Salamone Federica Lina, Molonia Maria Sofia, Muscarà Claudia, Saija Antonella, Cimino Francesco, Speciale Antonio
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno D'Alcontres 31, 98166 Messina, Italy.
Antioxidants (Basel). 2024 Dec 10;13(12):1507. doi: 10.3390/antiox13121507.
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.) Mill. cladodes and L. leaves. Pre-treatment with OFI+OE prevented INDO-induced intestinal epithelial barrier damage, as demonstrated by TEER measurement, fluorescein permeability, and tight junction protein expression. The extract showed positive effects against INDO-induced oxidative stress and correlated activation of apoptosis, decreasing pro-apoptotic markers BAX and Caspase-3 and increasing anti-apoptotic factor Bcl-2. Moreover, the extract inhibited the NF-κB pathway and pro-inflammatory cascade. In conclusion, these data support the use of OFI+OE extract as a natural strategy for therapy and prevention of intestinal mucosal damage, demonstrating its beneficial effects against INDO-induced intestinal damage, through modulation of oxidative, apoptotic, and inflammatory pathways.
非甾体抗炎药（NSAIDs）可在胃肠道（GI）黏膜中诱发严重不良反应，增加肠道通透性并导致线粒体功能障碍、氧化应激、细胞凋亡和炎症。由于质子泵抑制剂对预防NSAID引起的胃病有效，但对NSAID引起的肠病无效，目前的研究集中在天然产物作为治疗和预防肠道损伤的保护物质。在此，通过使用基于吲哚美辛（INDO）引起的肠上皮细胞（Caco-2）损伤的体外模型，我们检测了市售标准化提取物（OFI+OE）（来自 （L.）Mill. 的叶状枝和 L. 的叶）的保护活性。如跨上皮电阻测量、荧光素通透性和紧密连接蛋白表达所示，用OFI+OE预处理可预防INDO诱导的肠上皮屏障损伤。该提取物对INDO诱导的氧化应激和相关的细胞凋亡激活具有积极作用，降低促凋亡标志物BAX和半胱天冬酶-3，并增加抗凋亡因子Bcl-2。此外，该提取物抑制NF-κB途径和促炎级联反应。总之，这些数据支持使用OFI+OE提取物作为治疗和预防肠黏膜损伤的天然策略，通过调节氧化、凋亡和炎症途径证明其对INDO诱导的肠道损伤具有有益作用。
