Article ; Online: Lizhong decoction ameliorates ulcerative colitis by inhibiting ferroptosis of enterocytes via the Nrf2/SLC7A11/GPX4 pathway.
2024 Volume 326, Page(s) 117966
Abstract: ... effective way to treat many diseases. Lizhong decoction (LZD), a classical prescription composed ...
Abstract | Ethnopharmacology relevance: Traditional herbal medicines have been considered as a novel and effective way to treat many diseases. Lizhong decoction (LZD), a classical prescription composed of Zingiber officinale Rosc., Panax ginseng C. A. Mey., Atractylodes macrocephala Koidz., and Glycyrrhiza uralensis Fisch., has been used to treat gastrointestinal disorders in clinical practices for thousands of years. However, the mechanism of LZD in alleviating ulcerative colitis (UC) is still unclear. Aim of the study: The purpose of this study was to clarify the potential molecular mechanism of LZD in improving UC. Materials and methods: The amelioration of LZD on dextran sodium sulfate (DSS)-induced UC mice was evaluated by body weight, colon length, pathology of colon tissues, pro-inflammatory cytokines, and intestinal tight junction (TJ) proteins. Moreover, the gene expression profiles of UC patients were extracted to investigate potential pathological mechanisms of UC. The influence of LZD on ferroptosis was analyzed by iron load, malondialdehyde (MDA), and the expression of ferroptosis-associated proteins. Meanwhile, the inhibition of LZD on oxidative stress (OS) was assessed by the superoxide dismutase (SOD) activity, as well as the expression levels of glutathione (GSH) and glutathione disulfide (GSSG). Furthermore, the influence of LZD on ferroptosis was assessed by inhibiting nuclear factor (erythroid-derived-2)-like 2 (Nrf2). Results: LZD showed significant therapeutic effects in UC mice, including reduction of intestinal injury and inflammation. Moreover, LZD treatment notably upregulated the expression of TJ proteins. Further investigation indicated that LZD significantly inhibited the ferroptosis of enterocytes by decreasing iron load and MDA, and increasing the expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in colon tissues. Furthermore, the decreased activity of SOD, reduced level of GSH, and increased content of GSSG in UC mice were notably reversed by LZD. Consistent with in vivo results, LZD could markedly inhibit ferroptosis and OS in RSL3-induced Caco-2 cells. Mechanistically, LZD alleviated ferroptosis by suppressing OS through the activation of Nrf2 signaling. Conclusions: Collectively, LZD remarkably improved intestinal pathological injury in UC mice, and its potential mechanism was the suppression of ferroptosis in enterocytes by the Nrf2/SLC7A11/GPX4 pathway. |
---|---|
MeSH term(s) | Humans ; Animals ; Mice ; Colitis, Ulcerative/chemically induced ; Colitis, Ulcerative/drug therapy ; Enterocytes ; Phospholipid Hydroperoxide Glutathione Peroxidase ; NF-E2-Related Factor 2 ; Glutathione Disulfide ; Caco-2 Cells ; Ferroptosis ; Glutathione ; Iron ; Superoxide Dismutase ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Colitis ; Amino Acid Transport System y+ |
Chemical Substances | Phospholipid Hydroperoxide Glutathione Peroxidase (EC 1.11.1.12) ; NF-E2-Related Factor 2 ; Glutathione Disulfide (ULW86O013H) ; Glutathione (GAN16C9B8O) ; Iron (E1UOL152H7) ; Superoxide Dismutase (EC 1.15.1.1) ; Dextran Sulfate (9042-14-2) ; SLC7A11 protein, human ; Amino Acid Transport System y+ |
Language | English |
Publishing date | 2024-02-22 |
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.2024.117966 |
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.