背景:胃溃疡是一个世界性的健康问题,以影响胃粘膜的糜烂为特征,甚至可能到达肌肉层,导致严重的并发症。许多天然产物已被评估为抗溃疡剂,并被认为是治疗或预防胃溃疡的新方法。本研究调查了苦参素(苦参素科)的预防益处,被称为芹菜,吲哚美辛诱导的大鼠胃溃疡的种子提取物。
方法:代谢组学分析,采用液相色谱结合高分辨率电喷雾电离质谱(LC-HR-ESI-MS),目的是调查种子的化学特征。胃组织的组织病理学分析,以及对众多炎性细胞因子和氧化应激指标的评估,证实了体内评估。
结果:与消炎痛组相比,先前用A.graveolens种子提取物处理导致溃疡指数大幅降低,提示胃粘膜损伤改善。此外,通过对氧化应激生物标志物的检查证明了胃保护作用,该生物标志物在用A.graveolens种子提取物预处理后显著减弱.血管内皮生长因子(VEGF),一种刺激血管生成的基本血管生成因子,吲哚美辛明显抑制。A.graveolens种子提取物恢复了这种降低的VEGF水平。NF-κB蛋白水平的显著降低表明吲哚美辛诱导的IKκB/NF-κBp65信号级联的显著减弱。这些活性也与初步特征的次级代谢物相关,包括,酚酸,香豆素和类黄酮,先前证明具有有效的抗炎和抗氧化活性。根据我们的网络药理学研究,鉴定的代谢物注释了379个独特的基因,其中只有17个基因与胃溃疡有关。PTGS2、MMP2和PTGS1是与胃溃疡相干的前几名基因。最前面的生物学途径是VEGF信号通路。
结论:A.graveolens种子提取物具有显著的抗溃疡活性,类似于法莫替丁,对吲哚美辛诱导的大鼠胃损伤。值得强调的是,该提取物克服了常规化学抗分泌药物的负面影响,因为它不会降低胃酸度。
BACKGROUND: Gastric ulcers represent a worldwide health problem, characterized by erosions that affect the mucous membrane of the stomach and may even reach the muscular layer, leading to serious complications. Numerous natural products have been assessed as anti-ulcerogenic agents, and have been considered as new approaches for treatment or prevention of gastric ulcers. The present research investigated the preventive benefits of
Apium graveolens L. (Apiaceae), known as celery, seed extract towards indomethacin-induced ulceration of the stomach in rats.
METHODS: Metabolomic profiling, employing liquid chromatography coupled to high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), was implemented with the aim of investigating the chemical profile of the seeds. Histopathological analysis of gastric tissues, as well as assessment of numerous inflammatory cytokines and oxidative stress indicators, confirmed the in vivo evaluation.
RESULTS: The prior treatment with A. graveolens seed extract resulted in a substantial reduction in the ulcer index when compared to the indomethacin group, indicating an improvement in stomach mucosal injury. Moreover, the gastroprotective effect was demonstrated through examination of the oxidative stress biomarkers which was significantly attenuated upon pre-treatment with A. graveolens seed extract. Vascular endothelial growth factor (VEGF), a fundamental angiogenic factor that stimulates angiogenesis, was markedly inhibited by indomethacin. A. graveolens seed extract restored this diminished level of VEGF. The dramatic reductions in NF-κB protein levels indicate a considerable attenuation of the indomethacin-induced IKκB/NF-κB p65 signaling cascade. These activities were also correlated to the tentatively featured secondary metabolites including, phenolic acids, coumarins and flavonoids, previously evidenced to exert potent anti-inflammatory and antioxidant activities. According to our network pharmacology study, the identified metabolites annotated 379 unique genes, among which only 17 genes were related to gastric ulcer. The PTGS2, MMP2 and PTGS1 were the top annotated genes related to gastric ulcer. The top biological pathway was the VEGF signaling pathway.
CONCLUSIONS: A. graveolens seed extract possesses significant anti-ulcer activity, similar to famotidine, against gastric lesions induced by indomethacin in rats. It is worth highlighting that the extract overcomes the negative effects of conventional chemical anti-secretory drugs because it does not lower stomach acidity.