{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:39:13Z","timestamp":1787067553958,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chongqing Academy of Animal Sciences","award":["23521C"],"award-info":[{"award-number":["23521C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Acute kidney injury (AKI) presents a critical clinical challenge due to its rapid progression and lack of effective targeted therapies. The herbal combination of rhubarb and Salvia miltiorrhiza, a cornerstone of Traditional Chinese Medicine (TCM) for renal protection, shows promise, yet its bioactive components and mode of action remain incompletely understood. This study identifies and characterizes inherent nanoscale entities from this herbal pair as a novel nanotherapeutic platform. Self-assembled nanoparticles (designated RSNPs) were isolated from the ethanol extract via differential centrifugation. Comprehensive characterization revealed that RSNPs form stable nanostructures through spontaneous self-assembly, primarily driven by supramolecular interactions (e.g., \u03c0-\u03c0 stacking and hydrogen bonding). UPLC-MS\/MS quantification confirmed the co-assembly of multiple bioactive constituents within RSNPs. Network pharmacology and molecular docking initially predicted their synergistic action on AKI-related pathways. In a cisplatin-induced murine AKI model, RSNP administration markedly attenuated renal dysfunction and histopathological damage, mechanistically linked to the mitigation of oxidative stress (e.g., decreased MDA and increased SOD) and inflammation (e.g., downregulated TNF-\u03b1 and IL-6). In vitro, RSNPs demonstrated enhanced cellular internalization and superior cytoprotection against cisplatin toxicity in renal tubular epithelial cells, significantly reducing apoptosis. These findings unveil that the therapeutic efficacy of the Rheum palmatum L.\u2013Salvia miltiorrhiza Bunge pair is intrinsically embedded within its nanoscale architecture. RSNPs represent a new class of TCM-derived nanotherapeutics with a well-defined material basis and multimodal mechanisms, offering a promising strategy for AKI treatment.<\/jats:p>","DOI":"10.3390\/antiox15040491","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:25:30Z","timestamp":1776255930000},"page":"491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Separation and Characterization of Self-Assembled Nanoparticles from Rheum palmatum L.\u2013Salvia miltiorrhiza Bunge Extract and Their Renoprotective Effects in Acute Kidney Injury"],"prefix":"10.3390","volume":"15","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghong","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Animal Sciences, Rongchang 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqiao","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Xia","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhang","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maixun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Animal Sciences, Rongchang 402460, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Ye","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Lv","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7949-3105","authenticated-orcid":false,"given":"Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinglun","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6505-5270","authenticated-orcid":false,"given":"Ling","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.kint.2020.03.032","article-title":"Arginase 2 is a mediator of ischemia-reperfusion injury in the kidney through regulation of nitrosative stress","volume":"98","author":"Hara","year":"2020","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103340","DOI":"10.1016\/j.redox.2024.103340","article-title":"Role of mitochondria in reno-cardiac diseases: A study of bioenergetics, biogenesis, and GSH signaling in disease transition","volume":"76","author":"Lorenzo","year":"2024","journal-title":"Redox Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103078","DOI":"10.1016\/j.redox.2024.103078","article-title":"DRD4 alleviates acute kidney injury by suppressing ISG15\/NOX4 axis-associated oxidative stress","volume":"70","author":"Gao","year":"2024","journal-title":"Redox Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1080\/15548627.2022.2084862","article-title":"Mitochondria ROS and mitophagy in acute kidney injury","volume":"19","author":"Su","year":"2023","journal-title":"Autophagy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1016\/j.apsb.2020.05.012","article-title":"Transporters (OATs and OATPs) contribute to illustrate the mechanism of medicinal compatibility of ingredients with different properties in yuanhuzhitong prescription","volume":"10","author":"Wang","year":"2020","journal-title":"Acta Pharm. Sinica. B"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41392-021-00553-z","article-title":"From purines to purinergic signalling: Molecular functions and human diseases","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1002\/med.21891","article-title":"Natural products as Zika antivirals","volume":"42","author":"Fong","year":"2022","journal-title":"Med. Res. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jare.2020.01.012","article-title":"Tanshinone and salvianolic acid biosynthesis are regulated by SmMYB98 in Salvia miltiorrhiza hairy roots","volume":"23","author":"Hao","year":"2020","journal-title":"J. Adv. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.tips.2021.03.007","article-title":"Nanotherapeutic-directed approaches to analgesia","volume":"42","author":"Mazaleuskaya","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101223","DOI":"10.1016\/j.nantod.2021.101223","article-title":"Nanotechnology for Pain Management: Current and Future Therapeutic Interventions","volume":"39","author":"Bhansali","year":"2021","journal-title":"Nano Today"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.jconrel.2021.01.028","article-title":"Zwitterionic self-assembled nanoparticles as carriers for Plasmodium targeting in malaria oral treatment","volume":"331","author":"Biosca","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121730","DOI":"10.1016\/j.biomaterials.2022.121730","article-title":"Self-carried nanodrug (SCND-SIS3): A targeted therapy for lung cancer with superior biocompatibility and immune boosting effects","volume":"288","author":"Lian","year":"2022","journal-title":"Biomaterials"},{"key":"ref_13","first-page":"643","article-title":"Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies","volume":"16","author":"Wang","year":"2021","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1111\/jipb.13181","article-title":"Effective methods for isolation and purification of extracellular vesicles from plants","volume":"63","author":"Huang","year":"2021","journal-title":"J. Integr. Plant Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1016\/j.apsb.2022.10.020","article-title":"The feasibility of oral targeted drug delivery: Gut immune to particulates?","volume":"13","author":"Ren","year":"2023","journal-title":"Acta Pharm. Sinica. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2000420","DOI":"10.1002\/advs.202000420","article-title":"Selenium-Doped Carbon Quantum Dots Act as Broad-Spectrum Antioxidants for Acute Kidney Injury Management","volume":"7","author":"Rosenkrans","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1021\/acsnano.1c08913","article-title":"Intrinsic Radical Species Scavenging Activities of Tea Polyphenols Nanoparticles Block Pyroptosis in Endotoxin-Induced Sepsis","volume":"16","author":"Chen","year":"2022","journal-title":"ACS Nano"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107045","DOI":"10.1016\/j.ultsonch.2024.107045","article-title":"A novel ultrasound-assisted enzyme extraction method of total flavonoids from Viticis Fructus and processed Viticis Fructus: Comparison of in vitro antioxidant activity","volume":"110","author":"Li","year":"2024","journal-title":"Ultrason. Sonochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"174025","DOI":"10.1016\/j.ejphar.2021.174025","article-title":"Novel arylidene malonate derivative, KM-34, showed neuroprotective effects on in vitro and in vivo models of ischemia\/reperfusion","volume":"899","author":"Salbego","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lu, R., Zhou, Y., Ma, J., Wang, Y., and Miao, X. (2022). Strategies and Mechanism in Reversing Intestinal Drug Efflux in Oral Drug Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061131"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101983","DOI":"10.1016\/j.artmed.2020.101983","article-title":"Detection-based prioritisation: Framework of multi-laboratory characteristics for asymptomatic COVID-19 carriers based on integrated Entropy-TOPSIS methods","volume":"111","author":"Albahri","year":"2021","journal-title":"Artif. Intell. Med."},{"key":"ref_22","first-page":"34","article-title":"Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan","volume":"8","author":"Duan","year":"2021","journal-title":"Mil. Med. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"116062","DOI":"10.1016\/j.biopha.2023.116062","article-title":"Maduramicin-guided nanotherapy: A polymeric micelles for targeted drug delivery in canine mammary tumors","volume":"170","author":"Song","year":"2024","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_24","first-page":"100830","article-title":"High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis","volume":"18","author":"Li","year":"2023","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Homaeigohar, S. (2020). The Nanosized Dye Adsorbents for Water Treatment. Nanomaterials, 10.","DOI":"10.3390\/nano10020295"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9712","DOI":"10.1002\/anie.202100153","article-title":"Macroscalar Helices Co-Assembled from Chirality-Transferring Temperature-Responsive Carbohydrate-Based Bolaamphiphiles and 1,4-Benzenediboronic Acid","volume":"60","author":"Wang","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34501","DOI":"10.1021\/jacs.4c11583","article-title":"Intricate Low-Symmetry Ag(6)L(4) Capsules Formed by Anion-Templated Self-Assembly of the Stereoisomers of an Unsymmetric Ligand","volume":"146","author":"Tashiro","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.addr.2021.01.006","article-title":"(Macro)molecular self-assembly for hydrogel drug delivery","volume":"172","author":"Webber","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Capretti, M., Giammaria, V., Santulli, C., Boria, S., and Del Bianco, G. (2023). Use of Bio-Epoxies and Their Effect on the Performance of Polymer Composites: A Critical Review. Polymers, 15.","DOI":"10.3390\/polym15244733"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"117258","DOI":"10.1016\/j.biopha.2024.117258","article-title":"Research progress in tumor therapy of carrier-free nanodrug","volume":"178","author":"An","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wakabayashi, R., Higuchi, A., Obayashi, H., Goto, M., and Kamiya, N. (2021). pH-Responsive Self-Assembly of Designer Aromatic Peptide Amphiphiles and Enzymatic Post-Modification of Assembled Structures. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073459"},{"key":"ref_32","first-page":"155265","article-title":"Qingjie Huagong decoction inhibits pancreatic acinar cell pyroptosis by regulating circHipk3\/miR-193a-5p\/NLRP3 pathway","volume":"126","author":"Feng","year":"2024","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"126340","DOI":"10.1016\/j.cej.2020.126340","article-title":"Antimicrobial Property of Halogenated Catechols","volume":"403","author":"Liu","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16166","DOI":"10.1021\/jacs.3c04810","article-title":"Stacking Interactions and Flexibility of Human Telomeric Multimers","volume":"145","author":"Rosi","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1021\/acs.biomac.2c01095","article-title":"Peptide-Protein Coassemblies into Hierarchical and Bioactive Tubular Membranes","volume":"24","author":"Majkowska","year":"2023","journal-title":"Biomacromolecules"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108492","DOI":"10.1016\/j.biotechadv.2024.108492","article-title":"Current innovations in mRNA vaccines for targeting multidrug-resistant ESKAPE pathogens","volume":"79","author":"Imani","year":"2025","journal-title":"Biotechnol. Adv."},{"key":"ref_37","first-page":"121","article-title":"Apoptosis of A549 cells by small interfering RNA targeting survivin delivery using poly-\u03b2-amino ester\/guanidinylated O-carboxymethyl chitosan nanoparticles","volume":"15","author":"Tang","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41392-023-01536-y","article-title":"Nanomedicine in cancer therapy","volume":"8","author":"Fan","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s40097-022-00472-7","article-title":"Exploring nano-enabled CRISPR-Cas-powered strategies for efficient diagnostics and treatment of infectious diseases","volume":"12","author":"Dubey","year":"2022","journal-title":"J. Nanostructure Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jare.2021.03.012","article-title":"Nano-Honokiol ameliorates the cognitive deficits in TgCRND8 mice of Alzheimer\u2019s disease via inhibiting neuropathology and modulating gut microbiota","volume":"35","author":"Qu","year":"2022","journal-title":"J. Adv. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40364-024-00558-0","article-title":"Simultaneous inhibition of FAK and ROS1 synergistically repressed triple-negative breast cancer by upregulating p53 signalling","volume":"12","author":"Tan","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"107658","DOI":"10.1016\/j.envint.2022.107658","article-title":"Human health risk assessment of cinnamate UV absorbers: In vitro and in silico investigations","volume":"171","author":"Tian","year":"2023","journal-title":"Environ. Int."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:33:53Z","timestamp":1776256433000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antiox15040491"],"URL":"https:\/\/doi.org\/10.3390\/antiox15040491","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}