Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice
Phellodendri Chinese Cortex has long been used to treat hyperuricemia and gout. Berberine (BBR), its characteristic ingredient, has also been shown to be effective in alleviating monosodium urate crystals-triggered gout inflammation in vitro and in vivo. Dihydroberberine (DHB) is a hydrogenated deri...
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Frontiers Media S.A.
2021-04-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.645879/full |
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| author | Lieqiang Xu Guoshu Lin Qiuxia Yu Qiuxia Yu Qiaoping Li Liting Mai Juanjuan Cheng Jianhui Xie Jianhui Xie Yuhong Liu Ziren Su Yucui Li |
| author_facet | Lieqiang Xu Guoshu Lin Qiuxia Yu Qiuxia Yu Qiaoping Li Liting Mai Juanjuan Cheng Jianhui Xie Jianhui Xie Yuhong Liu Ziren Su Yucui Li |
| author_sort | Lieqiang Xu |
| collection | DOAJ |
| description | Phellodendri Chinese Cortex has long been used to treat hyperuricemia and gout. Berberine (BBR), its characteristic ingredient, has also been shown to be effective in alleviating monosodium urate crystals-triggered gout inflammation in vitro and in vivo. Dihydroberberine (DHB) is a hydrogenated derivative of BBR that showed improved in vivo efficacy on many metabolic disorders. However, its anti-hyperuricemia effect remains underexplored. In the present work, the hypouricemic and renoprotective effects of DHB on hyperuricemic mice were investigated. The hyperuricemic mice model was induced by intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) combined with intragastric administration of hypoxanthine (HX, 300 mg/kg) for 7 days. Different dosages of DHB (25, 50 mg/kg), BBR (50 mg/kg) or febuxostat (Feb, 5 mg/kg) were orally given to mice 1 h after modeling. The molecular docking results showed that DHB effectively inhibited xanthine oxidase (XOD) by binding with its active site. In vitro, DHB exhibited significant XOD inhibitory activity (IC50 value, 34.37 μM). The in vivo results showed that DHB had obvious hypouricemic and renoprotective effects in hyperuricemic mice. It could not only lower the uric acid and XOD levels in serum, but also suppress the activities of XOD and adenosine deaminase (ADA) in the liver. Furthermore, DHB noticeably down-regulated the renal mRNA and protein expression of XOD. Besides, DHB remarkably and dose-dependently ameliorated renal damage, as evidenced by considerably reducing serum creatinine and blood urea nitrogen (BUN) levels, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-18) levels and restoring kidney histological deteriorations. Further mechanistic investigation showed that DHB distinctly down-regulated renal mRNA and protein levels of URAT1, GLUT9, NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), caspase-1 and IL-1β. Our study revealed that DHB had outstanding hypouricemic and renoprotective effects via suppressing XOD, URAT1, GLUT9 and NLRP3 inflammasome activation in the kidney. |
| first_indexed | 2024-12-14T22:22:49Z |
| format | Article |
| id | doaj.art-0a1331cab5004e35a835ee7ea6f28851 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T22:22:49Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-0a1331cab5004e35a835ee7ea6f288512022-12-21T22:45:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.645879645879Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic MiceLieqiang Xu0Guoshu Lin1Qiuxia Yu2Qiuxia Yu3Qiaoping Li4Liting Mai5Juanjuan Cheng6Jianhui Xie7Jianhui Xie8Yuhong Liu9Ziren Su10Yucui Li11School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, ChinaPhellodendri Chinese Cortex has long been used to treat hyperuricemia and gout. Berberine (BBR), its characteristic ingredient, has also been shown to be effective in alleviating monosodium urate crystals-triggered gout inflammation in vitro and in vivo. Dihydroberberine (DHB) is a hydrogenated derivative of BBR that showed improved in vivo efficacy on many metabolic disorders. However, its anti-hyperuricemia effect remains underexplored. In the present work, the hypouricemic and renoprotective effects of DHB on hyperuricemic mice were investigated. The hyperuricemic mice model was induced by intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) combined with intragastric administration of hypoxanthine (HX, 300 mg/kg) for 7 days. Different dosages of DHB (25, 50 mg/kg), BBR (50 mg/kg) or febuxostat (Feb, 5 mg/kg) were orally given to mice 1 h after modeling. The molecular docking results showed that DHB effectively inhibited xanthine oxidase (XOD) by binding with its active site. In vitro, DHB exhibited significant XOD inhibitory activity (IC50 value, 34.37 μM). The in vivo results showed that DHB had obvious hypouricemic and renoprotective effects in hyperuricemic mice. It could not only lower the uric acid and XOD levels in serum, but also suppress the activities of XOD and adenosine deaminase (ADA) in the liver. Furthermore, DHB noticeably down-regulated the renal mRNA and protein expression of XOD. Besides, DHB remarkably and dose-dependently ameliorated renal damage, as evidenced by considerably reducing serum creatinine and blood urea nitrogen (BUN) levels, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-18) levels and restoring kidney histological deteriorations. Further mechanistic investigation showed that DHB distinctly down-regulated renal mRNA and protein levels of URAT1, GLUT9, NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), caspase-1 and IL-1β. Our study revealed that DHB had outstanding hypouricemic and renoprotective effects via suppressing XOD, URAT1, GLUT9 and NLRP3 inflammasome activation in the kidney.https://www.frontiersin.org/articles/10.3389/fphar.2021.645879/fullhyperuricemiainflammationxanthine oxidaseNLRP3 inflammasomeurate transportersdihydroberberine |
| spellingShingle | Lieqiang Xu Guoshu Lin Qiuxia Yu Qiuxia Yu Qiaoping Li Liting Mai Juanjuan Cheng Jianhui Xie Jianhui Xie Yuhong Liu Ziren Su Yucui Li Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice Frontiers in Pharmacology hyperuricemia inflammation xanthine oxidase NLRP3 inflammasome urate transporters dihydroberberine |
| title | Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice |
| title_full | Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice |
| title_fullStr | Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice |
| title_full_unstemmed | Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice |
| title_short | Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice |
| title_sort | anti hyperuricemic and nephroprotective effects of dihydroberberine in potassium oxonate and hypoxanthine induced hyperuricemic mice |
| topic | hyperuricemia inflammation xanthine oxidase NLRP3 inflammasome urate transporters dihydroberberine |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.645879/full |
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