{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:20:48Z","timestamp":1783059648176,"version":"3.54.6"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Tripterygium<\/jats:italic>\n                      glycosides tablet (TGT), the major preparation of\n                      <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                      Hook. f (TWHF), is widely used in treating chronic kidney disease (CKD). However, its complex composition and overlap between active and toxic constituents often lead to adverse effects, limiting precise clinical use. This study aimed to clarify the therapeutic mechanisms of TGT in CKD and identify its potential toxic ingredients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using constituent knock-out\/knock-in technology and HPLC fingerprinting,\n                      <jats:italic>Tripterygium<\/jats:italic>\n                      glycosides tablet was divided into an alkaloid-enriched fraction and a non-alkaloid-enriched fraction An adenine-induced CKD rat model was used to evaluate efficacy and toxicity. Non-targeted metabolomics and 16S rRNA sequencing identified key metabolites and gut microbiota, while a UPLC-MS\/MS method quantified gut-derived uremic toxins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TGT reduced serum creatinine, urea nitrogen, and uric acid levels, improved renal filtration, and restored kidney morphology. Metabolomic and microbiota analyses revealed decreased indole and amino acid derivatives and regulation of\n                      <jats:italic>g_Bacteroides<\/jats:italic>\n                      and\n                      <jats:italic>g_Rodentibacter<\/jats:italic>\n                      . UPLC-MS\/MS confirmed reductions in indoxyl sulfate (IS) and\n                      <jats:italic>p<\/jats:italic>\n                      -cresyl sulfate (pCS), mainly via inhibition of the tryptophan\u2013indole\u2013IS pathway. Conversely, AEF increased creatinine, urea nitrogen, cystatin C, and trimethylamine N-oxide (TMAO), exacerbating glomerular dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TGT exerts renoprotective effects partly by modulating the gut\u2013liver\u2013kidney axis and reducing gut-derived uremic toxins, while alkaloids likely contribute to its toxicity. These findings offer new insights into the safe and effective use of TGT in CKD therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1739319","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:38:15Z","timestamp":1783057095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tripterygium glycosides tablet ameliorates chronic kidney disease via gut-derived uremic toxins reduction in rats: alkaloids as major toxic ingredients"],"prefix":"10.3389","volume":"17","author":[{"given":"He","family":"Gong","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sixian","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuohua","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"He","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University","place":["Guangzhou, China"]},{"name":"Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University","place":["Guangzhou, China"]},{"name":"Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3390\/biom15010041","article-title":"The metabolism of creatinine and its usefulness to evaluate kidney function and body composition in clinical practice","volume":"15","author":"\u00c1vila","year":"2025","journal-title":"Biomolecules"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1093\/ndt\/gfk056","article-title":"Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis","volume":"21","author":"Bain","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"B3","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/s0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990\u20132017: a systematic analysis for the global burden of disease study 2017","volume":"395","author":"Bikbov","year":"2020","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.phytochem.2018.10.001","article-title":"Anti-inflammatory abietanes diterpenoids isolated from Tripterygium hypoglaucum","volume":"156","author":"Chen","year":"2018","journal-title":"Phytochemistry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e12954","DOI":"10.1111\/jpi.12954","article-title":"Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism","volume":"76","author":"Chen","year":"2024","journal-title":"J. Pineal Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"21307","DOI":"10.1073\/pnas.1215689109","article-title":"Microbial conversion of choline to trimethylamine requires a glycyl radical enzyme","volume":"109","author":"Craciun","year":"2012","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.19540\/j.cnki.cjcmm.20191221.304","article-title":"Research progress on identification of pharmacodynamic substance basis of traditional Chinese medicine based on target constituent knock-out\/knock-in technology","volume":"45","author":"Cui","year":"2020","journal-title":"China J. Chin. Materia Medica"},{"key":"B8","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1002\/jbt.20261","article-title":"Segment-specific proximal tubule injury in tripterygium glycosides intoxicated rats","volume":"22","author":"Dan","year":"2008","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.chom.2016.10.021","article-title":"Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota","volume":"20","author":"Devlin","year":"2016","journal-title":"Cell Host and Microbe"},{"key":"B10","doi-asserted-by":"publisher","first-page":"605","DOI":"10.2174\/1389200219666180302152752","article-title":"Pharmacokinetic and toxicological characteristics of tripterigium glycosides and their derivatives","volume":"19","author":"Du","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1681\/asn.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1097\/01.Asn.0000022017.96399.B2","article-title":"Role of organic anion transporters in the tubular transport of indoxyl sulfate and the induction of its nephrotoxicity","volume":"13","author":"Enomoto","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1007\/s00467-016-3527-x","article-title":"The gut\u2013kidney axis","volume":"32","author":"Evenepoel","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1016\/s0140-6736(18)31694-5","article-title":"Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016\u201340 for 195 countries and territories","volume":"392","author":"Foreman","year":"2018","journal-title":"Lancet"},{"key":"B15","doi-asserted-by":"publisher","first-page":"202","DOI":"10.3390\/toxins10050202","article-title":"Role of uremic toxins for kidney, cardiovascular, and bone dysfunction","volume":"10","author":"Fujii","year":"2018","journal-title":"Toxins"},{"key":"B16","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.phymed.2018.03.031","article-title":"Wilforine, the Q-marker and PK-maker of tripterygium glycosides tablet: based on preparation quantitative analysis and PK-PD study","volume":"54","author":"Gao","year":"2019","journal-title":"Phytomedicine"},{"key":"B17","doi-asserted-by":"publisher","first-page":"154813","DOI":"10.1016\/j.phymed.2023.154813","article-title":"Toxic effects of tripterygium glycoside tablets on the reproductive system of Male rats by metabolomics, cytotoxicity, and molecular docking","volume":"114","author":"Ge","year":"2023","journal-title":"Phytomedicine"},{"key":"B18","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.addr.2017.01.005","article-title":"Xenobiotic transporters and kidney injury","volume":"116","author":"George","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"6659","DOI":"10.1038\/s41598-018-25139-8","article-title":"Contribution of multidrug and toxin extrusion protein 1 (MATE1) to renal secretion of trimethylamine-N-oxide (TMAO)","volume":"8","author":"Gessner","year":"2018","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.jpha.2023.03.004","article-title":"Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice","volume":"13","author":"Guo","year":"2023","journal-title":"J. Pharm. Analysis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1354823","DOI":"10.3389\/fmicb.2024.1354823","article-title":"Dysfunction of cecal microbiota and CutC activity in mice mediating diarrhea with kidney-yang deficiency syndrome","volume":"15","author":"Guo","year":"2024","journal-title":"Front. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"997","DOI":"10.2215\/cjn.0000000000000203","article-title":"Comparison of cystatin C and creatinine in the assessment of measured kidney function during critical illness","volume":"18","author":"Haines","year":"2023","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1111\/febs.12205","article-title":"Benzimidazole analogs of l\u2010tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli","volume":"280","author":"Harris","year":"2013","journal-title":"FEBS J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.molcel.2017.03.008","article-title":"Celastrol-induced Nur77 interaction with TRAF2 alleviates inflammation by promoting mitochondrial ubiquitination and autophagy","volume":"66","author":"Hu","year":"2017","journal-title":"Mol. Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1186\/s12967-023-04259-4","article-title":"Sodium butyrate ameliorates diabetic retinopathy in mice via the regulation of gut microbiota and related short-chain fatty acids","volume":"21","author":"Huang","year":"2023","journal-title":"J. Transl. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"780924","DOI":"10.3389\/fphar.2021.780924","article-title":"Rhubarb enema decreases circulating trimethylamine N-Oxide level and improves renal fibrosis accompanied with gut microbiota change in chronic kidney disease rats","volume":"12","author":"Ji","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.aca.2009.10.024","article-title":"Recent analytical approaches in quality control of traditional Chinese medicines\u2014A review","volume":"657","author":"Jiang","year":"2010","journal-title":"Anal. Chim. Acta"},{"key":"B28","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.jep.2013.03.018","article-title":"Fishing and knockout of bioactive compounds using a combination of high-speed counter-current chromatography (HSCCC) and preparative HPLC for evaluating the holistic efficacy and interaction of the components of herba epimedii","volume":"147","author":"Jin","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"571","DOI":"10.3109\/00498254.2014.1003113","article-title":"Inhibitory mechanisms of celastrol on human liver cytochrome P450 1A2, 2C19, 2D6, 2E1 and 3A4","volume":"45","author":"Jin","year":"2015","journal-title":"Xenobiotica"},{"key":"B30","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/s0140-6736(21)00519-5","article-title":"Chronic kidney disease","volume":"398","author":"Kalantar-Zadeh","year":"2021","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1038\/s41467-019-09735-4","article-title":"Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease","volume":"10","author":"Kikuchi","year":"2019","journal-title":"Nat. Commun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e00413-20","DOI":"10.1128\/mSystems.00413-20","article-title":"An expanded genetic code enables trimethylamine metabolism in human gut bacteria","volume":"5","author":"Kivenson","year":"2020","journal-title":"mSystems"},{"key":"B33","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.cmet.2014.10.006","article-title":"\u03b3-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-Carnitine to TMAO","volume":"20","author":"Koeth","year":"2014","journal-title":"Cell Metab."},{"key":"B34","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3390\/toxins15020116","article-title":"Food-derived uremic toxins in chronic kidney disease","volume":"15","author":"Lauriola","year":"2023","journal-title":"Toxins"},{"key":"B35","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.1002\/jcph.735","article-title":"Renal transporter\u2010mediated drug-drug interactions: are they clinically relevant?","volume":"56","author":"Lepist","year":"2016","journal-title":"J. Clin. Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1097\/cm9.0000000000000228","article-title":"Roles of short-chain fatty acids in kidney diseases","volume":"132","author":"Li","year":"2019","journal-title":"Chin. Med. J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3390\/toxins13020142","article-title":"Uremic toxins in the progression of chronic kidney disease and cardiovascular disease: mechanisms and therapeutic targets","volume":"13","author":"Lim","year":"2021","journal-title":"Toxins"},{"key":"B38","doi-asserted-by":"publisher","first-page":"608703","DOI":"10.3389\/fphar.2020.608703","article-title":"Clinical practice guideline for tripterygium glycosides\/tripterygium wilfordii tablets in the treatment of rheumatoid arthritis","volume":"11","author":"Lin","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"104190","DOI":"10.1016\/j.fitote.2019.104190","article-title":"The genus tripterygium: a phytochemistry and pharmacological review","volume":"137","author":"Lv","year":"2019","journal-title":"Fitoterapia"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1093\/ndt\/gfq785","article-title":"Organic anion transporters play an important role in the uptake of p-cresyl sulfate, a uremic toxin, in the kidney","volume":"26","author":"Miyamoto","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"B41","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"B42","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1124\/pr.116.013326","article-title":"Biomarkers for in vivo assessment of transporter function","volume":"70","author":"M\u00fcller","year":"2018","journal-title":"Pharmacol. Rev."},{"key":"B43","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.chroma.2015.04.048","article-title":"Comprehensive two-dimensional liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for chemical constituents analysis of tripterygium glycosides tablets","volume":"1400","author":"Qu","year":"2015","journal-title":"J. Chromatogr. A"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1171517","DOI":"10.3389\/fcimb.2023.1171517","article-title":"Causal effects between gut microbiota and IgA nephropathy: a bidirectional Mendelian randomization study","volume":"13","author":"Ren","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1016\/j.athoracsur.2015.05.074","article-title":"Triptolide inhibits lung cancer cell migration, invasion, and metastasis","volume":"100","author":"Reno","year":"2015","journal-title":"Ann. Thorac. Surg."},{"key":"B46","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/s12882-020-01805-w","article-title":"The gut microbiota profile of adults with kidney disease and kidney stones: a systematic review of the literature","volume":"21","author":"Stanford","year":"2020","journal-title":"BMC Nephrol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int."},{"key":"B48","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1016\/j.bbrc.2017.09.108","article-title":"Gut microbial metabolite TMAO contributes to renal dysfunction in a mouse model of diet-induced obesity","volume":"493","author":"Sun","year":"2017","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B49","doi-asserted-by":"publisher","first-page":"153716","DOI":"10.1016\/j.phymed.2021.153716","article-title":"Purslane (portulacae oleracea L.) attenuates cadmium-induced hepatorenal and colonic damage in mice: role of chelation, antioxidant and intestinal microecological regulation","volume":"92","author":"Tian","year":"2021","journal-title":"Phytomedicine"},{"key":"B50","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1038\/ki.2012.345","article-title":"Chronic kidney disease alters intestinal microbial flora","volume":"83","author":"Vaziri","year":"2013","journal-title":"Kidney Int."},{"key":"B51","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.jpba.2018.08.018","article-title":"Identification of hepatotoxic and nephrotoxic potential markers of triptolide in mice with delayed-type hypersensitivity","volume":"160","author":"Wang","year":"2018","journal-title":"J. Pharm. Biomed. Analysis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1001\/jamainternmed.2022.6817","article-title":"Prevalence of chronic kidney disease in China","volume":"183","author":"Wang","year":"2023","journal-title":"JAMA Intern. Med."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1145196","DOI":"10.3389\/fcimb.2023.1145196","article-title":"Increased abundance of bacteria of the family muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats","volume":"13","author":"Wang","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"910923","DOI":"10.3389\/fphar.2022.910923","article-title":"Differences in multicomponent pharmacokinetics, tissue distribution, and excretion of tripterygium glycosides tablets in normal and adriamycin\u2013induced nephrotic syndrome rat models and correlations with efficacy and hepatotoxicity","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.kint.2018.04.011","article-title":"Analysis of the global burden of disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016","volume":"94","author":"Xie","year":"2018","journal-title":"Kidney Int."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e0029124","DOI":"10.1128\/spectrum.00291-24","article-title":"Interplay between gut microbiota and tryptophan metabolism in type 2 diabetic mice treated with metformin","volume":"12","author":"Xie","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1001\/jamainternmed.2016.4687","article-title":"Efficacy of folic acid therapy on the progression of chronic kidney disease","volume":"176","author":"Xu","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1952","DOI":"10.1039\/d2fo03475a","article-title":"Identification of yeast \u03b1-glucosidase inhibitors from Pueraria Lobata by ligand fishing based on magnetic mesoporous silicon combined with knock-out\/knock-in technology","volume":"14","author":"Xu","year":"2023","journal-title":"Food and Funct."},{"key":"B59","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41581-018-0018-2","article-title":"The gut microbiota and the brain\u2013gut\u2013kidney axis in hypertension and chronic kidney disease","volume":"14","author":"Yang","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"463118","DOI":"10.1016\/j.chroma.2022.463118","article-title":"A trinity fingerprint evaluation system of traditional Chinese medicine","volume":"1673","author":"Yang","year":"2022","journal-title":"J. Chromatogr. A"},{"key":"B61","doi-asserted-by":"publisher","first-page":"121721","DOI":"10.1016\/j.jchromb.2019.121721","article-title":"Identification of the chemical components and metabolites of tripterygium glycoside tablets in mice by HPLC-Q\/TOF MS","volume":"1125","author":"Zhang","year":"2019","journal-title":"J. Chromatogr. B"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1002\/med.21762","article-title":"Tripterygium wilfordii: an inspiring resource for rheumatoid arthritis treatment","volume":"41","author":"Zhang","year":"2020","journal-title":"Med. Res. Rev."},{"key":"B63","doi-asserted-by":"publisher","first-page":"4268","DOI":"10.1073\/pnas.1316569111","article-title":"Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota","volume":"111","author":"Zhu","year":"2014","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s12010-020-03301-1","article-title":"Purification and biochemical characterization of a tyrosine phenol-lyase from Morganella morganii","volume":"192","author":"Zhu","year":"2020","journal-title":"Appl. Biochem. Biotechnol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1739319\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:38:17Z","timestamp":1783057097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1739319\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":64,"alternative-id":["10.3389\/fphar.2026.1739319"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1739319","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]},"article-number":"1739319"}}