{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:03:18Z","timestamp":1791468198542,"version":"4.3.4"},"reference-count":78,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This research was funded by Fundamental Fund 2023, Chiang Mai University","award":["FF66\/023"],"award-info":[{"award-number":["FF66\/023"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Foods"],"abstract":"<jats:p>Thai fermented soybeans (TFSs) contain phytochemicals with anti-diabetic benefits. In this study, an initial non-optimized TFS extract (TFSE) was prepared using a conventional triplicate 80% ethanol extraction method and evaluated for its biological activity. TFSE effectively reversed TNF-\u03b1-induced insulin resistance in 3T3-L1 adipocytes by enhancing insulin-stimulated glucose uptake, indicating anti-diabetic potential. TFSE also upregulated the phosphorylation of AKT (a key insulin signaling mediator) and the expression of adipogenic proteins (PPAR\u03b3, CEBP\u03b1) in TNF-\u03b1-exposed 3T3-L1, suggesting the mitigation of adipocyte dysfunction; however, the results did not reach statistical significance. The conventional extraction process was labor-intensive and time-consuming, and to enhance extraction efficiency and bioactivity, the process was subsequently optimized using environmentally friendly microwave-assisted extraction (MAE) in combination with the Box\u2013Behnken design (BBD) and response surface methodology (RSM). The optimized extract (O-TFSE) was obtained over a significantly shorter extraction time and exhibited higher levels of total flavonoids and antioxidant activity in comparison to TFSE, while showing reduced levels of isoflavones (daidzein, genistein, and glycitein) in relation to TFSE. Interestingly, O-TFSE retained similar efficacy in reversing TNF-\u03b1-induced insulin resistance and demonstrated significantly stronger \u03b1-glucosidase and \u03b1-amylase inhibitory activities, indicating its enhanced potential for diabetes management. These results support the use of MAE as an efficient method for extracting functional compounds from TFS for functional foods targeting insulin resistance and type 2 diabetes mellitus.<\/jats:p>","DOI":"10.3390\/foods14152603","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T14:11:44Z","timestamp":1753366304000},"page":"2603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhancement of Phytochemicals and Antioxidant Activity of Thai Fermented Soybean Using Box\u2013Behnken Design Guided Microwave-Assisted Extraction"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-7024","authenticated-orcid":false,"given":"Piya","family":"Temviriyanukul","sequence":"first","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya 73170, Nakhon Pathom, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4282-4908","authenticated-orcid":false,"given":"Woorawee","family":"Inthachat","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya 73170, Nakhon Pathom, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ararat","family":"Jaiaree","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jirarat","family":"Karinchai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6764-0801","authenticated-orcid":false,"given":"Pensiri","family":"Buacheen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-2283","authenticated-orcid":false,"given":"Supachai","family":"Yodkeeree","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8087-8269","authenticated-orcid":false,"given":"Tanongsak","family":"Laowanitwattana","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-3777","authenticated-orcid":false,"given":"Teera","family":"Chewonarin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5887-6329","authenticated-orcid":false,"given":"Uthaiwan","family":"Suttisansanee","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Salaya 73170, Nakhon Pathom, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2787-2461","authenticated-orcid":false,"given":"Arisa","family":"Imsumran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-0447","authenticated-orcid":false,"given":"Ariyaphong","family":"Wongnoppavich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-386X","authenticated-orcid":false,"given":"Pornsiri","family":"Pitchakarn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Muang Chiang Mai 50200, Chiang Mai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th Edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. 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