<meta charset="utf8"></head><body>在小鼠模型中用 Dioscin 治疗免疫球蛋白 A 肾病 （IgAN）

<ol>
	<li>Knoppova, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+origin+and+activities+of+IgA1-containing+immune+complexes+in+IgA+nephropathy.">The origin and activities of IgA1-containing immune complexes in IgA nephropathy.</a> Frontiers in Immunology. 7, 117 (2016).</li><li>Suzuki, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pathophysiology+of+IgA+nephropathy.">The pathophysiology of IgA nephropathy.</a> Journal of The American Society of Nephrology. 22 (10), 1795-1803 (2011).</li><li>He, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthetic+double-stranded+RNA+poly(I:C)+aggravates+IgA+nephropathy+by+triggering+IgA+class+switching+recombination+through+the+TLR3-BAFF+axis.">Synthetic double-stranded RNA poly(I:C) aggravates IgA nephropathy by triggering IgA class switching recombination through the TLR3-BAFF axis.</a> American Journal of Nephrology. 42 (3), 185-197 (2015).</li><li>Zhao, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+level+of+galactose-deficient+IgA1+in+the+sera+of+patients+with+IgA+nephropathy+is+associated+with+disease+progression.">The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression.</a> Kidney International. 82 (7), 790-796 (2012).</li><li>Xing, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=C1GALT1+expression+is+associated+with+galactosylation+of+IgA1+in+peripheral+B+lymphocyte+in+immunoglobulin+a+nephropathy.">C1GALT1 expression is associated with galactosylation of IgA1 in peripheral B lymphocyte in immunoglobulin a nephropathy.</a> BMC Nephrology. 21 (1), 18 (2020).</li><li>Qin, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=External+suppression+causes+the+low+expression+of+the+Cosmc+gene+in+IgA+nephropathy.">External suppression causes the low expression of the Cosmc gene in IgA nephropathy.</a> Nephrology Dialysis Transplantation. 23 (5), 1608-1614 (2008).</li><li>Sakai, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lactobacillus+gasseri+SBT2055+induces+TGF-&#946;+expression+in+dendritic+cells+and+activates+TLR2+signal+to+produce+IgA+in+the+small+intestine.">Lactobacillus gasseri SBT2055 induces TGF-&#946; expression in dendritic cells and activates TLR2 signal to produce IgA in the small intestine.</a> PLoS One. 9 (8), 105370 (2014).</li><li>Gutzeit, C., Magri, G., Cerutti, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intestinal+IgA+production+and+its+role+in+host-microbe+interaction.">Intestinal IgA production and its role in host-microbe interaction.</a> Immunological Reviews. 260 (1), 76-85 (2014).</li><li>Serino, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+a+retrospective+international+study,+circulating+miR-148b+and+let-7b+were+found+to+be+serum+markers+for+detecting+primary+IgA+nephropathy.">In a retrospective international study, circulating miR-148b and let-7b were found to be serum markers for detecting primary IgA nephropathy.</a> Kidney International. 89 (3), 683-692 (2016).</li><li>Lu, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Therapeutic+effect+of+Rhizoma+Dioscoreae+Nipponicae+on+gouty+arthritis+based+on+the+SDF-1/CXCR+4+and+p38+MAPK+pathway:+an+in+vivo+and+in+vitro+study.">Therapeutic effect of Rhizoma Dioscoreae Nipponicae on gouty arthritis based on the SDF-1/CXCR 4 and p38 MAPK pathway: an in vivo and in vitro study.</a> Phytotherapy research: PTR. 28 (2), 280-288 (2014).</li><li>Wang, W., Xu, L., Zhou, L., Wan, S., Jiang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Network+pharmacology+approach+to+reveal+the+underlying+mechanisms+of+Rhizoma+Dioscoreae+Nipponicae+in+the+treatment+of+asthma.">A Network pharmacology approach to reveal the underlying mechanisms of Rhizoma Dioscoreae Nipponicae in the treatment of asthma.</a> Evidence-Based Complementary and Alternative Medicine: eCAM. 2022, 4749613 (2022).</li><li>Tian, W. W., Wei, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Professor+TONG+Xiaolin+used+the+experience+of+Dioscoreae+Nipponicae.">Professor TONG Xiaolin used the experience of Dioscoreae Nipponicae.</a> Jilin Journal of Chinese Medicine. 40 (05), 589-592 (2020).</li><li>Rao, X. R., Bai, Y. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Das+Xiwen's+experience+in+treating+IgA+nephropathy.">Das Xiwen's experience in treating IgA nephropathy.</a> Beijing Journal of Traditional Chinese Medicine. 9, 691-693 (2008).</li><li>Si, Y., Zhang, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+data+mining+study+on+the+pattern+of+medication+use+in+the+treatment+of+IgA+nephropathy+by+Professor+Zhang+Yu.">A data mining study on the pattern of medication use in the treatment of IgA nephropathy by Professor Zhang Yu.</a> Journal of Chinese Physician. 20 (01), 109-111 (2018).</li><li>Jiang, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimization+of+the+enzymatic+extraction+technology+of+Diosgenin+from+Dioscorea+nipponica.">Optimization of the enzymatic extraction technology of Diosgenin from Dioscorea nipponica.</a> Chinese Traditional Patent Medicine. 39 (03), 621-624 (2017).</li><li>Qi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dioscin+alleviates+lipopolysaccharide-induced+inflammatory+kidney+injury+via+the+microRNA+let-7i/TLR4/MyD88+signaling+pathway.">Dioscin alleviates lipopolysaccharide-induced inflammatory kidney injury via the microRNA let-7i/TLR4/MyD88 signaling pathway.</a> Pharmacological Research. 111, 509-522 (2016).</li><li>Yang, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+advances+in+the+pharmacological+activities+of+Dioscin.">Recent advances in the pharmacological activities of Dioscin.</a> BioMed Research International. 2019, 5763602 (2019).</li><li>Nal Zou, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toll-like+receptor+4+signaling+pathway+in+the+protective+effect+of+Pioglitazone+on+experimental+immunoglobulin+A+nephropathy.">Toll-like receptor 4 signaling pathway in the protective effect of Pioglitazone on experimental immunoglobulin A nephropathy.</a> Chinese Medical Journal. 130 (8), 906-913 (2017).</li><li>Xu, S. Y., Bian, R. L., Chen, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmacological+experiments+methodology.">Pharmacological experiments methodology.</a> Chinese Pharmacological Bulletin. 1, 19 (1992).</li><li>Shen, J. C., Ren, Y., Rao, X. R., You, Y., Li, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Network+pharmacology,+molecular+docking,+and+in+vitro+experiments+to+explore+the+molecular+mechanism+of+Dioscorea+Nipponica+Makion+in+the+treatment+of+IgA+nephropathy.">Network pharmacology, molecular docking, and in vitro experiments to explore the molecular mechanism of Dioscorea Nipponica Makion in the treatment of IgA nephropathy.</a> World Journal of Integrated Traditional and Western Medicine. 16 (12), 2246-2254 (2021).</li><li>Mestecky, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=IgA+nephropathy:+molecular+mechanisms+of+the+disease.">IgA nephropathy: molecular mechanisms of the disease.</a> Annual Review of Pathology. 8, 217-240 (2013).</li><li>Novak, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=IgA1-containing+immune+complexes+in+IgA+nephropathy+differentially+affect+proliferation+of+mesangial+cells.">IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells.</a> Kidney International. 67 (2), 504-513 (2005).</li><li>Nihei, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+of+IgA+autoantibodies+targeting+mesangial+cells+redefines+the+pathogenesis+of+IgA+nephropathy.">Identification of IgA autoantibodies targeting mesangial cells redefines the pathogenesis of IgA nephropathy.</a> Science Advances. 9 (12), (2023).</li><li>Raska, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Identification+and+characterization+of+CMP-NeuAc:+GalNAc-IgA1+alpha2,6-sialyltransferase+in+IgA1-producing+cells.">Identification and characterization of CMP-NeuAc: GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells.</a> Journal of Molecular Biology. 369 (1), 69-78 (2007).</li></ol>

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Anti-CD20/MS4A1 Antibody</td>
			<td>Boster Biotechnology Company</td>
			<td>A03780-3</td>
			<td></td>
		</tr>
		<tr>
			<td>Antifade mounting medium</td>
			<td>Beyotime, Shanghai, China</td>
			<td>P0128S</td>
			<td></td>
		</tr>
		<tr>
			<td>Balb/c mice</td>
			<td>Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd.</td>
			<td>110322220101424000</td>
			<td></td>
		</tr>
		<tr>
			<td>blocking serum</td>
			<td>Solarbio, Beijing, China</td>
			<td>SL038</td>
			<td></td>
		</tr>
		<tr>
			<td>Bovine gamma globulin</td>
			<td>ShangHai YuanYe Biotechnology Company</td>
			<td>S12031</td>
			<td></td>
		</tr>
		<tr>
			<td>C1GALT1 polyclonal antibody</td>
			<td>Proteintech Group, Inc,USA</td>
			<td>27569-1-AP</td>
			<td></td>
		</tr>
		<tr>
			<td>Citrate antigen retrieval solution(50&#215;)</td>
			<td>Phygene Biotechnology Company</td>
			<td>PH0422</td>
			<td></td>
		</tr>
		<tr>
			<td>COSMC polyclonal antibody</td>
			<td>Proteintech Group, Inc,USA</td>
			<td>19254-1-AP</td>
			<td></td>
		</tr>
		<tr>
			<td>Cytotoxiciy detection kit</td>
			<td>Roche Company</td>
			<td>4744926001</td>
			<td></td>
		</tr>
		<tr>
			<td>Dako REAL EnVision detection system, Peroxidase/DAB+</td>
			<td>Dako</td>
			<td>K5007</td>
			<td></td>
		</tr>
		<tr>
			<td>DAPI</td>
			<td>Invitrogen</td>
			<td>D1306</td>
			<td></td>
		</tr>
		<tr>
			<td>Dioscin</td>
			<td>National Institute For Food and Drug Control</td>
			<td>111707-201703</td>
			<td></td>
		</tr>
		<tr>
			<td>DIO tablets</td>
			<td>Chengdu No 1 Pharmaceutical Co. Ltd.</td>
			<td>H51023866</td>
			<td></td>
		</tr>
		<tr>
			<td>ECL working solution</td>
			<td>Merck Biotechnology, Inc</td>
			<td>WBKLS0100&#160;</td>
			<td></td>
		</tr>
		<tr>
			<td>Enhanced cell counting kit-8</td>
			<td>Beyotime, Shanghai, China</td>
			<td>C0043</td>
			<td></td>
		</tr>
		<tr>
			<td>Fasking one-step removal of gene cDNA first-strand synthesis premix</td>
			<td>TIANGEN,Beijing, China</td>
			<td>KR118-02</td>
			<td></td>
		</tr>
		<tr>
			<td>Glycogen Periodic acid Schiff (PAS) stain kit&#160;</td>
			<td>BaSO Biotechnology Company</td>
			<td>BA4080A</td>
			<td></td>
		</tr>
		<tr>
			<td>Goat anti-mouse IgA-AF488</td>
			<td>SouthernBiotech</td>
			<td>1040-30</td>
			<td></td>
		</tr>
		<tr>
			<td>Goat anti-rabbit IgG antibody (H+L), HRP conjugated</td>
			<td>BeiJing Bioss Biotechnology Company</td>
			<td>BS-0295G-HRP</td>
			<td></td>
		</tr>
		<tr>
			<td>Human Gd-IgA1 ELISA kit</td>
			<td>IBL</td>
			<td>27600</td>
			<td></td>
		</tr>
		<tr>
			<td>Human IgA ELISA kit</td>
			<td>MultiSciences (LiankeBio)</td>
			<td>70-EK174-96</td>
			<td></td>
		</tr>
		<tr>
			<td>Pierce BCA protein assay kit</td>
			<td>Thermo Scientific</td>
			<td>23227</td>
			<td></td>
		</tr>
		<tr>
			<td>PMSF solution</td>
			<td>Beyotime, Shanghai, China</td>
			<td>ST507</td>
			<td></td>
		</tr>
		<tr>
			<td>Proteinase K&#160;</td>
			<td>Phygene Biotechnology Company</td>
			<td>PH1521</td>
			<td></td>
		</tr>
		<tr>
			<td>Rabbit anti-CXCR5 polyclonal antibody&#160;</td>
			<td>BeiJing Bioss Biotechnology Company</td>
			<td>bs-23570R</td>
			<td></td>
		</tr>
		<tr>
			<td>RIPA lysis buffer</td>
			<td>Beyotime, Shanghai, China</td>
			<td>P0013B</td>
			<td></td>
		</tr>
		<tr>
			<td>RNAsimple total RNA extraction kit</td>
			<td>TIANGEN,Beijing, China</td>
			<td>DP419</td>
			<td></td>
		</tr>
		<tr>
			<td>RPMI Medium 1640</td>
			<td>Solarbio, Beijing, China</td>
			<td>31800</td>
			<td></td>
		</tr>
		<tr>
			<td>Super-Bradford protein assay kit</td>
			<td>CWBIO, Beijing, China</td>
			<td>CW0013</td>
			<td></td>
		</tr>
		<tr>
			<td>Triton&#160;X-100</td>
			<td>Beyotime, Shanghai, China</td>
			<td>ST795</td>
			<td></td>
		</tr>
		<tr>
			<td>&#946;-Actin Rabbit mAb</td>
			<td>Abclonal, Wuhan, China</td>
			<td>AC026</td>
			<td></td>
		</tr>
	</tbody>
</table>

dioscin mediated iga nephropathy alleviation by inhibiting b cell activation in vivo and decreasing galactose-deficient iga1 production in vitro

IgA Nephropathy (IgAN) is the most common type of primary glomerulonephritis, for which there is no specific treatment, and it remains a significant cause of end-stage renal disease1. Although the pathogenesis of IgAN is still not fully understood, the &#34;multi-hit hypothesis&#34; is generally accepted and supported by a large body of clinical and experimental research evidence2. The pathogenesis of IgAN involves activating B cells and producing Galactose-deficient IgA1 (Gd-IgA1)3. The increase in circulating Gd-IgA1 due to the excessive proliferation and activation of IgA-secreting cells during the mucosal immune response is a critical link in the pathogenesis of IgAN4,5,6. As the central place for the proliferation and activation of B lymphocyte phenotype conversion to IgA-secreting cells, Peyer&#39;s patch is the primary source of IgA secretion, closely related to the occurrence and development of IgAN7,8. In addition, the proliferation of IgA1-secreting cells, as well as expression of Core 1&#946;-1,3-galactosyltransferase(C1GalT1) and C1GalT1-specific molecular chaperone (Cosmc), were associated with abnormal glycosylation of IgA1, which causes GD-IgA1 production in IgAN patients6,9.
Clinical study on IgAN treatment with herbal medicine has progressed in recent years. Yiqi Qingjie Formula is an essential formula for treating IgAN by the Department of Nephrology of Guang&#39;anmen Hospital. The previous study of our group found that Gd-IgA1 decreased in the serum of IgAN patients after treatment with Yiqi Qingjie Formula. As one of the most used herbs in the Yiqi Qingjie Formula, Dioscoreae Nipponicae Rhizoma (DNR) is the dried rhizome of Dioscorea Nipponica Makino, which has various functions such as regulating immunity, suppressing inflammation, relieving cough and asthma10,11. Several scholars treated IgAN with DNR and achieved good results12,13,14. As the main active ingredient in DNR15, Dioscin (DIO) lowers uric acid, inhibits fibrosis, inhibits inflammatory response, and anti-oxidative stress16,17. Therefore, DIO may have a novel action mechanism to inhibit the cellular secretion of excessive Gd-IgA1 and exert specific kidney protection effects. Still, no study has been reported on DIO&#39;s action mechanism for treating IgAN.
To explore the potential therapeutic mechanism of DIO on IgAN and provide a new method for the treatment of IgAN, we carried out experiments for the therapeutic effects of DIO on IgAN in vivo and in vitro.

<meta charset="utf8"></head><body>作者聚焦：研究中草药活性薯片素治疗 IgA 肾病的潜力

Dioscin 通过抑制体内 B 细胞活化和减少体外半乳糖缺乏型 IgA1 的产生来缓解 IgA 肾病

Our main research area is how Chinese herbal medicine works to treat chronic kidney disease like IGA nephropathy. In this study, based on our clinical experience and treatment of IGA nephropathy, using Dioscorea Nipponica Rhizoma, abbreviation DNR, and our research result of the main active substance of DNR, we try to confirm the potential value of dioscin as one of the main active substance of DNR. And Discover is possible mechanism of action in the treatment of IGA nephropathy through in vivo and in vitro experiments.Abnormal IgA1 production, that is the increased lactose deficient IgA1, is important in the pathogenesis of IgA nephropathy, and there is strong evidence that glycan associated lymphoid tissue plays a significant role in the production of galactose-deficient IgA1. In vitro experiments, we found that dioscin has a very distinct inhibitory effect on the proliferation of IgA-secreting cells, dark cell line at relatively low concentration, as well as an inhibitory effect on the secretion of GD-IgA1 by dark cells. These findings indicate that dioscin may have a potential therapeutic value for IGA nephropathy as well as disease linked to excessive B cell activation, such as systemic lupus erythematosus.Due to the complexity of Chinese herbal ingredients, the study of the therapeutic mechanism of Chinese herbal medicine faces considerable difficulties, especially in cell experiments in which a mechanism discussion like ours, using the main active ingredient of a non-herbal medicine as the representative substance of the drug may be commonly adopted research method. And we hope these kinds of works may provide the foundation for the discovery of new drugs for natural medicine.

Watch this Scientific Journal Video about Dioscin Mediated IgA Nephropathy Alleviation by Inhibiting B Cell Activation In Vivo and Decreasing Galactose-Deficient IgA1 Production In Vitro at JoVE.com

The increase of circulating galactose-deficient IgA1 (Gd-IgA1) is caused by excessive activation of IgA-positive secretory cells in the process of mucosal ...

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Dioscin Mediated IgA Nephropathy Alleviation by Inhibiting B Cell Activation In Vivo and Decreasing Galactose-Deficient IgA1 Production In Vitro

609 次观看.  Guanganmen Hospital. 我们的主要研究领域是中草药如何治疗慢性肾病，如 IGA 肾病。在这项研究中，根据我们对 IGA 肾病的临床经验和治疗，使用日本薯蓣（Dioscorea Nipponica Rhizoma，简称 DNR）以及我们对 DNR 主要活性物质的研究结果，我们试图确认薯蓣皂苷作为 DNR 主要活性物质之一的潜在价值。Discover 是通过体内和体外实验治疗 IGA 肾病的可能作用机制。异常的 IgA1 ?...