The Mechanism of Xuanyu Tongjing Decoction Regulating NOD/NFκB Pathway to Inhibit Ectopic Tissue Inflammation to Reduce Ovarian Damage in Rats with Ovarian Endometriosis.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-04-09 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S500129

Weisen Fan, Fengting Zhai, Zheng Yuan, Guotao Hu, Li Wang

{"title":"The Mechanism of Xuanyu Tongjing Decoction Regulating NOD/NFκB Pathway to Inhibit Ectopic Tissue Inflammation to Reduce Ovarian Damage in Rats with Ovarian Endometriosis.","authors":"Weisen Fan, Fengting Zhai, Zheng Yuan, Guotao Hu, Li Wang","doi":"10.2147/DDDT.S500129","DOIUrl":null,"url":null,"abstract":"Introduction: In traditional Chinese medicine texts, Xuanyu Tongjing Decoction (XYTJD) is a prescribed remedy for premenstrual belly pain and dysmenorrhea. It is currently routinely used to treat ovarian endometriosis (OEM) with good outcomes.Aim: In order to investigate the underlying processes of Xuanyu Tongjing Decoction in treating OEM inflammation and reducing ovarian damage.Methods: We created a rat model of OEM and carried out transcriptome sequencing. Batch molecular docking technique in conjunction with Ultra-high-performance liquid chromatography-quadrupole-time-of-flight-high-resolution mass spectrometry was used to screen the main active components in Xuanyu Tongjing Decoction.Results: The ectopic cyst was firmly attached to the ovary in our successfully created rat model of ovarian endometriosis. According to GSEA enrichment study, XYTJD may up-regulate pathways linked to oocyte formation in ovarian tissues and down-regulate immunological and inflammatory pathways in ectopic tissues. Rat ectopic tissues and human ectopic tissues showed a similar pattern in the expression of the NOD/NFκB pathway during the proliferative phase. In ectopic tissues of rats, XYTJD may down-regulate the NOD/NFκB pathway and suppress the expression of TNF-α and IL-1β, which are downstream inflammatory factors in this pathway. In addition, XYTJD may restore the down-regulation of cAMP/PI3K/AKT and lower the expression of apoptotic factor CASP9, endoplasmic reticulum stress protein SEC61B and antioxidant protein GSTM5 in the ovary with ectopic tissue attachment. Following identification, the three samples' intersection included 10 active compounds in total. There was a 21-component overlap in active ingredients between rat and human serum. After a preliminary virtual screening, β-Hederin, Proanthocyanidin A2, and Cimiside E were suggested to be the essential components that interfere with NOD/NFκB.Conclusion: In rats with proliferative OEM, XYTJD may down-regulate the NOD/NFκB pathway in ectopic tissues, consequently alleviating ovarian tissue damage by reducing inflammation brought on by ectopic tissues.","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"2717-2735"},"PeriodicalIF":4.7000,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994466/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S500129","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: In traditional Chinese medicine texts, Xuanyu Tongjing Decoction (XYTJD) is a prescribed remedy for premenstrual belly pain and dysmenorrhea. It is currently routinely used to treat ovarian endometriosis (OEM) with good outcomes.

Aim: In order to investigate the underlying processes of Xuanyu Tongjing Decoction in treating OEM inflammation and reducing ovarian damage.

Methods: We created a rat model of OEM and carried out transcriptome sequencing. Batch molecular docking technique in conjunction with Ultra-high-performance liquid chromatography-quadrupole-time-of-flight-high-resolution mass spectrometry was used to screen the main active components in Xuanyu Tongjing Decoction.

Results: The ectopic cyst was firmly attached to the ovary in our successfully created rat model of ovarian endometriosis. According to GSEA enrichment study, XYTJD may up-regulate pathways linked to oocyte formation in ovarian tissues and down-regulate immunological and inflammatory pathways in ectopic tissues. Rat ectopic tissues and human ectopic tissues showed a similar pattern in the expression of the NOD/NFκB pathway during the proliferative phase. In ectopic tissues of rats, XYTJD may down-regulate the NOD/NFκB pathway and suppress the expression of TNF-α and IL-1β, which are downstream inflammatory factors in this pathway. In addition, XYTJD may restore the down-regulation of cAMP/PI3K/AKT and lower the expression of apoptotic factor CASP9, endoplasmic reticulum stress protein SEC61B and antioxidant protein GSTM5 in the ovary with ectopic tissue attachment. Following identification, the three samples' intersection included 10 active compounds in total. There was a 21-component overlap in active ingredients between rat and human serum. After a preliminary virtual screening, β-Hederin, Proanthocyanidin A2, and Cimiside E were suggested to be the essential components that interfere with NOD/NFκB.

Conclusion: In rats with proliferative OEM, XYTJD may down-regulate the NOD/NFκB pathway in ectopic tissues, consequently alleviating ovarian tissue damage by reducing inflammation brought on by ectopic tissues.

查看原文本刊更多论文

玄育通经汤调节NOD/NFκB通路抑制异位组织炎症减轻卵巢内膜异位症大鼠卵巢损伤的机制

简介：在中医文献中，玄瘀通经汤是治疗经前腹痛和痛经的处方药。目前常规用于治疗卵巢子宫内膜异位症（OEM），效果良好。目的：探讨玄育通经汤治疗OEM炎症、减轻卵巢损伤的作用机制。方法：建立大鼠OEM模型，进行转录组测序。采用间歇分子对接技术结合超高效液相色谱-四极杆飞行时间高分辨率质谱技术对玄瘀通经汤中主要有效成分进行筛选。结果：成功建立卵巢子宫内膜异位症大鼠模型，异位囊肿与卵巢牢固附着。根据GSEA富集研究，XYTJD可能上调卵巢组织中与卵母细胞形成相关的通路，下调异位组织中的免疫和炎症通路。大鼠异位组织和人异位组织在增殖期NOD/NFκB通路的表达模式相似。在大鼠异位组织中，XYTJD可能下调NOD/NFκB通路，抑制该通路下游炎症因子TNF-α和IL-1β的表达。此外，XYTJD可恢复异位组织附着卵巢中cAMP/PI3K/AKT的下调，降低凋亡因子CASP9、内质网应激蛋白SEC61B、抗氧化蛋白GSTM5的表达。经鉴定，三种样品的交集共含有10种活性化合物。大鼠血清和人血清的活性成分有21个成分重叠。经过初步的虚拟筛选，β-Hederin，原花青素A2和Cimiside E被认为是干扰NOD/NFκB的重要成分。结论：在增殖性OEM大鼠中，XYTJD可能下调异位组织中NOD/NFκB通路，从而减轻异位组织引起的炎症，从而减轻卵巢组织损伤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.