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The increasing prevalence and limited therapeutic options for liver fibrosis necessitates more medical attention. Our study aims to investigate the potential molecular targets by which Moringa oleifera Lam leaf extract (Mor) and/or telmisartan (Telm) alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 (1 ml/kg) every 72 hours, for 8 weeks. Intoxicated rats with CCl4 were simultaneously orally administrated Mor (400 mg/kg/day for 8 weeks) and/or Telm (10 mg/kg/day for 8 weeks). Treatment of CCl4-intoxicated rats with Mor/Telm significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to CCl4 intoxicated group (P < 0.001). Additionally, Mor/Telm treatment significantly reduced the level of hepatic inflammatory, profibrotic, and apoptotic markers including; nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-βeta1 (TGF-β1), and caspase-3. Interestingly, co-treatment of CCl4-intoxicated rats with Mor/Telm downregulated m-RNA expression of histone deacetylase 2 (HDAC2) (71.8%), and reduced protein expression of mothers against decapentaplegic homolog 3 (p-SMAD3) (70.6%) compared to untreated animals. Mor/Telm regimen also elevated p-SMAD7 protein expression as well as m-RNA expression of peroxisome proliferator-activated receptor γ (PPARγ) (3.6 and 3.1 fold, respectively p < 0.05) compared to CCl4 intoxicated group. Histopathological picture of the liver tissue intoxicated with CCl4 revealed marked improvement by Mor/Telm co-treatment. Conclusively, this study substantiated the hepatoprotective effect of Mor/Telm regimen against CCl4-induced liver fibrosis through suppression of TGF-β1/SMAD3, and HDAC2/NF-κB signaling pathways and up-regulation of SMAD7 and PPARγ expression. [ABSTRACT FROM AUTHOR] more...

The rising incidence of vulvovaginal candidiasis (VVC) has been leading to the development of alternative antifungal therapies. This study aimed to develop a topical chitosan–oleic acid nanoparticle (CH-OA-NP) cream loaded with lemon peel essential oil (LPEO) for VVC treatment. The characterization of the optimal nanoparticle formulation (F4: 10 g/L CH, 2:1 OA/LPEO ratio) showed high encapsulation efficiency, stability, and controlled release. Moreover, it was characterized regarding its particle size, polydispersity index, zeta potential, and chemical/morphological profile. LPEO-related compounds (e.g., eriodictyol) were identified through LC-ESI-QqTOF-HRMS in the cream matrix, suggesting the preservation of LPEO potential bioactivities after formulation. In silico docking of 12 LPEO metabolites revealed that compounds such as citronellic acid exerted inhibitory effects against several inflammation-associated enzymes (e.g., 14-α-Demethylase). In vitro antimicrobial tests demonstrated remarkable activity against Candida albicans, Gram-negative (e.g., Escherichia coli), and Gram-positive (e.g., Staphylococcus aureus) bacteria. In vivo studies in a rat model of VVC revealed significant antifungal, anti-inflammatory, and immunomodulatory effects of the LPEO-CH-OA-NP cream (5% and 10%), leading to reduced MDA, MPO, and IL-1β levels and increased GSH activity. This novel formulation potentially offers a promising alternative therapy for VVC, addressing the current antifungal therapies' limitations, counteracting drug resistance. [ABSTRACT FROM AUTHOR] more...

Eriobotrya japonica Lindl. (Loquat) fruit is a subtropical edible fruit originally from China. It grows well in Egypt, but it is not widely known. In the current study, the fruit was extracted with 80% ethanol to get the total ethanol extract (TEE). A part of which was fractionated by dichloromethane to yield polar and nonpolar fractions (PF and NPF). The antioxidant and anti‐inflammatory activities of the TEE were in vitro evaluated. The complete Freund's adjuvant (CFA) arthritis model was used to explore the in vivo biological assessment of the anti‐arthritic properties in vivo of the TEE, PF, and NPF of the fruit. Additionally, the inspected limbs detached from all animals were subjected to histological inspection. Moreover, GC/MS analysis of the unsaponifiable (USF) and saponifiable (SF) fractions of the NPF was performed. Furthermore, 64 metabolites from various chemical classes were identified using UHPLC/HR‐MS/MS analysis of the TEE of the fruit in both positive and negative ionization modes. The positive ionization mode of loquat fruit allowed for the first time the detection of two kinds of lyso‐glycerophospholipids (Lyso‐GPLs): lyso‐glycerophosphoethanolamines (Lyso‐PtdEtn) and lyso‐glycerophosphocholines (Lyso‐PtdCho). The fruit extracts exhibited a notable in vivo anti‐arthritic activity by decreasing paw thickness in the treated rats and adjusting the inflammatory mediators. The TEE showed the highest anti‐arthritic activity, followed by the PF that showed an observed activity, while the NPF exhibited the lowest activity. Histopathological findings showed a marked improvement in the arthritic condition of the excised limbs. Thus, E. japonica fruit may be considered as a promising natural antioxidant and anti‐arthritic agent. [ABSTRACT FROM AUTHOR] more...