<i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation
Acute kidney injury (AKI) is described as the abrupt decrease in kidney function always accompanied by inflammation. The roots of <i>Oxybaphus himalaicus</i> Edgew. have long been used in Tibetan folk medicine for the treatment of nephritis. Nevertheless, modern pharmacological studies,...
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MDPI AG
2022-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/12/2307 |
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| author | Honghong Zhan Qingxiu Pu Xiaoliang Long Wei Lu Guowei Wang Fancheng Meng Zhihua Liao Xiaozhong Lan Min Chen |
| author_facet | Honghong Zhan Qingxiu Pu Xiaoliang Long Wei Lu Guowei Wang Fancheng Meng Zhihua Liao Xiaozhong Lan Min Chen |
| author_sort | Honghong Zhan |
| collection | DOAJ |
| description | Acute kidney injury (AKI) is described as the abrupt decrease in kidney function always accompanied by inflammation. The roots of <i>Oxybaphus himalaicus</i> Edgew. have long been used in Tibetan folk medicine for the treatment of nephritis. Nevertheless, modern pharmacological studies, especially about the underlying mechanism of <i>O. himalaicus</i> medications, are still lacking. Here, in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, the <i>O. himalaicus</i> extract (OE) showed significant anti-inflammatory activity with the dose dependently reducing the LPS-stimulated release of nitric oxide and the mRNA level and protein expression of inflammatory cytokines and reversed the activation of nuclear factor kappa B (NF-κB). Co-immunoprecipitation assay indicated that OE inhibited Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2) complex formation and further suppressed both myeloid differentiation factor 88 (MyD88)-dependent and TIR-domain-containing adapter-inducing interferon-β (TRIF)-dependent cascades activation. In addition, OE could restrain NADPH oxidase 2 (NOX2) endocytosis by blocking TLR4/MD2 complex formation to prevent reactive oxygen species production. In LPS-induced AKI mice, OE treatment mitigated renal injury and inflammatory infiltration by inhibiting TLR4/MD2 complex formation. UPLC-MS/MS analysis tentatively identified 41 components in OE. Our results indicated that OE presented significant anti-inflammatory activity by inhibiting TLR4/MD2 complex formation, which alleviated LPS-induced AKI in mice. |
| first_indexed | 2024-03-09T17:24:17Z |
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| id | doaj.art-ab7f89963b6d4e4caed01e14c46efa48 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T17:24:17Z |
| publishDate | 2022-11-01 |
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| series | Antioxidants |
| spelling | doaj.art-ab7f89963b6d4e4caed01e14c46efa482023-11-24T12:55:47ZengMDPI AGAntioxidants2076-39212022-11-011112230710.3390/antiox11122307<i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex FormationHonghong Zhan0Qingxiu Pu1Xiaoliang Long2Wei Lu3Guowei Wang4Fancheng Meng5Zhihua Liao6Xiaozhong Lan7Min Chen8Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaKey Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaSchool of Life Sciences, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City and Southwest University, The Provincial and Ministerial Co-Founded Collaborative Innovation Center for R&D in Tibet Characteristic Agricultural and Animal Husbandry Resources, TAAHC-SWU Medicinal Plant Joint R&D Centre, Southwest University, Chongqing 400715, ChinaKey Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaKey Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaKey Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaSchool of Life Sciences, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City and Southwest University, The Provincial and Ministerial Co-Founded Collaborative Innovation Center for R&D in Tibet Characteristic Agricultural and Animal Husbandry Resources, TAAHC-SWU Medicinal Plant Joint R&D Centre, Southwest University, Chongqing 400715, ChinaTAAHC-SWU Medicinal Plant R&D Center, Tibet Agricultural and Animal Husbandry University, Nyingchi 860000, ChinaKey Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, ChinaAcute kidney injury (AKI) is described as the abrupt decrease in kidney function always accompanied by inflammation. The roots of <i>Oxybaphus himalaicus</i> Edgew. have long been used in Tibetan folk medicine for the treatment of nephritis. Nevertheless, modern pharmacological studies, especially about the underlying mechanism of <i>O. himalaicus</i> medications, are still lacking. Here, in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, the <i>O. himalaicus</i> extract (OE) showed significant anti-inflammatory activity with the dose dependently reducing the LPS-stimulated release of nitric oxide and the mRNA level and protein expression of inflammatory cytokines and reversed the activation of nuclear factor kappa B (NF-κB). Co-immunoprecipitation assay indicated that OE inhibited Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2) complex formation and further suppressed both myeloid differentiation factor 88 (MyD88)-dependent and TIR-domain-containing adapter-inducing interferon-β (TRIF)-dependent cascades activation. In addition, OE could restrain NADPH oxidase 2 (NOX2) endocytosis by blocking TLR4/MD2 complex formation to prevent reactive oxygen species production. In LPS-induced AKI mice, OE treatment mitigated renal injury and inflammatory infiltration by inhibiting TLR4/MD2 complex formation. UPLC-MS/MS analysis tentatively identified 41 components in OE. Our results indicated that OE presented significant anti-inflammatory activity by inhibiting TLR4/MD2 complex formation, which alleviated LPS-induced AKI in mice.https://www.mdpi.com/2076-3921/11/12/2307<i>Oxybaphus himalaicus</i>TLR4/MD2NADPH oxidase 2inflammationreactive oxygen speciesacute kidney injury |
| spellingShingle | Honghong Zhan Qingxiu Pu Xiaoliang Long Wei Lu Guowei Wang Fancheng Meng Zhihua Liao Xiaozhong Lan Min Chen <i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation Antioxidants <i>Oxybaphus himalaicus</i> TLR4/MD2 NADPH oxidase 2 inflammation reactive oxygen species acute kidney injury |
| title | <i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation |
| title_full | <i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation |
| title_fullStr | <i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation |
| title_full_unstemmed | <i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation |
| title_short | <i>Oxybaphus himalaicus</i> Mitigates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/MD2 Complex Formation |
| title_sort | i oxybaphus himalaicus i mitigates lipopolysaccharide induced acute kidney injury by inhibiting tlr4 md2 complex formation |
| topic | <i>Oxybaphus himalaicus</i> TLR4/MD2 NADPH oxidase 2 inflammation reactive oxygen species acute kidney injury |
| url | https://www.mdpi.com/2076-3921/11/12/2307 |
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