{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:10:59Z","timestamp":1791817859665,"version":"4.3.4"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"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:p><jats:bold>Purpose:<\/jats:bold> Our recent research is dedicated to finding effective drugs for the treatment of knee osteoarthritis (KOA) from traditional Chinese medicine and trying to make full use of modern science and technology to uncover the mechanisms and targets behind them. Synovial inflammation is one of the key pathological features of KOA, and a growing number of researchers realize that early intervention of synovial inflammation may be able to reverse disease progression. The close association of traditional natural products with modern nanotechnology may be important for improving the anti-synovitis efficacy. The purpose of our research was to explore the anti-synovitis mechanism of NEs-SP-EO that might be associated with the ERS\/TXNIP\/NLRP3 signalling axis.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Chemical composition of \u201cSanse Powder\u201d essential oil (SP-EO) and NEs-SP-EO were analyzed by GC-MS. NEs-SP-EO were prepared and characterized by nanoparticle tracking analysis, polydispersity index (PDI), zeta potential (ZP), ultraviolet-visible spectroscopy, and transmission electronic microscopy. The CCK8 assay for cell viability of NEs-SP-EO was performed on fibroblast-like synovial cells (FLSs) and the inflammatory environment was stimulated by LPS to explore the therapeutic mechanisms <jats:italic>in vitro<\/jats:italic>. Experiments of NEs-SP-EO <jats:italic>in vivo<\/jats:italic> were performed in male SD rats.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The GC-MS results showed that 30 compounds were present in SP-EO and 11 components of NEs-SP-EO were identified. The results also showed that the formulation of NEs-SP-EO exhibited suitable particle size, negative charge, and stable system. <jats:italic>In vitro<\/jats:italic> and vivo testing, NEs-SP-EO produced anti-synovitis efficacy by reduced the induction of the ERS\/TXNIP\/NLRP3 signaling axis as well as regulating the overproduction of IL-1\u03b2, IL-18.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We have developed a new type of essential oil nanoemulsion from \u201cSanse Powder\u201d and demonstrated that it can managing synovitis of KOA. Besides, we have initially explored the anti-inflammatory mechanism that may be related to the ERS\/TXNIP\/NLRP3 signaling axis.<\/jats:p>","DOI":"10.3389\/fphar.2021.739644","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T02:30:00Z","timestamp":1630722600000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Interventional Efects of the Topical of \u201cSanse Powder\u201d Essential Oils Nanoemulsion on Knee Osteoarthritis in Rats by Targeting the ERS\/TXNIP\/NLRP3 Signaling Axis"],"prefix":"10.3389","volume":"12","author":[{"given":"Zixiu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.2174\/1389200219666180723144850","article-title":"Essential Oils: Extraction Techniques, Pharmaceutical and Therapeutic Potential - A Review","volume":"19","author":"Aziz","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI Guidelines for the Non-Surgical Management of Knee, Hip, and Polyarticular Osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthritis Cartilage."},{"key":"B3","doi-asserted-by":"publisher","first-page":"623","DOI":"10.14148\/j.issn.1672-0482.2019.0623","article-title":"Progress and Prospects on the Development of Liposomes for Dermal and Transdermal Delivery Application in the Field of Traditional Chinese Medicine","volume":"35","author":"Chen","year":"2019","journal-title":"J. Nanjing Univ. Tradit Chin. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"4495","DOI":"10.2147\/IJN.S110486","article-title":"Nanoemulsion as a Carrier to Improve the Topical Anti-inflammatory Activity of Stem Bark Extract of Rapanea Ferruginea","volume":"11","author":"Dal Mas","year":"2016","journal-title":"Int. J. Nanomedicine."},{"key":"B5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/DER.0000000000000175","article-title":"Essential Oils, Part I: Introduction","volume":"27","author":"de Groot","year":"2016","journal-title":"Dermatitis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3390\/biom9040138","article-title":"Essential Oils and Isolated Terpenes in Nanosystems Designed for Topical Administration: A Review","volume":"9","author":"de Matos","year":"2019","journal-title":"Biomolecules."},{"key":"B7","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/foods8020053","article-title":"Variations in the Volatile Compositions of Curcuma Species","volume":"8","author":"Dosoky","year":"2019","journal-title":"Foods."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.3390\/nu10091196","article-title":"Chemical Composition and Biological Activities of Essential Oils of Curcuma Species","volume":"10","author":"Dosoky","year":"2018","journal-title":"Nutrients."},{"key":"B9","doi-asserted-by":"publisher","first-page":"10481","DOI":"10.2147\/IJN.S275258","article-title":"Improved In Vitro and In Vivo Anti-Candida Albicans Activity of Cymbopogon Nardus Essential Oil by its Incorporation into a Microemulsion System","volume":"15","author":"Gaspar de Toledo","year":"2020","journal-title":"Int. J. Nanomedicine."},{"key":"B10","doi-asserted-by":"publisher","first-page":"7338","DOI":"10.18632\/aging.102603","article-title":"Regulation of Cartilage Damage Caused by Lack of Klotho With Thioredoxin\/Peroxiredoxin (Trx\/Prx) System and Succedent NLRP3 Activation in Osteoarthritis Mice","volume":"11","author":"Gu","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2985","DOI":"10.1016\/j.celrep.2018.07.068","article-title":"FXR Inhibits Endoplasmic Reticulum Stress-Induced NLRP3 Inflammasome in Hepatocytes and Ameliorates Liver Injury","volume":"24","author":"Han","year":"2018","journal-title":"Cell Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.3390\/molecules24091675","article-title":"Antispasmodic Effect of Essential Oils and Their Constituents: A Review","volume":"24","author":"Heghes","year":"2019","journal-title":"Molecules."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrrheum.2014.44","article-title":"The Individual and Socioeconomic Impact of Osteoarthritis","volume":"10","author":"Hunter","year":"2014","journal-title":"Nat. Rev. Rheumatol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"572136","DOI":"10.3389\/fimmu.2020.572136","article-title":"Immunomodulatory Effects of Diterpenes and Their Derivatives Through NLRP3 Inflammasome Pathway: A Review","volume":"11","author":"Islam","year":"2020","journal-title":"Front. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.vph.2016.03.004","article-title":"Amelioration of ER Stress by 4-Phenylbutyric Acid Reduces Chronic Hypoxia Induced Cardiac Damage and Improves Hypoxic Tolerance through Upregulation of HIF-1\u03b1","volume":"83","author":"Jain","year":"2016","journal-title":"Vascul Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"545","DOI":"10.3390\/nano8070545","article-title":"Enhancement of Antibacterial Activity of Orange Oil in Pectin Thin Film by Microemulsion","volume":"8","author":"Jantrawut","year":"2018","journal-title":"Nanomaterials (Basel)."},{"key":"B18","doi-asserted-by":"publisher","first-page":"5153","DOI":"10.1007\/s13197-019-03986-1","article-title":"A Critical Review of Analytical Methods for Determination of Curcuminoids in Turmeric","volume":"56","author":"Kotra","year":"2019","journal-title":"J. Food Sci. Technol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1140\/epje\/i2018-11679-6","article-title":"Binding of Trivalent Metal Ions (Al3+, In3+, La3+) With Phosphatidylcholine Liposomal Membranes Investigated by Microelectrophoresis","volume":"41","author":"Koty\u0144ska","year":"2018","journal-title":"Eur. Phys. J. E."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.2147\/DDDT.S85356","article-title":"Innovation of Natural Essential Oil-Loaded Orabase for Local Treatment of Oral Candidiasis","volume":"9","author":"Labib","year":"2015","journal-title":"Drug Des. Devel Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e1879","DOI":"10.1038\/cddis.2015.248","article-title":"ER Stress Induces NLRP3 Inflammasome Activation and Hepatocyte Death","volume":"6","author":"Lebeaupin","year":"2015","journal-title":"Cell Death Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"681","DOI":"10.3390\/molecules23030681","article-title":"Transdermal and Topical Drug Administration in the Treatment of Pain","volume":"23","author":"Leppert","year":"2018","journal-title":"Molecules."},{"key":"B23","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.jbspin.2015.10.007","article-title":"MicroRNA-20a Negatively Regulates Expression of NLRP3-Inflammasome by Targeting TXNIP in Adjuvant-Induced Arthritis Fibroblast-like Synoviocytes","volume":"83","author":"Li","year":"2016","journal-title":"Jt. Bone Spine."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.2147\/DDDT.S261216","article-title":"Chrysin Attenuates the NLRP3 Inflammasome Cascade to Reduce Synovitis and Pain in KOA Rats","volume":"14","author":"Liao","year":"2020","journal-title":"Drug Des. Devel Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"134","DOI":"10.14148\/j.issn.1672-0482.2014.02.014","article-title":"The Effect of Layers Adjusting External Application Therapy on Matrix Metalloproteinases in Synovial Membrane in the Rabbit Knee Osteoarthritis","volume":"30","author":"Mao","year":"2014","journal-title":"J. Nanjing Univ. Tradit Chin. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13075-017-1229-9","article-title":"Synovitis in Osteoarthritis: Current Understanding With Therapeutic Implications","volume":"19","author":"Mathiessen","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1080\/17425247.2018.1504018","article-title":"Solid Lipid Nanocarriers in Drug Delivery: Characterization and Design","volume":"15","author":"Mu","year":"2018","journal-title":"Expert Opin. Drug Deliv."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e53627","DOI":"10.7554\/eLife.53627","article-title":"Thioredoxin-1 Distinctly Promotes NF-\u039ab Target DNA Binding and NLRP3 Inflammasome Activation Independently of Txnip","volume":"9","author":"Muri","year":"2020","journal-title":"eLife."},{"key":"B29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.cmet.2012.07.005","article-title":"Thioredoxin-Interacting Protein Mediates ER Stress-Induced \u03b2 Cell Death Through Initiation of the Inflammasome","volume":"16","author":"Oslowski","year":"2012","journal-title":"Cell Metab."},{"key":"B30","doi-asserted-by":"publisher","first-page":"20091","DOI":"10.3390\/molecules191220091","article-title":"The Chemistry of Curcumin: From Extraction to Therapeutic Agent","volume":"19","author":"Priyadarsini","year":"2014","journal-title":"Molecules."},{"key":"B31","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1124\/mol.104.001339","article-title":"Sodium 4-phenylbutyrate Protects against Cerebral Ischemic Injury","volume":"66","author":"Qi","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4859","DOI":"10.2147\/IJN.S245170","article-title":"Nano-Encapsulation of Coenzyme Q10 in Secondary and Tertiary Nano-Emulsions for Enhanced Cardioprotection and Hepatoprotection in Human Cardiomyocytes and Hepatocytes during Exposure to Anthracyclines and Trastuzumab","volume":"15","author":"Quagliariello","year":"2020","journal-title":"Int. J. Nanomedicine."},{"key":"B33","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1146\/annurev-food-032818-121727","article-title":"Improving the Efficacy of Essential Oils as Antimicrobials in Foods: Mechanisms of Action","volume":"10","author":"Rao","year":"2019","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"4","DOI":"10.2174\/2589977511666191024173508","article-title":"Nanoemulsion as Oral Drug Delivery - A Review","volume":"12","author":"Sabjan","year":"2020","journal-title":"Curr. Drug Res. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"661505","DOI":"10.3389\/fnagi.2021.661505","article-title":"PKC Delta Activation Promotes Endoplasmic Reticulum Stress (ERS) and NLR Family Pyrin Domain-Containing 3 (NLRP3) Inflammasome Activation Subsequent to Asynuclein-Induced Microglial Activation: Involvement of Thioredoxin-Interacting Protein (TXNIP)\/Thioredoxin (Trx) Redoxisome Pathway","volume":"13","author":"Samidurai","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"E20","DOI":"10.3390\/molecules21010020","article-title":"Analgesic Potential of Essential Oils","volume":"21","author":"Sarmento-Neto","year":"2015","journal-title":"Molecules."},{"key":"B37","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/s0378-5173(03)00135-2","article-title":"Preparation of Solid Lipid Nanoparticles by a Solvent Emulsification-Diffusion Technique","volume":"257","author":"Trotta","year":"2003","journal-title":"Int. J. Pharm."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1016\/j.joca.2014.07.015","article-title":"Current and Future Impact of Osteoarthritis on Health Care: a Population-Based Study With Projections to Year 2032","volume":"22","author":"Turkiewicz","year":"2014","journal-title":"Osteoarthritis Cartilage."},{"key":"B39","first-page":"646","article-title":"Burden of Major Musculoskeletal Conditions","volume":"81","author":"Woolf","year":"2003","journal-title":"Bull. World Health Organ."},{"key":"B40","doi-asserted-by":"publisher","first-page":"547","DOI":"10.14148\/j.issn.1672-0482.2019.0547","article-title":"Effect of Yiceng on the Synovial Fibrosis in KOA Rats Based on HMGB1","volume":"35","author":"Wu","year":"2019","journal-title":"J. Nanjing Univ. Tradit Chin. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1080\/15548627.2019.1606647","article-title":"MTORC1 Coordinates the Autophagy and Apoptosis Signaling in Articular Chondrocytes in Osteoarthritic Temporomandibular Joint","volume":"16","author":"Yang","year":"2020","journal-title":"Autophagy."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1111\/bph.14967","article-title":"Eucalyptol Alleviates Inflammation and Pain Responses in a Mouse Model of Gout Arthritis","volume":"177","author":"Yin","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2165918","DOI":"10.1155\/2019\/2165918","article-title":"Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis","volume":"2019","author":"Zhang","year":"2019","journal-title":"Mediators Inflamm."},{"key":"B44","doi-asserted-by":"publisher","first-page":"13790","DOI":"10.1021\/acs.jafc.9b00433","article-title":"Anxiolytic Effect of Essential Oils and Their Constituents: A Review","volume":"67","author":"Zhang","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"5463","DOI":"10.3892\/mmr.2018.8520","article-title":"NLRP1 and NLRP3 Inflammasomes Mediate LPS\/ATP Induced Pyroptosis in Knee Osteoarthritis","volume":"17","author":"Zhao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"4077","DOI":"10.1096\/fj.201801851R","article-title":"Mechanical Loading Mitigates Osteoarthritis Symptoms by Regulating Endoplasmic Reticulum Stress and Autophagy","volume":"33","author":"Zheng","year":"2019","journal-title":"FASEB J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-Interacting Protein Links Oxidative Stress to Inflammasome Activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat. Immunol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.739644\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T02:30:11Z","timestamp":1630722611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.739644\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,2]]},"references-count":47,"alternative-id":["10.3389\/fphar.2021.739644"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.739644","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,2]]},"article-number":"739644"}}