BIOMEDICAL CHROMATOGRAPHY
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2024
·Vol. 38
·期 6
·e5866
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IF 1.8
Zhijian Zha,Ruihua Wang,Qian Wang,Fahui Chen,Ziyang Ye,Yafeng Li
Immunoglobulin nephropathy (IgAN) stands as the most prevalent primary glomerular nephropathy globally, typically diagnosed through an invasive renal biopsy. Emerging research suggests the significant involvement of chiral amino acids in kidney disease progression. This study introduces a nonderivative LC–tandem mass spectrometry approach, offering efficient separation outcomes within 15 min for identifying chiral amino acids in human urine samples. Subsequently, using this method, the analysis of l - and d -amino acids in the urine of both patients with IgAN and healthy individuals was conducted. Fourteen d -amino acids and 20 l -amino acids were identified in the urine samples obtained from 17 patients with IgAN and 21 healthy individuals. The results indicated notable variances in the concentrations of both l - and d -amino acids between the IgAN and healthy control groups. In contrast to the healthy group, the IgAN group exhibited higher mean urine concentrations of most l -amino acids and lower concentrations of d -amino acids. Furthermore, correlations between amino acids and clinical markers were investigated. These results propose a novel method for monitoring trace amino acids in urine samples and introduce a new concept for potential markers of IgAN.
研究领域:
医学
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分析化学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2019
·
IF 4.825
Lixia Bai,Jicheng Li,Honglian Li,Jianping Song,Yuan Zhou,Ruirui Lu,Bihao Liu,Yu Pang,Peichun Zhang,Junqi Chen,Xusheng Liu,Junbiao Wu,Chunling Liang,Jiuyao Zhou
Immunoglobulin A nephropathy (IgAN) is an autoimmune kidney disease with complex pathogenesis leading to end-stage renal damage . The prime pathological characteristics of IgAN are IgA immune complexes deposition accompany with mesangial cell proliferation and urine protein elevation. Artemisinin (ART) is extracted from traditional Chinese medicine Artemisia annua L. Hydroxychloroquine (HCQ) is a classical antimalarial drug applied in the treatment of autoimmune diseases. Both of them possess anti-inflammatory and immunomodulatory properties. The purpose of this research was to investigate the pharmacological effects of ART combined with HCQ (AH) and discuss thoroughly the potential molecular mechanisms in IgAN. In vivo , our results demonstrated that AH could efficiently ameliorate kidney damage by improving kidney dysfunction and reducing the levels of 24 h urine protein, IgA and IgG immune complexes deposition in glomerulus of IgAN rats. Interestingly, AH obviously promoted the secretion of exosomes in renal tissues, inhibited the expressions of nuclear factor- κ B (NF- κ B) signaling and NLRP3 inflammasome-related proteins, including I κ B- α , p-p65, NLRP3, ASC, IL-1 β and caspase-1 in IgAN rats. In vitro , further mechanistic study illustrated that exosomes derived from human renal tubular epithelial cells (HK-2) were significantly enhanced by AH, which could be utterly taken up in human mesangial cells (HMCs) and inhibited the activation of NF- κ B pathway and NLRP3 inflammasome after AH intervention. However, GW4869 interdicted the promotive effect of AH on exosomes from HK-2 cells and the suppression of exosomes on NF- κ B/NLRP3 activation in HMCs. Taken together, this study demonstrated that there was an inhibitory effect of AH therapy on NF- κ B/NLRP3 signaling via mediating exosomes release in IgAN rats, which provided an alternative approach for IgAN treatment.
研究领域:
药理学
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免疫学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Huaxi Liu,Weijie Chen,Chunyang Tian,Yijian Deng,Liangwo Xu,Wenkun Ouyang,Renjie Qiu,Yanting You,Pingping Jiang,Lin Zhou,Jingru Cheng,Hiu Yee Kwan,Xiaoshan Zhao,Xiaomin Sun
Background IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p -Akt. Conclusion This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.
研究领域:
药理学
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肾病学
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分子生物学
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中医药
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Huan Song,Guo-Qiang Liang,Man-Shu Yu,Yun Shan,Jun Shi,Chun-Bo Jiang,Dao-Lei Ni,Mei-Xiao Sheng
Ethnopharmacological relevance Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world, it is one of the most common causes of kidney disease and can lead to end-stage kidney disease, however, its pathogenesis is still complicated. The Shen-yan-yi-hao oral solution (SOLI) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. Aim of the study This study investigates SOLI's effects on IgAN in rats, particularly on the intestinal mucosal barrier, and identifies potential therapeutic targets through network pharmacology and molecular docking, validated experimentally. Materials and methods Target genes for SOLI in IgAN were identified and analysed through molecular docking and KEGG pathway enrichment. An IgAN rat model examined SOLI's effect on renal biomarkers and cytokines involved in specific pathways, ileum mucosal lesions, and the intestinal immune system. The IL-17 pathway's role was studied in IEC-6 cells with SOLI in vitro. Result Rats developed increased proteinuria and kidney damage marked by IgA deposition and inflammation. SOLI treatment significantly ameliorated these symptoms, reduced galactose-deficient Ig A1 (Gd-IgA1), and decreased cytokines like IL-17, TNF-α, IL-6 and IL-1β etc. SOLI also normalized intestinal tight junction protein expression, ameliorated intestinal damage, and regulated intestinal immune response (focused on IL-17/NF-κB signal pathway). SOLI moderated the abnormally activated IL-17 pathway, which damages intestinal epithelial cells, suggesting IgAN treatment potential. Conclusion SOLI reduces proteinuria and enhances intestinal mucosal function in IgAN rats, kidney protection in the IgAN rat model may initiate from modulating the intestinal IL-17/NF-κB pathway and subsequent Gd-IgA1 accumulation.
研究领域:
药理学
·
免疫学
·
肾病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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