Vinpocetine alleviated alveolar epithelial cells injury in experimental pulmonary fibrosis by targeting PPAR-γ/NLRP3/NF-κB and TGF-β1/Smad2/3 pathways

Abstract

This study aimed to investigate the potential anti-fibrotic activity of vinpocetine in an experimental model of pulmonary fibrosis by bleomycin and in the MRC-5 cell line. Pulmonary fibrosis was induced in BALB/c mice by oropharyngeal aspiration of a single dose of bleomycin (5 mg/kg). The remaining induced animals received a daily dose of pirfenidone (as a standard anti-fibrotic drug) (300 mg/kg/PO) and vinpocetine (20 mg/kg/PO) on day 7 of the induction till the end of the experiment (day 21). The results of the experiment revealed that vinpocetine managed to alleviate the fibrotic endpoints by statistically improving (P ≤ 0.05) the weight index, histopathological score, reduced expression of fibrotic-related proteins in immune-stained lung sections, as well as fibrotic markers measured in serum samples. It also alleviated tissue levels of oxidative stress and inflammatory and pro-fibrotic mediators significantly elevated in bleomycin-only induced animals (P ≤ 0.05). Vinpocetine managed to express a remarkable attenuating effect in pulmonary fibrosis both in vivo and in vitro either directly by interfering with the classical TGF-β1/Smad2/3 signaling pathway or indirectly by upregulating the expression of Nrf2 enhancing the antioxidant system, activating PPAR-γ and downregulating the NLRP3/NF-κB pathway making it a candidate for further clinical investigation in cases of pulmonary fibrosis.

Mitigative Effects of Topical Norfloxacin on an Imiquimod-Induced Murine Model of Psoriasis

“…The tissue MDA generation was estimated by counting the amount of thiobarbituric acid reactive substances via spectrophotometry (TBARS). 3 mL of 1% phosphoric acid and 1 mL of 0.6% thiobarbituric acid were mixed with a sufficient quantity of skin homogenates and poured into the container. ,, The blended contents were heated up for around 50 min in a pot of water. Following the cooling of the mixture, the colored portion was separated into 4 mL of n -butanol.…”

Development and Optimization of Dipyridamole- and Roflumilast-Loaded Nanoemulsion and Nanoemulgel for Enhanced Skin Permeation: Formulation, Characterization, and In Vitro Assessment

“…The viscosity of nanoemulgel formulations was measured at various rotational speeds (10,12,20,30,50,60,100, and 200 rpm) and a fixed temperature of 25 • C. Viscosity measurements are shown in Table S1.…”

“…Roflumilast is an anti-inflammatory medication known to participate in multiple inflammatory processes. It reduces the levels of leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-1b, IL-2, IL-13, interferon (IFN)-γ, and reactive oxygen species (ROS) [ 8 , 9 , 10 ]. The US Food and Drug Administration (FDA) has approved the use of roflumilast cream 0.3% (Zorvye; Arcutis Biotherapeutics) in the treatment of plaque psoriasis in both adolescents and adults [ 11 ].…”