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Modulation of PI3K/AKT signaling and DFT modeling via selected pharmaceutical compounds attenuates carrageenan-induced inflammation and oxidative stress in rats.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, 12622, Egypt.
The main goal of the current study is to estimate the in vivo anti-inflammatory/antioxidant ability of four selected pharmaceutical compounds: bisoprolol (Biso), piracetam (Pirc), clopidogrel (Clop), and cinnarizine (Cinna). Indomethacin (Indo) was used as a reference drug to perform a realistic comparison between the four compounds and the Indo in vivo through tracking PI3K/AKT signaling and computational chemistry via density functional theory (DFT) modeling to analyze the electrostatic potential across the molecule and provide insight into the regions for receptor binding of the studied compounds. To achieve the safe dose of these compounds, cytotoxicity was performed against isolated adipose tissue-derived mesenchymal stem cells (ADMSCs) using MTT assay.
View Article and Find Full Text PDFIn Vitro Protective Effects of a Standardized Extract of (L.) Mill. Cladodes and L. Leaves Against Indomethacin-Induced Intestinal Epithelial Cell Injury.
Antioxidants (Basel)
December 2024
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D'Alcontres 31, 98166 Messina, Italy.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce serious adverse effects in gastrointestinal (GI) mucosa, increasing intestinal permeability and leading to mitochondrial dysfunction, oxidative stress, apoptosis and inflammation. As proton pump inhibitors are effective in protecting against NSAID-induced gastropathy but not NSAID-induced enteropathy, current research is focused on natural products as protective substances for therapy and prevention of intestinal injury. Herein, through the use of an in vitro model based on intestinal epithelial cell (Caco-2) damage caused by indomethacin (INDO), we examined the protective activity of a commercially available standardized extract (OFI+OE) from (L.
View Article and Find Full Text PDFPregnane C-Steroids with Anti-Inflammatory Activity from the Roots of Cynanchum bungei.
Chem Biodivers
January 2025
School of Pharmacy, Guangdong Medical University, Dongguan, P. R. China.
Article Synopsis
- Five new pregnane C21-steroids were identified from the roots of Cynanchum bungei, including three previously unknown 5,6-epoxy steroids and two 8,14-seco-steroids.
- Compound 3 is notable for being the first 5a,6a-epoxy steroid discovered in Cynanchum plants, with their structures confirmed through various spectroscopic methods and theoretical calculations.
- All isolated compounds showed anti-inflammatory properties by inhibiting nitric oxide release in RAW264.7 cells, with compounds 3 and 4 demonstrating stronger activity than the commonly used anti-inflammatory drug indomethacin at a concentration of 50 μM.
PGE and HCN2 ion channels are critical mediators of pain initiated by angiotensin II.
Brain Behav Immun
December 2024
Wolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. Electronic address:
Angiotensin II is well known to have an important influence on blood pressure, mediated via the angiotensin II type 1 receptor (AT1R), and more recent studies have shown that angiotensin II may play an important additional role in eliciting pain via a distinct action at the angiotensin II type 2 receptor (AT2R). Signalling pathways that link activation of AT2R to a sensation of pain are, however, incompletely understood. Here we use rodent inflammatory pain models to confirm that selective activation of AT2R triggers aversive responses, and that these are abolished by either antagonism or genetic deletion of AT2R.
View Article and Find Full Text PDFSulfonamide-Pyrazole derivatives as next-generation Cyclooxygenase-2 enzyme inhibitors: From molecular design to in vivo efficacy.
Int J Biol Macromol
December 2024
Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt. Electronic address:
The current research focuses on the design and synthesis of celecoxib analogues incorporating sulphonamide and pyrazole moieties (4, 5, 6a-e, and 7a-f) with the aim of achieving a broad range of COX-2 selectivity in vitro. Among these, compounds 6b-d, 7a, 7e, and 7d exhibited potent inhibition, with IC values ranging between 0.05 and 0.
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