{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:17:07Z","timestamp":1760149027820,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"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":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"],"award-info":[{"award-number":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Jiangsu Province","award":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"],"award-info":[{"award-number":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"]}]},{"name":"Natural Science Foundation of the Jiangsu Higher Education Institutions of China","award":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"],"award-info":[{"award-number":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"]}]},{"name":"Open Project of the State Key Laboratory of Natural Medicines","award":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"],"award-info":[{"award-number":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"]}]},{"name":"College Students\u2019 Innovation and Entrepreneurship Training Program","award":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"],"award-info":[{"award-number":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"]}]},{"name":"Funding Supporting Projects of the National Natural Science Foundation of China","award":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"],"award-info":[{"award-number":["82204420","81373295","81473420","BK20220474","22KJB310004","SKLNMKF202202","202210315144Z","XPT82204420"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Liver cancer continues to be a focus of scientific research due to its low five-year survival rate. One of its main core issues is the high metastasis of cells, for which there is no effective treatment. Neferine was originally isolated from Plumula nelumbinis and demonstrated to have a good antitumor effect. In order to extract high-purity Neferine in a more efficient and environmentally friendly manner, response surface methodology (RSM) was used to optimize the isolation and purification procedures in this study. The extract conditions of a 7:3 ratio for the eluent of dichloromethane: methanol, 1:60 for the mass ratio of the extract amount: silica gel, and 3 mL\/min of the elution flow rate were shown to be the optimal conditions. These conditions resulted in the highest yield of 6.13 mg per 66.60 mg of starting material, with productivity of 8.76% and purity of 87.04%. Compared with the previous methods, this method can prepare Neferine in large quantities more quickly. We subsequently evaluated the antitumor activity of the purified Neferine against HepG2 hepatic cancer cells. The purified Neferine was found to inhibit the proliferation of HepG2 cells through the CCK-8 assay, with an IC50 of 33.80 \u03bcM in 24 h, 29.47 \u03bcM in 48 h, 24.35 \u03bcM in 72 h and 2.78 \u03bcM in 96 h of treatment. Neferine at a concentration of 3 \u03bcM could significantly inhibit the migration and invasion abilities of the HepG2 cells in vitro. We also explored the mechanism of action of Neferine via Western blot. We showed that Neferine could reduce RhoA expression by effectively inhibiting the phosphorylation of MYPT1, thereby effectively exerting anti-metastasis activity against HepG2 cells. Thus, we have optimized the isolation procedures for highly pure Neferine by response surface methodology (RSM) in this study, and purified Neferine is shown to play an essential role in the anti-metastasis process of liver cancer cells. The Neferine purification procedure may make a wide contribution to the follow-up development of other anti-metastasis lead compounds.<\/jats:p>","DOI":"10.3390\/molecules28135086","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T01:14:12Z","timestamp":1688087652000},"page":"5086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimization of Neferine Purification Based on Response Surface Methodology and Its Anti-Metastasis Mechanism on HepG2 Cells"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9469-436X","authenticated-orcid":false,"given":"Xinzhu","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7936-1471","authenticated-orcid":false,"given":"Zhenhuan","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weibo","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-366X","authenticated-orcid":false,"given":"Zhixin","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2234-8847","authenticated-orcid":false,"given":"Israa","family":"Assani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-0354","authenticated-orcid":false,"given":"Guangming","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-7333","authenticated-orcid":false,"given":"Yang","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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