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基于其分子作用机制,Argel 的 stemmoside C 作为一种新型天然药物可用于治疗酒精诱导的胃溃疡的小鼠。

Argel's stemmoside C as a novel natural remedy for mice with alcohol-induced gastric ulcer based on its molecular mechanistic pathways.

机构信息

Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.

Department of Cytology & Histology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.

出版信息

J Ethnopharmacol. 2024 Jun 12;327:117970. doi: 10.1016/j.jep.2024.117970. Epub 2024 Feb 29.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Solenostemma argel is widely distributed in Africa & Asia with traditional usage in alleviating abdominal colic, aches, & cramps. This plant is rich in phytochemicals, which must be explored for its pharmacological effects.

PURPOSE

Peptic Ulcer Disease (PUD) is the digestion of the digestive tube. PUD not only interferes with food digestion & nutrient absorption, damages one of the largest defensive barriers against pathogenic micro-organisms, but also impedes drug absorption & bioavailability, rendering the oral route, the most convenient way, ineffective. Omeprazole, one of the indispensable cost-effective proton-pump inhibitors (PPIs) extensively prescribed to control PUD, is showing growing apprehensions toward multiple drug interactions & side effects. Hence, finding a natural alternative with Omeprazole-like activity & limited side effects is a medical concern.

STUDY DESIGN

Therefore, we present Stemmoside C as a new gastroprotective phytochemical agent isolated from Solenostemma argel to be tested in upgrading doses against ethanol-induced gastric ulcers in mice compared to negative, positive, & reference Omeprazole groups.

METHODS

We carried out in-depth pharmacological & histopathological studies to determine the possible mechanistic pathway.

RESULTS

Our results showed that Stemmoside C protected the stomach against ethanol-induced gastric ulcers parallel to Omeprazole. Furthermore, the mechanistic studies revealed that Stemmoside C produced its effect using an orchestrated array of different mechanisms. Stemmoside C stimulates stomach defense by increasing COX-2, PGE-2, NO, & TFF-1 healing factors, IL-10 anti-inflammatory cytokine, & Nrf-2 & HO-1 anti-oxidant pathways. It also suppresses stomach ulceration by inhibiting leucocyte recruitment, especially neutrophils, leading to subsequent inhibition of NF-κBp65, TNF-α, IL-1β, & iNOS pro-inflammatory cytokines & JAK-1/STAT-3 inflammation-induced carcinogenicity cascade in addition to MMP-9 responsible for tissue degradation.

CONCLUSION

These findings cast light on Stemmoside C's clinical application against gastric ulcer progression, recurrence, & tumorigenicity & concurrently with chemotherapy.

摘要

民族药理学相关性

Solenostemma argel 广泛分布于非洲和亚洲,传统上用于缓解腹痛、疼痛和痉挛。这种植物富含植物化学物质,必须探索其药理作用。

目的

消化性溃疡病(PUD)是消化管的消化。PUD 不仅干扰食物消化和营养吸收,破坏对致病微生物的最大防御屏障之一,而且还会阻碍药物吸收和生物利用度,使口服成为最方便的途径无效。奥美拉唑是广泛用于控制 PUD 的必不可少的高性价比质子泵抑制剂(PPIs)之一,但其越来越多的药物相互作用和副作用引起了人们的担忧。因此,寻找一种具有奥美拉唑样活性和有限副作用的天然替代品是一个医学关注点。

研究设计

因此,我们提出 Stemmoside C 作为一种从 Solenostemma argel 中分离出来的新型胃保护植物化学物质,以与阴性、阳性和参考奥美拉唑组进行比较,在升级剂量下测试其对乙醇诱导的小鼠胃溃疡的作用。

方法

我们进行了深入的药理学和组织病理学研究,以确定可能的机制途径。

结果

我们的结果表明,Stemmose C 可保护胃免受乙醇诱导的胃溃疡,与奥美拉唑相似。此外,机制研究表明,Stemmose C 通过一系列不同的机制发挥作用。Stemmose C 通过增加 COX-2、PGE-2、NO 和 TFF-1 愈合因子、IL-10 抗炎细胞因子、Nrf-2 和 HO-1 抗氧化途径,刺激胃防御。它还通过抑制白细胞募集,特别是中性粒细胞,从而抑制随后的 NF-κBp65、TNF-α、IL-1β 和 iNOS 促炎细胞因子和 JAK-1/STAT-3 炎症诱导的致癌性级联反应,以及负责组织降解的 MMP-9,抑制胃溃疡形成。

结论

这些发现为 Stemmoside C 在临床应用中对抗胃溃进展、复发和肿瘤发生提供了依据,并与化疗同时进行。

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