Ahmed M. El-Dessouki

Tirmania pinoyi is an edible desert truffle valued for its nutritional properties; however, information regarding its biological activity and chemical composition is still limited. The current investigation sought to describe the chemical makeup of T. pinoyi CCASU-TP-03 extract and assess its biological properties. Molecular identification based on 25S rDNA and ITS1–5.8S–ITS2 sequence analysis placed CCASU-TP-03 within the T. pinoyi lineage, supporting the morphological identification. The extract was characterized by its chemical composition, while its antioxidant, antimicrobial, cytotoxic, and anti-inflammatory activities were evaluated using DPPH/ORAC, broth microdilution, SRB, and Griess assays, respectively. Western blotting was used to assess iNOS protein expression. The methanolic extract contained total carbohydrate content expressed as glucose equivalents (354.25 ± 7.71 mg glucose equivalents/g extract), total phenolics (72.57 ± 0.12 mg GAE/g extract), total flavonoids (9.83 ± 0.02 mg RE/g extract), and protein (11.12 ± 0.57 mg/g extract). Targeted qualitative HPLC-PDA profiling detected selected phenolic and flavonoid constituents, including gallic acid, isoferulic acid, ellagic acid, quercetin, and rutin. The T. pinoyi CCASU-TP-03 extract exhibited measurable antioxidant capacity in both DPPH and ORAC assays. Antimicrobial evaluation demonstrated inhibitory activity against several of the tested bacterial and yeast strains, whereas no activity was detected against Aspergillus niger under the tested conditions. Cytotoxicity screening showed the greatest reduction in viability in CaCo-2 cells, whereas PANC-1, HepG2, and HCT-116 cells maintained comparatively high viability over the investigated concentration range. The extract showed measurable inhibition of LPS-induced NO production accompanied by reduced iNOS protein expression. In conclusion, the findings demonstrate measurable antioxidant capacity, inhibitory activity against several tested microorganisms, differential cytotoxic effects among the tested cancer cell lines, and inhibition of NO production accompanied by reduced iNOS protein expression. Further studies are required to isolate the respective pure metabolites followed by preclinical evaluation for potential use in humans.

This study examined whether bempedoic acid (BPA) suppresses SEC progression through an integrated pharmacological framework with toxicological relevance, targeting metabolic, inflammatory, oxidative, angiogenic, proliferative, and apoptotic pathways. Fifty female Swiss albino mice were assigned to five groups (n = 10): normal control, untreated SEC control, SEC + bempedoic acid (10 or 30 mg/kg, orally), and SEC + doxorubicin (5 mg/kg, i.p.) three times weekly for two weeks as a reference chemotherapeutic comparator with established clinical toxicity relevance. After experiment completion, blood and tumor tissues were obtained for molecular assessment. SEC-bearing mice showed lipid dysregulation, with elevated ACLY, ACC, FASN, total cholesterol, and triglycerides, alongside suppressed AMPK. BPA counteracted these changes by inhibiting ACLY-driven lipogenesis and restoring AMPK-related signaling, thereby reducing NF-κB pathway activity and iNOS, IL-6, and TNF-α. It also attenuated oxidative stress, increasing SOD and lowering p-carbonyls. Moreover, BPA reduced VEGF, MMP-2, MMP-9, Hes-1, DLL4, Notch-1, and Jagged-1, indicating impaired angiogenic remodeling and endothelial differentiation. Decreased Cyclin-D1 and PCNA reflected reduced proliferation, while increased p53, Bax, and Caspase-3 indicated enhanced apoptosis. Histologically, BPA promoted dose-dependent tumor necrosis, reduced viable anaplastic cell clusters, and induced fibrovascular granulation tissue with peripheral inflammatory cell infiltration, indicating tumor regression and reparative remodeling. These findings provide preclinical evidence that BPA reduces SEC tumor burden by modulating the ACLY/AMPK-related metabolic pathway, accompanied by suppression of inflammatory, angiogenic, proliferative, survival, oxidative stress, and apoptosis-related dysregulation, supporting its repurposing potential as a multi-target therapeutic candidate for solid tumors.

Kaempferol is a ubiquitous dietary flavonol found in fruits, vegetables, and medicinal plants, existing in both aglycone and glycosylated forms which contribute to its structural and functional diversity. This review provides a comprehensive overview of kaempferol, focusing on its biosynthesis, pharmacokinetic challenges, and the mechanistic basis for its diverse pharmacological properties. Its biosynthesis originates from phenylalanine, with subsequent enzymatic modifications yielding derivatives of varying bioactivity. The principal mechanism of kaempferol is rooted in its potent antioxidant capacity, acting through both direct radical scavenging and the upregulation of the cytoprotective Nrf2 pathway. This redox modulation is intricately linked to its anti-inflammatory effects, which are mediated by the suppression of key signaling cascades including NF-κB, MAPKs, and STATs. In preclinical models, kaempferol demonstrates significant antidiabetic activity by activating AMPK and enhancing insulin sensitivity. Its anticancer properties are equally notable, involving the induction of apoptosis, cell cycle arrest, and inhibition of metastasis through the disruption of pathways such as PI3K/AKT and Wnt/β-catenin. Furthermore, it exhibits antimicrobial effects and hepatoprotective actions by modulating SIRT1/AMPK signaling. Despite these promising bioactivities, therapeutic translation is severely hampered by its poor aqueous solubility and extensive first-pass metabolism, which critically limit oral bioavailability. Consequently, while kaempferol is a compelling polypharmacological agent with the potential to address complex diseases, its unfavorable pharmacokinetic profile remains the critical bottleneck for clinical advancement. A promising direction for future research is to prioritize the development of advanced drug delivery systems and the execution of rigorous clinical trials to translate its extensive preclinical promise into validated clinical applications.

Baicalin, a polyphenolic flavonoid, is the main bioactive flavone extracted from the roots of Scutellaria baicalensis. It has received increasing interest due to its broad spectrum of pharmacological activities and therapeutic benefits demonstrated in preclinical research. However, its molecular mechanisms and translational potential remain underdefined. This review systematically evaluates current evidence on baicalin, including its natural sources, chemical structure, biosynthesis, extraction techniques, pharmacokinetic features, molecular mechanisms, and therapeutic applications, as well as developments in drug delivery platforms designed to overcome its biopharmaceutical limitations. This structured literature review was conducted using data extracted from various databases, including the Egyptian Knowledge Bank, Scopus, Web of Science, PubMed, Google Scholar, and Elsevier. All possible keywords relevant to baicalin were utilized. Recent original articles, systematic reviews, meta-analysis, clinical studies, and high-quality reviews were prioritized. Baicalin exerts its therapeutic effects through modulation of various signaling pathways, primarily involving oxidative stress and inflammation. It exhibits anticancer, antimicrobial, antiviral, immunomodulatory, metabolic, and dermatological effects and alleviates various system disorders and drug-induced toxicity. Despite promising preclinical data, clinical translation is hindered by its poor solubility, limited bioavailability, and insufficient clinical validation. Emerging nano-delivery systems, such as liposomes, solid lipid nanoparticles, polymeric nanoparticles, and surface-modified nanoplatforms, have greatly improved the pharmacokinetic performance of baicalin. Nevertheless, the clinical translation of these approaches remains limited. While baicalin represents a promising multi-target therapeutic option, substantial research gaps remain. Future research should give priority to deeper mechanistic investigations, standardized formulation approaches, and well-designed clinical trials to bridge the gap between preclinical efficacy and clinical application, and to establish its optimal dosing, safety profile, and long-term efficacy. Graphical Abstract The alternative text for this image may have been generated using AI.

This study evaluates the protective potential of Fondaparinux (Fond), a selective antithrombin-mediated Factor Xa inhibitor, in methotrexate-induced hepatotoxicity. The work explores its ability to correct coagulation imbalance, improve endothelial function, and attenuate oxidative and inflammatory cascades (TLR4/NLRP3, NF-κB p65/IL-1β/MCP-1). Animals were allocated into 4 groups. A control group was given distilled water via the intraperitoneal route (i.p.); an MTX group was given a single intraperitoneal injection of MTX (20 mg/kg) on the seventh experimental day; and two groups received prior prophylactic administration of Fondaparinux (at doses of 5 or 10 mg/kg, intraperitoneally) throughout seven consecutive days before as well as for an additional four-day period following MTX administration. MTX significantly elevated hepatic injury markers (AST, ALT, ALP), induced oxidative stress with depleted antioxidants (SOD, GSH), and activated TLR4/NLRP3 signaling, resulting in upregulation of inflammatory mediators (TNF-α, NF-κB p65, IL-18, IL-1β, MCP-1, caspase-1, iNOS, ICAM-1, MPO) and suppression of IL-10 (p < 0.05). Endothelial dysfunction was evidenced by reduced eNOS. MTX also triggered marked coagulation disturbances, including enhanced Factor Xa–dependent thrombin generation, increased tissue factor, fibrin deposition, and elevated PAI-1. Mitochondrial apoptotic signaling was promoted, as indicated by elevated expression of cytochrome c along with induced caspase-3 and caspase-9 activation . Histologically, MTX caused extensive hepatic damage characterized by periportal fibrosis, inflammatory infiltration, bile duct proliferation, hepatocellular necrosis, vacuolation, and vascular congestion. Fondaparinux pretreatment dose-dependently restored hemostatic balance, improved endothelial function, suppressed oxidative and inflammatory responses, attenuated apoptosis, and markedly ameliorated histopathological alterations. Fondaparinux limits methotrexate-associated liver damage through inhibition of Factor Xa–dependent coagulation pathways while providing antioxidant, anti-inflammatory, anti-apoptotic, and hepatoprotective actions.

The intensive use of antibiotics resulted in the development of resistance, posing a significant global threat to human health. Natural products have garnered significant attention in modern drug discovery and development. Utilizing natural compounds and extracts, either alone or in combination with conventional antimicrobial drugs, could be a significant development in overcoming pathogen resistance mechanisms. Among these natural compounds, iridoids exhibited diverse biological activities, such as anti-inflammatory, antioxidant, anticancer, antidiabetic, antimicrobial, and neuroprotective properties. They are present in some widely available fruits, such as olives, noni, and berries. In this concise review, the utilization of iridoids as a promising approach to combat antimicrobial resistance is discussed. Iridoids exert their antimicrobial effects through various mechanisms including inhibition of microbial growth, disruption and permeability of microbial cell membranes, interference with metabolic pathways, and inhibition of bacterial efflux pumps. Their structural versatilities give them an advantage in targeting a variety of microorganisms. Graphical Abstract

Aims This study examined the renoprotective effect of Piribedil against cyclophosphamide (CP)-induced nephrotoxicity through modulation of adenosine monophosphate–activated protein kinase (AMPK)/sirtuin-1 (SIRT1), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinases (MAPKs), and Toll-like receptor-4 (TLR4)/NOD-like receptor protein-3 (NLRP3) pathways, as well as renal injury markers kidney injury molecule-1 (KIM-1) and neutrophil gelatinase–associated lipocalin (NGAL). Main methods Male rats were divided into four groups (n = 8). Controls received distilled water plus saline; the CP group received a single CP dose (200 mg/kg, i.p.) on day 7; Piribedil groups received 15 or 40 mg/kg/day for 10 days with CP on day 7. Renal function, oxidative stress, inflammation, and injury markers (KIM-1 and NGAL) were assessed via biochemical assays, histopathology, immunohistochemistry, and quantitative real-time PCR (qRT-PCR). Key findings CP caused significant renal dysfunction, elevating blood urea nitrogen (BUN), serum creatinine (SCr), NGAL, and KIM-1, increasing oxidative stress (malondialdehyde [MDA], inducible nitric oxide synthase [iNOS]) and reducing nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione (GSH). CP also upregulated inflammatory mediators (interleukin-1β [IL-1β], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α], nuclear factor-κB p65 [NF-κB p65]) and enhanced TLR4, NLRP3, and MAPKs, while suppressing AMPK, SIRT1, and PI3K/Akt signaling. Piribedil reversed these changes, improving renal function, lowering oxidative and inflammatory markers, and normalizing BUN, SCr, KIM-1, and NGAL. Histology confirmed reduced renal damage. Significance Piribedil effectively protects against CP-induced nephrotoxicity by modulating AMPK/SIRT1 and related oxidative and inflammatory pathways, supporting its potential use in drug-induced kidney injury.

Non-communicable diseases, such as diabetes, cancer, as well as cardiovascular, metabolic, and central nervous system disorders stand for significant global health burden. Statins, as HMG-CoA reductase inhibitors, have emerged as a basis in the management of hypercholesterolemia and the prevention of cardiovascular disorders. In this review, we summarize the role of statins in a variety of pathologies, ranging from their well-recognized effects in cardiovascular disorders, to the newly revealed favorable effects in cancer, eye, autoimmune, kidney, gastrointestinal, bone, and autoimmune disorders. Additionally, the current review explores insights into the potential role of natural products as HMG-CoA reductase inhibitors. Future research should focus on the synergistic effects of natural therapies with synthetic statins to improve health outcomes in populations burdened by non-communicable diseases.