Explore the vast range of titles available.

Background: Migraine, a complex neurological condition, poses significant challenges for both sufferers and healthcare providers. While prescription medications play a vital role in managing migraine attacks, the quest for natural, non-pharmacological alternatives has garnered increasing interest. This review explores the efficacy and safety of natural supplements as treatments for migraine relief, comparing them with conventional prescription medications. Methods: The review delves into herbal supplements, clinical studies on natural remedies, aromatherapy, dietary influences, and lifestyle modifications in the context of migraine management in several databases. Results: The findings shed light on the potential of natural supplements as complementary or alternative approaches to traditional migraine therapies, offering insights into a holistic and personalized treatment paradigm for migraine sufferers. Conclusions: Natural supplements have gained attention as potential treatments for migraine relief, often perceived as safer alternatives to conventional medications.

Ischemic heart disease (IHD) is one of the major cardiovascular disorders leading to global morbidity and mortality and represents a huge burden on individuals and the healthcare system worldwide. Classically, it is attributed to obstructive atherosclerotic plaques in the epicardial coronary arteries; however, it is now understood to be a heterogeneous disease that also includes microvascular dysfunction, vasospasm, and ischemia with non-obstructive coronary arteries (INOCA). IHD is triggered by modifiable and non-modifiable risk factors, and its diagnosis relies on clinical assessment, electrocardiography, cardiac biomarkers, and advanced imaging techniques. Extensive investigations and trials have established the management of IHD, including lifestyle modifications, pharmacological therapies, and revascularization, while novel interventional, regenerative, and molecularly targeted therapies are under active investigation. This review provides a comprehensive overview of IHD, integrating its epidemiology, risk factors, pathophysiology, diagnostics, and therapeutics. IHD pathogenesis is complex, involving coronary atherosclerosis, plaque disruption, thrombosis, and myocardial ischemia-reperfusion injury that are modulated by oxidative stress, inflammation, and other signaling pathways. The review also addresses the molecular mechanisms and therapeutic potential of natural bioactive compounds, including polyphenols, terpenoids, and alkaloids, which exhibit antioxidant, anti-inflammatory, and cardioprotective effects. In addition, it highlights the multifaceted nature of IHD and underscores the need for integrated, mechanism-driven approaches to improve prevention, early detection, and personalized treatment for this global health burden.

Vascular dementia (VaD) is a degenerative cerebrovascular disorder that leads to progressive decline in cognitive abilities and memory. Several reports demonstrated that oxidative stress and endothelial dysfunction are principal pathogenic factors in VaD. The present study was constructed to determine the possible neuroprotective effects of simvastatin in comparison with cilostazol in VaD induced by l -methionine in rats. Male Wistar rats were divided into four groups. Group I (control group), group II received l -methionine (1.7 g/kg, p.o.) for 32 days. The remaining two groups received simvastatin (50 mg/kg, p.o.) and cilostazol (100 mg/kg, p.o.), respectively, for 32 days after induction of VaD by l -methionine. Subsequently, rats were tested for cognitive performance using Morris water maze test then sacrificed for biochemical and histopathological assays. l -methionine induced VaD reflected by alterations in rats’ behavior as well as the estimated neurotransmitters, acetylcholinesterase activity as well as increased brain oxidative stress and inflammation parallel to histopathological changes in brain tissue. Treatment of rats with simvastatin ameliorated l -methionine-induced behavioral, neurochemical, and histological changes in a manner comparable to cilostazol. Simvastatin may be regarded as a potential therapeutic strategy for the treatment of VaD. To the best of our knowledge, this is the first study to reveal the neuroprotective effects of simvastatin or cilostazol in l -methionine-induced VaD. Graphical Abstract ᅟ

Flavonoids, well-known as key bioactive compounds in numerous medicinal plants, help protect these plants against both biotic and abiotic stresses and are linked to the prevention of various degenerative diseases. The diverse pharmacological effects and therapeutic potential of flavonoids are influenced by factors such as their level of hydroxylation, structural classification, additional substitutions and conjugations, extent of polymerization, and their ability to chelate metals. Data from various databases such as the Egyptian Knowledge Bank (EKB), Scopus, Web of Science, PubMed, Google Scholar, and Elsevier databases were gathered until April 2025. All possible keywords pertaining to taxifolin, natural origins, isolation, structure, solubility, synthesis, bioavailability, applications, biological activities, mechanisms of actions, pharmacokinetics, and clinical studies were utilized in the search. Taxifolin, a bioactive flavonoid commonly found in dietary sources such as onions, milk thistle, and Douglas fir bark, has garnered significant attention for its extensive health-promoting properties. It exhibits potent antioxidant, anti-inflammatory, anticancer, antimicrobial, cardioprotective, neuroprotective, and hepatoprotective effects. Notably, taxifolin demonstrates superior antioxidant capacity linked to its phenolic hydroxyl groups and structural features, enabling effective free radical scavenging. Despite these promising pharmacological activities, further research is necessary to elucidate its detailed molecular mechanisms, pharmacokinetic profile, and comprehensive safety through well-designed randomized clinical trials to facilitate its development as a therapeutic agent for human use.

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, characterized by a range of metabolic and reproductive complications, including insulin resistance, hyperandrogenism, and menstrual irregularities. The complexity of PCOS necessitates innovative therapeutic strategies that extend beyond conventional pharmacological treatments. Main body Ursolic acid (UA), a natural pentacyclic triterpenoid found in various plants, has gained significant attention for its diverse pharmacological properties including anti-inflammatory, antioxidant, anticancer, antidiabetic, antimicrobial, antihyperlipidemic, anti-obesity, neuroprotective, hepatoprotective, and cardioprotective activities. Additionally, the integration of predictive tools, such as artificial intelligence and bioinformatics databases like STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) and KEGG (Kyoto Encyclopedia of Genes and Genomes), allows for the identification of key protein targets and pathways influenced by UA, including TP53 (Tumor Protein P53), AR (Androgen Receptor), ESR1 (Estrogen Receptor 1), BCL2 (B-cell Lymphoma 2), STAT3 (Signal Transducer and Activator of Transcription 3), and IL6 (Interleukin 6). These pathways are crucial for inflammatory regulation and have been linked to the symptoms of PCOS. Further in silico studies were conducted to validate these findings, highlighting the need for additional preclinical and clinical research. Conclusion Comprehensive guidelines for the effective use of UA in managing PCOS are warranted to ensure optimal treatment strategies.

Background Acute kidney injury (AKI) is closely associated with rhabdomyolysis (RM), characterized by tubular damage and cell death through altered pyroptotic signaling pathways. This study aimed to explore the efficacy of Wheatgrass (WG) as a potential protective agent in ameliorating nephrotoxicity caused by glycerol-induced oxidative stress (OS) in rats, emphasizing the involvement of nuclear factor kappa p65 (NF-kB p65)/kidney injury molecule-1 (KIM-1)/neutrophil gelatinase-associated lipocalin (NGAL) signaling pathway. Methods RM induction was achieved via a single intramuscular administration of 50% v/v glycerol dissolved in 0.9% saline solution (10 ml/kg), following a 6-h period of water deprivation. WG was administered daily at 75 mg/kg for 7 days prior to glycerol administration in the WG-pretreated groups. Renal function, OS, inflammatory, and tubular injury markers were assessed using Enzyme-Linked Immunosorbent Assay. Histopathological and immunohistochemical analyses were conducted to evaluate renal structural changes and NF-kB p65 expression. Results The glycerol-injected group exhibited significant increases in renal injury markers (blood urea nitrogen, serum creatinine, creatine kinase) and elevations in NGAL, KIM-1, malondialdehyde, interleukin-6, and interleukin-18 levels, alongside decreased activity of antioxidant enzymes (glutathione transferase, superoxide dismutase, catalase) ( p  < 0.001). Moreover, immunohistochemical analysis indicated a heightened expression level of NF-kB p65, correlating with the observed histopathological alterations, which confirmed renal tubular degeneration, inflammation, and vascular alterations. However, WG pretreatment markedly reduced the concentrations of biomarkers associated with oxidative and renal damage, alongside evident decrease in the levels of inflammatory markers. Additionally, a significant restoration in immunohistochemical and histopathological changes was noted. Conclusions These findings demonstrate that WG holds notable protection against glycerol-induced acute kidney injury by mitigating OS and inflammation, particularly through NF-kBp65/KIM-1/NGAL pathway modulation. The observed biochemical and histological improvements highlight WG’s potential as a natural therapeutic candidate for AKI, warranting further clinical exploration.

Prenylflavonoids are widespread in plants, which are considered valuable sources of natural polyphenolic compounds with isoprenyl groups, including flavones, flavanones, chalcones and aurones. Among the notable prenylated flavonoids, morusin-a prenylated flavone isolated from the bark of white mulberry, has garnered attention for its multifaceted biological activities. Extensive research has demonstrated that morusin exhibits pronounced analgesic, antioxidant, anti-inflammatory, bone repair, antitumor, cardioprotective, neuroprotective, hepatoprotective, antidiabetic, and antimicrobial effects. The enhanced lipophilicity imparted by prenylation is believed to facilitate greater cellular membrane interaction, contributing to the superior bioactivity of these compounds compared to their non-prenylated derivatives. Unlike previous reviews that mainly emphasize morusin’s bioactivities, this article critically addresses its pharmacokinetic limitations, translational challenges, and safety concerns, offering a more integrated perspective on its path toward clinical application. This review aims to get current insights into the health-promoting effects of morusin, thereby informing the development of novel plant-derived pharmaceuticals and nutraceuticals within the prenylflavonoid category.

This research investigated the hepatoprotective effects of esomeprazole (ESOM) and canagliflozin (CANA) against methotrexate-induced liver toxicity, focusing on AMPK modulation and its regulation of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt pathways. Fifty male Wistar rats were divided into five groups: control, MTX, and three pretreatment groups receiving ESOM (30 mg/kg), CANA (30 mg/kg), or their combination. ESOM and CANA were administered for 8 days before and 1 day after a single MTX injection (20 mg/kg, intraperitoneally) on day 9 to induce hepatotoxicity. Liver injury, oxidative stress, inflammation, and apoptosis were assessed using biochemical, histopathological, immunohistochemical, qRT-PCR, and western blot analyses. Data were analyzed by one-way analysis of variance (ANOVA) and Tukey’s post hoc test, with significance at p  < 0.05. Results were presented as mean ± standard error (SE). Rats that received MTX showed significant liver damage, marked by elevated ALT, AST, MDA, MPO, iNOS, TNF-α, IL-6, and IL-1β levels ( p  < 0.01) and decreased antioxidant enzymes (HO-1, Nrf2, and GSH). Immunohistochemistry revealed increased NF-kB p65 and caspase-9 expression ( p  < 0.01), correlating with histopathological changes. Pretreatment with ESOM and CANA reduced liver enzyme levels, improved histology, restored antioxidant balance, and inhibited inflammatory pathways via p38MAPK/NF-kB p65 and JAK1/STAT3 ( p  < 0.01). Moreover, ESOM and CANA preserved PI3K/Akt activity and prevented caspase-dependent apoptosis ( p  < 0.01). Additionally, the combination treatment showed synergistic hepatoprotective effects, demonstrated by significant improvements in all measured parameters. These findings suggested that ESOM and CANA had significant potential as therapeutic agents for alleviating MTX-induced hepatotoxicity and warranted further investigation in future research.

This study examines Dabigatran’s (Dab) capacity to mitigate methotrexate (MTX)-induced coagulation disorders and endothelial dysfunction, while exploring its effects on oxidative stress and inflammatory pathways (NF-kB/IL-1β/MCP-1, TLR4/NLRP3) in reducing hepatotoxicity. Rats were assigned to four groups: a control group receiving saline intraperitoneally (i.p.); an MTX group with a single MTX dose (20 mg/kg, i.p.) to induce hepatotoxicity; and two pretreatment groups receiving Dab orally at 15 mg/kg and 25 mg/kg for seven days before and 4 days after MTX administration. MTX-treated rats showed significant increases in liver enzymes (ALT, AST, ALP) and reductions in antioxidant enzymes (SOD, GSH), along with elevated coagulation parameters (tissue factor (TF), thrombin, fibrin, plasminogen activator inhibitor-1 (PAI-1)), leading to coagulation disorders. Endothelial dysfunction was evident with reduced eNOS expression, while inflammation increased through elevated iNOS, ICAM-1, and pro-inflammatory cytokines (MPO, NF-kB, TNF-α, IL-1β, MCP-1), alongside activation of the TLR4/NLRP3 inflammasome pathway and decreased IL-10 ( p  < 0.05). Immunohistochemistry revealed increased cytochrome c and caspase-3 expression, with histopathological damage. Dabigatran mitigated these effects, downregulating liver enzymes, modulating coagulation factors, restoring eNOS levels, and reducing histopathological and inflammatory markers. Dabigatran demonstrates significant therapeutic potential in alleviating methotrexate-induced hepatotoxicity through its antioxidant, anti-inflammatory, anticoagulant, and anti-apoptotic effects. Its regulation of coagulation parameters and endothelial function suggests a protective role against tissue damage, warranting further investigation.

Doxorubicin (DOX) is a highly potent broad-spectrum anticancer drug, but it has severe side effects, including hepatotoxicity. Therefore, we evaluated the efficacy of febuxostat (FBX), a specific inhibitor of xanthine oxidase and antioxidant, in blocking hepatotoxicity associated with DOX in rats. Rats were treated with FBX (10 or 15 mg/kg/day orally for 2 weeks) and given DOX (15 mg/kg as single dose at the 7th day, intraperitoneal) to induce hepatotoxicity. The results indicated that FBX could reduce the pathological alterations of liver tissues induced by DOX and ameliorate the inappropriate changes in liver function biomarkers (AST, ALT, and ALP) in serum, oxidative stress parameters (catalase, superoxide dismutase, NOX1, NQO-1, HO-1, Keap-1, and Nrf2) and inflammatory markers in the liver (NF-κB p65, TNF-α, NLRP3). Additionally, FBX attenuated the p53, BAX, cytochrome C, caspase-9, and caspase-3 levels to restrain cell apoptosis. In addition, FBX therapy was found to increase protein levels of SIRT-1 and AMPK in the liver. These findings demonstrate that FBX can reduce the hepatotoxicity caused by DOX in rats through mechanisms that counteract oxidative stress, inflammation, and apoptosis.