Displaying all 14 publications

Abstract:
Sort:
  1. Khan MU, Ahmad A, Fayyaz M, Ashraf N, Bhagavathula A
    BMC Res Notes, 2016;9(1):183.
    PMID: 27005815 DOI: 10.1186/s13104-016-1996-4
    The objective of this study was to assess the association of the constructs of theory of planned behaviour (behavioural beliefs, normative beliefs, control beliefs) and demographic variables with the intentions of pharmacy students to become pharmacy owner.
  2. Suroowan S, Llorent-Martínez EJ, Zengin G, Buskaran K, Fakurazi S, Abdalla AN, et al.
    Molecules, 2023 Jan 06;28(2).
    PMID: 36677655 DOI: 10.3390/molecules28020599
    This study documents for the first time the phytochemical composition and biological activities of Tambourissa peltata Baker, an endemic plant from Mauritius. Phytochemical extraction was performed using ethyl acetate, methanol and distilled water as solvents. The phytochemical composition was determined through HPLC-MS and other standard assays. The DPPH, ABTS, FRAP, CUPRAC and phosphomolybdenum assays were employed for the determination of the antioxidant potential, whereas cell viability assays were used to determine the cytotoxicity. The highest phenolic and phenolic acid contents were obtained in the aqueous extract (179.91 ± 0.67 gallic acid equivalents/g and 55.74 ± 1.43 caffeic acid equivalents/g). The highest quantity of flavonoids was obtained in the ethyl acetate extract (28.97 ± 0.46 rutin equivalents/g). The methanolic extract was the highest source of flavonols (33.71 ± 0.13 mg catechin equivalents/g). A total of 34 phytochemicals were identified, mainly proanthocyanidins and flavonoid glycosides. The highest antioxidant activity in DPPH (973.40 ± 5.65 mg TE (Trolox equivalents)/g), ABTS (2030.37 ± 40.83 mg TE/g), FRAP (1461.39 ± 5.95 mg TE/g), CUPRAC (1940.99 ± 20.95 mg TE/g) and phosphomolybdenum (8.37 ± 0.23 mmol TE/g) assays was recorded for the aqueous extract. The ethyl acetate extract was the most active metal chelator. The highest acetylcholinesterase inhibitor was the methanolic extract, whereas the ethyl acetate extract was the most active against BChE. The tyrosinase enzyme was most inhibited by the methanolic extract. Alpha-amylase and glucosidase were most inhibited by the aqueous extract. The methanolic extract was capable of inducing cell cytotoxicity to the human colorectal carcinoma without damaging normal cells. T. peltata warrants further attention from the scientific community given its multifaceted biological properties.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Bouyahya A, Taha D, Benali T, Zengin G, El Omari N, El Hachlafi N, et al.
    Biomed Pharmacother, 2023 May;161:114337.
    PMID: 36812715 DOI: 10.1016/j.biopha.2023.114337
    Cynaroside is a flavonoid, isolated from several species belonging to the Apiaceae, Poaceae, Lamiaceae, Solanaceae, Zingiberaceae, Compositae and other families and it can be extracted from seeds, roots, stems, leaves, barks, flowers, fruits, aerial parts, and the whole plant of these species. This paper discloses the current state of knowledge on the biological/pharmacological effects and mode of action to better understand the numerous health benefits of cynaroside. Several research works revealed that cynaroside could have beneficial effects on various human pathologies. Indeed, this flavonoid exerts antibacterial, antifungal, antileishmanial, antioxidant, hepatoprotective, antidiabetic, anti-inflammatory, and anticancer effects. Additionally, cynaroside exhibits its anticancer effects by blocking MET/AKT/mTOR axis by decreasing the phosphorylation level of AKT, mTOR, and P70S6K. For antibacterial activity, cynaroside reduces biofilm development of Pseudomonas aeruginosa and Staphylococcus aureus. Moreover, the incidence of mutations leading to ciprofloxacin resistance in Salmonella typhimurium was reduced after the treatment with cynaroside. In addition, cynaroside inhibited the production of reactive oxygen species (ROS), which reduced the damage to mitochondrial membrane potential caused by hydrogen peroxide (H2O2). It also enhanced the expression of the anti-apoptotic protein Bcl-2 and lowered that of the pro-apoptotic protein Bax. Cynaroside abrogated the up-regulation of c-Jun N-terminal kinase (JNK) and p53 protein expression triggered by H2O2. All these findings suggest that cynaroside could be used to prevent certain human diseases.
  9. El Menyiy N, Aboulaghras S, Bakrim S, Moubachir R, Taha D, Khalid A, et al.
    Biomed Pharmacother, 2023 Sep;165:115159.
    PMID: 37481929 DOI: 10.1016/j.biopha.2023.115159
    Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging and the pathogenesis of many chronic diseases, often accompanied by increased oxidative stress and low-grade inflammation. Dietary antioxidants, including genkwanin, could decrease oxidative stress and the expression of pro-inflammatory cytokines or pathways. The present study is the first comprehensive review of genkwanin, a methoxyflavone found in several plant species. Indeed, natural sources, and pharmacokinetics of genkwanin, the biological properties were discussed and highlighted in detail. This review analyzed and considered all original studies related to identification, isolation, quantification, investigation of the biological and pharmacological properties of genkwanin. We consulted all published papers in peer-reviewed journals in the English language from the inception of each database to 12 May 2023. Different phytochemical demonstrated that genkwanin is a non-glycosylated flavone found and isolated from several medicinal plants such as Genkwa Flos, Rosmarinus officinalis, Salvia officinalis, and Leonurus sibiricus. In vitro and in vivo biological and pharmacological investigations showed that Genkwanin exhibits remarkable antioxidant and anti-inflammatory activities, genkwanin, via activation of glucokinase, has shown antihyperglycemic activity with a potential role against metabolic syndrome and diabetes. Additionally, it revealed cardioprotective and neuroprotective properties, thus reducing the risk of cardiovascular diseases and assisting against neurodegenerative diseases. Furthermore, genkwanin showed other biological properties like antitumor capability, antibacterial, antiviral, and dermato-protective effects. The involved mechanisms include sub-cellular, cellular and molecular actions at different levels such as inducing apoptosis and inhibiting the growth and proliferation of cancer cells. Despite the findings from preclinical studies that have demonstrated the effects of genkwanin and its diverse mechanisms of action, additional research is required to comprehensively explore its therapeutic potential. Primarily, extensive studies should be carried out to enhance our understanding of the molecule's pharmacodynamic actions and pharmacokinetic pathways. Moreover, toxicological and clinical investigations should be undertaken to assess the safety and clinical efficacy of genkwanin. These forthcoming studies are of utmost importance in fully unlocking the potential of this molecule in the realm of therapeutic applications.
  10. Bouyahya A, Bakrim S, Aboulaghras S, El Kadri K, Aanniz T, Khalid A, et al.
    Biomed Pharmacother, 2024 Mar 22;174:116432.
    PMID: 38520868 DOI: 10.1016/j.biopha.2024.116432
    Oxidative stress results from a persistent imbalance in oxidation levels that promotes oxidants, playing a crucial role in the early and sustained phases of DNA damage and genomic and epigenetic instability, both of which are intricately linked to the development of tumors. The molecular pathways contributing to carcinogenesis in this context, particularly those related to double-strand and single-strand breaks in DNA, serve as indicators of DNA damage due to oxidation in cancer cases, as well as factors contributing to epigenetic instability through ectopic expressions. Oxidative stress has been considered a therapeutic target for many years, and an increasing number of studies have highlighted the promising effectiveness of natural products in cancer treatment. In this regard, we present significant research on the therapeutic targeting of oxidative stress using natural molecules and underscore the essential role of oxidative stress in cancer. The consequences of stress, especially epigenetic instability, also offer significant therapeutic prospects. In this context, the use of natural epi-drugs capable of modulating and reorganizing the epigenetic network is beginning to emerge remarkably. In this review, we emphasize the close connections between oxidative stress, epigenetic instability, and tumor transformation, while highlighting the role of natural substances as antioxidants and epi-drugs in the anti-tumoral context.
  11. Ashraf N, Asari A, Yousaf N, Ahmad M, Ahmed M, Faisal A, et al.
    Front Chem, 2022;10:1003816.
    PMID: 36405310 DOI: 10.3389/fchem.2022.1003816
    Tyrosine threonine kinase (TTK) is the key component of the spindle assembly checkpoint (SAC) that ensures correct attachment of chromosomes to the mitotic spindle and thereby their precise segregation into daughter cells by phosphorylating specific substrate proteins. The overexpression of TTK has been associated with various human malignancies, including breast, colorectal and thyroid carcinomas. TTK has been validated as a target for drug development, and several TTK inhibitors have been discovered. In this study, ligand and structure-based alignment as well as various partial charge models were used to perform 3D-QSAR modelling on 1H-Pyrrolo[3,2-c] pyridine core containing reported inhibitors of TTK protein using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches to design better active compounds. Different statistical methods i.e., correlation coefficient of non-cross validation (r2), correlation coefficient of leave-one-out cross-validation (q2), Fisher's test (F) and bootstrapping were used to validate the developed models. Out of several charge models and alignment-based approaches, Merck Molecular Force Field (MMFF94) charges using structure-based alignment yielded highly predictive CoMFA (q2 = 0.583, Predr2 = 0.751) and CoMSIA (q2 = 0.690, Predr2 = 0.767) models. The models exhibited that electrostatic, steric, HBA, HBD, and hydrophobic fields play a key role in structure activity relationship of these compounds. Using the contour maps information of the best predictive model, new compounds were designed and docked at the TTK active site to predict their plausible binding modes. The structural stability of the TTK complexes with new compounds was confirmed using MD simulations. The simulation studies revealed that all compounds formed stable complexes. Similarly, MM/PBSA method based free energy calculations showed that these compounds bind with reasonably good affinity to the TTK protein. Overall molecular modelling results suggest that newly designed compounds can act as lead compounds for the optimization of TTK inhibitors.
  12. Bouyahya A, Bakrim S, Chamkhi I, Taha D, El Omari N, El Mneyiy N, et al.
    Biomed Pharmacother, 2024 Jan;170:115989.
    PMID: 38103309 DOI: 10.1016/j.biopha.2023.115989
    Cyanobacteria and microalgae contain various phytochemicals, including bioactive components in the form of secondary metabolites, namely flavonoids, phenolic acids, terpenoids, and tannins, with remarkable anticancer effects. This review highlights the recent advances in bioactive compounds, with potential anticancer activity, produced by cyanobacteria and microalgae. Previous in vitro investigations showed that many of these bioactive compounds exhibit potent effects against different human cancer types, such as leukemia and breast cancers. Multiple mechanisms implicated in the antitumor effect of these compounds were elucidated, including their ability to target cellular, subcellular, and molecular checkpoints linked to cancer development and promotion. Recent findings have highlighted various mechanisms of action of bioactive compounds produced by cyanobacteria and microalgae, including induction of autophagy and apoptosis, inhibition of telomerase and protein kinases, as well as modulation of epigenetic modifications. In vivo investigations have demonstrated a potent anti-angiogenesis effect on solid tumors, as well as a reduction in tumor volume. Some of these compounds were examined in clinical investigations for certain types of cancers, making them potent candidates/scaffolds for antitumor drug development.
  13. Rafi MS, Naqvi SB, Khan MU, Fayyaz M, Ashraf N, Khan MA, et al.
    J Clin Diagn Res, 2015 Jul;9(7):FC05-8.
    PMID: 26393139 DOI: 10.7860/JCDR/2015/13437.6207
    Limited resources of healthcare system and high use of antidepressants have raised some serious concerns regarding proper surveillance system of prescribed medicines. Not much literature is available from Pakistan regarding the potential drug-drug interactions (pDDIs) associated with antidepressants.
  14. Arif H, Qayyum S, Akhtar W, Fatima I, Kayani WK, Rahman KU, et al.
    Micromachines (Basel), 2023 Jun 23;14(7).
    PMID: 37512596 DOI: 10.3390/mi14071285
    The current study attempts to evaluate the formation, morphology, and physico-chemical properties of zinc oxide nanoparticles (ZnO NPs) synthesized from Clinopodium vulgare extract at different pH values and to investigate their antimicrobial and biomedical application potential. The reduction of zinc ions to ZnO NPs was determined by UV spectra, which revealed absorption peaks at 390 nm at pH 5 and 348 nm at pH 9, respectively. The spherical morphology of the nanoparticles was observed using scanning electron microscopy (SEM), and the size was 47 nm for pH 5 and 45 nm for pH 9. Fourier-transformed infrared spectroscopy (FTIR) was used to reveal the presence of functional groups on the surface of nanoparticles. The antibacterial activity was examined against Staphylococcus aureus, Streptococcus pyogenes, and Klebsiella pneumonia via the agar-well diffusion method. Comparatively, the highest activities were recorded at pH 9 against all bacterial strains, and among these, biogenic ZnO NPs displayed the maximum inhibition zone (i.e., 20.88 ± 0.79 mm) against S. aureus. ZnO NPs prepared at pH 9 exhibited the highest antifungal activity of 80% at 25 mg/mL and antileishmanial activity of 82% at 400 mg/mL. Altogether, ZnO NPs synthesized at pH 9 show promising antimicrobial potential and could be used for biomedical applications.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links