Keywords: Methotrexate, Propolis extract, Oxidative damage, Liver, Brain, Antioxidant enzymes, Rats Methotrexate (MTX) is an anti-folate drug that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of MTX is often limited by its severe side effects and toxic sequelae. Propolis (bee glue) is a natural bee product rich in polyphenolic compounds known for antioxidant activity. The present study was designed to evaluate the protective role of propolis (PP) extract against oxidative stress induced by methotrexate drug (MTX) on liver and brain of rats. The nutritive value and some main active polyphenolic compounds and antioxidant capacity of the propolis extract were evaluated. The total phenolic and flavonoid contents of propolis extract recorded in terms of mg gallic acid and catechin equivalent/100 ml extract were 1122.4 mg and 2885 mg respectively. In addition highly total antioxidant capacity presented as 178 mg ascorbic acid equivalent. Gas chromatography mass spectrometry (GC-MS) was performed for qualitative screening of phenolic compounds in the propolis. One hundred and twenty male Wistar albino rats with mean body weights 90 g ± 5 g were classified into 5 groups. Rats were administered their respective doses of propolis extract and/or MTX for 3, 6 and 9 weeks intervals. Control groups (G1 and G2), propolis extract group (G3), MTX group (G4) and MTX plus propolis extract group (G5). Results suggested that co-administration of the PP extract with MTX reduced the deleterious effects of methotrexate, through the significant increase in concentration of reduced glutathione (GSH) and inhibition of lipid peroxidation as observed by significant decrease in malondialdehyde (MDA) level in brain tissue. As well as, significant increase in antioxidant enzyme activities (superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR)) in liver and brain tissues as compared to MTX group alone at p<0.05 in a time dependent manner to approach the values found in control rats. Data showed that propolis has a powerful antioxidant capacity. It is capable of modulating the antioxidant enzyme activities and suppressing the oxidative damage induced by MTX drug in liver and brain tissues. Propolis administration for 9 weeks proved to have remarkable protective effect against toxicity of MTX than 6 or 3 weeks.

Introduction: Acute pancreatitis (AP) is an inflammatory disease with a high incidence of morbidity and mortality rate. The present study aimed to evaluate the protective effect of licorice extract administration on L-arginine-induced AP and associated lung tissue damage in rats. Methods: The experimental groups were the healthy control group (G1), L-arginine group (G2), licorice extract group (G3), and licorice extract +L-arginine; (protection group; G4). The protective effect of licorice extract was evaluated by measuring serum amylase and lipase, oxidative stress markers (malondialdehyde, nitric oxide, and myeloperoxidase), and inflammatory biomarkers levels (interleukin-6, tumor necrosis factor-alpha, toll-like receptor 4, and vascular cell adhesion molecule 1), as well as apoptosis assessment via caspase-3 activity and beclin-1 expression. Furthermore, an immunohistochemical assessment of heme oxygenase-1 (HO-1) and a histopathological examination of lung and pancreatic tissues were performed. Results: Licorice extract administration significantly reduced serum amylase, lipase, and inflammatory markers levels that pointed to the local and systemic inflammatory condition of AP induced by L-arginine. Moreover, the administration of licorice extract reversed the significant elevation in oxidative stress markers levels in the pancreas and lung tissues. Furthermore, licorice extract downregulated pancreatic gene expression of beclin-1 and caspase-3 which reversed dysregulated pancreatic autophagy. Conclusion: Licorice extract administration causes modulation of oxidative damage and systemic inflammation associated with acute pancreatic damage. Moreover, licorice extract markedly decreases the biochemical and histopathologic changes in AP, preserving the pancreatic and lung tissues through its antioxidant, anti-inflammatory, and antiapoptotic effects.

يعد إستهداف محور الهيبسيدين- فيروبورتن هو الآلية الرئيسية المشاركة في الصحه الايضيه. تهدف هذه الدراسه إلي دراسة العلاقه المتشابكه بين حالة فيتامين د وتوازن الحديد في متلازمة التمثيل الغذائي الناجم عن إتباع نظام غذائي عالي الدهون وعالي الفركتوز في الجرذان .كانت المجموعات التجريبيه علي النحو التالي G1 التحكم السلبي ، G2التحكم الموجب ، G3 و G4(نظام غذائي متوازن ومدعم بفيتامين د 12و24 ميكروجرام / كجم من وزن الجسم علي التوالي مرتين في الاسبوع ). G5 و G6(نظام غذائي عالي الدهون و عالي الفركتوزلومدعم بفيتامين د 12و24 ميكروجرام / كجم من وزن الجسم علي التوالي مرتين في الاسبوع). تم تقييم العديد من العوامل البيوكيميائيه والجزيئيه والنسيجيه في السيرم وانسجة الكبد . أظهرت النتائج أن تناول فيتامين د عدل بشكل كبير توازن الحديد المضطرب الناتج عن النظام الغذائي العالي في الدهون والفركتوز من خلال تنظيم محور الهيبسيدين-الفيروبروتين مما يؤدي إلي تحسن كبير في مستوي الحديد في السيرم ، كما أن تناول فيتامين د يعزز حالة مضادات الاكسده عن طريق تقليل نشاط مستوى الMDA وزيادة نشاط HO-1 في السيرم بالإضافه إلي تنظيم التعبير الجيني لNrf2 . كما أنه يخفف من إرتفاع...

Titanium dioxide nanoparticles (TiO2-NPs) can harm the brain, causing neurotoxicity. Functional foods such as quinoa and moringa seeds have many pharmacological benefits and neuroprotective effects. This study investigates the impact of quinoa and moringa seeds ethanolic extracts (QSE and MSE) administration on neurotoxicity induced by TiO2-NPs in rats. TiO2-NPs were synthesized and characterized by several methods. Sixty adult male rats were categorized into six groups: two control groups designated as healthy, and TiO2-NPs-intoxicated groups. The other groups received the same dose of TiO2-NPs with either low (100 mg/kg) or high (200 mg/kg) doses of QSE or MSE orally. HPLC analysis of the phytochemical components of each extract was performed. Several behavioral and biochemical measures were assessed. In addition, the gene expression of endoplasmic reticulum stress (ERS) and apoptosis markers, cerebral mitochondrial activity, and DNA fragmentation were also evaluated. The results indicated a higher total phenolic and flavonoid content in red QSE than in MSE. The study reported the potential neuroprotective effects of QSE and MSE against TiO2-NPs neurological intoxication, targeting neuronal ERS, apoptosis, and restoring cerebral mitochondrial activity.

Introduction: Sarcopenia is an inflammatory disease caused by a disruption of muscle homeostasis. Lonicera caerulea L. (Haskap berry) (HB) extract and omega-3 (ω−3) possess antioxidant and anti-inflammatory activities. This study assesses the potential ameliorating effects of HB extract and ω−3 supplementation on dexamethasone (DEXA)-induced sarcopenia. Methods: Rats were divided into five groups; the negative control group was injected with saline (i.p.); groups 2, 3, 4, and 5 were injected with DEXA (2 mg/kg/d, i.p.); groups 3 and 4 also received 400 mg/kg/d and 100 mg/kg/d of HB extract and ω−3, respectively, while group 5 received both treatments daily for 21 days. The ameliorative effects of treatments were investigated by measuring lysosomal proteolytic enzyme cathepsin activity, phosphatidylinositol 3 kinase (PI3K) activity, nuclear factor kappa beta (NF-κB) level, and heme oxygenase-1 (HO-1) activity. The gene expression levels of muscle ring-finger protein (MuRF) and forkhead box O (FOXO) transcription factor were also evaluated. Biochemical and histological examinations were done on muscle tissues. Results: DEXA caused a significant elevation (P<0.05) in NF-κβ level and cathepsin activity in muscle tissue. Also, it significantly upregulated the muscle atrophy markers. Meanwhile, PI3K and HO-1 activities were significantly reduced. HB extract and ω−3 administration significantly (P≤0.05) reversed these effects and downregulated the mRNA expression levels of MuRF and FOXO. Also, the histopathological examination confirmed these results. Conclusion: The current study proved the ameliorative effects of HB extract and ω−3 on sarcopenia parameters. Therefore, they might be potential therapeutic agents for myopathy/sarcopenia.

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by persistent synovitis, progressive joint destruction, and significant morbidity. Despite advances in targeted therapies, achieving sustained remission remains challenging, necessitating the exploration of novel, multi-targeted therapeutic strategies. This study investigates the therapeutic potential of a self-emulsifying nanoformulation, quercetin-loaded pumpkin seed oil nanoemulsion (Qu-PSONE), in a complete Freund’s adjuvant (CFA)-induced RA rat model, focusing on elucidating its integrated molecular mechanisms. Methods: Adult male Wistar rats (n = 50) were divided into a normal control group (n = 10) and an RA-induced rat model (n = 40), with the latter being further subdivided into four experimental groups: RA control, free quercetin (Qu), pumpkin seed oil nanoemulsion (PSONE), and Qu-PSONE-treated groups. We performed comprehensive analyses, including physicochemical characterization of the nanoformulations and quantification of synovial protein levels of key mediators (IL-17, TLR-4, NF-κBp65, Nrf2, OPG, RANKL, JAK1, and STAT3) via ELISA. In parallel, synovial gene expression of GSDMD and miRNA-146a was assessed using RT-qPCR. Treatment efficacy was further evaluated through paw thickness measurements, clinical arthritis scoring, radiographic assessment of joint erosion, and histopathological examination, alongside immunohistochemical staining for TNF-α and MMP-9. Results: Our findings demonstrate that Qu-PSONE exerts a superior nutrigenomic inhibitory effect on the inflammatory cascade and joint deformity associated with CFA-induced adjuvant arthritis. The Qu-PSONE significantly modulated miRNA-146a expression, serving as a sensitive indicator of attenuated synoviocyte activation. This treatment concurrently increased Nrf2 synovial level, suppressed synovial NF-κBp65, TLR-4, and IL-17 levels, which in turn downstream-inhibited the JAK/STAT pathway, balanced RANKL/OPG signaling, and downregulated transcriptional priming of the pyroptotic marker GSDMD. Together, these findings demonstrate that Qu-PSONE effectively breaks the inflammatory cascade in adjuvant arthritis. These palliative effects of Qu-PSONE were robustly correlated with reduced paw edema, improved arthritis scores, mitigated radiographic joint damage, and diminished synovial infiltration and MMP-9 expression, as confirmed by histological and immunohistochemical analyses. Conclusions: Qu-PSONE halts arthritic progression and curtails joint damage through multitarget suppression of the NF-κBp65/TLR-4/IL-17 inflammatory axis at the synovial level. This response is accompanied by reduced JAK1 and STAT3 protein expression, re-established RANKL/OPG homeostasis to mitigate bone destruction, and attenuated GSDMD transcript levels, with miRNA-146a serving as a responsive biomarker of disease resolution.