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The Inhibitory Effects of Pentacyclic Triterpenes from Loquat Leaf against Th17 Differentiation.

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机构: [a]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China [b]Department of Biochemistry and molecular biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China [c]ICU Center, Department of Infection Control, Sun Yat-sen University Cancer Center, Guangzhou, China [d]Animal Experiment Center, Sun Yat-sen University First Affiliated Hospital, Guangzhou, China [e]School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China [f]Animal Experiment Center, South China Agricultural University, Guangzhou, China [g]Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
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关键词: Systemic lupus erythematosus (SLE) lupus nephritis (LN) loquat leaf oleanolic acid (OA) T helper 17 (Th17) retinoic acid receptor-related orphan receptor gamma t (RORγt)

摘要:
Background: Loquat leaf is an herb that is commonly used in traditional Chinese medicine (TCM) for its anti-inflammatory properties. Numerous studies have demonstrated that Th17 cells play a fundamental role in mediating SLE pathological deterioration. In our study, we investigated the inhibitory effect of pentacyclic triterpenes from loquat leaf on T helper 17 (Th17) cells and the therapeutic efficacy of OA in Lupus nephritis (LN) development.Methods: We isolated three pentacyclic triterpene compounds rom loquat leaf by bioassay-directed fractionation and separation method. There were methyl corosolate (MC), uvaol (UL), and oleanolic acid (OA) Firstly, we elucidated Retinoic acid receptor-related orphan receptor gamma t (RORγt) inhibitory activity of these three compounds in the cell-based assay and Th17 differentiation in vitro assay. Then, we used OA-treated pristine-induced LN mice to evaluate the therapeutic effects of OA in LN development. Anti-dsDNA level in serum was detected by enzyme-linked immunosorbent assay (ELISA), interleukin 17A (IL-17A) and interferon-γ (IFN-γ) expression in spleen cells by Flow cytometry (FCM), histomorphologic examination of kidneys were performed by periodic acid schiff (PAS) staining and immunofluorescence analysis.Results: Pentacyclic triterpene compounds (MC, UL, OA) displayed inhibition of RORγt activity in cell-based assay and Th17 differentiation in vitro. Furthermore, our results also showed that OA could significantly decrease serum anti-dsDNA antibody levels, IL-17A and IFN-γ expression and alleviate renal pathological damage in OA-treated group mice than in the model group mice.Conclusion: These results demonstrated that OA can improve the clinical manifestation of LN, indicating potential application in SLE therapy.

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出版当年[2019]版:
大类 | 3 区 医学
小类 | 4 区 免疫学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 免疫学
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出版当年[2018]版:
Q3 IMMUNOLOGY
最新[2023]版:
Q3 IMMUNOLOGY

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第一作者机构: [a]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China [b]Department of Biochemistry and molecular biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
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通讯机构: [a]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China [b]Department of Biochemistry and molecular biology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China [e]School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China [*1]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, N1311 Rm, No.10 Bld, 74 Zhongshan 2nd Rd, Guangzhou 510080, China [*2]School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Room C118, Pharmaceutical building, 232#, Waihuan Dong Road, High Education Mega Center, Guangzhou 510006, P. R. China
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