Shaik Rasheed A, Eid Basma G
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Life (Basel). 2022 Feb 28;12(3):356. doi: 10.3390/life12030356.
One of the major aggressive factors that affect gastric injury is non-steroidal anti-inflammatory drugs (NSAIDs). Indomethacin (Indo) showed higher potentiality in gastric injury over conventional NSAIDs. Piceatannol (PIC) is a natural polyphenolic stilbene that possesses potent antioxidant and anti-inflammatory properties. The gastroprotective properties of PIC have been overlooked previously. Hence, we aim to study gastric injury induced by Indo and the protective action manifested by PIC, as well as to elucidate the likely underlying mechanisms of action in a rat model. The rats have been treated with vehicle, Indo alone, combined treatment with Indo, and PIC at (5 mg/kg or 10 mg/kg), respectively. The rats were also treated with Indo and omeprazole. In our study, we found that PIC at both 5 and 10 mg/kg doses was effective by averting the rise in ulcer and lesion indices, acid production, and histological variations persuaded by Indo. Mechanistically, PIC significantly reduced lipid peroxidation product (MDA), increased the GSH content, and enhanced SOD and CAT activity. In addition, PIC exhibits a distinct reduction in the levels of inflammatory parameters (Cox-2, IL-6, TNF-α, and NFκB). Contrastingly, PIC augmented both mucin and PGE2 content. Moreover, PIC fostered angiogenesis by increasing the expression of proangiogenic factors (VEGF, bFGF, and PDGF). Overall, the above results suggest PIC exhibits a potential protective effect against Indo-induced gastric ulcers by the antioxidant, anti-inflammatory, and angiogenic mechanisms.
影响胃损伤的主要侵袭性因素之一是非甾体抗炎药（NSAIDs）。与传统的NSAIDs相比，吲哚美辛（Indo）对胃损伤具有更高的潜在风险。白皮杉醇（PIC）是一种天然的多酚芪类化合物，具有强大的抗氧化和抗炎特性。PIC的胃保护特性此前一直被忽视。因此，我们旨在研究Indo诱导的胃损伤以及PIC所表现出的保护作用，并阐明在大鼠模型中可能的潜在作用机制。分别用赋形剂、单独的Indo、Indo与PIC（5mg/kg或10mg/kg）联合治疗大鼠。大鼠还接受了Indo和奥美拉唑治疗。在我们的研究中，我们发现5mg/kg和10mg/kg剂量的PIC均能有效避免Indo诱导的溃疡和损伤指数升高、胃酸分泌增加以及组织学变化。从机制上讲，PIC显著降低脂质过氧化产物（MDA），增加谷胱甘肽（GSH）含量，并增强超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。此外，PIC使炎症参数（Cox-2、白细胞介素-6、肿瘤坏死因子-α和核因子κB）水平明显降低。相反，PIC增加了粘蛋白和前列腺素E2的含量。此外，PIC通过增加促血管生成因子（血管内皮生长因子、碱性成纤维细胞生长因子和血小板衍生生长因子）的表达促进血管生成。总体而言，上述结果表明PIC通过抗氧化、抗炎和血管生成机制对Indo诱导的胃溃疡具有潜在的保护作用。
