Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathway

ObjectiveTo evaluate the therapeutic efficacy of Shanling Jiangzhi Tea (SLJZ) on hyperuricemia (HUA) mice and to investigate its mechanism.MethodsA HUA mouse model was established using a combination of uric acid (UA)and potassium oxonate. Following SLJZ intervention, changes in body weight were mon...

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Main Authors: Hao-nan Chen, He-zhen Wu, Yan-fang Yang
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.2025.1623111/full
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author Hao-nan Chen
Hao-nan Chen
He-zhen Wu
He-zhen Wu
He-zhen Wu
Yan-fang Yang
Yan-fang Yang
Yan-fang Yang
author_facet Hao-nan Chen
Hao-nan Chen
He-zhen Wu
He-zhen Wu
He-zhen Wu
Yan-fang Yang
Yan-fang Yang
Yan-fang Yang
author_sort Hao-nan Chen
collection DOAJ
description ObjectiveTo evaluate the therapeutic efficacy of Shanling Jiangzhi Tea (SLJZ) on hyperuricemia (HUA) mice and to investigate its mechanism.MethodsA HUA mouse model was established using a combination of uric acid (UA)and potassium oxonate. Following SLJZ intervention, changes in body weight were monitored. Renal lesions and renal fibrosis were assessed via H&E staining and Masson trichrome staining. Serum levels of UA, creatinine (Cr), blood urea nitrogen (BUN), and xanthine oxidase (XOD) were measured to evaluate the UA-lowering effects of SLJZ. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to identify the bioactive components of SLJZ that entered the bloodstream. Network pharmacology, molecular docking, and transcriptomics analyses were conducted to elucidate the key targets and signaling pathways involved in SLJZ’s therapeutic effects on HUA. Protein expression levels were further validated using immunohistochemistry.ResultsSLJZ significantly reduces the levels of UA, Cr, BUN, and XOD in the blood of HUA mice, alleviates inflammatory cell infiltration, attenuates renal interstitial fibrosis, and demonstrates therapeutic potential for hyperuricemia. RNA-seq analysis reveals that SLJZ reverses 280 HUA-induced differentially expressed genes (DEGs) in the kidneys. Based on the findings from network pharmacology and molecular docking analyses, SERPINE1, p53, NLRP3, COMT, and MAOA are identified as potential key proteins involved in SLJZ’s treatment of HUA. Kit-based assays indicate that SLJZ increases dopamine (DA) levels in the kidneys of mice while reducing the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Immunohistochemical results confirm that SERPINE1, p53, NLRP3, COMT, and MAOA are significantly upregulated in the kidneys of HUA model mice, but their expression is normalized following SLJZ intervention.ConclusionSLJZ exhibits a significant anti-HUA effect by inhibiting the COMT/MAOA signaling pathway and the p53/SERPINE1/NLRP3 signaling pathway. Through these mechanisms, SLJZ is involved in the DA metabolic process, modulates the inflammatory response mediated by the SERPINE1 fibrinolytic system, alleviates renal tubulointerstitial fibrosis, and mitigates oxidative stress, thereby exerting therapeutic effects on HUA.
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spelling doaj-art-adb7d898519b4a32abf4a483d59daa732025-08-20T02:35:57ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-07-011610.3389/fendo.2025.16231111623111Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathwayHao-nan Chen0Hao-nan Chen1He-zhen Wu2He-zhen Wu3He-zhen Wu4Yan-fang Yang5Yan-fang Yang6Yan-fang Yang7Hubei Key Laboratory of Chinese Medicine Resources and Chinese Medicine Chemistry, School of Pharmacy, Hubei University of Traditional Chinese Medicine, Wuhan, Hubei, ChinaHubei Engineering Research Center of Modern Chinese and Ethnic Medicine, Wuhan, Hubei, ChinaHubei Key Laboratory of Chinese Medicine Resources and Chinese Medicine Chemistry, School of Pharmacy, Hubei University of Traditional Chinese Medicine, Wuhan, Hubei, ChinaHubei Engineering Research Center of Modern Chinese and Ethnic Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaHubei Key Laboratory of Chinese Medicine Resources and Chinese Medicine Chemistry, School of Pharmacy, Hubei University of Traditional Chinese Medicine, Wuhan, Hubei, ChinaHubei Engineering Research Center of Modern Chinese and Ethnic Medicine, Wuhan, Hubei, ChinaHubei Shizhen Laboratory, Wuhan, Hubei, ChinaObjectiveTo evaluate the therapeutic efficacy of Shanling Jiangzhi Tea (SLJZ) on hyperuricemia (HUA) mice and to investigate its mechanism.MethodsA HUA mouse model was established using a combination of uric acid (UA)and potassium oxonate. Following SLJZ intervention, changes in body weight were monitored. Renal lesions and renal fibrosis were assessed via H&E staining and Masson trichrome staining. Serum levels of UA, creatinine (Cr), blood urea nitrogen (BUN), and xanthine oxidase (XOD) were measured to evaluate the UA-lowering effects of SLJZ. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to identify the bioactive components of SLJZ that entered the bloodstream. Network pharmacology, molecular docking, and transcriptomics analyses were conducted to elucidate the key targets and signaling pathways involved in SLJZ’s therapeutic effects on HUA. Protein expression levels were further validated using immunohistochemistry.ResultsSLJZ significantly reduces the levels of UA, Cr, BUN, and XOD in the blood of HUA mice, alleviates inflammatory cell infiltration, attenuates renal interstitial fibrosis, and demonstrates therapeutic potential for hyperuricemia. RNA-seq analysis reveals that SLJZ reverses 280 HUA-induced differentially expressed genes (DEGs) in the kidneys. Based on the findings from network pharmacology and molecular docking analyses, SERPINE1, p53, NLRP3, COMT, and MAOA are identified as potential key proteins involved in SLJZ’s treatment of HUA. Kit-based assays indicate that SLJZ increases dopamine (DA) levels in the kidneys of mice while reducing the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Immunohistochemical results confirm that SERPINE1, p53, NLRP3, COMT, and MAOA are significantly upregulated in the kidneys of HUA model mice, but their expression is normalized following SLJZ intervention.ConclusionSLJZ exhibits a significant anti-HUA effect by inhibiting the COMT/MAOA signaling pathway and the p53/SERPINE1/NLRP3 signaling pathway. Through these mechanisms, SLJZ is involved in the DA metabolic process, modulates the inflammatory response mediated by the SERPINE1 fibrinolytic system, alleviates renal tubulointerstitial fibrosis, and mitigates oxidative stress, thereby exerting therapeutic effects on HUA.https://www.frontiersin.org/articles/10.3389/fendo.2025.1623111/fullShanling Jiangzhi Teahyperuricemiatranscriptomicsnetwork pharmacologymechanism
spellingShingle Hao-nan Chen
Hao-nan Chen
He-zhen Wu
He-zhen Wu
He-zhen Wu
Yan-fang Yang
Yan-fang Yang
Yan-fang Yang
Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathway
Frontiers in Endocrinology
Shanling Jiangzhi Tea
hyperuricemia
transcriptomics
network pharmacology
mechanism
title Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathway
title_full Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathway
title_fullStr Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathway
title_full_unstemmed Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathway
title_short Shanling Jiangzhi Tea treats hyperuricemia by inhibition of COMT/MAOA signaling pathway and p53/SERPINE1/NLRP3 signaling pathway
title_sort shanling jiangzhi tea treats hyperuricemia by inhibition of comt maoa signaling pathway and p53 serpine1 nlrp3 signaling pathway
topic Shanling Jiangzhi Tea
hyperuricemia
transcriptomics
network pharmacology
mechanism
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1623111/full
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