{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:22:52Z","timestamp":1787638972982,"version":"build-2736575974"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"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>Background<\/jats:title>\n                    <jats:p>Renal fibrosis is the principal pathological hallmark of progressive chronic kidney disease (CKD). However, the clinical availability of effective, targeted anti-fibrotic therapeutics remains severely constrained. Astragaloside IV (AS-IV), a predominant bioactive metabolite isolated from Astragali Radix, has exhibited substantial renoprotective and anti-fibrotic properties in diverse preclinical models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We systematically searched eight electronic databases (PubMed, Web of Science, Embase, ProQuest, CNKI, SinoMed, VIP, and Wanfang Data) from inception to 30 November 2025, to identify relevant\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies. Risk of bias was assessed using the SYRCLE tool. Statistical analyses were performed using Review Manager 5.3 and Stata 18.0.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 34 studies involving 769 animals were included. Compared with the control group, AS-IV treatment significantly reduced the levels of serum creatinine (Scr), blood urea nitrogen (BUN), proteinuria, transforming growth factor-\u03b21 (TGF-\u03b21), fibronectin, and \u03b1-smooth muscle actin (\u03b1-SMA) (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.0001). Subgroup analyses revealed that intragastric dose was a source of heterogeneity for Scr; publication year for BUN; treatment duration for TGF-\u03b21; and the underlying animal disease model alongside treatment duration for \u03b1-SMA. Dose-response analyses revealed that Scr, BUN, TGF-\u03b21, fibronectin, and \u03b1-SMA showed overall negative dose-dependent trends. In addition, AS-IV significantly modulated the expression of other indicators related to fibrosis, oxidative stress, and inflammatory responses. Methodologically, the overall quality of the included studies was suboptimal, and there was considerable statistical heterogeneity. Additionally, the presence of publication bias cannot be definitively excluded. These results suggest that AS-IV holds renoprotective potential in animal models of renal fibrosis; however, these results should be interpreted prudently.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides the first systematic review evaluating AS-IV across etiologically diverse models of renal fibrosis, showing its broad-spectrum anti-fibrotic pharmacological effects. The synthesized evidence suggests that these renoprotective effects may be mediated through multi-target modulation, including mitigating inflammation and oxidative stress, modulating autophagy and apoptosis, and reducing extracellular matrix (ECM) accumulation. Nevertheless, given the significant heterogeneity and overall suboptimal methodological quality of the included studies, these positive findings should be interpreted with caution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261372263<\/jats:ext-link>\n                      , identifier CRD420261372263.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1867891","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:36:29Z","timestamp":1787636189000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects and potential mechanisms of astragaloside IV in animal models of renal fibrosis: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Shijie","family":"Li","sequence":"first","affiliation":[{"name":"Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cui","sequence":"additional","affiliation":[{"name":"Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youping","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiology, First Affiliated Hospital, Henan University of Traditional Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/s41581-025-00934-5","article-title":"Advances and challenges in kidney fibrosis therapeutics","volume":"21","author":"Abbad","year":"2025","journal-title":"Nat. Reviews. Nephrol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e72860","DOI":"10.1371\/journal.pone.0072860","article-title":"The gap between estimated incidence of end-stage renal disease and use of therapy","volume":"8","author":"Anand","year":"2013","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.3923\/ijp.2024.1331.1338","article-title":"Exploring the protective effects of astragaloside IV against cisplatin-induced kidney injury in rats","volume":"20","author":"Arda","year":"2024","journal-title":"Int. J. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.3390\/antiox13121454","article-title":"Oxidative stress in kidney injury and hypertension","volume":"13","author":"Arendshorst","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e190836","DOI":"10.1172\/jci.insight.190836","article-title":"TNF-\u03b1 represses fibroblast to myofibroblast transition through the histone methyltransferase Setdb2","volume":"10","author":"Bauer","year":"2025","journal-title":"JCI Insight"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.3390\/antiox12122083","article-title":"Oxidative stress induced by lipotoxicity and renal hypoxia in diabetic kidney disease and possible therapeutic interventions: targeting the lipid metabolism and hypoxia","volume":"12","author":"Chae","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"58","DOI":"10.16254\/j.cnki.53-1120\/r.2016.02.027","article-title":"A preliminary study on the protection mechanism of astragaloside for diabetic nephropathy rats","volume":"37","author":"Chen","year":"2016","journal-title":"Yunnan J. Traditional Chin. Med. Materia Medica"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1007\/s40620-023-01878-4","article-title":"Interpretable machine learning model integrating clinical and elastosonographic features to detect renal fibrosis in Asian patients with chronic kidney disease","volume":"37","author":"Chen","year":"2024","journal-title":"J. Nephrol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"117198","DOI":"10.1016\/j.jep.2023.117198","article-title":"Efficacy and potential mechanisms of the main active ingredients of astragalus mongholicus in animal models of liver fibrosis: a systematic review and meta-analysis","volume":"319","author":"Dan","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41392-024-01764-w","article-title":"TGF-\u03b2 signaling in health, disease, and therapeutics","volume":"9","author":"Deng","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.mam.2018.06.002","article-title":"Cellular and molecular mechanisms of kidney fibrosis","volume":"65","author":"Djudjaj","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"B12","first-page":"294","article-title":"Effects of astragaloside IV on renal damage in streptozotocin STZ-induced diabetic rats","volume":"32","author":"Fan","year":"2017","journal-title":"Chin. J. Tradit. Chin. Med. Pharm."},{"key":"B13","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41581-024-00820-6","article-title":"Chronic kidney disease and the global public health agenda: an international consensus","volume":"20","author":"Francis","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"610102","DOI":"10.3389\/fphar.2020.610102","article-title":"Astragaloside IV alleviates tacrolimus-induced chronic nephrotoxicity via p62-Keap1-Nrf2 pathway","volume":"11","author":"Gao","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1093\/cvr\/cvv147","article-title":"Monocyte trafficking across the vessel wall","volume":"107","author":"Gerhardt","year":"2015","journal-title":"Cardiovasc Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1742-7843.2004.t01-1-pto950508.x","article-title":"Transport and bioavailability studies of astragaloside IV, an active ingredient in Radix Astragali","volume":"95","author":"Gu","year":"2004","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"500","DOI":"10.3389\/fphar.2016.00500","article-title":"Astragaloside IV attenuates podocyte apoptosis mediated by endoplasmic reticulum stress through upregulating sarco\/endoplasmic reticulum Ca2+-ATPase 2 expression in diabetic nephropathy","volume":"7","author":"Guo","year":"2016","journal-title":"Front. Pharmacol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3969\/j.issn.1671-4091.2025.06.008","article-title":"Astragaloside IV alleviates renal fibrosis in unilateral ureteral obstruction rats by inhibiting ferroptosis through the regulation of the cAMP\/PKA signaling pathway","volume":"24","author":"He","year":"2025","journal-title":"Chin. J. Blood Purif."},{"key":"B19","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41584-019-0324-5","article-title":"Evasion of apoptosis by myofibroblasts: a hallmark of fibrotic diseases","volume":"16","author":"Hinz","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.2147\/DDDT.S360346","article-title":"Astragaloside IV alleviates renal tubular epithelial-mesenchymal transition via CX3CL1-RAF\/MEK\/ERK signaling pathway in diabetic kidney disease","volume":"16","author":"Hu","year":"2022","journal-title":"Drug Des. Devel Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/BF03190635","article-title":"Absorption enhancement study of astragaloside IV based on its transport mechanism in caco-2 cells","volume":"31","author":"Huang","year":"2006","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.3389\/fphar.2018.01117","article-title":"Chinese herbal medicine improves the long-term survival rate of patients with chronic kidney disease in Taiwan: a nationwide retrospective population-based cohort study","volume":"9","author":"Huang","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1146\/annurev-physiol-022516-034227","article-title":"Mechanisms of renal fibrosis","volume":"80","author":"Humphreys","year":"2018","journal-title":"Annu. Rev. Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"701","DOI":"10.3969\/j.issn.1009-587X.2022.08.014","article-title":"Renoprotective effects of astragaloside IV on chronic renal failure rats via the TGF-\u03b21\/Smads signaling pathway","volume":"23","author":"Jiang","year":"2022","journal-title":"Chin. J. Integr. Tradit. West Nephrol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"157308","DOI":"10.1016\/j.phymed.2025.157308","article-title":"Astragaloside IV reduces hepatitis B surface antigen level via monocyte\/macrophages in chronic HBV infection mice","volume":"148","author":"Jiang","year":"2025","journal-title":"Phytomedicine"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1661644","DOI":"10.3389\/fphar.2025.1661644","article-title":"Mitochondria-target ubiquinone attenuates bleomycin-induced pulmonary fibrosis","volume":"16","author":"Jiang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1767822","DOI":"10.3389\/fphys.2026.1767822","article-title":"Research trends of mitochondrial dysfunction in hepatic fibrosis: a bibliometric analysis","volume":"17","author":"Jin","year":"2026","journal-title":"Front. Physiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1489701","DOI":"10.3389\/fonc.2025.1489701","article-title":"Recent advances in therapeutic use of transforming growth factor-beta inhibitors in cancer and fibrosis","volume":"15","author":"Jing","year":"2025","journal-title":"Front. Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"11677","DOI":"10.1074\/jbc.M111.308460","article-title":"Autophagy promotes intracellular degradation of type I collagen induced by transforming growth factor (TGF)-\u03b21","volume":"287","author":"Kim","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"670076","DOI":"10.3389\/fphar.2021.670076","article-title":"Coordinated contribution of NADPH Oxidase- and mitochondria-derived reactive oxygen species in metabolic syndrome and its implication in renal dysfunction","volume":"12","author":"Lee","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1080\/15548627.2015.1049799","article-title":"Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis","volume":"11","author":"Lenoir","year":"2015","journal-title":"Autophagy"},{"key":"B32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.ejphar.2012.09.033","article-title":"Astragaloside IV attenuates toll-like receptor 4 expression via NF-\u03baB pathway under high glucose condition in mesenchymal stem cells","volume":"696","author":"Li","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1080\/15548627.2016.1190071","article-title":"Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2\/M arrest and renal fibrosis","volume":"12","author":"Li","year":"2016","journal-title":"Autophagy"},{"key":"B34","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/s41581-022-00590-z","article-title":"The fibrogenic niche in kidney fibrosis: components and mechanisms","volume":"18","author":"Li","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.3390\/cells12131777","article-title":"Astragaloside IV blunts epithelial-mesenchymal transition and G2\/M arrest to alleviate renal fibrosis via regulating ALDH2-mediated autophagy","volume":"12","author":"Li","year":"2023","journal-title":"Cells"},{"key":"B36","doi-asserted-by":"publisher","first-page":"701","DOI":"10.13359\/j.cnki.gzxbtcm.2023.03.027","article-title":"Study on the effect and mechanism of astragaloside IV on rats with diabetic kidney disease based on AMPK\/eNOS signaling pathway","volume":"40","author":"Li","year":"2023","journal-title":"J. Guangzhou Univ. Trad. Chin. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"6053","DOI":"10.3390\/ijms24076053","article-title":"Insights into the molecular mechanisms of NRF2 in kidney injury and diseases","volume":"24","author":"Lin","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s12272-024-01489-y","article-title":"Astragali Radix: comprehensive review of its botany, phytochemistry, pharmacology and clinical application","volume":"47","author":"Liu","year":"2024","journal-title":"Arch. Pharm. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"111784","DOI":"10.1016\/j.cbi.2025.111784","article-title":"Oxidative stress and inflammation in renal fibrosis: novel molecular mechanisms and therapeutic targets","volume":"421","author":"Liu","year":"2025","journal-title":"Chem. Biol. Interact."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.3390\/medicina60111821","article-title":"Proteinuria and progression of renal damage: the main pathogenetic mechanisms and pharmacological approach","volume":"60","author":"Longhitano","year":"2024","journal-title":"Med. (Kaunas)"},{"key":"B41","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.matbio.2017.11.010","article-title":"Inflammation and fibrosis","author":"Mack","year":"2018","journal-title":"Matrix Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/ndt\/gfad215","article-title":"Tubular toxicity of proteinuria and the progression of chronic kidney disease","volume":"39","author":"Makhammajanov","year":"2024","journal-title":"Nephrol. Dial. Transpl."},{"key":"B43","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.3892\/etm.2019.7887","article-title":"Astragaloside IV inhibits excessive mesangial cell proliferation and renal fibrosis caused by diabetic nephropathy via modulation of the TGF-\u03b21\/Smad\/miR-192 signaling pathway","volume":"18","author":"Mao","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrneph.2016.48","article-title":"TGF-\u03b2: the master regulator of fibrosis","volume":"12","author":"Meng","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2539936","DOI":"10.1080\/0886022X.2025.2539936","article-title":"Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine","volume":"47","author":"Meng","year":"2025","journal-title":"Ren. Fail"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.3390\/antiox14101259","article-title":"Stress pathways in chronic kidney disease: linking cortisol, oxidative stress, and inflammation","volume":"14","author":"Motrenikova","year":"2025","journal-title":"Antioxidants (Basel)"},{"key":"B47","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.3390\/jcm4061325","article-title":"Horizon 2020 in diabetic kidney disease: the clinical trial pipeline for Add-On therapies on top of renin angiotensin system blockade","volume":"4","author":"Perez-Gomez","year":"2015","journal-title":"J. Clin. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1021\/acsptsci.4c00240","article-title":"Sodium-glucose cotransporter 2 (SGLT2) inhibitors: guardians against mitochondrial dysfunction and endoplasmic reticulum stress in heart diseases","volume":"7","author":"Pham","year":"2024","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s13318-018-0515-5","article-title":"Pharmacokinetics comparison, intestinal absorption and acute toxicity assessment of a novel water-soluble astragaloside IV derivative (astragalosidic acid, LS-102)","volume":"44","author":"Qing","year":"2019","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.13359\/j.cnki.gzxbtcm.2024.09.030","article-title":"Exploring the effect of astragaloside IV on the immune function of systemic lupus erythematosus mouse model based on NF-\u03baB\/NLRP3 inflammasome","volume":"41","author":"Qing","year":"2024","journal-title":"J. Guangzhou Univ. Trad. Chin. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"110712","DOI":"10.1016\/j.cellsig.2023.110712","article-title":"NQO1 alleviates renal fibrosis by inhibiting the TLR4\/NF-\u03baB and TGF-\u03b2\/Smad signaling pathways in diabetic nephropathy","volume":"108","author":"Qiu","year":"2023","journal-title":"Cell Signal"},{"key":"B53","doi-asserted-by":"publisher","first-page":"4745","DOI":"10.1038\/s41467-025-59997-4","article-title":"Multiomic analysis of human kidney disease identifies a tractable inflammatory and pro-fibrotic tubular cell phenotype","volume":"16","author":"Reck","year":"2025","journal-title":"Nat. Commun."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1335094","DOI":"10.3389\/fphar.2023.1335094","article-title":"The nuclear factor kappa B signaling pathway is a master regulator of renal fibrosis","volume":"14","author":"Ren","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41581-019-0248-y","article-title":"Targeting the progression of chronic kidney disease","volume":"16","author":"Ruiz-Ortega","year":"2020","journal-title":"Nat. Rev. Nephrol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"3678","DOI":"10.3390\/ijms25073678","article-title":"Assessment and risk prediction of chronic kidney disease and kidney fibrosis using non-invasive biomarkers","volume":"25","author":"Rupprecht","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1161\/CIRCRESAHA.122.321761","article-title":"Fibrosis in pathology of heart and kidney: from deep RNA-sequencing to novel molecular targets","volume":"132","author":"Schreibing","year":"2023","journal-title":"Circ. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.freeradbiomed.2023.03.022","article-title":"Astragaloside IV attenuates podocyte apoptosis through ameliorating mitochondrial dysfunction by up-regulated Nrf2-ARE\/TFAM signaling in diabetic kidney disease","volume":"203","author":"Shen","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"155196","DOI":"10.1016\/j.phymed.2023.155196","article-title":"Pharmacological potential of Astragali Radix for the treatment of kidney diseases","volume":"123","author":"Shi","year":"2024","journal-title":"Phytomedicine"},{"key":"B60","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1007\/s43440-025-00801-x","article-title":"Formononetin as a multifaceted modulator of renal pathology: insights into fibrotic, oxidative, inflammatory, and apoptotic pathways","volume":"78","author":"Singh","year":"2026","journal-title":"Pharmacol. Reports"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-026-00858-2","article-title":"Unraveling the therapeutic potential of luteolin in renal pathology: a comprehensive pathway oriented approach","author":"Singh","year":"2026","journal-title":"Pharmacol. Rep."},{"key":"B62","doi-asserted-by":"publisher","first-page":"2883","DOI":"10.1177\/0300060518778711","article-title":"Astragaloside IV ameliorates early diabetic nephropathy by inhibition of MEK1\/2-ERK1\/2-RSK2 signaling in streptozotocin-induced diabetic mice","volume":"46","author":"Song","year":"2018","journal-title":"J. Int. Med. Res."},{"key":"B63","first-page":"25","article-title":"Mechanism of astragaloside IV in regulating M2 macrophage polarization via the HIF-1\u03b1 signaling pathway in diabetic nephropathy","volume":"35","author":"Su","year":"2025","journal-title":"Chin. J. Comp. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/s41581-019-0110-2","article-title":"Macrophages: versatile players in renal inflammation and fibrosis","volume":"15","author":"Tang","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3390\/jpm13010059","article-title":"Astragaloside IV targets macrophages to alleviate renal ischemia-reperfusion injury via the crosstalk between Hif-1\u03b1 and NF-\u03baB (p65)\/Smad7 pathways","volume":"13","author":"Tang","year":"2022","journal-title":"J. Pers. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e0205360","DOI":"10.1371\/journal.pone.0205360","article-title":"PEGylated pUR4\/FUD peptide inhibitor of fibronectin fibrillogenesis decreases fibrosis in murine unilateral ureteral obstruction model of kidney disease","volume":"13","author":"Tomasini-Johansson","year":"2018","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.ekir.2017.03.011","article-title":"A phase 2, double-blind, placebo-controlled, randomized study of fresolimumab in patients with steroid-resistant primary focal segmental glomerulosclerosis","volume":"2","author":"Vincenti","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"B68","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1681\/ASN.2015111230","article-title":"Anti-TGF-\u03b21 antibody therapy in patients with diabetic nephropathy","volume":"28","author":"Voelker","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3870\/j.issn.1672-8009.2019.02.014","article-title":"Effects of astragaloside IV on renal fibrosis in rats with diabetic nephropathy","volume":"16","author":"Wang","year":"2019","journal-title":"J. Med. Mol. Biol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"455","DOI":"10.3390\/antiox13040455","article-title":"Oxidative stress: a culprit in the progression of diabetic kidney disease","volume":"13","author":"Wang","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"B71","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1177\/1535370214532597","article-title":"Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-\u03b2\/Smad signaling pathway in vivo and in vitro","volume":"239","author":"Wang","year":"2014","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"B72","doi-asserted-by":"publisher","first-page":"596","DOI":"10.3969\/j.issn.1671-8348.2017.05.007","article-title":"The effect of astragaloside on TGF-\u03b21,SMAD2\/3,and \u03b1-SMA expression in the kidney tissues of diabetic KKAy mice","volume":"46","author":"Wang","year":"2017","journal-title":"Chongqing Med. J."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2971","DOI":"10.2147\/DDDT.S174058","article-title":"Astragaloside IV represses high glucose-induced mesangial cells activation by enhancing autophagy via SIRT1 deacetylation of NF-\u03baB p65 subunit","volume":"12","author":"Wang","year":"","journal-title":"Drug Des. Devel Ther."},{"key":"B74","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.2147\/DDDT.S170840","article-title":"Astragaloside IV improves renal function and fibrosis via inhibition of miR-21-induced podocyte dedifferentiation and mesangial cell activation in diabetic mice","volume":"12","author":"Wang","year":"","journal-title":"Drug Des. Devel Ther."},{"key":"B75","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/s41598-018-36911-1","article-title":"Astragaloside IV inhibits glucose-induced epithelial-mesenchymal transition of podocytes through autophagy enhancement via the SIRT-NF-\u03baB p65 axis","volume":"9","author":"Wang","year":"2019","journal-title":"Sci. Rep."},{"key":"B76","doi-asserted-by":"publisher","first-page":"2489715","DOI":"10.1080\/0886022X.2025.2489715","article-title":"Development and validation of multi-center serum creatinine-based models for noninvasive prediction of kidney fibrosis in chronic kidney disease","volume":"47","author":"Wu","year":"2025","journal-title":"Ren. Fail"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1016\/j.phymed.2013.05.004","article-title":"Pharmacokinetics and tolerance of toal astragalosides after intravenous infusion of astragalosides injection in healthy Chinese volunteers","volume":"20","author":"Xu","year":"2013","journal-title":"Phytomedicine"},{"key":"B78","doi-asserted-by":"publisher","first-page":"770","DOI":"10.3760\/cma.j.issn.1001-7097.2014.10.008","article-title":"Astragaloside IV attenuates renal tubulointerstitial fibrosis by inhibiting p38 MAPK signaling","volume":"30","author":"Xu","year":"2014","journal-title":"Chin. J. Nephrol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1124\/jpet.114.214205","article-title":"Astragaloside IV ameliorates renal fibrosis via the inhibition of mitogen-activated protein kinases and antiapoptosis in vivo and in vitro","volume":"350","author":"Xu","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B80","doi-asserted-by":"publisher","first-page":"838256","DOI":"10.3389\/fmed.2022.838256","article-title":"Efficacy of huangqi injection in the treatment of hypertensive nephropathy: a systematic review and meta-analysis","volume":"9","author":"Xu","year":"2022","journal-title":"Front. Med. (Lausanne)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"5049","DOI":"10.7501\/j.issn.0253-2670.2025.14.011","article-title":"Astragaloside IV inhibits renal fibrosis induced by renal ischemia-reperfusion injury in mice through modulation of TPL2-CTGF signaling pathway","volume":"56","author":"Xu","year":"2025","journal-title":"Chin. Traditional Herb. Drugs"},{"key":"B82","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.7501\/j.issn.0253-2670.2017.18.017","article-title":"Effect of astragaloside IV based on Toll\/MyD88 dependent signaling pathway in treatment of renal fibrosis mice","volume":"48","author":"Yang","year":"2017","journal-title":"Chin. Trad. Herb. Drugs"},{"key":"B83","doi-asserted-by":"publisher","first-page":"3729","DOI":"10.19540\/j.cnki.cjcmm.20180426.001","article-title":"Effect and mechanism of astragaloside IV on toll-like receptor pathway in fibrotic mice after renal ischemia-reperfusion","volume":"43","author":"Yang","year":"2018","journal-title":"China J. Chin. Materia Medica"},{"key":"B84","doi-asserted-by":"publisher","first-page":"10004","DOI":"10.12998\/wjcc.v10.i28.10004","article-title":"Review of the pharmacological effects of astragaloside IV and its autophagic mechanism in association with inflammation","volume":"10","author":"Yang","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.3760\/j:issn:0376-2491.2004.17.003","article-title":"Effect of astrgaloside IV on the long-term consequences of renal ischemia-reperfusion injury in rat","volume":"84","author":"Yu","year":"2004","journal-title":"Natl. Med. J. China"},{"key":"B86","doi-asserted-by":"publisher","first-page":"115535","DOI":"10.1016\/j.jep.2022.115535","article-title":"A network pharmacology-based study on the mechanism of astragaloside IV alleviating renal fibrosis through the AKT1\/GSK-3\u03b2 pathway","volume":"297","author":"Yu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"998","DOI":"10.3969\/j.issn.1009-587X.2022.11.014","article-title":"Effect of astragaloside IV on NLRP and Caspase-1 expression in renal interstitial fibrosis of diabetic nephropathy rats","volume":"23","author":"Yuan","year":"2022","journal-title":"Chin. J. Integr. Trad. West. Nephrol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"107035","DOI":"10.1016\/j.intimp.2020.107035","article-title":"Triptolide attenuates renal damage by limiting inflammatory responses in DOCA-salt hypertension","volume":"89","author":"Zhang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"9542165","DOI":"10.1155\/2020\/9542165","article-title":"Transcriptomic analysis reveals the protection of astragaloside IV against diabetic nephropathy by modulating inflammation","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxid. Med. Cell Longev."},{"key":"B90","doi-asserted-by":"publisher","first-page":"11","DOI":"10.19656\/j.cnki.1002-2406.20220702","article-title":"Ameliorative effects of astragaloside-IV on renal injury in infant rats with hypothyroidism based on TGF-\u03b21\/Smad3 signaling pathway","volume":"39","author":"Zhang","year":"2022","journal-title":"Inf. Trad. Chin. Med."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1564290","DOI":"10.3389\/fphar.2025.1564290","article-title":"Therapeutic effects and potential mechanisms of astragaloside IV on pulmonary fibrosis: a systematic review and meta-analysis of preclinical studies","volume":"16","author":"Zhang","year":"","journal-title":"Front. Pharmacol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1080\/13880209.2025.2488994","article-title":"Anti-fibrosis effect of astragaloside IV in animal models of cardiovascular diseases and its mechanisms: a systematic review","volume":"63","author":"Zhang","year":"","journal-title":"Pharm. Biol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"155913","DOI":"10.1016\/j.metabol.2024.155913","article-title":"Role of mitochondria in pathogenesis and therapy of renal fibrosis","volume":"155","author":"Zhao","year":"2024","journal-title":"Metabolism"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.3969\/j.issn.1671-7171.2021.10.030","article-title":"Experimental study of astragaloside IV regulating p38 MAPK signaling pathway in the treatment of renal tubulointerstitial fibrosis","volume":"38","author":"Zhou","year":"2021","journal-title":"J. Clin. Res."},{"key":"B95","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.intimp.2016.11.006","article-title":"Astragaloside IV from astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4\/NF-\u043aB in vivo and in vitro","volume":"42","author":"Zhou","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"105192","DOI":"10.1016\/j.phrs.2020.105192","article-title":"Renal protective effects of astragaloside IV, in diabetes mellitus kidney damage animal models: a systematic review, meta-analysis","volume":"160","author":"Zhou","year":"2020","journal-title":"Pharmacol. Res."},{"key":"B97","doi-asserted-by":"publisher","first-page":"2700","DOI":"10.13192\/j.issn.1000-1719.2014.12.078","article-title":"Antagonistic effect of Astragalus Saponin I on renal interstitial fibrosis","volume":"41","author":"Zhu","year":"2014","journal-title":"Liaoning J. Trad. Chin. Med."},{"key":"B98","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1093\/ndt\/gfu261","article-title":"Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration","volume":"30","author":"Zoja","year":"2015","journal-title":"Nephrol. Dial. Transpl."},{"key":"B99","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/S2213-8587(17)30104-3","article-title":"Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials","volume":"5","author":"Zoungas","year":"2017","journal-title":"Lancet Diabetes Endocrinol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1867891\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:36:48Z","timestamp":1787636208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1867891\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":99,"alternative-id":["10.3389\/fphar.2026.1867891"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1867891","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"article-number":"1867891"}}