摘要:
Ulcerative colitis is a common digestive disorder worldwide, with increasing incidence in recent years. It is an urgent problem to be solved, as it seriously affects and threatens the health and life of the global population. Studies have shown that dysfunction of the intestinal mucosal barrier is a critical pathogenic factor and molecular basis of ulcerative colitis, and some scholars have described it as a "barrier organ disease." While the Notch signalling pathway affects a series of cellular processes, including proliferation, differentiation, development, migration, and apoptosis. Therefore, it can regulate intestinal stem cells, CD4(+) T cells, innate lymphoid cells, macrophages, and intestinal microbiota and intervene in the chemical, physical, immune, and biological mucosal barriers in cases of ulcerative colitis. The Notch signalling pathway associated with the pathogenesis of ulcerative colitis has distinct characteristics, with good regulatory effects on the mucosal barrier. However, research on ulcerative colitis has mainly focused on immune regulation, anti-inflammatory activity, and antioxidant stress; therefore, the study of the Notch signalling pathway suggests the possibility of understanding the pathogenesis of ulcerative colitis from another perspective. In this article we explore the role and mechanism of the Notch signalling pathway in the pathogenesis of ulcerative colitis from the perspective of the intestinal mucosal barrier to provide new targets and theoretical support for further research on the pathogenesis and clinical treatment of ulcerative colitis.
期刊:
Journal of Ethnopharmacology,2024年318(Pt B):116945 ISSN:0378-8741
通讯作者:
Long, Hongping;Tian, Xuefei
作者机构:
[Tian, Xuefei; Dai, Xinjun; Feng, Ting; Li, Qian; Tan, Nianhua; Hu, Yuxing; Deng, Zhe] College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan Province, China;[Ouyang, Zhaoguang] School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, Tianjin Province, China;[Ouyang, Zhaoguang] Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong, Guangzhou, China;[Mei, Si] Department of Physiology, Faculty of Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan Province, China;[Meng, Fanying; Zhang, Xue; Dai, Jingjing] College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan Province, China
通讯机构:
[Long, Hongping] T;[Tian, Xuefei] K;The First Hospital of Hunan University of Chinese Medicine, Changsha, 410021, Hunan Province, China. Electronic address:;Key Laboratory of Traditional Chinese Medicine for Mechanism of Tumor Prevention &Treatment, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. Electronic address:
关键词:
Antitumor immunity;Gut microbiota;Hepatocellular carcinoma;Primary bile acid;Xiayuxue decoction
摘要:
ETHNOPHARMACOLOGICAL RELEVANCE: 'Xiayuxue decoction' (XYXD) is a traditional Chinese medicine compound, composing of three natural medicines: Rheum officinale Baill., Prunus persica (L.) Batsch and Eupolyphaga sinensis Walker. It is derived from the famous traditional Chinese medical classics 'Jingui Yaolue' and has been used for thousands of years. In the Guidelines for the Diagnosis and Treatment of Primary liver Cancer issued by China's Health Commission, XYXD was applied in the treatment of primary liver cancer. AIM OF THE STUDY: To clarify the pharmacodynamic material basis and mechanism of XYXD in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Firstly, the active components of XYXD and its distribution in vivo were identified by Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the effective components and mechanism of XYXD against HCC were explored by network pharmacology combined with cell experiments in vitro. Furthermore, the anti-HCC effect of XYXD was determined by animal experiments in vivo. Metagenomic sequencing was used to detect its effect in gut microbiota, and targeted metabolism was used to detect the changes of bile acids in the liver. Finally, the related targets of NKT cell immune function activation were detected by RT-qPCR and Elisa. RESULTS: A total of 113 active ingredients in XYXD were identified, and the distribution of active ingredients in blood, liver, tumor, cecum, intestinal contents and feces was clarified. The circulation process and active ingredient group of XYXD were preliminarily clarified. In addition, we found five anti-HCC active ingredients in XYXD through network pharmacology combined with cell experiments in vitro, among which aloe emodin had the most significant effect, and predicted the potential mechanism of XYXD against HCC through NKT cell pathway. Moreover, the inhibitory effect of XYXD on liver tumor growth was clarified by animal experiments in vivo. The mechanism was mainly to promote the production of bile salt hydrolase (BSH) by increasing the abundance of Bacteroides and Lactobacillus, BSH converts conjugated bile acids into primary bile acids, and reduces the conversion of primary bile acids to secondary bile acids by reducing the abundance of Eubacterium, thereby increasing the content of primary bile acids. Primary bile acids trigger NKT cells in the liver to produce interferon-γ to exert anti-HCC immune effects. CONCLUSION: This study found that the traditional Chinese herbal formula XYXD can trigger the immune effect of NKT cells against HCC by regulating the interaction between gut microbiota and bile acids.
作者机构:
[Zibing Zhu; Yisi Tan; Jin Tan; Keke Zhu] Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China;[Chengyong Liu; Yetong Wang; Han Zhou; Xuan Zhu] Hunan University of Traditional Chinese Medicine, Changsha, China;[Rong Zhou] Changsha Hospital for Maternal and Child Health Care, Changsha, China;[Zhengrui Li] College of Stomatology, Shanghai Jiao Tong University, Shanghai, China;[Xufeng Huang] Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
通讯机构:
[Keke Zhu] D;Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China
摘要:
While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear. This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk. MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167–1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007–1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005–1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147–1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139–1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation. This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.
作者机构:
湖南中医药大学中西医结合学院;湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室;湖南中医药大学中医学院;[吴琴; 蔡昱哲; 陈静; 罗政; 张亚男; 阳晶晶; 刘艺璇] School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China, Hunan Province Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[李定祥] School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
通讯机构:
[Deng, Y.] H;Hunan Province Key Laboratory of Cerebrovascular Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine, China
摘要:
Objective:To investigate the mechanism of Xumingtang in Gu Jin Lu Yan(《古今录验》)in regulating cell pyroptosis through the hypoxia-inducible factor-1α(HIF-1α)/NOD-like receptor pyrin domaincontaining protein 3(NLRP3)pathway in ischemic stroke(IS).Method:SD rats were randoml...MORE Objective:To investigate the mechanism of Xumingtang in Gu Jin Lu Yan(《古今录验》)in regulating cell pyroptosis through the hypoxia-inducible factor-1α(HIF-1α)/NOD-like receptor pyrin domaincontaining protein 3(NLRP3)pathway in ischemic stroke(IS).Method:SD rats were randomly divided into a sham operation group,a model group,low-and high-dose Xumingtang groups,and a metformin group,with 20 rats in each group.Oral administration was performed for 3 days,and tissue samples were collected.Differential messenger RNA(mRNA)was screened using high-throughput sequencing,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on key differentially expressed genes.The modified neurological severity score(mNSS)and 2,3,5-triphenyltetrazolium chloride(TTC)staining were used to evaluate the effect of brain infarction.Hematoxylin-eosin(HE)staining was used for pathological morphological observation of brain tissue.Enzyme-linked immunosorbent assay(ELISA)was used to compare the levels of interleukin-1β(IL-1β)and interleukin-18(IL-18)in the ischemic cortical region.Double staining immunohistochemistry was used to detect the co-localization of HIF-1αand NLRP3.Real-time quantitative polymerase chain reaction(PCR)was performed to detect the mRNA expression of NLRP3,HIF-1α,Caspase-1(CASP-1),and gasdermin D(GSDMD).Western blot was used to detect the protein expression of HIF-1α,NLRP3,CASP-1,and GSDMD.Result:A total of 5705 differentially expressed genes(2733 downregulated and 2972 upregulated)were obtained by mRNA sequencing.After conversion to homologous genes and intersection with the pyroptosis gene set,95 key differentially expressed pyroptosis genes were obtained.Compared with the sham operation group,the model group showed significantly increased mNSS scores,larger brain infarction areas(P<0.01),diverse neuronal morphology,disordered arrangement,widened cell gaps,significantly increased levels of IL-1βand IL-18 in the ischemic cortical region(P<0.01),enhanced co-localization fluorescence intensity,and significantly increased mRNA and protein expression levels of HIF-1α,NLRP3,CASP-1,and GSDMD(P<0.01).Compared with the model group,the high-dose Xumingtang group showed the most significant improvement in neurological function scores and brain infarction areas(P<0.01).The neuronal integrity and arrangement were more complete,and the cell gaps were narrower in all groups with drug treatment,with significantly reduced co-localization fluorescence intensity.Xumingtang could reduce the levels of IL-1β,IL-18,and the mRNA and protein expression of HIF-1α,NLRP3,CASP-1,and GSDMD(P<0.05,P<0.01),with the high-dose Xumingtang group showing the most significant effect(P<0.01).Conclusion:Xumingtang in Gu Jin Lu Yan can inhibit cell pyroptosis and promote neurological function recovery after IS,which may be related to the inhibition of the HIF-1α/NLRP3 pathway.FEWER
作者机构:
[谢晨磊; 王宇萌; 洪恺祺; 陈丽; 丁雅容] Medical College of Hunan University of Chinese Medicine, Changsha, 410208, China;[袁忠行; 王巍; 周忠志] The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China