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

Fan W, Zhai F, Yuan Z, Hu G, Wang L
2025 · W7058210044
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Xuanyu Tongjing Decoction down-regulates the NOD/NFκB pathway in ectopic tissues, reducing inflammation and ovarian damage in rats with ovarian endometriosis.

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This study investigated the therapeutic mechanisms of Xuanyu Tongjing Decoction in a rat model of ovarian endometriosis using transcriptome sequencing and molecular docking techniques. The researchers found that the decoction down-regulates the NOD/NFκB inflammatory pathway in ectopic tissues, thereby reducing the expression of pro-inflammatory factors like TNF-α and IL-1β while alleviating associated ovarian damage. Additionally, the treatment helped restore cAMP/PI3K/AKT signaling and modulate apoptotic and stress-related proteins in the ovary, with β-Hederin, Proanthocyanidin A2, and Cimiside E identified as potential active components targeting this pathway. This paper is centrally about endometriosis — specifically the pharmacological intervention of ovarian endometriosis lesions to reduce inflammation and tissue damage.

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Abstract

Weisen Fan,1 Fengting Zhai,2 Zheng Yuan,2 Guotao Hu,1 Li Wang2 1Department of Gynecology, Guang ‘anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250013, People’s Republic of ChinaCorrespondence: Fengting Zhai, Email [email protected]: 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.Keywords: ovarian endometriosis, inflammation, ovarian damage, pharmacology of traditional Chinese medicine
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Drug Design, Development and Therapy (Apr 2025) The Mechanism of Xuanyu Tongjing Decoction Regulating NOD/NFκB Pathway to Inhibit Ectopic Tissue Inflammation to Reduce Ovarian Damage in Rats with Ovarian Endometriosis Abstract Weisen Fan,1 Fengting Zhai,2 Zheng Yuan,2 Guotao Hu,1 Li Wang2 1Department of Gynecology, Guang ‘anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250013, People’s Republic of ChinaCorrespondence: Fengting Zhai, Email [email protected]: 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.Keywords: ovarian endometriosis, inflammation, ovarian damage, pharmacology of traditional Chinese medicine

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