The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway
Sonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperu...
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2021-08-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.698219/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu-Lin Wu Jin-Fen Chen Lin-Yun Jiang Xiao-Li Wu Yu-Hong Liu Chang-Jun Gao Chang-Jun Gao Yan Wu Xiao-Qing Yi Zi-Ren Su Jian Cai Jian Cai Jian-Nan Chen |
spellingShingle |
Yu-Lin Wu Jin-Fen Chen Lin-Yun Jiang Xiao-Li Wu Yu-Hong Liu Chang-Jun Gao Chang-Jun Gao Yan Wu Xiao-Qing Yi Zi-Ren Su Jian Cai Jian Cai Jian-Nan Chen The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway Frontiers in Pharmacology Sonneratia apetala leaves and branches hyperuricemia renal uric acid transporters oxidative stress JAK/STAT pathway |
author_facet |
Yu-Lin Wu Jin-Fen Chen Lin-Yun Jiang Xiao-Li Wu Yu-Hong Liu Chang-Jun Gao Chang-Jun Gao Yan Wu Xiao-Qing Yi Zi-Ren Su Jian Cai Jian Cai Jian-Nan Chen |
author_sort |
Yu-Lin Wu |
title |
The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway |
title_short |
The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway |
title_full |
The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway |
title_fullStr |
The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway |
title_full_unstemmed |
The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway |
title_sort |
extract of sonneratia apetala leaves and branches ameliorates hyperuricemia in mice by regulating renal uric acid transporters and suppressing the activation of the jak/stat signaling pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-08-01 |
description |
Sonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in renal levels of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), and transforming growth factor-β (TGF-β). SAL remarkably reduced suppressor of cytokine signaling 3 (SOCS3), Janus kinase 2 (JAK2), and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) expression. In addition, SAL inhibited the activation of nuclear factor kappa-B (NF-κB) in the kidney. Furthermore, SAL protected against HUA by regulating renal UA transporters of organic anion transporter (OAT1), urate reabsorption transporter 1 (URAT1), and glucose transporter 9 (GLUT9). These findings suggested that SAL ameliorated HUA by inhibiting the production of uric acid and enhancing renal urate excretion, which are related to oxidative stress and inflammation, and the possible molecular mechanisms include its ability to inhibit the JAK/STAT signaling pathway. Thus, SAL might be developed into a promising agent for HUA treatments. |
topic |
Sonneratia apetala leaves and branches hyperuricemia renal uric acid transporters oxidative stress JAK/STAT pathway |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.698219/full |
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doaj-2694b4012578444ca39a5d60dac0532c2021-08-16T04:54:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.698219698219The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling PathwayYu-Lin Wu0Jin-Fen Chen1Lin-Yun Jiang2Xiao-Li Wu3Yu-Hong Liu4Chang-Jun Gao5Chang-Jun Gao6Yan Wu7Xiao-Qing Yi8Zi-Ren Su9Jian Cai10Jian Cai11Jian-Nan Chen12Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Academy of Forestry, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Silviculture, Protection and Utilization, Guangzhou, ChinaGuangdong Academy of Forestry, Guangzhou, ChinaGuangdong Academy of Forestry, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Academy of Forestry, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Silviculture, Protection and Utilization, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in renal levels of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), and transforming growth factor-β (TGF-β). SAL remarkably reduced suppressor of cytokine signaling 3 (SOCS3), Janus kinase 2 (JAK2), and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) expression. In addition, SAL inhibited the activation of nuclear factor kappa-B (NF-κB) in the kidney. Furthermore, SAL protected against HUA by regulating renal UA transporters of organic anion transporter (OAT1), urate reabsorption transporter 1 (URAT1), and glucose transporter 9 (GLUT9). These findings suggested that SAL ameliorated HUA by inhibiting the production of uric acid and enhancing renal urate excretion, which are related to oxidative stress and inflammation, and the possible molecular mechanisms include its ability to inhibit the JAK/STAT signaling pathway. Thus, SAL might be developed into a promising agent for HUA treatments.https://www.frontiersin.org/articles/10.3389/fphar.2021.698219/fullSonneratia apetala leaves and brancheshyperuricemiarenal uric acid transportersoxidative stressJAK/STAT pathway |