Khalid Saad Alharbi

Cisplatin (CP) is a highly effective, heavy-metal chemotherapeutic agent widely utilized in the treatment of various solid tumors. But its use in therapeutic settings is fundamentally constrained by dosage toxicities, most notably severe nephrotoxicity. Aloesin, a bioactive C-glycosylated chromone naturally derived from Aloe vera, possesses strong antioxidant and anti-inflammatory properties. This investigation clarifies the precise molecular mechanisms by which aloesin attenuates CP-induced renal injury in a rodent model. A total of 36 male Wistar rats were randomly assigned to six experimental groups: (I) Normal control (vehicle only), (II) CP (5 mg/kg, i.p.), (III) CP + Aloesin (20 mg/kg, p.o.), (IV) CP + Aloesin (40 mg/kg, p.o.), (V–VI) Aloesin alone (20 and 40 mg/kg, p.o.). The study followed a preventive design; aloesin was administered orally throughout the 25-day experimental period, concurrent with CP. Nephrotoxicity was induced in the respective groups via four intraperitoneal injections of CP (5 mg/kg) administered at 5-day intervals (days 1, 6, 11, and 16). At the conclusion of the 25-day timeline, physiological parameters, serum creatinine (Scr), blood urea nitrogen (BUN), and lipid profiles were evaluated. Additionally, inflammatory modulators (TNF-α, IL-1β, IL-6, NF-κB), tissue apoptotic indicators (Caspase-3, Caspase-9, Bax, Bcl-2), and oxidative stress markers (MDA, SOD, GSH, CAT) were quantified from renal tissue homogenates alongside semi-quantitative histopathological evaluation. CP administration induced profound renal impairment, characterized by elevated Scr and BUN, extensive lipid peroxidation, and the depletion of endogenous antioxidants. Concurrent treatment with aloesin significantly preserved renal function, reduced MDA levels, and restored SOD, CAT, and reduced GSH activities. Furthermore, aloesin significantly reduced renal tissue levels of NF-κB, TNF-α, IL-1β, IL-6, Bax, Caspase-3, and Caspase-9, while improving Bcl-2 levels and decreasing the Bax/Bcl-2 ratio, suggesting attenuation of inflammatory and apoptotic pathways. Histopathological evaluation confirmed that aloesin effectively preserved renal tubular morphology without causing any independent physiological or systemic toxicity. These findings demonstrate that aloesin exerts robust prophylactic nephroprotective efficacy against CP-induced acute kidney injury. This protective action is driven by the clear suppression of oxidative stress, restriction of macro-inflammatory signaling, and the direct inhibition of mitochondrial-mediated apoptotic pathways.

Alzheimer's disease (AD), a leading cause of dementia worldwide, is a neurological disorder characterized by progressive cognitive decline. AD is also considered a significant socioeconomic burden. While definitive diagnostic tools such as positron emission tomography (PET) imaging and cerebrospinal fluid (CSF) biomarker analysis offer high sensitivity and specificity, they are limited by high cost, invasiveness, and limited accessibility. Consequently, these gold standard approaches hinder their applicability for large-scale screening and longitudinal follow-up. Recent advances in blood-based biomarkers hold promise in capturing systemic molecular changes associated with AD. In particular, transcriptomic signatures derived from RNA sequencing (RNA-seq) are promising in capturing systemic molecular changes associated with AD. Gene expression profiles in peripheral blood reveal underlying pathological processes. These pathological processes can be listed as synaptic dysfunction, neuroinflammation, and metabolic dysregulation. Together with the high-dimensional datasets and AI approaches enable the identification of robust predictive models which has the assistance of estimating AD-related biomarker status. We further discussed the integration of multiple omics data, including genomics, proteomics, and metabolomics to improve biomarker robustness. We also addressed key challenges related to reproducibility, repeatibility, cohort heterogeneity, and clinical application. And we outline future directions of standardized, scalable, and clinically applicable diagnostic machineries.

Background and Objectives: Methamphetamine (METH) is a potent psychostimulant known to induce neurotoxicity and neurodegeneration, leading to cognitive impairment. This study aimed to explore cubebin’s potential neuroprotective effects against METH-induced cognitive deficits by investigating its ability to suppress lipid peroxidation and pro-inflammatory markers and modulate neurotransmitter levels. Material and Methods: A total of 30 rats were taken and randomly grouped into five groups: group I—control; group II—METH 100 mg/kg/i.p.; group III—METH + cubebin (10 mg/kg/p.o.); group IV—METH + cubebin (20 mg/kg/p.o.); and group V—cubebin per os at 20 mg/kg. After a 14-day oral regimen, behavioral activities were assessed utilizing the Morris water maze (MWM). Biochemical analysis included neurotransmitters, including dopamine (DA), norepinephrine (NE), and gamma-aminobutyric acid (GABA); oxidative stress markers (malondialdehyde (MDA); nitric oxide (NO), catalase (CAT), reduced glutathione (GSH)); inflammatory cytokines [interleukin (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)]; neurotrophic factors (BDNF, CREB); and apoptotic markers (caspase-3 and caspase-9). Furthermore, molecular docking and simulation studies were conducted. Results: Treatment with cubebin led to a marked reduction in latency during the MWM task. It significantly modulated the oxidative stress markers (SOD, GSH, CAT, MDA, and NO), inflammatory cytokines (IL-6, IL-1β, TNF-α), neurotrophic factors (CREB, BDNF), apoptotic markers (NFkB, caspase-3, caspase-9), and neurotransmitters (NE, DA, and GABA) in METH-induced memory-impaired rats. The results of molecular dynamics simulation (MDS) provided insight into the mechanisms that associate proteins CREB, BDNF, and caspase-3 in conformational dynamics upon binding to cubebin. Conclusions: In conclusion, cubebin administration improved cognitive function in rats by modulating antioxidant enzyme activity, reducing pro-inflammatory cytokines, and regulating neurotransmitter levels, demonstrating its potential neuroprotective effects against MA-induced neurodegeneration.

Cyclophosphamide is a widely used chemotherapeutic agent known for its effectiveness in treating various cancers; however, it is associated with significant immunosuppressive side effects. This study investigates the potential of sakuranetin, a natural flavonoid, in mice under cyclophosphamide-induced immunosuppressive conditions. Mice were grouped into four groups: one control group, two treated with cyclophosphamide and two sakuranetin-treated groups receiving different doses (10 and 20 mg/kg). Immune organ indices, lymphocyte proliferation, hematological parameters, nitric oxide levels, cytokines (tumor necrosis factor alpha-TNF-α, interferon γ-IFN-γ), interleukins (interleukin-1β-IL-1β, IL-4, IL-6), immunoglobulin G (IgG), IgM levels, plague-forming cells quantification, qualitative hemolysis, and delayed-type hypersensitivity were assessed. Cyclophosphamide significantly (P < 0.05) reduced immune organ indices, lymphocyte proliferation, changes in hematological parameters, and nitric oxide levels. Treatment with both sakuranetin doses restored these parameters and normalized cytokine, IgG, and IgM levels (P < 0.05). Sakuranetin significantly (P < 0.05) improved the immunomodulatory action with elevated immune response with downregulation in immune response mediated by cells. Sakuranetin effectively counteracts cyclophosphamide-induced immunosuppression by modulating the IFN-γ, TNF-α, IgG, and interleukin pathway, suggesting its potential as a protective agent. Graphical Abstract

The present investigation determines the effects of rosiridin in cisplatin (CP)-induced renal toxicity in rats. The experimental animals were used and divided into four groups. Experimental rats were randomly divided into group-I normal control, group-II CP group (8 mg/kg i.p.), group-III CP + rosiridin (10 mg/kg, p.o.) and group-IV rosiridin (10 mg/kg p.o.). Various biochemical parameters, i.e., creatinine, urea, uric acid, cholesterol, blood urea nitrogen, antioxidant levels, inflammatory markers such as interleukins-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), apoptosis markers including B cell lymphoma-2 (Bcl-2), caspase-3 and histopathological investigations were evaluated. Additionally, molecular docking and dynamics were performed to assess the interaction of rosiridin with target proteins. Rosiridin significantly minimized alteration in creatinine, urea, uric acid, cholesterol, blood urea nitrogen, antioxidant levels, and inflammatory, i.e., IL-1β, IL-6, TNF-α, NF-κB, Bcl-2, and caspase-3 which CP induced in rats. The interaction of rosiridin showed a favorable docking energy. The MD simulation results showed the higher stability of the complex generated from rosiridin. The current study exhibited rosiridin having a protective effect on CP-induced renal toxicity. Graphical abstract

Background and Objectives: Rosiridin is a monoterpene with outstanding monoamine inhibitory activity that is useful to treat depressive episodes and rapid-onset dementia. The current investigation aims to evaluate the neurologically protective impact of rosiridin, which opposes aluminum chloride (AlCl₃) and causes memory dysfunction in rats. Materials and Methods: Memory impairment was developed in Wistar rats by administering AlCl₃ (100 mg/kg p.o.) orally for 42 days and then supplemented with rosiridin at 10 and 20 mg/kg/p.o. Upon completion of the investigation, the behavior factor was performed utilizing the Y-maze, Morris Water Maze, and open field tests. Estimating numerous biological factors, such as nitric oxide (NO), oxidative stress (malondialdehyde MDA), acetylcholinesterase (AChE), butyrylcholinesterase levels (BuChE), antioxidants (glutathione GSH, catalase CAT, and superoxide dismutases SODs) and neurotransmitter (serotonin-5HT, dopamine-DA, acetylcholine-Ach) in the brain. Furthermore, interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF-α), brain-derived neurotrophic factor (BNDF), nuclear factor kappa B (NFᴋB), phosphatidylinositol 3-kinase (PI3K), and pAkt were assessed in the diffused brain cells. Results: The rosiridin-treated group significantly improved in terms of behavioral parameters, including in the Y-maze, Morris Water Maze, and open field tests. Further, rosiridin restored biochemical parameters, including NO, oxidative stress AChE, BuChE, antioxidants, neurotransmitters, IL-6, IL-1β, TNF-α, BNDF, NFᴋB, PI3K, and pAkt compared to AlCl₃. Conclusions: The current investigation reveals that rosiridin could ameliorate the impairment of memory that AlCl3 causes in rats via improvements in behavioral and restored biochemical parameters.