The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice
Lupus nephritis (LN), the most severe organ manifestation of systemic lupus erythematosus (SLE), is generally treated with glucocorticoids (GC) in clinical practice, leading to drug resistance and adverse effects in the long term. Fortunately, the combination of GC and traditional Chinese medical pr...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.943827/full |
| _version_ | 1818187989997584384 |
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| author | Ying Li Tao Ding Jing Chen Jinjun Ji Weijie Wang Bin Ding Weihong Ge Yongsheng Fan Li Xu |
| author_facet | Ying Li Tao Ding Jing Chen Jinjun Ji Weijie Wang Bin Ding Weihong Ge Yongsheng Fan Li Xu |
| author_sort | Ying Li |
| collection | DOAJ |
| description | Lupus nephritis (LN), the most severe organ manifestation of systemic lupus erythematosus (SLE), is generally treated with glucocorticoids (GC) in clinical practice, leading to drug resistance and adverse effects in the long term. Fortunately, the combination of GC and traditional Chinese medical prescriptions can attenuate the adverse effects and improve therapeutic efficiency. Hedyotis diffusa Willd (HDW) is one of the most commonly used herbal compounds for LN treatment, which exhibits “heat-clearing” and “detoxification” effects. However, the underlying pharmacological mechanism remains unclear. The present study identified the chemical compounds in HDW extract with UPLC-Q-TOF-MS/MS. A total of 49 components were identified in the HDW extract, and the IL-17 signaling pathway was highly enriched by network pharmacological analysis. MRL/lpr model mice, reflecting the spontaneous development of LN, were used to evaluate the protective activity and investigate the underlying mechanism of the combination treatment. The white blood cell content (WBC), including lymphocytes and neutrophils, cytokines (IL-6, MCP-1, TNF-a), and various autoantibodies (ANA, ab-dsDNA, ab-snRNP/sm) in the blood of MRL/lpr mice were significantly improved by the intragastric administration of HDW. Additionally, the expression of STAT3, IL-17, Ly6G, and MPO in the kidney and neutrophil NETosis were ameliorated with HDW treatment. The pathological and morphological analysis suggested that HDW application could reduce urinary protein levels and inflammatory cell infiltration and inhibit glomerular interstitial cell proliferation. Hence, HDW might ameliorate lupus nephritis by inhibiting IL-6 secretion and STAT3-induced IL-17 expression. The active compounds in HDW were predictively selected with computational methods. The docking affinity of asiatic acid, neoandrographolide to IL-6, glycyrrhetinic acid, oleanolic acid, ursolic acid, and wilforlide A to STAT3 are extremely high. In conclusion, the IL-6 and STAT3/IL-17signaling pathways could be critical regulative targets of HDW on LN. |
| first_indexed | 2024-12-11T23:19:48Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T23:19:48Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-081b7c813ef945209b79377839d124f22022-12-22T00:46:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.943827943827The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr miceYing Li0Tao Ding1Jing Chen2Jinjun Ji3Weijie Wang4Bin Ding5Weihong Ge6Yongsheng Fan7Li Xu8School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Life Science, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, ChinaLupus nephritis (LN), the most severe organ manifestation of systemic lupus erythematosus (SLE), is generally treated with glucocorticoids (GC) in clinical practice, leading to drug resistance and adverse effects in the long term. Fortunately, the combination of GC and traditional Chinese medical prescriptions can attenuate the adverse effects and improve therapeutic efficiency. Hedyotis diffusa Willd (HDW) is one of the most commonly used herbal compounds for LN treatment, which exhibits “heat-clearing” and “detoxification” effects. However, the underlying pharmacological mechanism remains unclear. The present study identified the chemical compounds in HDW extract with UPLC-Q-TOF-MS/MS. A total of 49 components were identified in the HDW extract, and the IL-17 signaling pathway was highly enriched by network pharmacological analysis. MRL/lpr model mice, reflecting the spontaneous development of LN, were used to evaluate the protective activity and investigate the underlying mechanism of the combination treatment. The white blood cell content (WBC), including lymphocytes and neutrophils, cytokines (IL-6, MCP-1, TNF-a), and various autoantibodies (ANA, ab-dsDNA, ab-snRNP/sm) in the blood of MRL/lpr mice were significantly improved by the intragastric administration of HDW. Additionally, the expression of STAT3, IL-17, Ly6G, and MPO in the kidney and neutrophil NETosis were ameliorated with HDW treatment. The pathological and morphological analysis suggested that HDW application could reduce urinary protein levels and inflammatory cell infiltration and inhibit glomerular interstitial cell proliferation. Hence, HDW might ameliorate lupus nephritis by inhibiting IL-6 secretion and STAT3-induced IL-17 expression. The active compounds in HDW were predictively selected with computational methods. The docking affinity of asiatic acid, neoandrographolide to IL-6, glycyrrhetinic acid, oleanolic acid, ursolic acid, and wilforlide A to STAT3 are extremely high. In conclusion, the IL-6 and STAT3/IL-17signaling pathways could be critical regulative targets of HDW on LN.https://www.frontiersin.org/articles/10.3389/fimmu.2022.943827/fullHedyotis diffusa Willdlupus nephritisnetwork pharmacologyinterleukin-17STAT3inflammation |
| spellingShingle | Ying Li Tao Ding Jing Chen Jinjun Ji Weijie Wang Bin Ding Weihong Ge Yongsheng Fan Li Xu The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice Frontiers in Immunology Hedyotis diffusa Willd lupus nephritis network pharmacology interleukin-17 STAT3 inflammation |
| title | The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice |
| title_full | The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice |
| title_fullStr | The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice |
| title_full_unstemmed | The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice |
| title_short | The protective capability of Hedyotis diffusa Willd on lupus nephritis by attenuating the IL-17 expression in MRL/lpr mice |
| title_sort | protective capability of hedyotis diffusa willd on lupus nephritis by attenuating the il 17 expression in mrl lpr mice |
| topic | Hedyotis diffusa Willd lupus nephritis network pharmacology interleukin-17 STAT3 inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.943827/full |
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