Ulcerative colitis (UC) is a recurrent and persistent nonspecific inflammatory bowel disease (IBD) that greatly affects human survival and social wealth. Despite the advances in the treatment of UC, there is still a high demand for novel therapeutic strategies for UC patients. Cell death is critical to the development and progression of UC. Understanding how intestinal cells die and how to prevent damage to intestinal cells is of great interest for the diagnosis and early treatment of UC. Ferroptosis, a novel form of regulated cell death (RCD) manifested by iron accumulation, lipid peroxidation, and excessive reactive oxygen species (ROS) production, has been shown to contribute to the development and progression of UC. Inhibitors of ferroptosis have been validated in models of UC. Here, we reviewed the mechanisms of initiation and control of ferroptosis and summarize the therapeutic activity of ferroptosis inhibitors in models of UC. We further discussed the possibility of inhibiting ferroptosis as a novel therapeutic target for UC. These findings revealed novel mechanisms to protect the colonic mucosa and highlighted the importance of ferroptosis in the disease process.

Background: Gegen Qinlian decoction (GQD) is a classic prescription for treating ulcerative colitis (UC) in traditional Chinese medicine. However, the therapeutic mechanism has not been fully clarified. Purpose: In the present study, we aimed to evaluate the role of ferroptosis-mediated IEC death in UC treated mice with GQD by using DSS-induced a colitis mouse model and RSL3-induced ferroptosis in intestinal organoids. Methods: The effects of GQD on DSS-treated colitis were examined via daily body weight, DAI, colon length, HE staining, PAS staining, ZO-1 and Occludin immunohistochemical staining. Ferroptosis was determined by analysis of iron load, MDA, GSH, mitochondrial morphology, and expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Results: In vivo, GQD administration reduced body weight loss and DAI scores, increased colon length, and improved intestinal histological characteristics and epithelial barrier dysfunction. GQD administration obviously improved the levels of ferroptosis markers (iron load, MDA, GSH, and mitochondrial morphology) and the expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Consistent with in vivo results, GQD administration partially reversed the levels of mtROS, Fe2⁺ and MDA in intestinal organoids induced by RSL3, and notably improved morphological destruction, histological damage and epithelial barrier dysfunction in organoids. Conclusions: In this study, we demonstrated that ferroptosis was triggered in DSS-induced experimental colitis and that GQD adiministration could protect against colonic damage and intestinal epithelial barrier dysfunction by inhibiting ferroptosis.

Vascular endothelial senescence induced by high glucose and palmitate (HG/PA) contributes to endothelial dysfunction, which leads to diabetic cardiovascular complications. Reduction of endothelial senescence may attenuate these pathogenic processes. This study is aimed at determining whether Ginseng-Sanqi-Chuanxiong (GSC) extracts, traditional Chinese medicine, can ameliorate human aortic endothelial cell (HAEC) senescence under HG/PA-stressed conditions and further explore the underlying mechanism. We found that GSC extracts significantly increased antisenescent activity by reducing the HG/PA-induced mitochondrial ROS (mtROS) levels in senescent HAECs. GSC extracts also induced cellular mitophagy formation, which mediated the effect of GSC extracts on mtROS reduction. Apart from this, the data showed that GSC extracts stimulated mitophagy via the AMPK pathway, and upon inhibition of AMPK by pharmacological and genetic inhibitors, GSC extract-mediated mitophagy was abolished which further led to reverse the antisenescence effect. Taken together, these data suggest that GSC extracts prevent HG/PA-induced endothelial senescence and mtROS production by mitophagy regulation via the AMPK pathway. Thus, the induction of mitophagy by GSC extracts may provide a novel therapeutic candidate for cardiovascular protection in metabolic syndrome.

Objectives. To reveal the molecular mechanisms of ulcerative colitis (UC) and provide potential biomarkers for UC gene therapy. Methods. We downloaded the GSE87473 microarray dataset from the Gene Expression Omnibus (GEO) and identified the differentially expressed genes (DEGs) between UC samples and normal samples. Then, a module partition analysis was performed based on a weighted gene coexpression network analysis (WGCNA), followed by pathway and functional enrichment analyses. Furthermore, we investigated the hub genes. At last, data validation was performed to ensure the reliability of the hub genes. Results. Between the UC group and normal group, 988 DEGs were investigated. The DEGs were clustered into 5 modules using WGCNA. These DEGs were mainly enriched in functions such as the immune response, the inflammatory response, and chemotaxis, and they were mainly enriched in KEGG pathways such as the cytokine‐cytokine receptor interaction, chemokine signaling pathway, and complement and coagulation cascades. The hub genes, including dual oxidase maturation factor 2 (DUOXA2), serum amyloid A (SAA) 1 and SAA2, TNFAIP3‐interacting protein 3 (TNIP3), C‐X‐C motif chemokine (CXCL1), solute carrier family 6 member 14 (SLC6A14), and complement decay‐accelerating factor (CD antigen CD55), were revealed as potential tissue biomarkers for UC diagnosis or treatment. Conclusions. This study provides supportive evidence that DUOXA2, A‐SAA, TNIP3, CXCL1, SLC6A14, and CD55 might be used as potential biomarkers for tissue biopsy of UC, especially SLC6A14 and DUOXA2, which may be new targets for UC gene therapy. Moreover, the DUOX2/DUOXA2 and CXCL1/CXCR2 pathways might play an important role in the progression of UC through the chemokine signaling pathway and inflammatory response.

Functional dyspepsia (FD) is a prevalent and challenging gastrointestinal disorder. Conventional medicine often faces limitations in providing effective treatment for FD, thus indicating the need to explore alternative approaches. Traditional Chinese medicine (TCM), which is rooted in ancient Chinese traditions and has evolved over thousands of years, offers a holistic approach to well-being. TCM incorporates herbal remedies, acupuncture, and other therapies while shaping the future of complementary and alternative medicine. To review the existing literature on the current status and future prospects of using TCM to treat FD. We extensively searched the PubMed, Google Scholar, Embase, an China National Knowledge Internet databases from inception to May 31, 2023 to identify relevant literature. We also searched the reference lists of the included articles. Clinical evidence-based research has explored the efficacy of TCM in treating FD. Recent research has illuminated the multifaceted mechanisms through which TCM interventions affect FD. TCM is a promising alternative, as it emphasizes a holistic approach and holds potential advantages in addressing the complex nature of FD. The integration of TCM and Western medicine offers a comprehensive approach to understanding and managing FD by bridging traditional wisdom with modern scientific understanding. This paper highlights the practical implications of this integration, the challenges to be addressed, and the potential for international collaboration to further elucidate the efficacy of TCM. However, continued research and dialog are needed to advance the modern development of TCM and to improve the quality of life of FD patients.

Objectives. Gegen Qinlian decoction (GQD), a Chinese herbal compound, has been widely used in the treatment of ulcerative colitis (UC) in China. However, evidence from systematic reviews (SRs)/meta-analyses (MAs) of GQD in UC remains highly controversial. To collate, evaluate, and synthesize the current evidence, we carried out this study. Methods. SRs/MAs of GQD for UC were obtained from eight databases. Methodological Quality of Systematic Reviews 2 (AMSTAR-2) was utilized to appraise the methodological quality, Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) for reporting quality, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for evidence quality. Results. Four eligible SRs/MAs were obtained. According to AMSTAR 2, all SRs/MAs were graded as critically low quality. According to PRISMA checklist, all SRs/MAs failed to report the information of protocol and registration. With GRADE, no outcome measure with high-quality evidence was found, and the evidence quality for outcome measures was in the moderate to critically low levels. Conclusions. GQD with conventional medicine (CM) seems to be more effective in UC than CM alone. This finding provides a new alternative strategy for the treatment of UC. However, owing to the limitations of the evidence provided by the included SRs/MAs, this conclusion must be treated with caution.