Background: In the current study, we evaluated the therapeutic potential of sinapic acid (SA) in terms of the mechanism underlying its gastroprotective action against ethanol-induced gastric ulcers in rats.Methods: These effects were examined through gross macroscopic evaluation of the stomach cavity [gastric ulcer index (GUI)], alteration in pH, gastric juice volume, free acidity, total acidity, total gastric wall mucus, and changes in PGE2. In addition, we evaluated lipid peroxidation (malondialdehyde), antioxidant systems (catalase and glutathione), inflammatory markers [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and myeloperoxidase (MPO)], apoptotic markers (caspase-3, Bax, and Bcl-2), nuclear factor-κB [NF-κB (p65)], NO levels, and histopathological staining (H and E and PAS).Results: In rats with ethanol-induced ulcers, pre-treatment with SA (40 mg/kg p. o.) decreased the sternness of ethanol-induced gastric mucosal injuries by decreasing the GUI, gastric juice volume, free acidity, and total acidity. In addition, the pH and total gastric mucosa were increased, together with histopathological alteration, neutrophil incursion, and increases in PGE2 and NO₂. These effects were similar to those observed for omeprazole, a standard anti-ulcer drug. SA was shown to suppress gastric inflammation through decreasing TNF-α, IL-6, and MPO, as well as curbing gastric oxidative stress through the inhibition of lipid peroxidation (MDA) and restoration of depleted glutathione and catalase activity. SA inhibited Bcl-2-associated X (Bax) and caspase-3 activity, and restored the antiapoptotic protein Bcl-2; these findings indicate the antiapoptotic potential of SA, leading to enhanced cell survival. SA also repressed NF-κB signaling and increased IκBα. Moreover, SA upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), thereby restoring depleted antioxidant defense enzymes and implicating the NRF2/HO-1 signaling pathways.Conclusion: These results suggest that the prophylactic administration of SA (40 mg/kg) can ameliorate ethanol-induced gastric ulcers in rats primarily via the modulation of Nrf2/HO-1 and NF-κB signaling and subsequent enhancement of cell viability.

Objective: The aim of this study was to investigate the in vitro and in vivo performance of self-nanoemulsifying drug delivery systems (SNEDDSs) of talinolol (TAL), a poorly water-soluble drug. Methods: Self-nanoemulsifying drug delivery systems of TAL were prepared using various oils, non-ionic surfactants and/or water-soluble co-solvents and assessed visually/by droplet size measurement. Equilibrium solubility of TAL in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The in vitro dissolution experiments and human red blood cells (RBCs) toxicity test, ex vivo gut permeation studies, and bioavailability of SNEDDS in rats were studied to compare the representative formulations with marketed product Cordanum^® 50 mg and raw drug. Results: The results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and higher TAL solubility. From the dissolution studies, it was found that the developed SNEDDS provided significantly higher rate of TAL release (>97% in 2.0 h) compared to raw TAL and marketed product Cordanum^®. The RBC lysis test suggested negligible toxicity of the formulation to the cells. The ex vivo permeability assessment and in vivo pharmacokinetics study of a selected SNEDDS formulation (F6) showed about four-fold increase in permeability and 1.58-fold enhanced oral bioavailability of TAL in comparison to pure drug, respectively. Conclusion: Talinolol loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, increased gut permeation, reduced/no human RBC toxicity, and enhanced oral bioavailability.

The present investigation was designed to investigate the protective effect of (Beta vulgarisL.) beat root ethanolic extract (BVEE) on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific kidney function parameters (urea, uric acid, total protein, creatinine, and histopathology of kidney tissue) were evaluated to access gentamicin-induced nephrotoxicity. The oxidative/nitrosative stress (Lipid peroxidation, MDA, NP-SH, Catalase, and nitric oxide levels) was assessed. The inflammatory response (TNF-α, IL-6, MPO, NF-κB (p65), and NF-κB (p65) DNA binding) and apoptotic marker (Caspase-3, Bax, and Bcl-2) were also evaluated. BVEE (250 and 500 mg/kg) treatment along with gentamicin restored/increased the renal endogenous antioxidant status. Gentamicin-induced increased renal inflammatory cytokines (TNF-αand IL-6), nuclear protein expression of NF-κB (p65), NF-κB-DNA binding activity, myeloperoxidase (MPO) activity, and nitric oxide level were significantly down regulated upon BVEE treatment. In addition, BVEE treatment significantly reduced the amount of cleaved caspase 3 and Bax, protein expression and increased the Bcl-2 protein expression. BVEE treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. These findings suggest that BVEE treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, inflammation, and apoptosis in the kidney.

The objective of the current study was to formulate the eprosartan mesylate loaded transfersomes using different proportions of Phospholipon^® 90 G and Tween^® 80 (95–75:5–25% w/w). The prepared transfersomes were characterized for their vesicles size, shape, polydispersity index, zeta potential, entrapment efficiency, in vitro skin permeation, confocal laser scanning microscopy, and in vivo skin irritation. Results revealed that the formulated transfersomes were negatively charged, spherical unilamellar structure of 71.18–85.66 nm with entrapment efficiency of 83.00–88.19%, and presented transdermal flux of 1.78–5.02 μg/cm²/h across rat skin. Confocal laser scanning microscopy confirmed that the formulated rhodamine 6 G loaded transfersomes could penetrate deeply and uniformly into rat skin. Additionally, in vivo skin irritation studies revealed that the prepared transfersomes were devoid of any skin irritation potential (erythema and edema). Results of this study revealed that the transfersomes prepared with Tween^® 80 could be used to enhance the transdermal delivery of eprosartan mesylate. In conclusion, transdermal transfersomes formulation may prove to be an encouraging drug carrier for eprosartan mesylate and other actives, particularly owing to their simple formulation and unsophisticated scale-up methods.