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Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway
Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity. Our study aimed to clarify the...
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| Published in: | Pharmaceutical biology 2023-12, Vol.61 (1), p.427-436 |
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| description | Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity.
Our study aimed to clarify the potential mechanism of SZP in improving chronic DN.
Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing.
SZP significantly reduced 24 h urine albumin (p |
| doi_str_mv | 10.1080/13880209.2023.2174145 |
| format | article |
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Our study aimed to clarify the potential mechanism of SZP in improving chronic DN.
Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing.
SZP significantly reduced 24 h urine albumin (p < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 μmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, Klebsiella and Escherichia-Shigella). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1β.
These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN.</description><identifier>ISSN: 1388-0209</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2023.2174145</identifier><identifier>PMID: 36772833</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Animals ; Biological activity ; chronic kidney diseases ; Creatinine ; Diabetes ; Diabetes Mellitus ; Diabetic Nephropathies - drug therapy ; Diabetic Nephropathies - metabolism ; Diabetic nephropathy ; Digestive system ; Enzyme-linked immunosorbent assay ; Gastrointestinal Microbiome ; Gastrointestinal tract ; Gram-negative bacteria ; Homeostasis ; Inflammation ; Insulin resistance ; Intestinal microbiota ; Intestinal microflora ; Lipopolysaccharides ; Male ; Metformin ; Mice ; Microbiota ; Nephropathy ; NF-kappa B - metabolism ; NF-κB protein ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; NLRP3 inflammasome ; Oral administration ; Polysaccharides ; Polysaccharides - pharmacology ; Polysaccharides - therapeutic use ; RNA, Ribosomal, 16S ; rRNA 16S ; Signal transduction ; TLR4 protein ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Traditional Chinese medicine ; Western blotting</subject><ispartof>Pharmaceutical biology, 2023-12, Vol.61 (1), p.427-436</ispartof><rights>2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2023</rights><rights>2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2023 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-4c9e3aed0371e5a073587b86503b44c9fc95781a9ca04e8ff87eddcce56a25c13</citedby><cites>FETCH-LOGICAL-c562t-4c9e3aed0371e5a073587b86503b44c9fc95781a9ca04e8ff87eddcce56a25c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930838/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2917546802?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27502,27924,27925,37012,37013,44590,53791,53793,59143,59144</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36772833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Fan</creatorcontrib><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Ren, LingZhi</creatorcontrib><creatorcontrib>Li, YanYang</creatorcontrib><creatorcontrib>Yang, HongMei</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Xu, WeiPing</creatorcontrib><title>Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway</title><title>Pharmaceutical biology</title><addtitle>Pharm Biol</addtitle><description>Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity.
Our study aimed to clarify the potential mechanism of SZP in improving chronic DN.
Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing.
SZP significantly reduced 24 h urine albumin (p < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 μmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, Klebsiella and Escherichia-Shigella). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1β.
These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN.</description><subject>Animals</subject><subject>Biological activity</subject><subject>chronic kidney diseases</subject><subject>Creatinine</subject><subject>Diabetes</subject><subject>Diabetes Mellitus</subject><subject>Diabetic Nephropathies - drug therapy</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic nephropathy</subject><subject>Digestive system</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Gastrointestinal Microbiome</subject><subject>Gastrointestinal tract</subject><subject>Gram-negative bacteria</subject><subject>Homeostasis</subject><subject>Inflammation</subject><subject>Insulin resistance</subject><subject>Intestinal microbiota</subject><subject>Intestinal microflora</subject><subject>Lipopolysaccharides</subject><subject>Male</subject><subject>Metformin</subject><subject>Mice</subject><subject>Microbiota</subject><subject>Nephropathy</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>NLRP3 inflammasome</subject><subject>Oral administration</subject><subject>Polysaccharides</subject><subject>Polysaccharides - pharmacology</subject><subject>Polysaccharides - therapeutic use</subject><subject>RNA, Ribosomal, 16S</subject><subject>rRNA 16S</subject><subject>Signal transduction</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><subject>Traditional Chinese medicine</subject><subject>Western blotting</subject><issn>1388-0209</issn><issn>1744-5116</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ks9u1DAQxiMEoqXwCCBLXLhk13_ixLkgoKJQaVVQKWdr4jiJqyRObafV8hQ8Dw_BM-F0txXlwMmjmd9847G_JHlJ8IpggdeECYEpLlcUU7aipMhIxh8lhzHIUk5I_jjGkUkX6CB55v0lxpgzxp8mBywvCioYO0x-foPxh2nnSo9osv3Wg1IdOFNrj8wwOXutUW2g0sEoNOqpc3aC0G2RGdFglEbVFjndzj0EM7aoncOSdrYyNgAKNnKdqUxAodPoYnOerc9O0t-_PqzPNudfGfKmHaHvl9ZF9ga2z5MnDfRev9ifR8n3k48Xx5_TzZdPp8fvN6niOQ1ppkrNQNeYFURzwAXjoqhEzjGrslhsVMkLQaBUgDMtmkYUuq6V0jwHyhVhR8npTre2cCknZwZwW2nByNuEda0EF5futSxVHFErTHiVZzllAiuaaVLmqsKNYDRqvd1pTXM16FrpMTjoH4g-rIymk629lmXJsGAiCrzZCzh7NWsf5GC80n0Po7azl7Qo4ta0wMus1_-gl3Z28REjVZKCZ7m4pfiOil_hvdPN_WUIlot_5J1_5OIfufdP7Hv19yb3XXeGicC7HWDGxroBbqzraxlg21vXOBiV8ZL9f8Yf_kTXQA</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Wang, Fan</creator><creator>Liu, Chang</creator><creator>Ren, LingZhi</creator><creator>Li, YanYang</creator><creator>Yang, HongMei</creator><creator>Yu, Yang</creator><creator>Xu, WeiPing</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>202312</creationdate><title>Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway</title><author>Wang, Fan ; Liu, Chang ; Ren, LingZhi ; Li, YanYang ; Yang, HongMei ; Yu, Yang ; Xu, WeiPing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-4c9e3aed0371e5a073587b86503b44c9fc95781a9ca04e8ff87eddcce56a25c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Biological activity</topic><topic>chronic kidney diseases</topic><topic>Creatinine</topic><topic>Diabetes</topic><topic>Diabetes Mellitus</topic><topic>Diabetic Nephropathies - drug therapy</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic nephropathy</topic><topic>Digestive system</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Gastrointestinal Microbiome</topic><topic>Gastrointestinal tract</topic><topic>Gram-negative bacteria</topic><topic>Homeostasis</topic><topic>Inflammation</topic><topic>Insulin resistance</topic><topic>Intestinal microbiota</topic><topic>Intestinal microflora</topic><topic>Lipopolysaccharides</topic><topic>Male</topic><topic>Metformin</topic><topic>Mice</topic><topic>Microbiota</topic><topic>Nephropathy</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>NLRP3 inflammasome</topic><topic>Oral administration</topic><topic>Polysaccharides</topic><topic>Polysaccharides - pharmacology</topic><topic>Polysaccharides - therapeutic use</topic><topic>RNA, Ribosomal, 16S</topic><topic>rRNA 16S</topic><topic>Signal transduction</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><topic>Traditional Chinese medicine</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Fan</creatorcontrib><creatorcontrib>Liu, Chang</creatorcontrib><creatorcontrib>Ren, LingZhi</creatorcontrib><creatorcontrib>Li, YanYang</creatorcontrib><creatorcontrib>Yang, HongMei</creatorcontrib><creatorcontrib>Yu, Yang</creatorcontrib><creatorcontrib>Xu, WeiPing</creatorcontrib><collection>Taylor & Francis_OA刊</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Pharmaceutical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Fan</au><au>Liu, Chang</au><au>Ren, LingZhi</au><au>Li, YanYang</au><au>Yang, HongMei</au><au>Yu, Yang</au><au>Xu, WeiPing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway</atitle><jtitle>Pharmaceutical biology</jtitle><addtitle>Pharm Biol</addtitle><date>2023-12</date><risdate>2023</risdate><volume>61</volume><issue>1</issue><spage>427</spage><epage>436</epage><pages>427-436</pages><issn>1388-0209</issn><eissn>1744-5116</eissn><abstract>Sanziguben (SZGB) is an empirical prescription used in traditional Chinese medicine to treat diabetic nephropathy (DN). As an abundant and primarily effective component of SZGB, Sanziguben polysaccharides (SZP) can be digested by flora to generate biological activity.
Our study aimed to clarify the potential mechanism of SZP in improving chronic DN.
Male db/db mice were randomized into DN, SZP (500 mg/kg) and metformin (MET, 300 mg/kg) groups. Wild-type littermates served as the normal control (NC) group. The drug was orally administered for 8 weeks. Enzyme-linked immunosorbent assay was used to detect the inflammatory factors. Proteins related to inflammation were evaluated using western blotting and immunohistochemical examination. Gut microbiota was analysed using 16S rRNA sequencing.
SZP significantly reduced 24 h urine albumin (p < 0.05) of DN mice. Compared to DN group, SZP significantly decreased the homeostasis model assessment of insulin resistance index, serum creatinine and blood urea nitrogen levels (20.27 ± 3.50 vs. 33.64 ± 4.85, 19.22 ± 3.77 vs. 32.52 ± 3.05 μmol/L, 13.23 ± 1.42 vs. 16.27 ± 0.77 mmol/L, respectively), and mitigated renal damage. SZP also regulated gut microbiota and decreased the abundance of Gram-negative bacteria (Proteobacteria, Klebsiella and Escherichia-Shigella). Subsequently, SZP reduced lipopolysaccharides levels (1.06- to 1.93-fold) of DN mice. Furthermore, SZP inhibited the expression levels of TLR4, phospho-NF-κB p65, NLRP3 proteins and interleukin (IL)-18 and IL-1β.
These results demonstrated that SZP improved intestinal flora disorder and inhibited the TLR4/NF-κB/NLRP3 pathway to alleviate DN.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>36772833</pmid><doi>10.1080/13880209.2023.2174145</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biological activity chronic kidney diseases Creatinine Diabetes Diabetes Mellitus Diabetic Nephropathies - drug therapy Diabetic Nephropathies - metabolism Diabetic nephropathy Digestive system Enzyme-linked immunosorbent assay Gastrointestinal Microbiome Gastrointestinal tract Gram-negative bacteria Homeostasis Inflammation Insulin resistance Intestinal microbiota Intestinal microflora Lipopolysaccharides Male Metformin Mice Microbiota Nephropathy NF-kappa B - metabolism NF-κB protein NLR Family, Pyrin Domain-Containing 3 Protein - metabolism NLRP3 inflammasome Oral administration Polysaccharides Polysaccharides - pharmacology Polysaccharides - therapeutic use RNA, Ribosomal, 16S rRNA 16S Signal transduction TLR4 protein Toll-Like Receptor 4 - metabolism Toll-like receptors Traditional Chinese medicine Western blotting |
| title | Sanziguben polysaccharides improve diabetic nephropathy in mice by regulating gut microbiota to inhibit the TLR4/NF-κB/NLRP3 signalling pathway |
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