{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:17:19Z","timestamp":1785406639081,"version":"3.56.0"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460731, 82003836"],"award-info":[{"award-number":["82460731, 82003836"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82460731, 82003836"],"award-info":[{"award-number":["82460731, 82003836"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Key R&amp;D Plan Project of Ningxia","award":["2024BEG01006"],"award-info":[{"award-number":["2024BEG01006"]}]},{"name":"Research Project of Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, Ningxia Medical University","award":["KFKT202313"],"award-info":[{"award-number":["KFKT202313"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Resveratrol is a naturally occurring polyphenolic stilbene compound exhibiting a wide range of biological activities, and it has been extensively utilized as both a food additive and a pharmaceutical active ingredient. Typically, it can be directly extracted from natural sources such as grapes, mulberries, and peanuts, or obtained through catalytic hydrolysis of polydatin. To establish an efficient and optimized method for resveratrol production, we conducted a comprehensive study to refine the acid-catalyzed hydrolysis conditions of polydatin. Methods: A high-performance liquid chromatography method was developed for the quantitative determination of polydatin and resveratrol. To identify the optimal ranges of reaction temperature, HCl concentration, and ethanol concentration, single-factor experiments were conducted by evaluating their influences on hydrolysis kinetics and resveratrol yield. Based on these results, response surface methodology incorporating a Box\u2013Behnken design was employed to optimize the hydrolysis process, using resveratrol yield as the response variable. Furthermore, time-course experiments were performed to determine the optimal reaction duration under the established optimal conditions. Results: Single-factor experiments demonstrated that increasing temperature and HCl concentration significantly accelerated hydrolysis, but resveratrol yield increased initially and then decreased with excessive increases in either factor. To further optimize the process, response surface methodology optimization experiments were conducted at temperatures of 60, 70, and 80 \u00b0C; HCl concentrations of 1.0, 1.5, and 2.0 M; and ethanol concentrations of 75%, 85%, and 95%. The optimal conditions were identified as follows: temperature, 70 \u00b0C; HCl concentration, 1.5 M; ethanol volume fraction 85%; and reaction time, 5 h. Under these conditions, the theoretical resveratrol yield was 85.68%, and the average yield from triplicate validation experiments was 86.01% (RSD = 0.56%), which was consistent with the theoretical value. Conclusions: The optimized acid-catalytic hydrolysis process using RSM is stable, feasible, and efficient, offering a promising approach for enhancing resveratrol production from polydatin.<\/jats:p>","DOI":"10.3390\/ph19050659","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:11:14Z","timestamp":1776931874000},"page":"659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimization of Polydatin Hydrolysis Process Through Response Surface Methodology for Efficient Resveratrol Production"],"prefix":"10.3390","volume":"19","author":[{"given":"Dong","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Xiao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Cai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5564-4610","authenticated-orcid":false,"given":"Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gerhardt, E., Gr\u00e4ber, S., Szego, E.M., Moisoi, N., Martins, L.M., Outeiro, T.F., and Kermer, P. (2011). Idebenone and resveratrol extend lifespan and improve motor function of HtrA2 knockout mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028855"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108413","DOI":"10.1016\/j.abb.2020.108413","article-title":"Resveratrol suppresses gastric cancer cell proliferation and survival through inhibition of PIM-1 kinase activity","volume":"689","author":"Kim","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.atherosclerosis.2018.01.043","article-title":"The protective effect of resveratrol on vascular aging by modulation of the renin-angiotensin system","volume":"270","author":"Kim","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"de S\u00e1 Coutinho, D., Pacheco, M.T., Frozza, R.L., and Bernardi, A. (2018). Anti-inflammatory effects of resveratrol: Mechanistic insights. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061812"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/mnfr.201200589","article-title":"Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans","volume":"58","author":"Cottart","year":"2014","journal-title":"Mol. Nutr. Food. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4819","DOI":"10.1016\/S0040-4039(03)01131-6","article-title":"Synthesis of resveratrol using a direct decarbonylative Heck approach from resorcylic acid","volume":"44","author":"Andrus","year":"2003","journal-title":"Tetrahedron Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1007\/s11947-021-02665-4","article-title":"Green Extraction Methods and Microencapsulation Technologies of Phenolic Compounds from Grape Pomace: A Review","volume":"14","author":"Moro","year":"2021","journal-title":"Food Bioprocess Technol."},{"key":"ref_8","first-page":"150","article-title":"Effects of trans-resveratrol in peanut red coat on antioxidant in HEK293T cells","volume":"24","author":"Sun","year":"2024","journal-title":"J. Chin. Inst. Food Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jpha.2012.12.001","article-title":"A simple method for the isolation and purification of resveratrol from Polygonum cuspidatum","volume":"3","author":"Wang","year":"2013","journal-title":"J. Pharm. Anal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1021\/jf030582e","article-title":"Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice","volume":"52","author":"Meng","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhou, J., Liang, M., Lin, Y., Pang, H., Wei, Y., Huang, R., and Du, L. (2022). Application of \u03b2-glucosidase in a biphasic system for the efficient conversion of polydatin to resveratrol. Molecules, 27.","DOI":"10.3390\/molecules27051514"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wang, C., Liu, X., Zhang, M., Shao, H., Zhang, M., Wang, X., Wang, Q., Bao, Z., Fan, X., and Li, H. (2019). Efficient enzyme-assisted extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum using thermostable cellulase and immobilized \u03b2-glucosidase. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00445"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.biortech.2013.03.027","article-title":"Biotransformation of polydatin to resveratrol in Polygonum cuspidatum roots by highly immobilized edible Aspergillus niger and Yeast","volume":"136","author":"Jin","year":"2013","journal-title":"Bioresour. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15448","DOI":"10.1039\/C9RA01338E","article-title":"An innovative biotransformation to produce resveratrol by Bacillus safensis","volume":"9","author":"Hu","year":"2019","journal-title":"RSC Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.procbio.2016.06.019","article-title":"Hydrolytic kinetics of piceid and its importance for the production of resveratrol","volume":"51","author":"Li","year":"2016","journal-title":"Process Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.cclet.2014.11.021","article-title":"Controlled acid hydrolysis and kinetics of flavone C-glycosides from trollflowers","volume":"26","author":"Dou","year":"2015","journal-title":"Chin. Chem. Lett."},{"key":"ref_17","unstructured":"Zhou, L. (2019). Study on Enzymatic Extraction of Resveratrol from Polygonum cuspidatum and Synthesis of Resveratrol Esters. [Ph.D. Thesis, Jiangnan University]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1021\/jf803948g","article-title":"Dose-dependent absorption and metabolism of trans-polydatin in rats","volume":"57","author":"Zhou","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/mnfr.200500010","article-title":"Metabolism and bioavailability of trans-resveratrol","volume":"49","author":"Wenzel","year":"2005","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/2213346110666230517114652","article-title":"Evaluation of nonconventional extraction methods of resveratrol from various plant sources\u2014A brief review","volume":"10","author":"Saidul","year":"2023","journal-title":"Curr. Green Chem."},{"key":"ref_21","first-page":"52","article-title":"Enzymatic preparation of resveratrol and baohuoside I by \u03b2-glucosidase An3987 from Aspergillus niger","volume":"41","author":"Gong","year":"2025","journal-title":"Mod. Food Sci. Technol."},{"key":"ref_22","first-page":"117","article-title":"Study on the impact factor of polydatin hydrolyzes","volume":"36","author":"Liu","year":"2010","journal-title":"Food Ferment. Ind."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zada, N.S., Belduz, A.O., Alessa, A.H., G\u00fcler, H.I., Karao\u011flan, M., Badshah, M., Shah, A.A., Kalsoom, A., and Khan, S. (2025). Comparison of active site mutations at subsite + 2 of Anoxybacillus ayderensis A9 \u03b2-glucosidase for hydrolysis of pNPG and polydatin. BMC Biotechnol., 25.","DOI":"10.1186\/s12896-025-00984-4"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2174\/15734064113096660053","article-title":"Chemistry, stability and bioavailability of resveratrol","volume":"10","author":"Francioso","year":"2014","journal-title":"Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yao, Y., Yuan, H., Chen, C., Liang, J., and Li, C. (2023). Study of the antioxidant capacity and oxidation products of resveratrol in soybean oil. Foods, 13.","DOI":"10.3390\/foods13010029"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"128498","DOI":"10.1016\/j.foodchem.2020.128498","article-title":"One-pot method based on deep eutectic solvent for extraction and conversion of polydatin to resveratrol from Polygonum cuspidatum","volume":"343","author":"Sun","year":"2021","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3390\/foods13020324","article-title":"Sustainable in silico-supported ultrasonic-assisted extraction of oligomeric stilbenoids from grapevine roots using natural deep eutectic solvents (NADES) and stability study of potential ready-to-use extracts","volume":"13","author":"Kiene","year":"2024","journal-title":"Foods"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/659\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T04:25:49Z","timestamp":1777091149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/5\/659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ph19050659"],"URL":"https:\/\/doi.org\/10.3390\/ph19050659","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}