Anti-ulcer properties, cytokines, and apoptosis regulatory effects of Olea europaea leaves from Hail Province, Saudi Arabia

This study investigated the anti-ulcer properties of raw olive leaf powder (OLP) and its immunomodulatory potential through the cytokine network. The efficacy of OLP extract in treating stomach ulcers in rats in ethanol-induced models was examined using a single dosage (100, 200, 400 mg/kg) in groups 4, 5, and 6. The OLP demonstrated substantial anti-ulcer action even at 100 mg/kg. The activity was better at 400 mg/kg and almost equivalent to the conventional omeprazole treatment at 20 mg/kg in group 3. The cytokine network was studied in groups 1, 2, 3, and 6. The cytokine network was efficiently regulated by reducing the production of cytokines such as IL-1β, IL-2, IL-4, IL-6, IL-10, and TNF-α. The levels of caspase-3 and caspase-9 were also lowered in groups 3 and 4 considerably at p < 0.05. It is interesting to note that the expression of IFN was greater in animals treated with OLP in group 4, as compared to animals treated with omeprazole in group 3, as well as animals from the disease control group 2, when analyzed at a significance level of p < 0.05. The results revealed that OLP has intriguing potential for anti-ulcer action, and possesses immunomodulatory capabilities to control inflammatory cytokines and apoptotic markers

Development of Tea Tree Oil Based Nanoemulgel Loaded with Azithromycin for Enhancing the Antibacterial Activity

Azithromycin (AZ) is an azalide macrolide antibiotic that is frequently employed for treating bacterial skin infections. It suffers from limited oral bioavailability, which results from incomplete absorption or extensive first-pass metabolism. Therefore, preparing azithromycin formulations for topical administration is highly recommended to avoid first-pass metabolism and to boost the concentration of the drug on the skin. The objective of our investigation was to formulate and evaluate the efficacy of AZ-loaded nanoemulgel as an antimicrobial drug. The physical appearance, spreadability, viscosity, particle size, in vitro drug release, ex vivo permeation investigations, and antimicrobial efficiency of the prepared formulations were evaluated. The prepared formulation loaded with AZ exhibited good physical quality. AZ-loaded nanoemulgel had a greater ex vivo drug permeation across rabbit skin than other formulations (AZ-loaded gel and AZ-loaded emulgel), revealing improved drug permeation and greater transdermal flux in addition to enhanced antibacterial efficacy (p < 0.05). Overall, our findings imply that tea-tree-oil-based nanoemulgel would be a promising delivery system for enhancing the antimicrobial efficiency of azithromycin

Development and Optimization of Erythromycin Loaded Transethosomes Cinnamon Oil Based Emulgel for Antimicrobial Efficiency

Erythromycin (EM) is a macrolide antibiotic that is frequently used to treat skin bacterial infections. It has a short half-life (1–1.5 h), instability in stomach pH, and a low oral bioavailability. These foregoing factors limit its oral application; therefore, the development of topical formulations loaded with erythromycin is an essential point to maximize the drug’s concentration at the skin. Accordingly, the current study’s goal was to boost the antimicrobial activity of EM by utilizing the advantages of natural oils such as cinnamon oil. Erythromycin-loaded transethosomes (EM-TE) were generated and optimized using a Box–Behnken design employing, phospholipid concentration (A), surfactant concentration (B), and ethanol content (C) as independent variables. Their effects on entrapment efficiency, EE, (Y1) and the total amount of erythromycin that penetrated the skin after 6 h, Q6h (Y2), were assessed. The optimized transethosome showed a particle size of 256.2 nm, EE of 67.96 ± 0.59%, and Q6h of 665.96 ± 5.87 (µg/cm2) after 6 h. The TEM analysis revealed that, the vesicles are well-known packed structures with a spherical shape. The optimized transethosomes formulation was further transformed into a cinnamon oil-based emulgel system using HPMC as a gelling agent. The generated EM-TE-emulgel was characterized by its physical features, in vitro, ex vivo studies, and antimicrobial activities. The formulation showed sufficient characteristics for effective topical application, and demonstrated a great stability. Additionally, EM-TE-Emulgel had the highest transdermal flux (120.19 μg/cm2·h), and showed considerably (p < 0.05) greater antimicrobial activity, than EM-TE-gel and placebo TE-Emulgel. The action of EM was subsequently augmented with cinnamon oil, which eventually showed a notable effect against bacterial growth. Finally, these results demonstrate that the transethosomes-loaded cinnamon oil-based emulgel is an alternative way to deliver erythromycin for the treatment of topical bacterial infections

Adrenomedullin Mitigates Doxorubicin-Induced Nephrotoxicity in Rats: Role of Oxidative Stress, Inflammation, Apoptosis, and Pyroptosis

Doxorubicin (DOX) is an anticancer antibiotic which has various effects in human cancers. It is one of the commonly known causes of drug-induced nephrotoxicity, which results in acute renal injury. Adrenomedullin (ADM), a vasodilator peptide, is widely distributed in many tissues and has potent protective effects. Therefore, the current study aimed to examine the protective potential mechanisms of ADM against DOX-induced nephrotoxicity. A total of 28 male Wistar rats were randomized into four groups: control group, doxorubicin group (15 mg/kg single intraperitoneal injection of DOX), adrenomedullin + doxorubicin group (12 μg/kg/day intraperitoneal injection of ADM) 3 days prior to DOX injection and continuing for 14 days after the model was established, and adrenomedullin group. Kidney function biomarkers, oxidative stress markers, and inflammatory mediators (TNF-α, NLRP3, IL-1β, and IL-18) were assessed. The expressions of gasdermin D and ASC were assessed by real-time PCR. Furthermore, the abundances of caspase-1 (p20), Bcl-2, and Bax immunoreactivity were evaluated. ADM administration improved the biochemical parameters of DOX-induced nephrotoxicity, significantly reduced oxidative damage markers and inflammatory mediators, and suppressed both apoptosis and pyroptosis. These results were confirmed by the histopathological findings and revealed that ADM’s antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties may have prospective applications in the amelioration of DOX-induced nephrotoxicity

Spectral Analysis and Antiulcer Potential of <i>Lactuca sativa</i> through the Amelioration of Proinflammatory Cytokines and Apoptosis Markers

The objective of this study was to characterize the bioactive ingredients and antiulcer effects of Lactuca sativa leaves. Several bioactive chemicals were found in the cold methanolic extract of Lactuca sativa leaves after gas chromatography-mass spectrometry (GC-MS) research: 9,12-octadecadienoic acid (Z,Z)-, cyclononasiloxane, octadecamethyl-, n-hexadecanoic acid, Hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl, octadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, 9-octadecenamide, (Z)-, hexadecanoic acid, stigmasterol, benzothiazole, ethyl iso-allocholate, and octacosane. Distinct fingerprint regions in GCMS indicated the existence of bioactive compounds. The leaf powder of Lactuca sativa (LPL) demonstrated substantial antiulcer properties at 400 mg/kg, which was almost equivalent to the standard drug at 20 mg/kg. The cytokine network was efficiently regulated by reducing the production of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α. The levels of caspase-3 and caspase-9 were also considerably lowered at p < 0.05 significant level