Frontiers in Pharmacology
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2020
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IF 4.225
Li Honglian,Lu Ruirui,Pang Yu,Li Jicheng,Cao Yiwen,Fu Hongxin,Fang Guoxing,Chen Qiuhe,Liu Bihao,Wu Junbiao,Zhou Yuan,Zhou Jiuyao
Immunoglobulin A nephropathy (IgAN) is one of the most frequent kinds of primary glomerulonephritis characterized by IgA immune complexes deposition and glomerular proliferation. Zhen-wu-tang (ZWT), a well-known traditional Chinese formula has been reported to ameliorate various kidney diseases. However, its pharmacological mechanism remains unclear. Exosomes have been described in diverse renal diseases by mediating cellular communication but rarely in the IgAN. The purpose of the present study is to explore whether the underlying mechanisms of the effect of ZWT on IgAN is correlated to exosomes. Our results demonstrated that in human renal tubular epithelial cells (HK-2) stimulated by lipopolysaccharide, exosomes are obviously released after ZWT-containing serum treatment especially with 10% ZWT. In addition, once released, HK-2-derived exosomes were uptaked by human mesangial cells (HMC), which impeded the activation of NF-κB/NLRP3 signaling pathway to exert anti-inflammatory effects in a lipopolysaccharide induced proliferation model. Moreover, IgAN rat model was established by bovine serum albumin, CCL4 mixed solution and LPS. We found that 10% ZWT could significantly promote the release of exosomes from HK-2 and inhibit HMC proliferation to improve inflammation. Thus HK-2-derived exosomes treated with 10% ZWT (ZWT-EXO) were administered to the rats by tail vein injection. Our results showed that ZWT-EXO decreased the levels of 24 h proteinuria, urinary erythrocyte, IgA deposition in glomerulus and renal pathological injury which ameliorated the kidney damage. In addition, ZWT was able to dramatically promote secretion of exosomes in renal tissues while blocked NF-κB nuclear translocation as well as activation of NLRP3 inflammasome, leading to the inhibition of IL-1β and caspase-1. In conclusion, our study reveal that ZWT has protective effects on IgAN by regulating exosomes secretion to inhibit the activation of NF-κB/NLRP3 pathway, thereby attenuating the renal dysfunction. These findings may provide a new therapeutic target for the treatment of IgAN.
研究领域:
药理学
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肾病学
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中医药
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Kidney International Reports
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2026
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IF 6.2
Shangbin Kao,Yuemiao Zhang,Shaoqing Dang,Shichao Hu,Mengwei Li,Tianyu Zheng,Yuan Qin,Biao Huang,Qiang He,Jicheng Lv
Introduction IgA nephropathy (IgAN) diagnosis remains dependent on invasive renal biopsy because currently available serologic biomarkers, including galactose-deficient IgA1 (Gd-IgA1), have limited diagnostic performance. This study aimed to develop and evaluate a high-sensitivity time-resolved fluorescence immunoassay (TRFIA) based on a novel anti-Gd-IgA1 monoclonal antibody (MH33) for Gd-IgA1 detection in IgAN. Methods MH33 glycoepitope specificity was characterized by surface plasmon resonance (SPR). A MH33-based TRFIA was developed and evaluated for analytical and diagnostic performance in healthy controls, non-IgAN renal disease controls, and IgAN patients, with comparison to a KM55-based assay. Results SPR analysis showed that MH33 recognized a GalNAc-modified IgA1 hinge-region glycopeptide distinct from the KM55 epitope. The MH33-based TRFIA achieved a detection limit of 0.20 Ru/mL, a quantification range of 0.20–600 Ru/mL, and acceptable analytical performance (intra-/inter-assay CVs: 2.32%–5.49% and 3.97%–5.23%; recoveries: 89.80%–103.76%). Correlation with KM55 was moderate (IgAN, r = 0.23, p =0.09). For distinguishing IgAN from combined controls (healthy controls and non-IgAN renal diseases), the MH33-based TRFIA yielded an AUC of 0.90 (95% CI: 0.86–0.93), compared with 0.78 (95% CI: 0.71–0.86) for KM55 . At the optimal cutoff value (22.0 Ru/mL), the assay achieved a specificity of 93.82% and sensitivity of 64.44%. Conclusion MH33-based TRFIA provides a sensitive approach for Gd-IgA1 detection and demonstrates favorable diagnostic performance for IgAN.
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DOI
PubMed
高影响因子
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2025
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IF 3.1
Meng-Si Li,Kai Liu
IgA nephropathy (IgAN), the most common form of glomerulonephritis, is a major and growing public health issue. It results from intestinal barrier dysfunction that leads to mesangial deposition of pathogenic galactose-deficient IgA1 (Gd-IgA1) and renal inflammation. This study aimed to investigate the therapeutic effects and associated mechanisms of forsythiaside A on intestinal barrier injury in IgAN in animal models. Rats were treated with bovine serum albumin (BSA), carbon tetrachloride (CCl 4 ), and lipopolysaccharide (LPS) to induce IgAN, followed by intragastric administration of forsythiaside A once daily from weeks 15 to 20 after model establishment. Biochemical markers, including 24-h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), renal and intestinal tissue pathology, and levels of pro-inflammatory cytokines in the serum, kidney, and intestine, intestinal tight junction proteins, and TLR4/NF-κB pathway components were examined. The results showed that forsythiaside A decreased 24-h urinary protein, BUN, and SCr levels, alleviated renal damage, and attenuated glomerular and tubular lesions, collagen deposition, and glomerular IgA deposition in IgAN rats. Forsythiaside A treatment inhibited CD68-positive macrophage infiltration in renal tissues and downregulated serum and renal levels of IL-1β, IL-6, and TNF-α, while also alleviating intestinal barrier injury and intestinal inflammation, as shown by reduced levels of IL-1β, IL-6, and TNF-α and increased expression of the intestinal tight junction proteins occludin and ZO-1. Lastly, forsythiaside A treatment lowered serum LPS concentrations, as well as renal and intestinal levels of TLR4, p-NF-κB p65, and p-IκBα, and raised both renal and intestinal levels of IκBα. Collectively, forsythiaside A was found to ameliorate the progression of IgAN in rats by alleviating inflammation and intestinal barrier injury by suppression of TLR4/NF-κB signaling.
研究领域:
肾病学
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免疫学
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药理学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Rongjia Xu,Jiajia Zhang,Xingge Hu,Penghao Xu,Shiqi Huang,Shiyan Cui,Yuxin Guo,Hongtao Yang,Xiangmei Chen,Chen Jiang
Ethnopharmacological relevance Controversy persists regarding the treatment of immunoglobulin A nephropathy (IgAN), thereby highlighting the demand for safer more effective therapeutic drugs. Although supplementary treatment using Yi-Shen-Hua-Shi (YSHS) granules has distinct advantages with respect to improving renal function in IgAN, a lack of clarity regarding the underlying mechanisms limits their clinical application. Aim of the study In this study, we aimed to elucidate the therapeutic mechanisms underlying the efficacy of YSHS granules in the treatment of IgAN. Materials and methods A rat model of IgAN was established based on lipopolysaccharide, carbon tetrachloride, and bovine serum albumin induction. In order to evaluate the effects of YSHS granules, we performed a range of techniques, including immunofluorescence assays, hematoxylin and eosin staining, and flow cytometry, to assess inflammation, immunity, and other relevant factors. Direct data-independent acquisition–mass spectrometry (DIA-MS) analysis and parallel reaction monitoring (PRM) were used for functional characterization and quantitative validation of differentially expressed proteins (DEPs), and Western blot analysis is used to identify downstream proteins associated with DEPs. Results Compared with the model group, the levels of proteinuria, urine red blood cells, serum creatinine, blood urea nitrogen, low-density lipoprotein-cholesterol, triglycerides, and pathological kidney damage were reduced in the YSHS group. A high dose of YSHS granules was found to raise the levels of CD8 T cells and reduce the CD4/CD8 ratio in the peripheral serum. To examine the mechanisms underlying the therapeutic effects YSHS granules, we performed direct DIA-MS analysis to identify proteins that were differentially expressed among the model, YSHS, and control groups. A total of 29 proteins were identified as being commonly expressed in all three groups. Further KEGG and protein–protein interaction (PPI) network analysis revealed that YSHS granules can contribute to the regulation of N -glycosylation-associated proteins, such as ALG3 and STT3A, in rats with IgAN. Detected changes in the expression of ALG3 and STT3A were consistent with the PRM results. We also established that the administration of YSHS granules can contribute to regulation of the ALG3-associated PPAR-γ/NF-κB signaling pathway. Conclusions Our findings in this study provide evidence to indicate the efficacy of YSHS granules in the treatment of IgAN, the putative underlying mechanisms of which involve the modulation of N-glycosylation, mediated via the PPAR-γ/NF-κB pathway.
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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蛋白质组学
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中医药
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DOI
PubMed
高影响因子
Food & Function
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2025
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IF 5.4
Yuhui Ye,Xiaoyi Jiang,Yijun Jiang,Longteng Zhang,Binsong Han,Yulong Wang,Pengyan Liu,Xin Lu,Cun-Zheng Zhang
Although often regarded as compromising the fruit’s sensory quality, pear peel is an edible component that enhances the nutritional and functional value of pears within a whole food diet. Rich in diverse polyphenols with demonstrated bioactivity, the pear peel represents a valuable dietary source of health-promoting compounds, however, its role in ulcerative colitis (UC) remains underexplored. In this study, the protective effect of pear peel polyphenols (PPP) against UC was investigated using both in vitro and in vivo models. PPP markedly suppressed proinflammatory cytokine and enzyme expressions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. In dextran sulfate sodium (DSS) induced colitis mice, PPP significantly mitigated UC symptoms, suppressed serum inflammatory cytokine production, and ameliorated histological damage in colon tissues. Moreover, PPP modulated the gut microbiota by reshaping microbial diversity, enriching beneficial taxa such as Akkermansia, and suppressing proinflammatory taxa including Bacteroides, Enterobacteriaceae, and Parabacteroides. Proteomic analysis further demonstrated that PPP modulated mucosal immunity, particularly by rebalancing immunoglobulin-related processes (IgM, IgD, and IgA) and attenuating antigen presentation responses involving major histocompatibility complex (MHC) class II molecules and cluster of differentiation (Cd40) signaling. Together, these findings suggest that PPP exerts a protective effect against colitis through the coordinated regulation of gut microbiota and mucosal immunity, highlighting its potential as a functional food ingredient for intestinal health.
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PubMed
高影响因子
Nano Research
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2023
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IF 9.9
Wang Daji,Wang Jie,Liu Dan,He Jiuyang,Wang Meiying,Huang Haibing,Nie Guohui,Ding Hui,Yan Xiyun
The correlation between Epstein-Barr virus (EBV) infection and nasopharyngeal carcinoma (NPC) risk has been extensively researched. The continual monitoring of EBV-IgAs provides a promising approach of NPC screening in its early stage. In this study, we successfully synthesized a single-atom nanozyme (SANzyme) through the application of iron-porphyrin based metal organic framework (MOF-FeP). The MOF-FeP possesses precisely-defined electronic and geometric structures that accurately mimic highly-evolved catalytic site of natural peroxidase. The peroxidase-like activity of MOF-FeP enables it to catalyze the chemiluminescence of luminol substrate. By integrating MOF-FeP into a traditional strip, we created a rapid and highly-sensitive evaluation tool for detecting EBV-IgAs. Importantly, the MOF-FeP strip enables the simultaneous detection of three EBV-IgAs, greatly improving the accuracy of EBV-associated NPC screening. The sensitivities of the MOF-FeP strip (75.56%–93.30%) surpass those of current enzyme-linked immunosorbent assay (ELISA) methods (64.44%–82.22%). This test takes only 16 min to perform as opposed to the customary 1–2 h required for standard ELISA. Additionally, the MOF-FeP strip is suitable for whole blood samples, thereby significantly simplifying the sample preparation and detection process. In conclusion, the MOF-FeP strip combines the simplicity of traditional strip with the high catalytic activity of SANzyme. Our innovative MOF-FeP strip offers a new point-of-care strategy for EBV-IgAs detection, which is expected to markedly facilitate early screening for EBV-associated diseases.
研究领域:
癌症生物学
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分子诊断
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纳米技术
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生物医学工程
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DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
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2020
·Vol. 64
·期 8
·1901251
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IF 5.309
Lingjun Tong,Haining Hao,Xinyi Zhang,Zhe Zhang,Youyou Lv,Lanwei Zhang,Huaxi Yi
Scope Milk-derived extracellular vesicles (mEVs) as nanoparticles are being developed as novel drug vehicles due to their pivotal role in cell–cell communication. As an important bioactive component in milk, little is known about their effect on the gut microbiota and intestinal immunity. Therefore, the effects of mEVs on gut microbiota and intestinal immunity in mice are investigated. Methods and results First, a new method to obtain high-yield mEVs is developed. Afterward, the colonic contents from C57BL/6 mice fed different doses of mEVs (8 weeks) are collected and the microbial composition via 16S rRNA gene sequencing is analyzed. It is found that mEVs could alter the gut microbiota composition and modulate their metabolites—short-chain fatty acids (SCFAs). Furthermore, the effects of mEVs on intestinal immunity are evaluated. It is observed that the expression levels of Muc2, RegIIIγ, Myd88, GATA4 genes, and IgA, sIgA are increased in the intestine, which are significant for the integrity of the mucus layer. Conclusion These findings reveal that the genes with critical importance for intestinal barrier function and immune regulation are modified in mice by oral administration mEVs, which also result in the changes of the relative composition of gut microbiome and SCFAs.
研究领域:
药理学
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微生物学
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免疫学
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营养科学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Zulikeyan Manafu,Ronglijiao Du,Tuerhong Kudereti,Gulimire Abulikemu,Shakeel Ahmed Lakho,Lijun Xue,Ayibike Bierdelieke,Faiz Muhammad Khand,Ambreen Leghari,Yuan Xie,Saifuding Abula,Bateer Bake,Qingyong Guo,Adelijiang Wusiman
This study investigated the structure of acid Alhagi camelorum Fischa polysaccharide (aAP) and its impact on intestinal activity in mice. The results showed that aAP comprised of the fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galacturonic acid, glucuronic acid with the molar ratio of 0.81:14.97:10.84:11.14:3.26:0.80:0.80:54.92:2.47 with the molecular weight (Mw) of 22.734 kDa. Additionally, the composition of aAP was assessed via FT-IR, methylation, and NMR analyses, indicating that the backbone of the aAP was consisted of →4)-α-D-Gal p A-6-OMe-(1 → 4)-α-Gal p A-(1 → and →4)-α-D-Gal p A-6-OMe-(1 → 2)-α-L-Rha p -(1→, as well as →4)-β-D-Gal p - and →5)-α-L-Ara f - for the branched chain. Furthermore, ICR mice underwent intragastric administration of different concentrations of aAP for 7 consecutive days. The results showed that aAP enhanced the murine spleen and thymus indices, promoted the secretion of serum lgG antibody, intestinal lgA antibody and intestinal cytokines, improved the morphology of intestinal villi and crypts, enhanced quantity of intestinal IELs and IgA+ cells, and activated T lymphocytes and DC cells in MLNs. In summary, these findings suggest that the utilization of aAP could enhance the immune response of the murine intestinal mucosa.
研究领域:
药理学
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免疫学
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生物化学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Changqing Wen,Hang Su,Jiaxuan Li,Jia Zou,Mingxu Gong,Fujiang Wang,Haitao Ge
Ethnopharmacological relevance IgA nephropathy (IgAN) is characterized by the deposition of thylakoid Gd-IgA1 and progresses to kidney dysfunction and failure. Thousands of years ago, Abelmoschus manihot (L.) Medic has been used as a traditional Chinese medicine to treat kidney diseases. The total flavonoid (TFA) of Abelmoschus manihot (L.) Medic is the main active ingredient of the medicine, which is known to have therapeutic effects on kidney diseases. However, the mechanism of action is still not further explored. Aim of study We aim to reveal the targets and potential mechanisms of TFA through comprehensive proteomics and Weighted Gene Co-expression Network Analysis (WGCNA), and to provide new ideas for the treatment of IgAN. Materials and methods In this study, we constructed a model of IgA nephropathy in rats and evaluated the efficacy of TFA in the IgAN model by assessing renal function, renal Gd-IgA1/IgA and serum markers. Integrated proteomics and WGCNA analysis identified core targets associated with TFA, and target validation was performed by immunohistochemistry. Results Kidney function (Scr, PCR, BUN) and serum markers (TGF-β1, TNF-α, BAFF, MCP-1) were significantly reduced after TFA treatment. Proteomics identified 2,757 differential expressed genes (DEGs). WGCNA highlighted four key modules associated with TFA effects. Six core targets (C1QBP, CYC1, Phab, VDAC2, CDH2, Dbn1) were validated by immunohistochemistry, confirming their roles in TFA renoprotection. Conclusion Induction of rat IgAN model, proteomics and WGCNA analyses demonstrated that TFA improves renal function, reduces histopathological damage and modulates inflammation. These findings further elucidate the treatment mechanism of TFA and provide new insights into the treatment of IgA nephropathy.
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DOI
PubMed
高影响因子
VETERINARY RESEARCH
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2025
·
IF 3.5
Su Kai,Ren Jing,Zhang Yanan,Yuan Chen,Wang Yawen,Yang Liu,Fu Lizhi,Fan Tingli,Song Qinye
Porcine epidemic diarrhea (PED), a highly contagious intestinal disease caused by PEDV, threatens newborn piglets and causes enormous losses in the swine industry. Intestinal mucosal immunity is vital for defense against PEDV. Chitosan (CS), a mucin-adhesive biodegradable polysaccharide, has emerged as a promising mucosal vaccine delivery vector and antigen adjuvant. To develop a PEDV mucosal vaccine, we prepared S1-CS nanoparticles (NPs) loaded with the S1 domain of the PEDV spike (S) protein. We evaluated their ability to induce mucosal immune responses in mice via different inoculation routes and to confer immune protection in piglets after oral inoculation. The results showed that S1-CS NPs exhibited no cytotoxicity and remained stable in simulated gastric fluid in vitro. Compared with oral administration, intramuscular inoculation of S1-CS NPs induced higher levels of PEDV-specific serum IgG in mice. However, PEDV-specific IgA was detected only in the serum and intestinal lavage fluid of orally vaccinated mice. Oral administration also elicited higher IFN-γ levels than intramuscular injection, suggesting stronger activation of cellular immunity. In piglets, oral S1-CS NPs induced serum neutralizing antibodies and IgA responses in both serum and intestinal mucosa, increased the number of IgA-secreting cells in the intestine, reduced viremia and virus shedding, and improved intestinal villus morphology. These findings indicate that the S1-CS NPs developed in this study represent promising candidates for an oral mucosal PEDV vaccine.
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DOI
PubMed
高影响因子
Food & Function
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2023
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IF 6.1
Jiachen Zhuang,Qianqian Wang,Fei Shen,Jing Wang,Juan Du,Peng Yu,Fengqin Feng,Minjie Zhao
This study investigated the immunomodulatory effects of soft-shelled turtle (Pelodiscus sinensis) peptide (TP) and Chinese pond turtle (Chinemys reevesii) peptide (TMP) on the intestinal mucosal immune system (IMIS). The results demonstrated that TP and TMP improved holistic immunity by restoring the vital immune organ atrophy and proliferation capacity of spleen immune cells. Moreover, TP and TMP significantly increased the serum content of IgA and cytokines that are responsible for immune cell activation and antigen clearance. TP and TMP promoted intestinal B cell activation, class switching recombination, and antibody secreting processes in a T cell-independent manner to increase the SIgA content. Furthermore, TP and TMP enhanced the intestinal barrier by increasing the protein expression of tight junctions (TJs) and adhesion junctions (AJs) and ameliorating the intestinal morphology. Mechanistically, TP and TMP activated the AHR/IL-22/STAT3/IL-6 axis to enhance the IgA response and improve the intestinal barrier, indicating their potential in intestinal health modulation.
研究领域:
免疫学
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胃肠病学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Linyan Lang,Yiping Fu,Jinxin Miao,Yagang Song,Xiaolei Zhang,Quanyou Zhao,Yuting Liu,Yu Zhang,Mingsan Miao,Xingyi Liu,Yueyang Zhang,Xiaoran Wang,Zhanzhan Li
In this study, we report that Fresh Rehmannia glutinosa extract (RGE), effectively prevents and treats Henoch-Schönlein Purpura (HSP) by regulating the PI3K-AKT-mTOR signaling pathway to restore the Treg/Th17 balance. • RGE, a traditional "medicinal and edible homology" herb recently added to China's 2024 list, demonstrates therapeutic potential for HSP by aligning with the TCM principle of "clearing descending fire and nourishing yin" to treat blood syndromes. • RGE and its core active component catalpol significantly alleviate HSP symptoms, reducing skin and renal purpura, pathological damage, and IgA deposition in mouse models. • RGE and its core active component catalpol restore Treg/Th17 balance and suppresses inflammatory cytokines by inhibiting the PI3K-AKT-mTOR/NF-κB signaling pathway, as confirmed by network pharmacology, molecular docking, and in vivo/in vitro experiments. • Multi-omics analysis reveals that RGE intervention reshapes gut microbiota structure and regulates metabolic homeostasis, suggesting a protective "gut-microbiota-immune" mechanism in HSP treatment. Background Therapeutic choices remain limited for Henoch-Schönlein purpura (HSP), an IgA-associated vasculitis. Rehmannia glutinosa , a medicinal and edible herb traditionally used to "clear heat and cool blood," shows clinical promise, yet its precise pathogenesis remains elusive. Purpose This study was designed to examine the therapeutic impact of Rehmannia glutinosa extract (RGE) on HSP, characterize its primary active components, and explore the mechanistic basis of its activity. Study design An integrative approach encompassing in vivo and in vitro HSP models, network pharmacology, LC-MS, molecular docking, dynamics simulations, microbiomics, and metabolomics was utilized to systematically identify the anti-HSP material basis and underlying mechanisms of RGE. Methods Forty-one active components in RGE were identified via LC-MS. A multi-level computational strategy-encompassing network pharmacology, docking studies, and molecular dynamics was applied to screen and identify Catalpol (Cat) as the key active candidate. ICR mouse HSP models and cell cultures were treated with RGE or Cat. Pathological injuries, IgA deposition, and immune cell proportion changes were evaluated using RT-qPCR, Western blot, flow cytometry, and multiplex immunofluorescence. Furthermore, microbiomics and metabolomics were utilized to decipher the mechanism by which RGE exerts its effects through gut microbiota regulation. Results RGE and Cat significantly alleviated skin and kidney injuries and reduced abnormal IgA deposition. By suppressing the PI3K-AKT-mTOR/NF-κB pathway, they successfully rectified the Treg/Th17 imbalance and mitigated inflammatory cytokine production. Additionally, RGE effectively reshaped the gut microbiota ecology and regulated the metabolome. Molecular simulations further confirmed Cat as a key active compound. Conclusion RGE exerts therapeutic effects on HSP through multi-target immunomodulation and gut microbiota remodeling, with Cat identified as a critical active component. These data support the herapeutic prospects of RGE and Cat in the prophylaxis and management of HSP. Download: Download high-res image (351KB) Download: Download full-size image
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