Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway
Background: Gegen Qinlian decoction (GGQLD) is a typical traditional Chinese medicine (TCM) prescription documented in Shang Han Lun. Clinically, GGQLD has been utilized to manage the inflammatory symptoms of metabolic diseases and to protect against renal damage in China. In the present study, a hy...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.665398/full |
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| author | Xiao-Jun Wang Xiao-Jun Wang Yi-Ding Qi Hao-Chen Guan Hua-Gang Lin Pei-Qing He Kang-Wei Guan Lei Fu Mao-Qing Ye Mao-Qing Ye Jing Xiao Jing Xiao Tao Wu Tao Wu |
| author_facet | Xiao-Jun Wang Xiao-Jun Wang Yi-Ding Qi Hao-Chen Guan Hua-Gang Lin Pei-Qing He Kang-Wei Guan Lei Fu Mao-Qing Ye Mao-Qing Ye Jing Xiao Jing Xiao Tao Wu Tao Wu |
| author_sort | Xiao-Jun Wang |
| collection | DOAJ |
| description | Background: Gegen Qinlian decoction (GGQLD) is a typical traditional Chinese medicine (TCM) prescription documented in Shang Han Lun. Clinically, GGQLD has been utilized to manage the inflammatory symptoms of metabolic diseases and to protect against renal damage in China. In the present study, a hypothesis was proposed that the multi-target solution of GGQLD produced anti-inflammatory effects on ameliorating hyperuricemia (HUA).Methods: A total of 30 primary HUA patients receiving GGQLD treatment (two doses daily) for 4 weeks were selected. Then, differences in uric acid (UA) levels and expression of peripheral blood mononuclear cells (PBMCs) and urinary exosomes before and after treatment were analyzed. The therapeutic indexes for the active ingredients in GGQLD against HUA were confirmed through pharmacological subnetwork analysis. Besides, the HUA rat model was established through oral gavage of potassium oxonate and treated with oral GGQLD. In addition, proximal tubular epithelial cells (PTECs) were stimulated by UA and intervened with GGQLD for 48 h. Subsequently, RNA-seq, flow cytometry, and confocal immunofluorescence microscopy were further conducted to characterize the differences in UA-mediated inflammation and apoptosis of human renal tubular epithelial cells pre- and post-administration of GGQLD. In the meanwhile, quantitative real-time PCR (qPCR) was carried out to determine gene expression, whereas a western blotting (WB) assay was conducted to measure protein expression.Results: Our network analysis revealed that GGQLD treated HUA via the anti-inflammatory and antiapoptotic pathways. Additionally, NLPR3 expression significantly decreased in PBMCs and urinary exosomes of HUA patients after GGQLD treatment. In vivo, GGQLD treatment alleviated HUA-induced renal inflammation, which was associated with decreased expression of NLRP3 inflammasomes and apoptosis-related mRNAs. Moreover, GGQLD promoted renal UA excretion by inhibiting the activation of GSDMD-dependent pyroptosis induced by NLRP3 inflammasomes and by reducing apoptosis via the mitochondrial apoptosis signaling pathway in vitro.Conclusion: This study indicates that GGQLD efficiently reduces inflammatory responses while promoting UA excretion in HUA. Our findings also provide compelling evidence supporting the idea that GGQLD protects against the UA-mediated renal tubular epithelial cell inflammation through the mitochondrial apoptosis signaling pathways. Taken together, these findings have demonstrated a novel therapeutic method for the treatment of HUA. |
| first_indexed | 2024-12-21T22:35:15Z |
| format | Article |
| id | doaj.art-dfcc61dc96c9415ab53cfd29d70c7424 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T22:35:15Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-dfcc61dc96c9415ab53cfd29d70c74242022-12-21T18:47:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.665398665398Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling PathwayXiao-Jun Wang0Xiao-Jun Wang1Yi-Ding Qi2Hao-Chen Guan3Hua-Gang Lin4Pei-Qing He5Kang-Wei Guan6Lei Fu7Mao-Qing Ye8Mao-Qing Ye9Jing Xiao10Jing Xiao11Tao Wu12Tao Wu13Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaShanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaBackground: Gegen Qinlian decoction (GGQLD) is a typical traditional Chinese medicine (TCM) prescription documented in Shang Han Lun. Clinically, GGQLD has been utilized to manage the inflammatory symptoms of metabolic diseases and to protect against renal damage in China. In the present study, a hypothesis was proposed that the multi-target solution of GGQLD produced anti-inflammatory effects on ameliorating hyperuricemia (HUA).Methods: A total of 30 primary HUA patients receiving GGQLD treatment (two doses daily) for 4 weeks were selected. Then, differences in uric acid (UA) levels and expression of peripheral blood mononuclear cells (PBMCs) and urinary exosomes before and after treatment were analyzed. The therapeutic indexes for the active ingredients in GGQLD against HUA were confirmed through pharmacological subnetwork analysis. Besides, the HUA rat model was established through oral gavage of potassium oxonate and treated with oral GGQLD. In addition, proximal tubular epithelial cells (PTECs) were stimulated by UA and intervened with GGQLD for 48 h. Subsequently, RNA-seq, flow cytometry, and confocal immunofluorescence microscopy were further conducted to characterize the differences in UA-mediated inflammation and apoptosis of human renal tubular epithelial cells pre- and post-administration of GGQLD. In the meanwhile, quantitative real-time PCR (qPCR) was carried out to determine gene expression, whereas a western blotting (WB) assay was conducted to measure protein expression.Results: Our network analysis revealed that GGQLD treated HUA via the anti-inflammatory and antiapoptotic pathways. Additionally, NLPR3 expression significantly decreased in PBMCs and urinary exosomes of HUA patients after GGQLD treatment. In vivo, GGQLD treatment alleviated HUA-induced renal inflammation, which was associated with decreased expression of NLRP3 inflammasomes and apoptosis-related mRNAs. Moreover, GGQLD promoted renal UA excretion by inhibiting the activation of GSDMD-dependent pyroptosis induced by NLRP3 inflammasomes and by reducing apoptosis via the mitochondrial apoptosis signaling pathway in vitro.Conclusion: This study indicates that GGQLD efficiently reduces inflammatory responses while promoting UA excretion in HUA. Our findings also provide compelling evidence supporting the idea that GGQLD protects against the UA-mediated renal tubular epithelial cell inflammation through the mitochondrial apoptosis signaling pathways. Taken together, these findings have demonstrated a novel therapeutic method for the treatment of HUA.https://www.frontiersin.org/articles/10.3389/fphar.2021.665398/fullGegen Qinlian decoctionhyperuricemiaNLRP3apoptosispharmacological network analysis |
| spellingShingle | Xiao-Jun Wang Xiao-Jun Wang Yi-Ding Qi Hao-Chen Guan Hua-Gang Lin Pei-Qing He Kang-Wei Guan Lei Fu Mao-Qing Ye Mao-Qing Ye Jing Xiao Jing Xiao Tao Wu Tao Wu Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway Frontiers in Pharmacology Gegen Qinlian decoction hyperuricemia NLRP3 apoptosis pharmacological network analysis |
| title | Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway |
| title_full | Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway |
| title_fullStr | Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway |
| title_full_unstemmed | Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway |
| title_short | Gegen Qinlian Decoction Ameliorates Hyperuricemia-Induced Renal Tubular Injury via Blocking the Inflammatory Signaling Pathway |
| title_sort | gegen qinlian decoction ameliorates hyperuricemia induced renal tubular injury via blocking the inflammatory signaling pathway |
| topic | Gegen Qinlian decoction hyperuricemia NLRP3 apoptosis pharmacological network analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.665398/full |
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