Protective effect of active components of Eucommia ulmoides leaves on gastric ulcers in rats: Involvement of the PI3K/Akt/NF‐κB pathway

Abstract

Eucommia ulmoides leaves are widely developed as food and medicines in China and Japan. Its main components have anti-inflammatory properties against gastric ulcers. The purpose of this study was to assess the protective role of an extract derived from the active components of Eucommia ulmoides leaves (EUL 50) against a gastric ulcer and analyze the underlying antiulcer mechanism. The main components of EUL 50 were identified using an ultra-performance liquid chromatography (UPLC) method. Network pharmacology and molecular docking were performed to predict the possible mechanism of action of EUL 50 in the treatment of gastric ulcers. The rats received EUL 50 intragastric administration twice a day for 3 days. Hydrochloric acid/ethanol (HCl/EtOH) was utilized to induce gastric ulcers, followed by histopathological and histochemical evaluation of the ulcer tissues and determination of the main oxidative stress parameters and inflammatory cytokines. The expression of PI3K/Akt/NF-κB pathway-related proteins was measured. Neochlorogenic acid, chlorogenic acid, rutin, and so on were identified as the major components of EUL 50 by UPLC. The prediction results identified the PI3K/Akt/NF-κB signaling pathway as the main possible protective mechanism against gastric ulcers. Furthermore, in a dose-dependent manner, EUL 50 reduced gastric tissue damage. In addition, the high dose of EUL 50 administration resulted in remarkable reductions in the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and interleukin-1β (IL-1β) by 22.64%, 42.61%, 57.78%, and 56.51%, respectively, and suppression of the phosphorylation of Akt, p65, IKKα, and IκBα by 60.87%, 67.65, 74.58%, and 59.57%, respectively, and increased the antioxidant enzyme activity. EUL 50 is rich in flavonoids and organic acids that can act on the PI3K/Akt/NF-κB signaling pathway; as a result, oxidative stress and inflammation are considerably reduced, and gastric ulcers caused by HCl/EtOH are reduced.

Protective Effect of Foxtail Millet Protein Hydrolysate on Ethanol and Pyloric Ligation-Induced Gastric Ulcers in Mice

“…Endogenous NO can inhibit the expression of endothelin-1 (ET-1) [ 31 ], which is an upstream effector of the PI3K/AKT signaling pathway and modulates the inflammatory response [ 32 ]. The Western blot results showed that ethanol induction significantly increased the expression of ET-1 and PI3K, and the phosphorylation level of Akt in the gastric tissues of mice ( Figure 5 C,D).…”

“…The increased secretion of ET-1 in the gastric mucosa can cause severe vasoconstriction under stress, which reduces the blood supply to the gastric tissue, leading to local hypoxia and acidosis [ 47 ]. ET-1 can also activate the PI3K/Akt signaling pathway, thereby activating the inflammatory response [ 32 ]. In this study, the FPH treatment decreased the expression of ET-1, PI3K, and the phosphorylation of Akt, indicating that the ET-1/PI3K/Akt signaling pathway played a role in the protective effect of FPH.…”

Eucommia ulmoides Leaves Alleviate Cognitive Dysfunction in Dextran Sulfate Sodium (DSS)-Induced Colitis Mice through Regulating JNK/TLR4 Signaling Pathway

“…The results showed that AEEL decreased MDA levels and increased GSH and SOD levels in brain and colon tissues (Figure 7). Gong et al (2022) reported that E. ulmoides extract reduced the MDA level and increased the SOD and GSH levels in 150 mM HCl in 60% of EtOH-induced rats [49]. Shi et al (2016) reported that the chlorogenic acid in E. ulmoides leaves decreased MDA levels and increased SOD, GSH, and CAT levels in the livers of rats with CCl 4 -induced liver fibrosis [50].…”

Gastroprotective effects of Pikad Tri-phol-sa-mut-than herbal remedy on multiple gastric ulcer models in rats

“…Histopathological examination (H&E staining) revealed that EtOH/HCl caused severe gastric ulcers with leucocyte infiltration in the submucosal layer, and TS remarkably prevented the EtOH/HCl-induced gastric damage and inflammatory response in rats. PAS staining technique is commonly used to determine the mucus glycoproteins in gastric mucosal tissues [ 63 , 64 ]. In this study, PAS staining showed gastric mucosal damage with mucus depletion in the control group that received EtOH/HCl.…”