:114886.
    PMID: 37224752 DOI: 10.1016/j.biopha.2023.114886
    Panobinostat, also known as Farydak®, LBH589, PNB, or panobinostat lactate, is a hydroxamic acid that has been approved by the Food and Drug Administration (FDA) for its anti-cancer properties. This orally bioavailable drug is classified as a non-selective histone deacetylase inhibitor (pan-HDACi) that inhibits class I, II, and IV HDACs at nanomolar levels due to its significant histone modifications and epigenetic mechanisms. A mismatch between histone acetyltransferases (HATs) and HDACs can negatively affect the regulation of the genes concerned, which in turn can contribute to tumorigenesis. Indeed, panobinostat inhibits HDACs, potentially leading to acetylated histone accumulation, re-establishing normal gene expression in cancer cells, and helping to drive multiple signaling pathways. These pathways include induction of histone acetylation and cytotoxicity for the majority of tested cancer cell lines, increased levels of p21 cell cycle proteins, enhanced amounts of pro-apoptotic factors (such as caspase-3/7 activity and cleaved poly (ADP-ribose) polymerase (PARP)) associated with decreased levels of anti-apoptotic factors [B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra-large (Bcl-XL)], as well as regulation of immune response [upregulated programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression] and other events. The therapeutic outcome of panobinostat is therefore mediated by sub-pathways involving proteasome and/or aggresome degradation, endoplasmic reticulum, cell cycle arrest, promotion of extrinsic and intrinsic processes of apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this investigation, we aimed to pinpoint the precise molecular mechanism underlying panobinostat's HDAC inhibitory effect. A more thorough understanding of these mechanisms will greatly advance our knowledge of cancer cell aberrations and, as a result, provide an opportunity for the discovery of significant new therapeutic perspectives through cancer therapeutics.
  5. Fulltext Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin
    El Omari N, Lee LH, Bakrim S, Makeen HA, Alhazmi HA, Mohan S, et al.
    Biomed Pharmacother, 2023 Aug;164:114774.
    PMID: 37224749 DOI: 10.1016/j.biopha.2023.114774
    Romidepsin, also known as NSC630176, FR901228, FK-228, FR-901228, depsipeptide, or Istodax®, is a natural molecule produced by the Chromobacterium violaceum bacterium that has been approved for its anti-cancer effect. This compound is a selective histone deacetylase (HDAC) inhibitor, which modifies histones and epigenetic pathways. An imbalance between HDAC and histone acetyltransferase can lead to the down-regulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by romidepsin indirectly contributes to the anticancer therapeutic effect by causing the accumulation of acetylated histones, restoring normal gene expression in cancer cells, and promoting alternative pathways, including the immune response, p53/p21 signaling cascades, cleaved caspases, poly (ADP-ribose) polymerase (PARP), and other events. Secondary pathways mediate the therapeutic action of romidepsin by disrupting the endoplasmic reticulum and proteasome and/or aggresome, arresting the cell cycle, inducing intrinsic and extrinsic apoptosis, inhibiting angiogenesis, and modifying the tumor microenvironment. This review aimed to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin. A more detailed understanding of these mechanisms can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy.
  6. Fulltext Anticancer clinical efficiency and stochastic mechanisms of belinostat
    El Omari N, Bakrim S, Khalid A, Albratty M, Abdalla AN, Lee LH, et al.
    Biomed Pharmacother, 2023 Sep;165:115212.
    PMID: 37541175 DOI: 10.1016/j.biopha.2023.115212
    Cancer progression is strongly affected by epigenetic events in addition to genetic modifications. One of the key elements in the epigenetic control of gene expression is histone modification through acetylation, which is regulated by the synergy between histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are thought to offer considerable potential for the development of anticancer medications, particularly when used in conjunction with other anticancer medications and/or radiotherapy. Belinostat (Beleodaq, PXD101) is a pan-HDAC unsaturated hydroxamate inhibitor with a sulfonamide group that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of refractory or relapsed peripheral T-cell lymphoma (PTCL) and solid malignancies or and other hematological tissues. This drug modifies histones and epigenetic pathways. Because HDAC and HAT imbalance can lead to downregulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by belinostat indirectly promotes anti-cancer therapeutic effect by provoking acetylated histone accumulation, re-establishing normal gene expressions in cancer cells and stimulating other routes such as the immune response, p27 signaling cascades, caspase 3 activation, nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) degradation, cyclin A (G2/M phase), cyclin E1 (G1/S phase) and other events. In addition, belinostat has already been discovered to increase p21WAF1 in a number of cell lines (melanoma, prostate, breast, lung, colon, and ovary). This cyclin-dependent kinase inhibitor actually has a role in processes that cause cell cycle arrest and apoptosis. Belinostat's clinical effectiveness, comprising Phase I and II studies within the areas of solid and hematological cancers, has been evidenced through several investigative trials that have supported its potential to be a valuable anti-cancer drug. The purpose of this research was to provide insight on the specific molecular processes through which belinostat inhibits HDAC. The ability to investigate new therapeutic options employing targeted therapy and acquire a deeper understanding of cancer cell abnormalities may result from a better understanding of these particular routes.
  7. Fulltext Anticancer properties and mechanism insights of α-hederin
    Belmehdi O, Taha D, Abrini J, Ming LC, Khalid A, Abdalla AN, et al.
    Biomed Pharmacother, 2023 Sep;165:115205.
    PMID: 37499451 DOI: 10.1016/j.biopha.2023.115205
    α-Hederin is a natural bioactive molecule very abundant in aromatic and medicinal plants (AMP). It was identified, characterized, and isolated using different extraction and characterization technologies, such as HPLC, LC-MS and NMR. Biological tests have revealed that this natural molecule possesses different biological properties, particularly anticancer activity. Indeed, this activity has been investigated against several cancers (e.g., esophageal, hepatic, breast, colon, colorectal, lung, ovarian, and gastric). The underlying mechanisms are varied and include induction of apoptosis and cell cycle arrest, reduction of ATP generation, as well as inhibition of autophagy, cell proliferation, invasion, and metastasis. In fact, these anticancer mechanisms are considered the most targeted for new chemotherapeutic agents' development. In the light of all these data, α-hederin could be a very interesting candidate as an anticancer drug for chemotherapy, as well as it could be used in combination with other molecules already validated or possibly investigated as an agent sensitizing tumor cells to chemotherapeutic treatments.
  8. Fulltext Proximate composition, lipid and elemental profiling of eight varieties of avocado (Persea americana)
    Nasri C, Halabi Y, Hajib A, Choukri H, Harhar H, Lee LH, et al.
    Sci Rep, 2023 Dec 20;13(1):22767.
    PMID: 38123687 DOI: 10.1038/s41598-023-50119-y
    Eight Moroccan avocado varieties were analyzed for their nutritional composition and physicochemical properties. The nutritional contents of the sample were determined through the evaluation of the moisture, oil, ash, protein, and carbohydrate contents, and energy value calculation. Additionally, macroelements (Ca, Mg, and Na) and microelements (Fe, Zn, Cu, and Mn) were determined in the mineral profile. Oils were examined also for their fatty acid, phytosterol, and tocopherol profiles. As a result of the study, the avocado presents significant differences between the eight studied varieties (p 
  9. Fulltext Phytosterols activating nuclear receptors are involving in steroid hormone-dependent cancers: Myth or fact?
    Bakrim S, El Omari N, Khan EJ, Khalid A, Abdalla AN, Chook JB, et al.
    Biomed Pharmacother, 2023 Dec 31;169:115783.
    PMID: 37944439 DOI: 10.1016/j.biopha.2023.115783
    Nuclear receptors (NRs) represent intracellular proteins that function as a signaling network of transcriptional factors to control genes in response to a variety of environmental, dietary, and hormonal stimulations or serve as orphan receptors lacking a recognized ligand. They also play an essential role in normal development, metabolism, cell growth, cell division, physiology, reproduction, and homeostasis and function as biological markers for tumor subclassification and as targets for hormone therapy. NRs, including steroid hormone receptors (SHRs), have been studied as tools to examine the fundamentals of transcriptional regulation within the development of mammals and human physiology, in addition to their links to disturbances. In this regard, it is widely recognized that aberrant NR signaling is responsible for the pathological growth of hormone-dependent tumors in response to SHRs dysregulation and consequently represents a potential therapeutic candidate in a range of diseases, as in the case of prostate cancer and breast cancer. On the other hand, phytosterols are a group of plant-derived compounds that act directly as ligands for NRs and have proven their efficacy in the management of diabetes, heart diseases, and cancers. However, these plants are not suggested in cases of hormone-dependent cancer since a certain group of plants contains molecules with a chemical structure similar to that of estrogens, which are known as phytoestrogens or estrogen-like compounds, such as lignans, coumestans, and isoflavones. Therefore, it remains an open and controversial debate regarding whether consuming a phytosterol-rich diet and adopting a vegetarian lifestyle like the Mediterranean diet may increase the risk of developing steroid hormone-dependent cancers by constitutively activating SHRs and thereby leading to tumor transformation. Overall, the purpose of this review is to better understand the relevant mechanistic pathways and explore epidemiological investigations in order to establish that phytosterols may contribute to the activation of NRs as cancer drivers in hormone-dependent cancers.
  10. Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model
    Fettach S, Thari FZ, Karrouchi K, Benbacer L, Lee LH, Bouyahya A, et al.
    Chem Biol Interact, 2024 Mar 01;391:110902.
    PMID: 38367680 DOI: 10.1016/j.cbi.2024.110902
    Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%-50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P 
  11. Fulltext Polymorphism of HLA and Susceptibility of Breast Cancer
    Aboulaghras S, Khalid A, Makeen HA, Alhazmi HA, Albratty M, Mohan S, et al.
    Front Biosci (Landmark Ed), 2024 Feb 05;29(2):55.
    PMID: 38420797 DOI: 10.31083/j.fbl2902055
    Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases, including tumors. The HLA system plays a key role in the escape of tumor cells from immune surveillance. This review aims to determine the correlation between BC susceptibility and HLA markers specific HLA alleles such as HLA-B07, HLA-DRB111, HLA-DRB113, and HLA-DRB115 are associated with an increased risk of developing BC. Furthermore, HLA-G mutations have been attributed to an elevated likelihood of metastasis in BC patients. Understanding the complex associations between the HLA system and BC development is critical for developing novel cancer prevention, detection, and treatment strategies. This review emphasizes the importance of analyzing HLA polymorphisms in the management of BC patients, as well as the urgent need for further research in this area.
  12. Fulltext Pharmacological Effects of Grifolin: Focusing on Anticancer Mechanisms
    Bouyahya A, El Allam A, Zeouk I, Taha D, Zengin G, Goh BH, et al.
    Molecules, 2022 Jan 03;27(1).
    PMID: 35011516 DOI: 10.3390/molecules27010284
    Grifolin is a volatile compound contained in essential oils of several medicinal plants. Several studies show that this substance has been the subject of numerous pharmacological investigations, which have yielded interesting results. Grifolin demonstrated beneficial effects for health via its multiple pharmacological activities. It has anti-microbial properties against bacteria, fungi, and parasites. In addition, grifolin exhibited remarkable anti-cancer effects on different human cancer cells. The anticancer action of this molecule is related to its ability to act at cellular and molecular levels on different checkpoints controlling the signaling pathways of human cancer cell lines. Grifolin can induce apoptosis, cell cycle arrest, autophagy, and senescence in these cells. Despite its major pharmacological properties, grifolin has only been investigated in vitro and in vivo. Therefore, further investigations concerning pharmacodynamic and pharmacokinetic tests are required for any possible pharmaceutical application of this substance. Moreover, toxicological tests and other investigations involving humans as a study model are required to validate the safety and clinical applications of grifolin.
  13. A Review of Recent Progresses on Olive Oil Chemical Profiling, Extraction Technology, Shelf-life, and Quality Control
    Gagour J, Hallouch O, Asbbane A, Bijla L, Laknifli A, Lee LH, et al.
    Chem Biodivers, 2024 Apr;21(4):e202301697.
    PMID: 38345352 DOI: 10.1002/cbdv.202301697
    Olive oil (OO) is widely recognized as a main component in the Mediterranean diet owing to its unique chemical composition and associated health-promoting properties. This review aimed at providing readers with recent results on OO physicochemical profiling, extraction technology, and quality parameters specified by regulations to ensure authentic products for consumers. Recent research progress on OO adulteration were outlined through a bibliometric analysis mapping using Vosviewer software. As revealed by bibliometric analysis, richness in terms of fatty acids, pigments, polar phenolic compounds, tocopherols, squalene, sterols, and triterpenic compounds justify OO health-promoting properties and increasing demand on its global consumption. OO storage is a critical post-processing operation that must be optimized to avoid oxidation. Owing to its great commercial value on markets, OO is a target to adulteration with other vegetable oils. In this context, different chemometric tools were developed to deal with this problem. To conclude, increasing demand and consumption of OO on the global market is justified by its unique composition. Challenges such as oxidation and adulteration stand out as the main issues affecting the OO market.
  14. Fulltext Variations in Antioxidant Capacity, Oxidative Stability, and Physicochemical Quality Parameters of Walnut (Juglans regia) Oil with Roasting and Accelerated Storage Conditions
    Elouafy Y, El Idrissi ZL, El Yadini A, Harhar H, Alshahrani MM, Al Awadh AA, et al.
    Molecules, 2022 Nov 09;27(22).
    PMID: 36431794 DOI: 10.3390/molecules27227693
    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 evaluation of radical scavenging activity by the DPPH method. The changes in these parameters were evaluated within 60 days at 60 ± 2 °C. The results showed that the levels of total phytosterols, the parameters of the acid and peroxide value, K232 and K270, increased slightly for both oils as well as the total tocopherol content and the antioxidant activity affected by the roasting process. In contrast, the fatty acid profiles did not change considerably during the 60 days of our study. After two months of oil treatment at 60 °C, the studied oils still showed an excellent physicochemical profile, which allows us to conclude that these oils are stable and can withstand such conditions. This may be due to the considerable content of tocopherols (vitamin E), which acts as an antioxidant.
  15. Fulltext Effects of Extraction Methods on the Bioactivities and Nutritional Value of Virginia and Valencia-Type Peanut Oil
    Idrissi ZLE, El Moudden H, Mghazli N, Bouyahya A, Guezzane CE, Alshahrani MM, et al.
    Molecules, 2022 Nov 09;27(22).
    PMID: 36431807 DOI: 10.3390/molecules27227709
    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 the Valencia oil. Analyzing the study, it can be inferred that extraction method and variety both affect the composition of the peanut oil's bioactive compounds and antioxidant activity. This information is relevant for extracting peanut oil with a greater level of compounds of industrial interest.
  16. Fulltext Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy
    Bouyahya A, El Allam A, Aboulaghras S, Bakrim S, El Menyiy N, Alshahrani MM, et al.
    Cancers (Basel), 2022 Nov 10;14(22).
    PMID: 36428613 DOI: 10.3390/cancers14225520
    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 different types of cancers such as colon, neck, cervical, head, lung, breast, reproductive, and bone cancers, as well as nasopharyngeal carcinoma. Moreover, recent investigations showed that targeting mTOR could be considered as cancer therapy. Accordingly, this review presents an overview of recent developments associated with the mTOR signaling pathway and its molecular involvement in various human cancer types. It also summarizes the research progress of different mTOR inhibitors, including natural and synthetised compounds and their main mechanisms, as well as the rational combinations with immunotherapies.
  17. Fulltext Traditional Knowledge, Phytochemistry, and Biological Properties of Vachellia tortilis
    Taha D, El Hajjaji S, Mourabit Y, Bouyahya A, Lee LH, El Menyiy N, et al.
    Plants (Basel), 2022 Dec 02;11(23).
    PMID: 36501387 DOI: 10.3390/plants11233348
    Vachellia tortilis is a medicinal plant of the Fabaceae family, widely distributed in arid and semi-arid regions of North, East and Southern Africa, the Middle East and the Arabian Peninsula. In traditional medicine. It's commonly used to treat certain ailments, including diabetes, asthma, hepatitis and burns. Different scientific search databases were used to obtain data on V. tortilis, notably Google Scholar, Scopus, Wiley Online, Scifinder, Web of Science, ScienceDirect, SpringerLink, and PubMed. The knowledge of V. tortilis was organized based on ethnomedicinal use, phytochemistry, and pharmacological investigations. Phytochemical studies revealed the presence of a variety of phytocompounds, including fatty acids, monosaccharides, flavonoids, chalcones, and alcohols. Essential oils and organic extracts prepared from V. tortilis showed several biological properties, specifically antibacterial, antifungal, antiparasitic, antioxidant, antiproliferative, anti-diabetic, and anti-inflammatory effects. Antimicrobial and antiparasitic activities are due to the disturbance of cellular membranes and ultra-structural changes triggered by V. tortilis phytochemicals. While physiological and molecular processes such as apoptosis induction, preventing cell proliferation, and inflammatory mediators are responsible for the anti-diabetic, anti-cancer, and anti-inflammatory activities. However, further investigations concerning pharmacodynamics and pharmacokinetics should be carried out to validate their clinical applications.
  18. Fulltext A Comprehensive Review of the Pharmacological Properties and Bioactive Components of Retama monosperma
    El Yadini A, Elouafy Y, Amiri-Ardekani E, Shafiee M, Firouzi A, Sasani N, et al.
    Molecules, 2023 Feb 10;28(4).
    PMID: 36838696 DOI: 10.3390/molecules28041708
    Retama monosperma L. (Boiss.) or Genista monosperma L. (Lam.), known locally as "R'tam", is a spontaneous and annual herb that belongs to the Fabaceae family. It is native to the Mediterranean regions, specifically in the desert areas and across the Middle Atlas in Morocco. This plant has been extensively used in folk medicine and it is rich in bioactive compounds, including polyphenols, flavonoids, and alkaloids. Current research efforts are focusing on the development of novel natural drugs as alternatives to various organic and non-organic chemical products from Retama monosperma. In addition, extract, and isolated compounds obtained from different parts of the chosen plant have been described to exhibit multiple biological and pharmacological properties such as antioxidant, anti-aging, anti-inflammatory, antihypertensive, anti-helminthic, disinfectant, diuretic, and hypoglycemic effects. The plant-derived extract also acts as an antimicrobial agent, which is highly efficient in the treatment of bacterial, viral, and fungal infections. Its antiproliferative effects are associated with some mechanisms, such as the inhibition of cell cycle arrest and apoptosis. In light of these assessments, we critically highlight the beneficial effects of the flowers, stems, seeds extracts, and isolated compounds from R. monosperma (L.) Boiss in human health care, industrial, and other applications, as well as the possible ways to be employed as a potential natural source for future drug discovery.
  19. Fulltext Association between Physical Activity, Body Composition, and Metabolic Disorders in Middle-Aged Women of Ksar el Kebir (Morocco)
    Harraqui K, Oudghiri DE, Mrabti HN, Hannoun Z, Lee LH, Assaggaf H, et al.
    Int J Environ Res Public Health, 2023 Jan 18;20(3).
    PMID: 36767104 DOI: 10.3390/ijerph20031739
    This study aimed to examine the association between physical activity (PA), body composition, and metabolic disorders in a population of Moroccan women classified by menopausal status. This cross-sectional study comprised 373 peri- and postmenopausal women aged 45-64 years old. PA levels were assessed using the short version of the International Physical Activity Questionnaire (IPAQ-SF). Body composition and metabolic disorders were assessed by measurements of anthropometric and biological parameters: weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), WC/HC ratio, percent body fat, systolic and diastolic blood pressure, fasting blood glucose, and serum lipids (total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C). Metabolic syndrome (MetS) was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Pearson correlations were used to test for associations. The mean total PA score of perimenopausal women was 1683.51 ± 805.36 MET-min/week, and of postmenopausal women was 1450.81 ± 780.67 MET-min/week. In all participants, peri- and postmenopausal women, PA was significantly and inversely associated with BMI, weight, percent body fat, HC, WC, and number of MetS components (p < 0.01), and with fasting blood glucose, TC, TG, and LDL-C (p < 0.05). The frequencies of metabolic disorders, obesity, abdominal obesity, type 2 diabetes, dyslipidemia, and MetS were significantly lower at moderate and intense levels of PA (p < 0.05), in also all participants. In middle-aged women, particularly those who are peri-menopausal, PA at moderate and intense levels is associated with more favorable body composition and less frequent metabolic disorders. However, in this particular study, PA does not appear to be associated with blood pressure and HDL-C concentrations. Future studies may be needed to further clarify these findings.
  20. Fulltext Influence of the Extraction Method on the Quality and Chemical Composition of Walnut (Juglans regia L.) Oil
    Elouafy Y, El Yadini A, El Moudden H, Harhar H, Alshahrani MM, Awadh AAA, et al.
    Molecules, 2022 Nov 08;27(22).
    PMID: 36431782 DOI: 10.3390/molecules27227681
    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 extracted by SE and UE (p > 0.05), 0.20 mg/kg and 0.16 mg/kg, respectively, while the lowest content was recorded in the cold-pressed oil with 0.13 mg/kg. Moreover, the analysis of phytosterols in walnut oil revealed significantly different contents (p < 0.05) for the three extraction techniques (between 1168.55 mg/kg and 1306.03 mg/kg). In addition, the analyses of tocopherol composition revealed that γ-tocopherol represented the main tocopherol isomer in all studied oils and the CP technique provided the highest content of total tocopherol with 857.65 mg/kg, followed by SE and UE with contents of 454.97 mg/kg and 146.31 mg/kg, respectively, which were significantly different (p < 0.05). This study presents essential information for producers of nutritional oils and, in particular, walnut oil; this information helps to select the appropriate method to produce walnut oil with the targeted quality properties and chemical compositions for the desired purpose. It also helps to form a scientific basis for further research on this plant in order to provide a vision for the possibility of exploiting these oils in the pharmaceutical, cosmetic, and food fields.
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