Therapeutic effect and mechanism of gigantol on hyperuricemia

This study aimed to evaluate the therapeutic effects of gigantol on hyperuricemia (HUA) and investigate the underlying mechanism of HUA. A mouse model of HUA was made by gavage of potassium oxonate, and HK-2 and AML12 cell models were made by adenosine and xanthine oxidase (XOD) induction. We tested...

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Main Authors: Yuanfan Wu, Xia Sun, Yuhan Jia, Tianshu Gao, Jin Xu, Youqiao Qian, Naiqi Pei, Lilin Wang, Qiaohong Zheng, Honglei Li, Zhen Chen, Yijiao Liu, Yang Ma, Hui Chen, Yuanyuan Ye, Jiaxin Zhao, Yi Zhou, Xiaoqing Chen, Baosheng Huang, Yefeng Liu, Yin Zhu, Ning Xue, Juan Zhang, Guangfeng Ji, Xing Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1474808/full
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author Yuanfan Wu
Xia Sun
Yuhan Jia
Tianshu Gao
Jin Xu
Youqiao Qian
Naiqi Pei
Lilin Wang
Qiaohong Zheng
Honglei Li
Zhen Chen
Yijiao Liu
Yang Ma
Hui Chen
Yuanyuan Ye
Jiaxin Zhao
Yi Zhou
Xiaoqing Chen
Baosheng Huang
Yefeng Liu
Yin Zhu
Ning Xue
Juan Zhang
Guangfeng Ji
Xing Wang
author_facet Yuanfan Wu
Xia Sun
Yuhan Jia
Tianshu Gao
Jin Xu
Youqiao Qian
Naiqi Pei
Lilin Wang
Qiaohong Zheng
Honglei Li
Zhen Chen
Yijiao Liu
Yang Ma
Hui Chen
Yuanyuan Ye
Jiaxin Zhao
Yi Zhou
Xiaoqing Chen
Baosheng Huang
Yefeng Liu
Yin Zhu
Ning Xue
Juan Zhang
Guangfeng Ji
Xing Wang
author_sort Yuanfan Wu
collection DOAJ
description This study aimed to evaluate the therapeutic effects of gigantol on hyperuricemia (HUA) and investigate the underlying mechanism of HUA. A mouse model of HUA was made by gavage of potassium oxonate, and HK-2 and AML12 cell models were made by adenosine and xanthine oxidase (XOD) induction. We tested the levels of uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), cellular UA, and XOD activity. The levels of NOD-like receptor thermal protein domain 3 (NLRP3) and other inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA) kits. XOD is a protein related to the NLRP3 pathway and also serves as an UA transporter. We found that the levels of UA, CRE, and BUN increased in serum but decreased in urine in HUA model mice. After gigantol treatment, UA, CRE, and BUN levels in serum decreased, whereas their levels in urine increased. The levels of NLRP3 and interleukin-1β (IL-1β) were lower and the expression of NLRP3-related protein decreased after gigantol treatment. In conclusion, gigantol exhibits a therapeutic effect on HUA, and the mechanism may be related to inhibiting XOD activity to reduce UA production, regulating the expression of UA transporters to increase UA excretion, and inhibiting the activation of NLRP3 inflammatory signaling.
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spelling doaj-art-d1c9e7c6ea5b4bdcbac45d35c71740f52025-07-29T04:10:26ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.14748081474808Therapeutic effect and mechanism of gigantol on hyperuricemiaYuanfan Wu0Xia Sun1Yuhan Jia2Tianshu Gao3Jin Xu4Youqiao Qian5Naiqi Pei6Lilin Wang7Qiaohong Zheng8Honglei Li9Zhen Chen10Yijiao Liu11Yang Ma12Hui Chen13Yuanyuan Ye14Jiaxin Zhao15Yi Zhou16Xiaoqing Chen17Baosheng Huang18Yefeng Liu19Yin Zhu20Ning Xue21Juan Zhang22Guangfeng Ji23Xing Wang24Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Medicine, Ju Rong Hospital of Traditional Chinese Medicine, Zhenjiang, Jiangsu, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaDepartment of Nephrology, Jurong Hospital Affiliated to Jiangsu University, Jurong, ChinaCollege of Mudi Meng Honors, China Pharmaceutical University, Nanjing, ChinaSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaCollege of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaDepartment of Pharmacy, Kangda College of Nanjing Medical University, Lianyungang, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaCollege of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaDepartment of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China0Department of General Surgery, Jurong Hospital Affiliated to Jiangsu University, Jiangsu, Zhenjiang, China1Department of General, Jurong Hospital Affiliated to Jiangsu University, Jiangsu, Zhenjiang, China2Department of Acupuncture, Jurong Hospital Affiliated to Jiangsu University, Jiangsu, Zhenjiang, China3The Fourth Department of Psychiatry, Shandong Daizhuang Hospital, Shandong, Jining, China3The Fourth Department of Psychiatry, Shandong Daizhuang Hospital, Shandong, Jining, ChinaSchool of Pharmacy, China Pharmaceutical University, Nanjing, ChinaThis study aimed to evaluate the therapeutic effects of gigantol on hyperuricemia (HUA) and investigate the underlying mechanism of HUA. A mouse model of HUA was made by gavage of potassium oxonate, and HK-2 and AML12 cell models were made by adenosine and xanthine oxidase (XOD) induction. We tested the levels of uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), cellular UA, and XOD activity. The levels of NOD-like receptor thermal protein domain 3 (NLRP3) and other inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA) kits. XOD is a protein related to the NLRP3 pathway and also serves as an UA transporter. We found that the levels of UA, CRE, and BUN increased in serum but decreased in urine in HUA model mice. After gigantol treatment, UA, CRE, and BUN levels in serum decreased, whereas their levels in urine increased. The levels of NLRP3 and interleukin-1β (IL-1β) were lower and the expression of NLRP3-related protein decreased after gigantol treatment. In conclusion, gigantol exhibits a therapeutic effect on HUA, and the mechanism may be related to inhibiting XOD activity to reduce UA production, regulating the expression of UA transporters to increase UA excretion, and inhibiting the activation of NLRP3 inflammatory signaling.https://www.frontiersin.org/articles/10.3389/fendo.2025.1474808/fullgigantolHUAxanthine oxidase inhibitorUA transportersNLRP3
spellingShingle Yuanfan Wu
Xia Sun
Yuhan Jia
Tianshu Gao
Jin Xu
Youqiao Qian
Naiqi Pei
Lilin Wang
Qiaohong Zheng
Honglei Li
Zhen Chen
Yijiao Liu
Yang Ma
Hui Chen
Yuanyuan Ye
Jiaxin Zhao
Yi Zhou
Xiaoqing Chen
Baosheng Huang
Yefeng Liu
Yin Zhu
Ning Xue
Juan Zhang
Guangfeng Ji
Xing Wang
Therapeutic effect and mechanism of gigantol on hyperuricemia
Frontiers in Endocrinology
gigantol
HUA
xanthine oxidase inhibitor
UA transporters
NLRP3
title Therapeutic effect and mechanism of gigantol on hyperuricemia
title_full Therapeutic effect and mechanism of gigantol on hyperuricemia
title_fullStr Therapeutic effect and mechanism of gigantol on hyperuricemia
title_full_unstemmed Therapeutic effect and mechanism of gigantol on hyperuricemia
title_short Therapeutic effect and mechanism of gigantol on hyperuricemia
title_sort therapeutic effect and mechanism of gigantol on hyperuricemia
topic gigantol
HUA
xanthine oxidase inhibitor
UA transporters
NLRP3
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1474808/full
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