{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:58:38Z","timestamp":1787068718717,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shaanxi Provincial Department of Science and Technology Key Research and Development Program for Social Development Challenges","award":["2024SF2-GJHX-60"],"award-info":[{"award-number":["2024SF2-GJHX-60"]}]},{"name":"Shaanxi University of Technology Qinba Biological Resources and Ecological Environment National Key Laboratory (cultivation) \u2018City-University Co-construction\u2019 Research Project","award":["SXC-2111:SXZC-2301"],"award-info":[{"award-number":["SXC-2111:SXZC-2301"]}]},{"award":["SXC-2111:SXZC-2301"],"award-info":[{"award-number":["SXC-2111:SXZC-2301"]}],"id":[{"id":"https:\/\/ror.org\/056m91h77","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shaanxi University of Technology Graduate Innovation Fund Project","award":["SLGYCX2534"],"award-info":[{"award-number":["SLGYCX2534"]}]},{"award":["SLGYCX2534"],"award-info":[{"award-number":["SLGYCX2534"]}],"id":[{"id":"https:\/\/ror.org\/056m91h77","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shaanxi University of Technology Talent Launch Project","award":["SLGRCQD2002"],"award-info":[{"award-number":["SLGRCQD2002"]}]},{"award":["SLGRCQD2002"],"award-info":[{"award-number":["SLGRCQD2002"]}],"id":[{"id":"https:\/\/ror.org\/056m91h77","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study aimed to screen for optimal Traditional Chinese medicine (TCM) combinations and subsequently optimize their extraction processes for developing antibacterial dressings by preparing aqueous and hydroethanolic extracts from Herba Centellae asiaticae, Flos Calendulae, Folium Aloe, Cortex Betulae and Rhizoma Curcumae longae and evaluating their inhibitory activity against E. coli, S. aureus, C. albicans, and T-Salmonella using an agar diffusion assay. Synergistic combinations were identified through a grid screening method, with extraction processes optimized via single-factor experiments and Box\u2013Behnken response surface design. The results demonstrated that the Folium Aloe and Cortex Betulae formulation exhibited the strongest synergistic antibacterial activity, with the inhibition zone expanding from 11.1\/12.8 mm for individual components to 17 mm after combination, representing an increase of 21\u201336%. Single-factor and response surface optimization identified optimal process parameters as a ratio of 1.53:1, a hydroethanolic concentration of 79.5%, and an extraction time of 2.6 h, with a model R2 value ranging from 0.9265 to 0.9783; the MIC values were reduced by 25\u201368.75%. The UPLC-QTOF-MS analysis of the optimized extract identified nine major constituents, including anthraquinones, chromones, and triterpenoids, providing the phytochemical basis for the observed bioactivities. Mechanistic studies via UV-Vis spectrophotometry and propidium iodide (PI) staining confirmed membrane disruption through nucleic acid and protein leakage. Cytocompatibility evaluation using L929 fibroblasts demonstrated &gt;90% cell viability even at 1000 \u03bcg\/mL. Additionally, the optimized extract exhibited concentration-dependent antibacterial activity, achieving a DPPH scavenging rate of 90% at 1.0 mg\/mL, whereas its ABTS scavenging rate was comparable to that of ascorbic acid. The Folium Aloe and Cortex Betulae pair demonstrates dual antibacterial and antioxidant activities, providing an experimental basis for developing functional wound dressings and green antibacterial biomaterials.<\/jats:p>","DOI":"10.3390\/molecules31152590","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:49:27Z","timestamp":1785131367000},"page":"2590","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic Antibacterial and Antioxidant Activities of Folium Aloe\u2013Cortex Betulae Drug Combination: Optimization via Box\u2013Behnken Design and In Vitro Validation"],"prefix":"10.3390","volume":"31","author":[{"given":"Shun","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyun","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China"},{"name":"Shaanxi Province Key Laboratory of Bio-Resources, Hanzhong 723000, China"},{"name":"Qinba State Key Laboratory of Biological Resources and Ecological Environment (Incubation), Hanzhong 723000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1039\/D3TB02714G","article-title":"Near-Infrared Light-Actuated on-Demand Botanicals Release and Hyperthermia by an Antibiotic-Free Polysaccharide-Based Hydrogel Dressing for the Synergistic Treatment of Wound Infections","volume":"12","author":"Sun","year":"2024","journal-title":"J. Mater. Chem. B"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e73536","DOI":"10.1002\/smll.73536","article-title":"pH-Adaptive Microneedle Patch Based on Cerium-Based Prussian Blue Analogues for the Treatment of MRSA-Associated Wound Infections","volume":"22","author":"Liang","year":"2026","journal-title":"Small"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177522","DOI":"10.1016\/j.cej.2026.177522","article-title":"Dual-Functional Isoquercitin-silver Nanoparticles Alleviate Bacterial-Induced Excessive Inflammation of Wound Infection and Sepsis","volume":"541","author":"Zhong","year":"2026","journal-title":"Chem. Eng. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"117174","DOI":"10.1016\/j.microc.2026.117174","article-title":"A Novel Flexible Sensor for Infected Wound Bacterial Identification and On-Demand Treatment","volume":"222","author":"Wang","year":"2026","journal-title":"Microchem. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123968","DOI":"10.1016\/j.biomaterials.2025.123968","article-title":"A Biomietic Filamentous Hydrogel with Enhanced Bacteria Contact and Bactericidal Efficiency for the Treatment of Various Skin Infections","volume":"330","author":"Tian","year":"2026","journal-title":"Biomaterials"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.chom.2026.01.002","article-title":"Enterococcus faecalis-Derived Lactic Acid Suppresses Macrophage Activation to Facilitate Persistent and Polymicrobial Wound Infections","volume":"34","author":"Tien","year":"2026","journal-title":"Cell Host Microbe"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Witkowska, K., Paczkowska-Walendowska, M., Plech, T., Szymanowska, D., Michniak-Kohn, B., and Cielecka-Piontek, J. (2023). Chitosan-Based Hydrogels for Controlled Delivery of Asiaticoside-Rich Centella asiatica Extracts with Wound Healing Potential. IJMS, 24.","DOI":"10.3390\/ijms242417229"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s10735-025-10433-3","article-title":"Field Marigold (Calendula arvensis L.) Accelerates Wound-Healing In Vivo: Role of Transforming Growth Factor-Beta1 (TGF-\u03921), Inflammatory, and Biochemical Molecules","volume":"56","author":"Jabbar","year":"2025","journal-title":"J. Mol. Histol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"121227","DOI":"10.1016\/j.jece.2026.121227","article-title":"Multifunctional Aloe Vera Composite Hydrogel with Photothermal Antibacterial and Antioxidant Properties for Infected Wound Healing","volume":"14","author":"Huang","year":"2026","journal-title":"J. Environ. Chem. Eng."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"158124","DOI":"10.1016\/j.phymed.2026.158124","article-title":"Aloe Vera Polysaccharides Facilitate Diabetic Wound Healing by Promoting Macrophage M2 Polarization through Inhibition of NLRP3 Inflammasome Activation","volume":"155","author":"Huang","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1055\/a-0850-0224","article-title":"The Wound Healing Properties of Betulin from Birch Bark from Bench to Bedside","volume":"85","author":"Scheffler","year":"2019","journal-title":"Planta Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mwiiri, F.K., Brandner, J.M., and Daniels, R. (2020). Electrospun Bioactive Wound Dressing Containing Colloidal Dispersions of Birch Bark Dry Extract. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080770"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1002\/ptr.5700","article-title":"Progress in the Development and Applicability of Potential Medicinal Plant Extract-Conjugated Polymeric Constructs for Wound Healing and Tissue Regeneration","volume":"30","author":"Das","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"213302","DOI":"10.1016\/j.bioadv.2023.213302","article-title":"Inflammation-Modulating Antibacterial Hydrogel Sustained Release Asiaticoside for Infection Wound Healing","volume":"147","author":"Chen","year":"2023","journal-title":"Biomater. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Barekat, S., Kaur, S., Hettiarachchy, N., and Ubeyitogullari, A. (2026). Utilization of Turmeric Leaf Phenolic Extracts as Natural Antioxidants in Emulsion Systems. Foods, 15.","DOI":"10.3390\/foods15030602"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"122845","DOI":"10.1016\/j.indcrop.2026.122845","article-title":"Enhancing Wood Preservatives from Cultivated Chinese Herbal Medicines: A Review of Synergistic Formulation, Nano-Modification, and Smart Release Technologies","volume":"241","author":"Wu","year":"2026","journal-title":"Ind. Crops Prod."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhou, J., Cai, H., Tu, S., Duan, Y., Pei, K., Xu, Y., Liu, J., Niu, M., Zhang, Y., and Shen, L. (2018). Identification and Analysis of Compound Profiles of Sinisan Based on \u2018Individual Herb, Herb-Pair, Herbal Formula\u2019 before and after Processing Using UHPLC-Q-TOF\/MS Coupled with Multiple Statistical Strategy. Molecules, 23.","DOI":"10.3390\/molecules23123128"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tuli, H.S., Sak, K., Gupta, D.S., Kaur, G., Aggarwal, D., Chaturvedi Parashar, N., Choudhary, R., Yerer, M.B., Kaur, J., and Kumar, M. (2021). Anti-Inflammatory and Anticancer Properties of Birch Bark-Derived Betulin: Recent Developments. Plants, 10.","DOI":"10.3390\/plants10122663"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Demets, O.V., Takibayeva, A.T., Kassenov, R.Z., and Aliyeva, M.R. (2022). Methods of Betulin Extraction from Birch Bark. Molecules, 27.","DOI":"10.3390\/molecules27113621"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102933","DOI":"10.1016\/j.cis.2023.102933","article-title":"The Bioavailability, Metabolism and Microbial Modulation of Curcumin-Loaded Nanodelivery Systems","volume":"318","author":"Chang","year":"2023","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"137405","DOI":"10.1016\/j.seppur.2026.137405","article-title":"Kinetic Modelling of Tomatine Extraction from Tomato Plant Waste: Influence of Solvent, Particle Size, Solvent Concentration and Solvent Ratio","volume":"394","author":"Katti","year":"2026","journal-title":"Sep. Purif. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105021","DOI":"10.1016\/j.ultsonch.2020.105021","article-title":"Influence of Ultrasonic Amplitude, Temperature, Time and Solvent Concentration on Bioactive Compounds Extraction from Propolis","volume":"64","author":"Oroian","year":"2020","journal-title":"Ultrason. Sonochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.3168\/jds.2025-28059","article-title":"Investigation of the Quality Properties and Functionality Improvement of Set-Type Yogurt Fortified with Different Ratios of Borage (Echium amoenum) and Nettle (Urtica dioica) Extracts","volume":"109","author":"Mohammadi","year":"2026","journal-title":"J. Dairy Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"106984","DOI":"10.1016\/j.jff.2025.106984","article-title":"Investigating the Effects of Different Ratios of Citrus limon, Citrus sinensis, and Vitis vinifera Extracts on Insulin Resistance in HepG2 Cells","volume":"133","author":"Pierdomenico","year":"2025","journal-title":"J. Funct. Foods"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kim, H.-Y., and Kim, J.-H. (2023). Chemical Influence of Scutellaria baicalensis\u2014Coptis chinensis Pair on the Extraction Efficiencies of Flavonoids and Alkaloids at Different Extraction Times and Temperatures. Separations, 10.","DOI":"10.3390\/separations10020131"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jgr.2016.07.001","article-title":"Effects of Panax Ginseng Extracts Prepared at Different Steaming Times on Thermogenesis in Rats","volume":"41","author":"Cho","year":"2017","journal-title":"J. Ginseng Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1021\/jf010179c","article-title":"Aloe Exudate: Characterization by Reversed Phase HPLC and Headspace GC-MS","volume":"49","author":"Bogoni","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1111\/ijfs.13093","article-title":"Comparison of Phytochemical Profiles, Antioxidant and Cellular Antioxidant Activities of Seven Cultivars of Aloe","volume":"51","author":"Lai","year":"2016","journal-title":"Int. J. Food Sci. Tech."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"032076","DOI":"10.1088\/1755-1315\/459\/3\/032076","article-title":"Research on Creation of Methods for Determining Betulin in Birch Bark Processing Products Using HPLC","volume":"459","author":"Gorelova","year":"2020","journal-title":"IOP Conf. Ser. Earth Environ. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, H., Xiao, H., and Pang, J. (2020). Parameter Optimization and Potential Bioactivity Evaluation of a Betulin Extract from White Birch Bark. Plants, 9.","DOI":"10.3390\/plants9030392"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.sajb.2018.10.001","article-title":"Comparative Assessment of In Vitro Thrombolytic and Fibrinolysis Activity of Four Aloe Species and Analysis of Their Phenolic Compounds by LC\u2013MS","volume":"119","author":"Fan","year":"2018","journal-title":"S. Afr. J. Bot."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Andrea, B., Dumitri\u021ba, R., Florina, C., Francisc, D., Anastasia, V., Socaci, S., and Adela, P. (2020). Comparative Analysis of Some Bioactive Compounds in Leaves of Different Aloe Species. BMC Chem., 14.","DOI":"10.1186\/s13065-020-00720-3"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.indcrop.2015.05.064","article-title":"Subcritical Water Extraction of Betulinic Acid from Birch Bark","volume":"74","author":"Liu","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_34","unstructured":"(2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5:2009)."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10650","DOI":"10.1038\/s41598-026-45012-3","article-title":"Integrated Experimental and Computational Evaluation of Anagallis foemina Derived Terpenoids against Carbapenem Resistant Acinetobacter Baumannii","volume":"16","author":"Afzal","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Klimoszek, D., Majewska, A., Jele\u0144, M., Struga, M., Morak-M\u0142odawska, B., and Do\u0142owy, M. (2026). Novel 8-Trifluoromethylquinobenzothiazines\u2014Synthesis and Evaluation for Antiproliferative and Antibacterial Activity. Pharmaceuticals, 19.","DOI":"10.3390\/ph19030422"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113868","DOI":"10.1016\/j.colsurfb.2024.113868","article-title":"An Antimicrobial Film of Silver\/Nanocellulose Crystal\/Oxalic Acid\/Polyvinyl Alcohol with Real-Time Bactericidal and Prevention of Biofilm Formation Properties","volume":"237","author":"Li","year":"2024","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111309","DOI":"10.1016\/j.jece.2023.111309","article-title":"A Novel Antibacterial and Anti-Biofilm Material: Biosynthetic Silver Nanoparticles Mediated by Extract from Oplopanax elatus Adventitious Roots","volume":"11","author":"Liu","year":"2023","journal-title":"J. Environ. Chem. Eng."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"14431","DOI":"10.1038\/s41598-026-50561-8","article-title":"Anti-Diabetic Potential of Artemisia monosperma Delile Extract Related to Anti-Inflammatory, Antioxidant, and Wound-Healing Properties","volume":"16","author":"Atya","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7349","DOI":"10.1021\/acsanm.6c00699","article-title":"Sprayable Antioxidative Dressing Based on Fullerene and Sodium Alginate for Accelerating Wound Healing","volume":"9","author":"Dong","year":"2026","journal-title":"ACS Appl. Nano Mater."},{"key":"ref_41","first-page":"231","article-title":"Preparation and Evaluation of a Water-in-Oil Nanoemulsion Drug Delivery System Loaded with Salidroside","volume":"19","author":"Liang","year":"2021","journal-title":"Chin. J. Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"117058","DOI":"10.1016\/j.carbpol.2020.117058","article-title":"Chitosan\/Polydopamine Layer by Layer Self-Assembled Silk Fibroin Nanofibers for Biomedical Applications","volume":"251","author":"Ma","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"116847","DOI":"10.1016\/j.carbpol.2020.116847","article-title":"New Synthetic Chitosan Derivatives Bearing Benzenoid\/Heterocyclic Moieties with Enhanced Antioxidant and Antifungal Activities","volume":"249","author":"Mi","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"32784","DOI":"10.1021\/acsami.4c08547","article-title":"Ultrastretchable Segmented Sensors for Functional Human\u2013Machine Interfaces","volume":"16","author":"Jamil","year":"2024","journal-title":"ACS Appl. Mater. 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