Abdelkader, N. F., A. I. El-Batal, Y. M. Amin, A. M. Hawas, S. H. M. Hassan, and N. I. Eid, "Possible mechanisms underlying the neuroprotective effects of gold nanoparticles and alpha-lipoic acid mixture on brain damage induced by radiation: A subacute study in rats", Journal of Drug Delivery Science and Technology, vol. 109, pp. 106977, 2025.
Kamal, M. - A. M., R. M. Essam, N. F. Abdelkader, and H. F. Zaki, "Modafinil Ameliorated Fibromyalgia Syndrome in Rats by Modulating Mast Cells and Microglia Activation Through Dopamine/Substance P/MRGPRX/Histamine and PI3K/p-Akt/NF-κB Signaling Pathways.", Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, vol. 20, issue 1, pp. 38, 2025 Apr 15. Abstract

Fibromyalgia syndrome (FMS) is characterized by prolonged, widespread musculoskeletal pain accompanied by various physical and psychological disturbances. Modafinil, a wake-promoting drug, manages pain symptoms in several diseases by inhibiting dopamine reuptake and exhibiting anti-inflammatory and immunomodulatory effects, including the impairment of cytokine production, microglia, and mast cell activation. Central inflammation may involve microglial activation, which is correlated with mast cell activation. Restoring dopamine levels and modulating the communication between mast cells and microglia may represent a promising approach to managing pain symptoms in FMS. Thus, this study intended to explore the interplay between brain mast cells and microglia as an underlying mechanism in the pathophysiology of FMS and how this interaction is controlled by modafinil, with a focus on dopamine/SP/MRGPRX2/histamine and PI3K/p-Akt/NF-κB signaling pathways. Rats were arbitrarily distributed between 4 groups. Group 1 served as normal control. Reserpine (1 mg/kg/day; s.c) was injected into the remaining groups for three consecutive days. In groups 3 and 4, modafinil (100 mg/kg/day; p.o) was administered either alone or in conjunction with haloperidol (1 mg/kg/day; ip), respectively, for the following 21 days. Modafinil ameliorated reserpine-induced thermal/mechanical allodynia (1.3-fold, 2.3-fold) and hyperalgesia (0.5-fold), attenuated depression (0.5-fold), and enhanced motor coordination (1.2-fold). It mitigated the histopathological alterations and increased dopamine levels in the thalamus of rats by 88.5%. Modafinil displayed anti-inflammatory effects via inhibiting mast cells and microglia activation, manifested by reductions in SP/MRGPRX2/IL-17/histamine (52%, 58%, 56.7%, and 63.7%) and PI3K/p-Akt/t-Akt/NF-κB/TNF-α/IL-6 (31.7%, 55.5%, 41%, 47.6%, and 76.9%), respectively. Ultimately, modafinil alleviated FMS behavioral, histopathological, and biochemical abnormalities and suppressed mast cell-microglial neuroinflammation in the thalamus of rats exposed to reserpine. This study highlights the potential of repurposing modafinil to improve FMS symptoms.

El-Kadi, R. A., M. S. Sedeek, N. F. Abdelkader, H. F. Zaki, and A. S. Kamel, "Ameliorative Effect of Moringa oleifera Against CUMS-Induced Anxiety in Rats: β-Catenin and 5-HT Crosstalk.", Molecular neurobiology, vol. 62, issue 9, pp. 11179-11195, 2025 Sep. Abstract

Serotonin 1 A receptor (5-HT1 AR) signaling is pivotal for stress response, determining vulnerability or resilience to psychopathology. However, the precise pathological mechanisms underlying its role remain inconsistent. Moringa oleifera (MO), a plant with purported medicinal properties, has demonstrated potential efficacy against psychiatric disorders. However, no available information exists regarding its effects on 5-HT1 A signaling under normal and stressed conditions. This study is aimed at elucidating the effects of MO in conjunction with 5-HT1 A signaling. Rats were randomly assigned to four groups: normal (NRML), normal rats receiving MO orally at 200 mg/kg (MO), rats exposed to chronic unpredictable mild stress (CUMS) for 21 days (CUMS), and stressed rats administered MO from day 15 (CUMS + MO). Behavioral analysis was conducted using forced swimming and open field tests. Serotonergic markers, β-catenin, p-Erk, c-myc, and mTOR were assessed via ELISA, while miRNA clusters and individual miRNAs were analyzed using PCR. No significant differences were observed between the NRML and MO groups, both of which exhibited approximately normal biochemical activity, except for a decreased 5-HIAA/5-HT ratio in the MO group, which was reflected behaviorally. Rats subjected to CUMS displayed defective β-catenin signaling, potentially leading to compensatory activation of 5-HT1 A. Consistently, the CUMS + MO group exhibited normalized 5-HT1 A and 5-HT signaling, accompanied by reduced pThr183-Erk and its downstream targets, c-myc and miR- 203, to mitigate pathological anxiety. Additionally, mTOR and its downstream target, miR- 217, were reduced compared to stressed rats. MO exhibited a promising anxiolytic effect by modulating 5-HT1 A signaling, as evidenced by improved neurobehavioral outcomes and restoring biochemical balance in stressed rats. These findings highlight its potential therapeutic role in anxiety management.

Ezeldine-Elmahalawy, N., N. F. Abdelkader, H. F. Zaki, A. I. Elbrairy, and S. S. Gad, "Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.", Inflammopharmacology, vol. 33, issue 10, pp. 6211-6226, 2025 Oct. Abstract

The neuroprotective potential of tyrosine kinase inhibitors (TKIs), potent anticancer drugs, was verified against various neurodegenerative insults, but not Huntington's disease (HD). These promising outcomes were due to their ability to modulate various intracellular signalling pathways. Hence, the current study aimed to evaluate the neuroprotective effects of lapatinib and pazopanib in the 3-nitropropionic (3-NP)-induced HD model in rats. After 14 days of 3-NP administration, rats received saline, lapatinib, or pazopanib for 21 days. Treatment with lapatinib or pazopanib improved the striatal microscopic architecture, neuronal survival, and neuroinflammatory responses, with a pronounced effect observed for pazopanib. At the molecular level, lapatinib and pazopanib reduced the striatal gene expression of NF-κB and TNF-α receptors, curbed the glutamate/calpain-2 axis, and modified the striatal content of inflammatory molecules as well as neurotransmitters. In addition, they activated the neuroprotective trajectory viz., m-Tor/ULK-1/Beclin-1/LC3-II, an effect dependent on tyrosine kinase inhibition. Moreover, treated groups showed normalised tyrosine hydroxylase and glial fibrillary acidic protein in the striatum. In conclusion, this study provides strong evidence that lapatinib or pazopanib significantly improved motor function, alleviated cognitive decline, and attenuated neurodegeneration in HD rats via modulating key signalling pathways implicated in HD pathogenesis. These results underscore the promising therapeutic potential of TKIs in managing HD and warrant further investigation into their clinical application.

Magdy, N., N. F. Abdelkader, H. F. Zaki, and A. S. Kamel, "Unleashing the pharmacological potential of taste receptors in reproductive processes beyond their gustatory role.", Steroids, vol. 217, pp. 109603, 2025 May. Abstract

Traditionally, taste receptors (TRs) have been understood to reside within the taste buds on the tongue, serving as initiators for different taste perceptions. However, recent research has expanded our understanding, revealing that TRs are found throughout the body and perform a wide range of functions beyond taste perception as non-tasting functions. These receptors, along with their genetic variations, have been linked to various human health conditions. They are activated by an array of substances, including hormones, nutrients, and toxins, indicating their involvement in numerous biological processes. Specifically, in males, TRs are notably present in the testes and epididymis, where they contribute to the hormonal production, spermatogenesis, and sperm maturation. In females, these receptors are found in the ovaries, uterus, and myometrium, playing crucial roles in ovulation, menstrual cycle regulation, and embryo implantation. There are a lot of missed areas regarding TRs research that imposes to fulfill the gaps in the current understanding of their role in reproduction. This review aims to provide a comprehensive overview of the emerging roles of extraoral TRs in reproductive health, highlighting their physiological and pathophysiological significance in various reproductive processes. As well, grabbing the attention towards the release of new pharmacological interventions to manage conception and contraception in male and female was considered.

El-Gowilly, S. M., H. A. Metwaly, D. Makhlouf, N. Elmansoury, S. A. Abuiessa, A. A. Sorour, M. H. Abdelgalil, M. Fawaz, A. M. Abushady, M. Gamaleldin, et al., "Analysis of the current situation of pharmacogenomics in terms of educational and healthcare needs in Egypt and Lebanon.", Pharmacogenomics, vol. 25, issue 10-11, pp. 429-440, 2024. Abstract

Pharmacogenomics (PGx) is a practice that investigates the link between genetic differences and drug response in patients. This can improve treatment effectiveness and reduce harmful side effects. However, has yet to be adequately realized in developing nations. Three surveys were conducted between November 2022 to March 2023 in Egypt and Lebanon. The first survey assessed availability of PGx testing in different healthcare facilities; the second one assessed knowledge, interest and attitude toward learning about PGx among pharmacists and physicians; and the third one assessed interest in providing PGx education at academic levels. In Egypt, a few of the surveyed healthcare facilities are conducting some form of pharmacogenetic testing. In Lebanon, very few germline pharmacogenomic tests are offered in Greater Beirut's leading hospitals, and no other testing was recorded. PGx education attracts considerable interest, with 34.3% of pharmacists very interested and 48.8% interested. Similarly, 24.8% of total physicians were very interested while 44.8% were interested. Academic professionals in the surveyed institutions in both countries agreed on the need for educational programs in PGx and 78.2% agreed that there were good opportunities for implementing PGx testing. These findings clearly indicate the need to develop and implement educational programs in PGx in the Middle-East.

Elbadawy, N. N., M. A. Saad, S. Elfarrash, M. A. E. Ahmed, and N. F. Abdelkader, "The GLP-1 agonist semaglutide ameliorates cognitive regression in P301S tauopathy mice model via autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization.", European journal of pharmacology, vol. 991, pp. 177305, 2025 Mar 15. Abstract

Tau hyper-phosphorylation has been recognized as an essential contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies. In the last decade, tau hyper-phosphorylation has gained considerable concern in AD therapeutic development. Tauopathies are manifested with a broad spectrum of symptoms, from dementia to cognitive decline and motor impairments. Tau undergoes conformational changes and abnormal phosphorylation that mediate its detaching from microtubules, forming neurofibrillary tangles (NFTs). In the current study, a widely used P301S transgenic mice model of tauopathy was employed to evaluate the possible neuroprotective effects of semaglutide as an autophagy regulator through modifications of the brain renin-angiotensin system (RAS). Mice were divided into two groups according to their genotypes (wild type (Wt) and P301S), which were further subdivided to receive either vehicle (saline) or semaglutide (25 nmol/kg, i. p.), once every 2 days for 28 days. Current data suggest that semaglutide ameliorated the hyperactive pattern and alleviated the cognitive decline of P301S mice. It also hastened the autophagic flux through augmenting angiotensin-converting enzyme 2/sirtuin 1/forkhead box protein O1 signaling. Semaglutide also hindered the expression of phosphorylated adenosine monophosphate-activated protein kinase and phosphorylated glycogen synthase kinase-3 beta at serine 9, reducing the propagation of neuroinflammatory cytokines and oxidative reactions. Finally, semaglutide protected against hippocampal degeneration and reduced the immunoreactivity for total tau and ionized calcium-binding adapter molecule. Semaglutide showed promising neuroprotective implications in alleviating tauopathy-related AD's molecular and behavioral deficits through controlling autophagy and brain RAS.

Magdy, N., N. F. Abdelkader, H. F. Zaki, and A. S. Kamel, "Potential exacerbation of polycystic ovary syndrome by saccharin sodium Via taste receptors in a letrozole rat model.", Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, vol. 191, pp. 114874, 2024. Abstract

The most common cause of anovulatory infertility is polycystic ovarian syndrome (PCOS), which is closely associated with obesity and metabolic syndrome. Artificial sweetener, notably saccharin sodium (SS), has been utilized in management of obesity in PCOS. However, accumulating evidence points towards SS deleterious effects on ovarian physiology, potentially through activation of ovarian sweet and bitter taste receptors, culminating in a phenotype reminiscent of PCOS. This research embarked on exploration of SS influence on ovarian functions within a PCOS paradigm. Rats were categorized into six groups: Control, Letrozole-model, two SS groups at 2 dose levels, and two groups receiving 2 doses of SS with Letrozole. The study underscored SS capability to potentiate PCOS-related anomalies. Elevated cystic profile with outer thin granulosa cells, were discernible. This owed to increased apoptotic markers as cleaved CASP-3, mirrored by high BAX and low BCL-2, with enhanced p38-MAPK/ERK pathway. This manifestation was accompanied by activation of taste receptors and disruption of steroidogenic factors; StAR, CYP11A1, and 17β-HSD. Thus, SS showed an escalation in testosterone, progesterone, estrogen, and LH/FSH ratio, insinuating a perturbation in endocrine regulation. It is found that there is an impact of taste receptor downstream signaling on ovarian steroidogenesis and apoptosis instigating pathophysiological milieu of PCOS.

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