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The most widely used cancer therapy is radiation therapy, but radiation damage to healthy tissues, particularly the gastrointestinal (GI) system, frequently reduces its effectiveness. This study investigates whether etoricoxib-loaded nanostructured lipid carriers (Et-NLC) could help shield the rat jejunum from radiation damage. Gamma irradiation (6 Gy) was used to damage the jejunum of Wistar albino rats, and then Et or Et-NLC (10 mg/kg b.w.) was administered orally for 14 days. It was found that the amounts of glutathione S-transferase (GST), superoxide dismutase (SOD), and nitric oxide (NO) decreased after irradiation but increased after Et-NLC therapy. Molecular analysis showed radiation-induced expression of microRNA-34a (miR34a), which may be involved in cellular stress response. Et-NLC treatments modulated the expression of miR34a, suggesting possible regulatory roles. Western blot analysis revealed changes in P53, interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) levels. Et-NLC treatments decreased TNF-α, IL-6, IL-10, and COX-2 levels, indicating anti-inflammatory actions. DNA fragmentation analysis revealed a decrease in apoptotic activity after Et-NLC treatments. A histopathological examination confirmed that Et-NLC treatments had attenuated radiation damage, which had improved vascularization and reduced inflammation. The findings show that Et-NLC is more effective than Et-alone at reducing damage to the jejunum caused by radiation by controlling inflammation, oxidative stress, and apoptotic activity.

Background Manganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl2) in the brain. Objectives To explore the neuroprotective effects of natural compounds, namely, micronized zeolite clinoptilolite (ZC) and punicalagin (PUN), either individually or in combination, against MnCl2‐induced Parkinson's disease (PD). Methods Fifty male albino rats were divided into 5 groups (Gps). Gp I was used as the control group, and the remaining animals received MnCl2 (Gp II–Gp V). Rats in Gps III and IV were treated with ZC and PUN, respectively. Gp V received both ZC and PUN as previously reported for the solo‐treated plants. Results ZC and/or PUN reversed the depletion of monoamines in the brain and decreased acetyl choline esterase activity, which primarily adjusted the animals' behavior and motor coordination. ZC and PUN restored the balance between glutamate/γ‐amino butyric acid content and markedly improved the brain levels of brain‐derived neurotrophic factor and nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 and decreased glycogen synthase kinase‐3 beta activity. ZC and PUN also inhibited inflammatory and oxidative markers, including nuclear factor kappa‐light‐chain‐enhancer of activated B cells, Toll‐like receptor 4, nucleotide‐binding domain, leucine‐rich‐containing family, pyrin domain‐containing‐3 and caspase‐1. Bcl‐2‐associated X‐protein and B‐cell leukemia/lymphoma 2 protein (Bcl‐2) can significantly modify caspase‐3 expression. ZC and/or PUN ameliorated PD in rats by decreasing the levels of endoplasmic reticulum (ER) stress markers (p‐protein kinase‐like ER kinase (PERK), glucose‐regulated protein 78, and C/EBP homologous protein (CHOP)) and enhancing the levels of an autophagy marker (Beclin‐1). Discussion and Conclusion ZC and/or PUN mitigated the progression of PD through their potential neurotrophic, neurogenic, anti‐inflammatory, antioxidant, and anti‐apoptotic activities and by controlling ER stress through modulation of the PERK/CHOP/Bcl‐2 pathway. ZC: zeolite clinoptilolite, PUN: punicalagin, PD: parkinsonism disease, Mn: manganese, ACHE: acetyl choline esterase, MDA: Malondialdehyde, SOD: Superoxide dismutase, TAC: total antioxidant capacity, DA: Dopamine, NE: norepinephrine, 5HT: serotonin, PCR: polymerase chain reaction, BAX: Bcl‐2‐associated X‐protein, Bcl2: B‐cell leukemia/lymphoma 2 protein, ELISA: Enzyme‐linked Immunosorbent Assay, Enzyme BDNF: Brain‐derived neurotrophic factor, GSK‐3β: Glycogen synthase kinase‐3 beta, glu: glutamate, PGE‐2: Prostaglandin E2, GABA: Gamma‐aminobutyric acid, CHOP: C/EBP Homologous Protein, GRP78: Glucose‐Regulated Protein 78, PERK: protein kinase‐like endoplasmic reticulum kinase, iNOS: Inducible nitric oxide synthase, IL‐1β: Interleukin ‐1β, NF‐kB: nuclear factor kappa‐light‐chain‐enhancer of activated B cells, TLR4: Toll like receptor 4, NLRP3: nucleotide‐binding domain, leucine‐rich–containing family, pyrin domain–containing‐3, COX‐2: Cyclooxygenase 2, TNF‐α: Tumor necrosis factor alpha, Nrf2: nuclear factor erythroid 2‐related factor 2, HO‐1: Heme oxygenase‐1, I.P: Intraperitoneal, P.O: oral.

Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl3) alone, AlCl3 with cocoa alone, AlCl3 with vinpocetine (VIN), AlCl3 with epigallocatechin-3-gallate (EGCG), AlCl3 with coenzyme Q10 (CoQ10), AlCl3 with wheatgrass (WG), AlCl3 with vitamin (Vit) B complex, and AlCl3 with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl3 administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl3 intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl3-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways.

Cancer cells can become resistant to existing treatments over time, so it is important to develop new treatments that target different pathways to stay ahead of this resistance. Many cancer treatments have severe side effects that can be debilitating and even life-threatening. Developing drugs that can effectively treat cancer while minimizing the risks of these side effects is essential for improving the quality of life of cancer patients. The study was designed to explore whether the combination of dicinnamoyl-L-tartaric (CLT) and sorafenib ((SOR), an anti-cancer drug)) could be used to treat hepatocellular carcinoma (HCC) in the animal model and to assess whether this combination would lead to changes in certain biomarkers associated with the tumour. In this study, 120 male mice were divided into 8 groups of 15 mice each. A number of biochemical parameters were measured, including liver functions, oxidative stress (malondialdehyde, (MDA); nitric oxide (NO)), and antioxidative activity (superoxide dismutase (SOD), and glutathione peroxidase (GPx)). Furthermore, the hepatic expressions of Bax , Beclin1 , TNF - α , IL1β , and BCl-2 genes were evaluated by qRT-PCR. The combination of SOR and CLT was found to reduce the levels of liver enzymes, such as AST, ALT, ALP, and GGT, and reduce the pathological changes caused by DAB and PB. The upregulation of TNF-α , IL1β , and Bcl-2 genes suggests that the CLT was able to initiate an inflammatory response to combat the tumor, while the downregulation of the Bax and Beclin1 genes indicates that the CLT was able to reduce the risk of apoptosis in the liver. Furthermore, the combination therapy led to increased expression of cytokines, resulting in an enhanced anti-tumor effect.

The intensive exposure of the liver cells to any type of noxae, such as viruses, drugs, alcohols, and xenobiotics could induce hepatic inflammation through the upregulation of gene expression of several fibrotic and inflammatory mediators. So, our study assessed the role of silymarin on the inflammatory response induced by carbon tetrachloride (CCl 4 ) as an example of xenobiotics on liver tissues in male rats. Forty-eight Wister male rats (weight: 130 ± 10) were housed for 14 days and then divided randomly into six groups: control, SLY: rats received only silymarin orally for 12 weeks (daily), CO: rats were injected with corn oil for 8 weeks (3 times weekly), CCl 4 : rats were injected with CCl 4 solubilized in corn oil for 8 weeks (day by day), Treated: rats received silymarin for 4 weeks after CCl 4 injection, Protected: rats received silymarin for 4 weeks before and 8 weeks during CCl 4 injection. When the treatment period for the rats was over, they underwent scarification after anesthesia. Then, the sera were extracted from the collected blood for the determination of irisin levels, liver functions, and lipid profiles. Liver tissues were separated for the histopathological examinations, the determination of oxidative stress (OS) parameters content, and the relative gene expression of inflammatory cytokines; nuclear factor kappa (NF)-κB, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, cyclooxygenase (COX)-2, and transforming growth factor beta (TGF-β). The findings showed that silymarin reduced liver inflammation by overcoming the OS process and inflammatory cytokines production which was stimulated by CCl 4 . These results were confirmed by histopathology of liver tissues.

We present here the FT-IR, DFT computation, XRD, optical, and photophysical characterization of a heterocyclic compound with thienopyrimidine and pyran moieties. TD-DFT/DMOl 3 and TD-DFT/CASTEP computations were used to study the geometry of isolated and dimer molecules and their optical behavior. The indirect (3.93 eV) and direct (3.29 eV) optical energy bandgaps, HOMO–LUMO energy gap (3.02 eV), and wavelength of maximum absorption (353 nm) were determined in the gas phase with M062X/6-31+G (d, p). A thin film of the studied molecule was studied using XRD, FT-IR, and UV–Vis spectroscopy. The average crystallite size was found as 74.95 nm. Also, the photoluminescence spectroscopy revealed that the compound exhibited different emission bands at the visible range with different intensities depending on the degree of molecular aggregation. For instance, solutions with different concentrations emitted blue, cyan, and green light. On the other hand, the solid-state material produced a dual emission with comparable intensities at λ max  = 455, 505, and 621 nm to cover the entire visible range and produce white emission from a single material with CIE coordinates of (0.34, 0.32) that are very similar to the ideal pure white light. Consequently, these findings could lead to the development of more attractive new luminous materials.

An optimization approach based on full factorial design was employed for developing an HPLC–UV method for simultaneous determination of a quaternary mixture used for the treatment of symptoms related to common cold and COVID-19. The quaternary mixture is composed of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride. The developed technique is a green, fast and simple method that uses isocratic elution of mobile phase consisting of 20:5:75 (v/v) of ethanol: acetonitrile: 2.5 mM heptane-1-sulphonic acid sodium salt at pH 6.5 ± 0.02. The chromatographic separation was carried out using Hypersil BDS Cyano LC Column (250 × 4.6 mm, 5 μm) with 230 nm UV detection and 1.0 mL/min. flow rate. Avoiding the routine methodology and resorting to the modern technology—represented in the usage of experimental design—allows rapid determination of the four drugs using the optimum quantity of chemicals to avoid any waste of resources. The quaternary mixture was eluted in less than 9 min., where retention times of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride were found to be 2.2, 3.8, 6.6 and 8.8 min., respectively. The calibration graphs of the four drugs were linear over concentration ranges of 50.0–500.0, 0.5–20.0, 0.5–20.0 and 0.5–100.0 µg/mL for paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride, respectively with correlation coefficients higher than 0.999. The method is accurate with mean recoveries between 99.87 and 100.04%, precise, as %RSD for the intraday and interday precision were between 0.61 and 1.64% and very sensitive with limit of detections (LOD)’s between 29 and 147 ng/mL and limit of quantification (LOQ)’s between 95 and 485 ng/mL. The proposed method was successfully applied for the analysis of the four drugs either in raw materials or in prepared tablet with the least amount of chemicals within short time. It is also validated following International Conference on Harmonization Guidelines. The proposed method was found to be green according to the most common greenness assessment tools; NEMI, GAPI, Analytical Eco-Scale and AGREE methods. The advantages of the proposed method qualify it for routine analysis of the studied drugs either in single or co-formulated dosage form in quality control labs.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the alarmingly rising clinical problems in the 21 st century with no effective drug treatment until now. Taurine is an essential amino acid in humans that proved efficacy as a non-pharmacological therapy in a plethora of diseases; however, its impact on NAFLD remains elusive. The aim of the current study is to evaluate the protective mechanism of taurine in experimental steatohepatitis induced by junk food given as cafeteria-diet (CAF-D) in male albino rats. Methods: Forty adult male albino rats of local strain between 8-10 weeks old, weighing 150 ± 20 g, were divided into four equal groups: Group I (control group), Group II (Taurine group), Group III (CAF-D for 12 weeks) and Group IV (CAF-D +Taurine). CAF-D was given in addition to the standard chow for 12 weeks, where each rat was given one piece of beef burger fried in 15 g of sunflower oil, one teaspoonful of mayonnaise, and one piece of petit pan bread, weighing 60g/ piece. In the serum, liver function tests; ALT, AST, ALP, GGT and the lipid profile; TG, TC, HDL-C added to reduced glutathione (GSH) were assessed colorimetrically, while fibroblast growth factor (FGF)-21, adiponectin & interleukin (IL)-6 via ELISA. The same technique was used for the assays of the hepatic levels of FGF-21, silent information regulator (SIRT1), malondialdehyde (MDA),IL-10, tumor necrosis factor-α (TNF-α) as well as the apoptotic markers; caspase-3 and B-cell lymphoma (Bcl-2). Results: The cafeteria-diet induced steatohepatitis was reflected by significantly increased body and liver weight gain, elevation of liver enzymes; ALT, AST, ALP and GGT added to the dyslipidemic panel, presented as increased TC, TG, LDL-C and decreased HDL-C levels. The steatosis-induced inflammatory milieu, marked by elevated serum levels of FGF-21, IL-6, hepatic TNF-α, as well as reduced IL-10 and adiponectin, was associated with steatosis- induced hepatic oxidative stress, reflected by increased hepatic MDA and decreased GSH levels, along with stimulated caspase-3 and decline in BcL-2 hepatic levels. These pathological disturbances were significantly ameliorated by taurine supplementation and evidenced histopathologically. The cross talk between hepatic FGF-21 and SIRT1 and their association to the induced perturbations are novel findings in this study. Taurine's efficacy in restoration of hepatic structure and function is partially via the increase in SIRT1 and associated reduction of FGF-21. Conclusion: The findings of the current study prove the protective role of taurine in NAFLD via a novel role in the amelioration of FGF-21/ SIRT1 axis, which could be considered a new therapeutic target.

Lower back pain is a universal dilemma leaving a negative effect on both health and life quality. It was found that a fixed dose combination of chlorzoxazone and ibuprofen gave a higher efficiency than analgesic alone in treatment of acute lower back pain. Based on the significant benefit of that combination, a green, sensitive, rapid, direct, and cost-effective method is created for concurrent determination of ibuprofen and chlorzoxazone in presence of 2-amino para chlorophenol (a synthetic precursor and potential impurity of chlorzoxazone) adopting the synchronous spectrofluorimetric technique. Synchronous spectrofluorimetric technique is adopted to avoid the highly overlapped native spectra of both drugs. The synchronous spectrofluorometric method was applied at Δλ = 50 nm, ibuprofen was measured at 227 nm while chlorzoxazone was measured at 282 nm with no hindering from one to another. The various experimental variables affecting the performance of the suggested technique were explored and adjusted. The suggested technique showed good linearity from 0.02 to 0.6 and 0.1 to 5.0 µg/mL for ibuprofen and chlorzoxazone, respectively. The produced detection limits were 0.27 × 10 –3 and 0.03, while the quantitation limits were 0.82 × 10 –3 and 0.09 µg/mL for ibuprofen and chlorzoxazone, respectively. The suggested approach was successfully applied for the analysis of the studied drugs in the synthetic mixture, different pharmaceutical preparations, and spiked human plasma. The suggested technique was validated with respect to the International Council of Harmonization (ICH) recommendations. The suggested technique was found to be simpler and greener with lower cost compared to the earlier reported methods which required complicated techniques, longer time of analysis, and less safe solvents and reagents. Green profile assessment for the developed method compared with the reported spectrofluorometric method was performed using four assessment tools. These tools confirmed that the recommended technique attained the most possible green parameters, so it could be used as a greener option in routine quality control for analyzing the two drugs in genuine form and pharmaceutical preparations.

The greenness of any analytical method has become a very important aspect of a good analytical method. However, most chromatographic methods depend on the usage of relatively large amounts of lethal and un-decaying chemicals and solvents. So, a green approach based on the full factorial design was employed to develop a simple and rapid HPLC technique for concurrent determination of paracetamol and dantrolene sodium in their combined capsules. Both drugs are highly recommended to be administered together in patients with severe musculoskeletal disorders. Avoiding the routine methodology and resorting to the modern technology represented in the usage of experimental design allows rapid determination of the studied drugs using the optimum quantity of chemicals to avoid any waste of resources. Simultaneous separation of a binary mixture of paracetamol and dantrolene sodium was accomplished using a reversed phase Hypersil C18 column using an eco-friendly isocratic eluent. The used mobile phase consisted simply of ethanol: water (40:60, v/v). Orthophosphoric acid was used to adjust the pH of the mobile phase to 4.5. Triethanolamine (0.2%) was added aiming to reduce the peak tailing. The assay was completed within less than 6 min adopting 0.8 mL/min as a flow rate. The detection was carried out using a UV-detector at 290 nm. The suggested technique shows a linear correlation over concentration ranges of 1.0–200 and 1.0–40 µg/mL for paracetamol and dantrolene sodium, respectively. The suggested technique allowed the simultaneous analysis of the two co-formulated drugs in their synthetic mixture and combined capsule. The suggested technique is considered a greener substitute for the other reported HPLC techniques through the usage of safer solvents and chemicals, along with decreasing both waste output and analysis time. The method is accurate with recoveries between 97.85 and 101.27%, precise, as %RSD for the intraday and interday precision were between 0.39 and 1.72% and very sensitive with limits of detection (LOD)’s 0.15 and 0.18 µg/ml and limits of quantification (LOQ)’s 0.48 and 0.61 µg/ml for paracetamol and dantrolene sodium, respectively. The method greenness was ensured through its assessment by four greenness metrics. It is also validated following the International Conference on Harmonization Guidelines. The recommended technique could be a good alternative to traditional methods in the routine quality control analysis of the studied drugs due to its minimum harm to the planet or human beings.