Al-Ameen College of Pharmacy

Euphorbia thymifolia L., a medicinal herb traditionally recognized for its many medicinal properties, was investigated in the present study to evaluate the antioxidant potential of its hexane fraction and to elucidate its possible mechanism of action through Keap1-Nrf2 pathway modulation using in silico analyses, along with validation through in vitro assays. The plant material was initially extracted using ethanol, followed by fractionation with hexane. The obtained hexane fraction was subjected to GC-MS analysis to identify its phytoconstituents, which were further evaluated through in silico molecular docking and molecular dynamics (MD) simulations against Keap1 to predict their potential to activate Nrf2 signaling. The antioxidant activity of the fraction was subsequently validated using DPPH, nitric oxide scavenging, and reducing power assays. Phytochemical screening and GC-MS analysis confirmed the presence of bioactive fatty acid constituents such as palmitic acid, linoleic acid, and linolenic acid. Antioxidant evaluation using DPPH and nitric oxide radical scavenging assays demonstrated concentration-dependent activity, with IC₅₀ values of approximately 204 µg/mL and 169.40 µg/mL, respectively, which were moderately comparable to the standard. Molecular docking studies revealed notable interactions of the key phytoconstituents with the Keap1 protein, particularly Taraxerol, which exhibited a binding affinity of - 11.6 kcal/mol. Furthermore, a 100 ns molecular dynamics simulation, along with post-simulation analyses, confirmed the stability of the ligand-protein complex. The present study shows that Euphorbia thymifolia L. includes bioactive compounds with significant antioxidant activity, as evidenced by in vitro experiments and Keap1-Nrf2 pathway interactions discovered in silico. The stable ligand-protein interaction shows that it has potential as a natural source for antioxidant therapy development and should be investigated further.

Gentamicin (GM), a widely used aminoglycoside antibiotic, has been related to dose-dependent nephrotoxicity caused by oxidative stress and inflammation. Satureja hortensis L. (SH), a polyphenol and terpenoid-rich herb, exhibits ‘antioxidant’ and ‘anti-inflammatory’ properties. This study investigated the nephroprotective potential of the hydroalcoholic extract of SH (HASH) using ‘in- vitro’,‘in-vivo’, and ‘in-silico’ approaches. Cytotoxicity and cytoprotection were tested in HEK-293 cells by MTT assay, while in-vivo nephroprotection was studied in Wistar rats treated with five groups, one of which was used as a control, and the others were gentamicin in addition to selenium, S. hortensis 200 and 400 mg. Serum and urine biochemical markers, antioxidant enzyme activities, immunohistochemistry, and histopathology were analyzed. In-silico molecular docking (AutoDock Vina v1.2.0) was performed on phytoconstituents of SH against TNF-α to explore molecular mechanisms. GM significantly increased nephrotoxicity markers (creatinine, BUN, urea, TNF-α, NF-κB, urinary calcium, protein) and reduced antioxidant defences (SOD, CAT, GSH), while elevating lipid peroxidation. HASH co-treatment improved renal function in a dose-dependent manner, increased antioxidant enzymes, and conserved renal histoarchitecture. The extract considerably lowered TNF-α levels (p ˂ 0.001). Docking research showed that phytoconstituents, notably β-sitosterol, had a stronger binding affinity with TNF-α (-8.2 kcal/mol) than the co-crystal ligand (-8.0 kcal/mol). Several sesquiterpenes exhibited moderate-to-strong affinity, indicating a synergistic inhibition of TNF-α signaling. HASH prevents GM-induced kidney damage through ‘antioxidant’,‘anti-inflammatory’, and ‘anti-apoptotic’ pathways. The combined data from in-vitro, invivo, and in-silico suggest that many phytoconstituents work synergistically, making SH a good option for natural nephroprotective therapies.

Chemotherapy-induced nausea and vomiting (CINV) significantly impairs children’s quality of life and treatment adherence. This study developed pullulan-based lyophilized orodispersible wafers of Fosaprepitant diglutamine as a non-invasive alternative to injections. The rapidly dissolving formulation aims to enhance comfort, ease of administration, and overall pediatric treatment acceptance. Orodispersible wafers were prepared using a lyophilization technique and optimized by adjusting polymer concentration, superdisintegrant, cryoprotectant, and natural sweetener levels. The prepared formulations were evaluated for thickness uniformity, surface pH, tensile strength, swelling index, disintegration time, and drug content. Drug–excipient compatibility was assessed using ATR-IR and DSC studies. In vitro dissolution, ex vivo permeation through goat buccal mucosa, pharmacokinetic analysis, stability testing, and antiemetic activity in a cisplatin-induced model were performed. The optimized formulation (F3) showed uniform drug distribution, a swelling index of 143–150

Schizophrenia is a chronic neuropsychiatric disorder requiring sustained therapeutic drug levels in the brain. Oral Cariprazine HCl is limited by extensive first-pass metabolism, low bioavailability, and delayed onset of action. A thermoresponsive, mucoadhesive intranasal in-situ gel of Cariprazine HCl was developed and optimized using a 32 Central Composite Design, with Poloxamer 407 and Carbopol 934P as independent variables. Formulations were evaluated for gelation behavior, mucoadhesion, rheological properties, drug release, and ex-vivo nasal permeation. The optimized formulation (F11) exhibited rapid sol–gel transition at physiological temperature (gelation time: 8.2 ± 0.2 s at 34 °C) and high mucoadhesive strength (5212.76 dyne/cm²). Sustained drug release of 97.17