Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment
This study explored the possible connection between the insulin resistance-targeting protein adipokine lipocalin-2 (LCN-2) and NF-κB signaling pathway in the inflammatory microenvironment in PCOS-IR model rats to determine the pharmacological mechanism of modified Cangfu Daotan decoction (MCDD) inte...
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Format: | Article |
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Frontiers Media S.A.
2022-11-01
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Series: | Frontiers in Endocrinology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.975724/full |
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author | Shuowen Liu Yao Zhang Fang Yang Jingna Gu Ruyue Zhang Yingying Kuang Wantong Mai Chengbo Zheng Yang Yu Ruling Lu Lei Zeng Hongying Cao Yongling Long |
author_facet | Shuowen Liu Yao Zhang Fang Yang Jingna Gu Ruyue Zhang Yingying Kuang Wantong Mai Chengbo Zheng Yang Yu Ruling Lu Lei Zeng Hongying Cao Yongling Long |
author_sort | Shuowen Liu |
collection | DOAJ |
description | This study explored the possible connection between the insulin resistance-targeting protein adipokine lipocalin-2 (LCN-2) and NF-κB signaling pathway in the inflammatory microenvironment in PCOS-IR model rats to determine the pharmacological mechanism of modified Cangfu Daotan decoction (MCDD) intervention for PCOS-IR. We used a high-fat diet (42 days) combined with letrozole (1 mg/kg/day, 42 days) to establish a PCOS-IR rat model. From the third week after modeling, the rats were given continuous administration of MCDD (high dose with 31.68 g/kg, medium dose with 15.84 g/kg, and low dose with 7.92 g/kg) for 28 days. Serum, ovarian tissue, liver, and adipose tissue were collected after the last gavage. Enzyme-linked immunosorbent assay, hematoxylin-eosin (HE) staining, Masson staining, qRT-PCR, and Western blot experiments were performed to detect various indicators. Our results showed that MCDD could reduce body weight and abdominal fat weight; restore normal estrous cycle and ovarian function; alleviate fatty liver; regulate HOMA-IR and OGTT index; reduce serum inflammatory factor levels, LCN-2 level, and gene expression; and regulate the insulin signal transduction and NF-κB pathways in PCOS-IR rats. Thus, MCDD may play a role in improving ovarian function in PCOS-IR rats by downregulating NF-κB/LCN-2 proteins and upregulating the gene expression of Insr/Irs-1/Glut4 in the insulin signaling pathway in the inflammatory environment. |
first_indexed | 2024-04-12T10:39:59Z |
format | Article |
id | doaj.art-12ca982d72e04ab9bee481b89e079c44 |
institution | Directory Open Access Journal |
issn | 1664-2392 |
language | English |
last_indexed | 2024-04-12T10:39:59Z |
publishDate | 2022-11-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Endocrinology |
spelling | doaj.art-12ca982d72e04ab9bee481b89e079c442022-12-22T03:36:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-11-011310.3389/fendo.2022.975724975724Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironmentShuowen Liu0Yao Zhang1Fang Yang2Jingna Gu3Ruyue Zhang4Yingying Kuang5Wantong Mai6Chengbo Zheng7Yang Yu8Ruling Lu9Lei Zeng10Hongying Cao11Yongling Long12School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Gynecology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Gynecology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThis study explored the possible connection between the insulin resistance-targeting protein adipokine lipocalin-2 (LCN-2) and NF-κB signaling pathway in the inflammatory microenvironment in PCOS-IR model rats to determine the pharmacological mechanism of modified Cangfu Daotan decoction (MCDD) intervention for PCOS-IR. We used a high-fat diet (42 days) combined with letrozole (1 mg/kg/day, 42 days) to establish a PCOS-IR rat model. From the third week after modeling, the rats were given continuous administration of MCDD (high dose with 31.68 g/kg, medium dose with 15.84 g/kg, and low dose with 7.92 g/kg) for 28 days. Serum, ovarian tissue, liver, and adipose tissue were collected after the last gavage. Enzyme-linked immunosorbent assay, hematoxylin-eosin (HE) staining, Masson staining, qRT-PCR, and Western blot experiments were performed to detect various indicators. Our results showed that MCDD could reduce body weight and abdominal fat weight; restore normal estrous cycle and ovarian function; alleviate fatty liver; regulate HOMA-IR and OGTT index; reduce serum inflammatory factor levels, LCN-2 level, and gene expression; and regulate the insulin signal transduction and NF-κB pathways in PCOS-IR rats. Thus, MCDD may play a role in improving ovarian function in PCOS-IR rats by downregulating NF-κB/LCN-2 proteins and upregulating the gene expression of Insr/Irs-1/Glut4 in the insulin signaling pathway in the inflammatory environment.https://www.frontiersin.org/articles/10.3389/fendo.2022.975724/fullLcn-2NF-kB signaling pathwayINSR/IRS-1/GLUT4PCOS-IRModified Cangfu Daotan decoction |
spellingShingle | Shuowen Liu Yao Zhang Fang Yang Jingna Gu Ruyue Zhang Yingying Kuang Wantong Mai Chengbo Zheng Yang Yu Ruling Lu Lei Zeng Hongying Cao Yongling Long Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment Frontiers in Endocrinology Lcn-2 NF-kB signaling pathway INSR/IRS-1/GLUT4 PCOS-IR Modified Cangfu Daotan decoction |
title | Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment |
title_full | Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment |
title_fullStr | Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment |
title_full_unstemmed | Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment |
title_short | Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment |
title_sort | modified cangfu daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via nf κb lcn 2 signaling pathway in inflammatory microenvironment |
topic | Lcn-2 NF-kB signaling pathway INSR/IRS-1/GLUT4 PCOS-IR Modified Cangfu Daotan decoction |
url | https://www.frontiersin.org/articles/10.3389/fendo.2022.975724/full |
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