This study investigates the neuroprotective effects of fucoxanthinol (FXL) against the toxic activities of two compounds known to induce neurotoxic effects in humans and animals. MPTP (1-methyl- 4-phenyl- 1,2,3,6-tetrahydropyridine) induces Parkinson’s disease (PD)-like phenotypes by inhibiting mitochondrial complex I in dopaminergic neurons. Chlorpyrifos (CPF), another neurotoxic agent, is associated with acute and long-term neurotoxicity primarily through acetylcholinesterase (AChE) inhibition. FXL demonstrated the ability to reverse the neurotoxic effects of CPF and MPTP in SH-SY5Y dopaminergic neuronal cell models. Treatment with FXL enhances mitochondrial function in SH-SY5Y cells exposed to CPF and MPTP, as demonstrated by increased levels of Adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), mitochondrial complexes activities, and oxygen consumption rates, pyruvate dehydrogenase (PDH) activities, and mitophagy pathways. This improvement highlights FXL’s ability to counteract the mitochondrial dysfunction induced by these neurotoxic agents. Additionally, FXL reduces oxidative damage and enhances cell viability. At the molecular level, the neuroprotective effects were also associated with the modulation of apoptotic cell markers, including Bcl- 2 and the oxidative damage markers. Molecular docking data further support the outcomes of our in vitro studies. Multivariable analysis highlights the neuroprotective effects of FXL. These findings indicate the potential of FXL to mitigate CPF- and MPTP-induced neurotoxicity, suggesting its promise as a therapeutic agent for managing neuronal damage observe in PD.

Ulcerative colitis (UC) is an autoimmune inflammatory condition characterized by significant mucosal destruction. Although Syzygium aromaticum (Clove oil; CO) oil is well-known for its antioxidant and anti-inflammatory properties, its high volatility, toxicity, and hydrophobicity can compromise its biological efficacy. Therefore, nanoencapsulation is a feasible approach for boosting its therapeutic potential, including stability, bioavailability, and target delivery. Herein, this study was designed to minimize acetic acid-mediated UC using CO alone or encapsulated in nano-vehicles including PCL, CS, and ALG. The developed nano-capsules CO were characterized by Zetasizer, FT-IR, and SEM, and subsequently, the encapsulation efficiency and controlled release profile of CO were determined. Forty adult rats were assigned to five groups ( n = 8) as follows: the control (CONT) group, which received dimethyl sulfoxide (DMSO) once daily; the UC group, which received rectal acetic acid (AA) instillation on day 8 of the experiment. CO group: rats were treated orally with clove oil (250 mg/kg) dissolved in DMSO once daily. PCL@CS + ALG group; rats were orally treated with nano-vehicle (250 mg/kg). CONPs group: rats received clove oil nanoparticles (PCL@CO(CS + ALG)NPs, 250 mg/kg). All groups received their respective treatments once a day for seven consecutive days, before and after UC induction. An in silico study revealed the binding affinities of eugenol, the principal bioactive constituent of CO, toward inflammatory molecules at both the mRNA and protein levels. Biologically, the colon outcomes showed that CO, either alone or loaded with nanoparticles (CONPs), significantly decreased MDA and NO levels and elevated antioxidant enzymatic activities (SOD, CAT, , GPx, and GR), with higher GSH levels. Additionally, the treatment of rats with CO or CONPs mitigated colon inflammation by decreasing the MPO activity, TNF- α , IFN- γ , IL-1 β , and PGE2 levels, as well as downregulating the expression of NF- κ B, IL-6, IL-8, and iNOS genes. Remarkably, CONPs prevented the colon oxidative damage by modulating the mRNA expression of Keap1/Nrf2/HO-1 signaling pathways. Unlike the rats exposed to AA, the treatment with CO and CONPs dramatically restored the mRNA expression of Cdc25c and RNF8 genes. Histologically, the CONPs-treated group showed a clear restoration of colonic tissue architecture toward normal, accompanied by normalization of VEGF and α-SMA immunoexpression patterns. Conclusively, CO, either alone or encapsulated in nanoparticles (CONPs), offers promising therapeutic potential for UC, likely through its anti-inflammatory, antioxidant, and anti-fibrotic effects, as well as superior regulation of angiogenesis compared with pure CO.

Problem/Gaps: Small ruminants in developing countries often rely on Berseem hay (BH) as a primary fodder, but alternative, locally available, and nutritious feed sources are needed to improve reproductive performance and health. Objectives: This study investigated the use of Spanish Panicum and cassava ( Manihot esculenta ) leaf meals as partial replacements for BH in the diets of Barki doe goats during the spring and autumn breeding seasons. Methods: A total of 42 healthy does (2–3 years old) were divided into three dietary groups: G1 (control, 40% concentrates + 60% BH), G2 (BH replaced by Panicum ), and G3 (BH replaced by cassava). After a 4-week diet adaptation period, goats were fed their respective rations throughout mating until weaning. Blood samples were collected biweekly from the jugular vein of all does. Complete blood counts were measured immediately, and plasma was separated and stored for subsequent biochemical and immunological analyses. Results: Both Panicum and cassava leaf meals significantly improved reproductive performance compared to BH. Conception and kidding rates reached 100% in spring, and the Panicum group achieved the highest fecundity (220%) and survival rate (95.5%) in autumn. Hematological parameters, including total erythrocyte count, hemoglobin, PCV, MCHC, and leukocyte count, increased significantly in the cassava group ( P < 0.0001). Pregnant does fed cassava also showed elevated plasma total protein, albumin, globulin, glucose, and ATP levels ( P < 0.0001). Immune status improved in both Panicum and cassava groups, with higher plasma TAC, IgG, and complement proteins C3 and C4 ( P < 0.0001). Conclusion: Our findings indicate that incorporating Panicum and cassava leaf meals as alternatives to Berseem hay enhances reproductive efficiency, hematological health, and immunity in Barki does during breeding seasons, supporting their use as effective local feed resources.

Methotrexate (MTX) is widely used for its chemotherapeutic and immunosuppressive properties, but is limited by oxidative stress-mediated hepatotoxicity. Nanoantioxidant delivery systems can enhance the stability, solubility, and in vivo efficacy of natural antioxidants. This study investigated the hepatoprotective effects of myricetin (MYR), a flavonoid with potent antioxidant activity, and its liposomal nanoantioxidant formulation (MYR-loaded liposomal nanoparticles, MYR-LNPs) against MTX-induced liver injury in male albino Sprague Dawley rats. Sixty rats were randomly allocated to six groups: control, MTX, MYR, MYR-LNPs, and combinations of MTX with MYR-LNPs. MYR-LNPs were successfully formulated and physicochemically characterized, exhibiting a mean particle size of 95.6 nm, a zeta potential of −32 mV, and a narrow polydispersity index, collectively confirming their colloidal stability and suitability for hepatic delivery. MTX markedly disrupted liver function, increasing serum AST, ALT, ALP, and bilirubin and decreasing total protein, albumin, and globulin, whereas co-treatment with MYR-LNPs substantially restored these parameters and outperformed free MYR. MTX-induced oxidative stress, reflected by depleted hepatic GSH and antioxidant enzymes (GPx, SOD, CAT, GST), elevated reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyls and downregulated NRF2/HO-1, was significantly counteracted by MYR-LNPs. In addition, MYR-LNPs mitigated MTX-evoked inflammation and nitrosative stress by reducing NF-κB, TNF-α, IL-1β, nitric oxide, and iNOS expression. They corrected apoptotic imbalance by lowering Bax and caspase 3 while increasing Bcl-2. Histopathological and ultrastructural assessments confirmed that MYR-LNPs preserved hepatic architecture and mitochondrial integrity. These findings indicate that MYR-loaded liposomal nanoantioxidants provide superior protection against MTX-induced hepatotoxicity by modulating oxidative stress, inflammation, and apoptosis, supporting their potential as an advanced nanodrug delivery strategy for antioxidant therapy.

High-fat diets (HFDs) play a central role in the onset and progression of metabolic syndrome. This study investigated the protective effects of silymarin (SM)-loaded phytosomal nanoparticles (SM-PNPs) against high-fat diet (HFD)-induced hepatic dysfunction and metabolic disorders, with emphasis on antioxidant and anti-inflammatory mechanisms. Sixty rats were randomly divided into six groups: control, SM-treated (200 mg/kg body weight), SM-PNPs-treated (200 mg/kg body weight), HFD-treated, and two combination groups receiving HFD along with either SM or SM-PNPs (200 mg/kg body weight) for 5 weeks during the final phase of a 20-week HFD feeding period. SM-PNPs therapy demonstrated stronger hepatoprotective activity than unencapsulated SM. It significantly improved metabolic abnormalities, including insulin resistance, dyslipidemia, and hepatopathy in HFD-fed rats. Moreover, SM-PNPs ameliorated HFD-induced alterations in fasting glucose and insulin levels and improved HOMA-IR indices, thereby restoring glucose homeostasis. Treatment also markedly reduced oxidative stress while enhancing the antioxidant defense system. RT-PCR analysis revealed significant downregulation of key inflammatory genes, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and inducible nitric oxide synthase (iNOS), along with a significant reduction in systemic inflammation, as indicated by decreased high-sensitivity C-reactive protein (hsCRP) levels, as well as apoptosis caspases activities. The in-silico analysis revealed significant interactions of SM with crucial proteins involved in regulating antioxidant defense and inflammatory pathways. Histopathological and ultrastructural examinations further supported these biochemical findings, showing that SM-PNPs attenuated hepatic steatosis, collagen deposition, and fibrosis. SM-PNPs exert a significant protective effect against HFD-induced hepatic damage and metabolic disturbances and represent a promising therapeutic strategy for metabolic dysfunction-associated steatotic liver disease (MASLD), potentially due to improved solubility, bioavailability, and sustained release in the nanoparticle formulation.

Ehrlich ascites carcinoma (EAC) is an aggressive experimental tumor model associated with severe oxidative stress, inflammation, and hepatorenal injury. Astaxanthin (ASX), a potent natural antioxidant carotenoid, has demonstrated anticancer and cytoprotective properties; however, its therapeutic application is limited by poor bioavailability and stability. Therefore, this study investigated the anticancer and hepatorenal protective effects of astaxanthin-loaded chitosan nanoparticles (ASX-CNPs) compared with free ASX in EAC-bearing mice. Ninety female Swiss albino mice were randomly allocated into six groups: control, ASX, ASX-CNPs, EAC, EAC + ASX, and EAC + ASX-CNPs. Tumor progression, survival rate, oxidative stress biomarkers, inflammatory mediators, apoptotic markers, and histopathological alterations in hepatic and renal tissues were evaluated. Antioxidant parameters included SOD, CAT, GPx, GSH, TAC, and TBARS. Inflammatory and apoptotic signaling pathways were assessed through measurement of COX-2, TNF-α, IFN-γ, IL-1β, Bcl-2, Bax, and caspase-3 expression levels. ASX-CNPs markedly suppressed tumor progression and improved survival compared with free ASX. Treatment with ASX-CNPs significantly downregulated Bcl-2 expression while upregulating Bax and caspase-3, indicating enhanced apoptotic activity. Antioxidant defenses were significantly restored, as evidenced by increased SOD, CAT, GPx, GSH, and TAC levels, alongside reduced TBARS. Inflammatory responses were attenuated through decreased COX-2 activity and reduced TNF-α, IFN-γ, and IL-1β levels. Histopathological examination confirmed substantial protection against EAC-induced hepatic and renal damage. Overall, ASX-CNPs demonstrated greater therapeutic efficacy than free ASX across biochemical, molecular, and histopathological assessments. ASX-loaded chitosan nanoparticles exerted potent anticancer, antioxidant, anti-inflammatory, and hepatorenal protective effects in EAC-bearing mice. The enhanced efficacy of ASX-CNPs relative to free ASX is likely attributable to improved bioavailability and targeted modulation of oxidative stress, inflammatory, and apoptotic pathways, supporting their potential as a promising nanotherapeutic strategy for cancer-associated organ injury.