Clinical Pharmacy Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, 11942 Al-Kharj, Saudi Arabia; Pharmacology Department, Faculty of Medicine, Tanta University, El-Gish Street, Postal No. 31527, Tanta, Egypt.
Clinical Pharmacy Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, 11942 Al-Kharj, Saudi Arabia.
Biomed Pharmacother. 2022 Jul;151:113200. doi: 10.1016/j.biopha.2022.113200. Epub 2022 May 27.
Gastric ulcer (GU) is a worldwide gastrointestinal disorder associated with NSAID use. Recently, amentoflavone proved to be a potent autophagy modulator, antioxidant, anti-inflammatory, and anti-apoptotic agent. Eight-week-old male Wistar rats received amentoflavone orally for 14 days at 25, 50, or 100 mg/kg/day. On day 14 of treatment, GU was induced by a single oral instillation of 100 mg/kg indomethacin, one hour after the last treatment. Amentoflavone dose-dependently alleviated indomethacin-induced GU, as demonstrated by repression of gastric mucosa pathological manifestations (ulcer index, ulcer surface area, histopathological deviations, and score) and increased ulcer inhibition percentage. These protective effects were due to the enhancement of gastric mucosa autophagy, as demonstrated by increased levels of beclin-1, MAP1LC3B, and CTSD, and reduced expression of p62 (SQSTM1). In addition, amentoflavone modulated the AMPK/mTOR pathway by increasing p-AMPK and reducing mTORC1 levels. Moreover, it hindered the redox aberrations by reducing MDA level and enhancing SOD activity, GSH level, and Nrf2/HO-1 cascade. Furthermore, a decrease in caspase-3 levels, Bax/Bcl-2 ratio and an increase in Bcl-2 expression suggest inhibition of the apoptotic process. Additionally, amentoflavone suppressed gastric mucosal inflammation by decreasing IL-1β, TNF-α, IFN-γ levels, IL-4, IL-6 mRNA expressions and MPO activity, and increasing IL-10 mRNA expresion. Therefore, amentoflavone could consider a promising natural agent protecting against indomethacin-induced GU.
胃溃瘍（GU）是一種與 NSAID 使用有關的全球性胃腸疾病。最近，芹菜甲素被證明是一種有效的自噬調節劑、抗氧化劑、抗炎劑和抗凋亡劑。8 周齡雄性 Wistar 大鼠每天口服芹菜甲素 25、50 或 100mg/kg，持續 14 天。在治療的第 14 天，在最後一次治療 1 小時後，單獨口服 100mg/kg 吲哚美辛誘發 GU。芹菜甲素劑量依賴性地緩解了吲哚美辛誘導的 GU，表現為胃黏膜病理表現（潰瘍指數、潰瘍面積、組織病理學偏差和評分）的抑制和潰瘍抑制率的增加。這些保護作用是由於胃黏膜自噬的增強，表現在 beclin-1、MAP1LC3B 和 CTSD 的水平增加和 p62（SQSTM1）的表達降低。此外，芹菜甲素通過增加 p-AMPK 和降低 mTORC1 水平來調節 AMPK/mTOR 通路。此外，它通過降低 MDA 水平、增強 SOD 活性、GSH 水平和 Nrf2/HO-1 級聯來阻斷氧化還原失衡。此外，降低 caspase-3 水平、Bax/Bcl-2 比值和增加 Bcl-2 表達表明抑制了凋亡過程。此外，芹菜甲素通過降低 IL-1β、TNF-α、IFN-γ 水平、IL-4、IL-6 mRNA 表達和 MPO 活性以及增加 IL-10 mRNA 表達來抑制胃黏膜炎症。因此，芹菜甲素可能是一種有前途的天然藥物，用於預防吲哚美辛誘導的 GU。
