Article ; Online: Huang-Qi-Jian-Zhong-Tang accelerates healing of indomethacin-induced gastric ulceration in rats via anti-inflammatory and antioxidant mechanisms.
2023 Volume 319, Issue Pt 2, Page(s) 117264
Abstract: Ethnopharmacological relevance: Huang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical ...
| Abstract | Ethnopharmacological relevance: Huang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China. Aim of the study: In the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved. Materials and methods: Observations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflammatory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-κB and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-IκBβ, and p-NF-κB were evaluated through immunofluorescence analysis. Results: The administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-κB and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of IκΒβ, NF-κB, JAK, and STAT. Conclusions: The therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-κB and STAT signaling pathways. |
|---|---|
| MeSH term(s) | Rats ; Animals ; Indomethacin/toxicity ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Antioxidants/metabolism ; Stomach Ulcer/chemically induced ; Stomach Ulcer/drug therapy ; Stomach Ulcer/pathology ; NF-kappa B/metabolism ; Pepsin A/metabolism ; Molecular Docking Simulation ; Anti-Ulcer Agents/pharmacology ; Anti-Ulcer Agents/therapeutic use ; Anti-Inflammatory Agents/pharmacology ; Gastric Mucosa ; Cytokines/metabolism ; Superoxide Dismutase/metabolism ; RNA, Messenger/metabolism |
| Chemical Substances | Indomethacin (XXE1CET956) ; Antioxidants ; NF-kappa B ; Pepsin A (EC 3.4.23.1) ; Anti-Ulcer Agents ; Anti-Inflammatory Agents ; Cytokines ; Superoxide Dismutase (EC 1.15.1.1) ; RNA, Messenger |
| Language | English |
| Publishing date | 2023-10-05 |
| Publishing country | Ireland |
| Document type | Journal Article |
| ZDB-ID | 134511-4 |
| ISSN | 1872-7573 ; 0378-8741 |
| ISSN (online) | 1872-7573 |
| ISSN | 0378-8741 |
| DOI | 10.1016/j.jep.2023.117264 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 1494: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.