Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells
5-Demethylnobiletin (5-DMN), a hydroxylated polymethoxyflavone (OH-PMF) identified in aged citrus peels, has demonstrated health benefiting effects in previous studies. 5-DMN undergoes biotransformation in vivo, yielding 5,3'-didemethylnobiletin (5,3'-DDMN), 5,4'-didemethylnobiletin (...
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Tsinghua University Press
2022-09-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453022000568 |
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| author | Yanping Xin Ting Zheng Man Zhang Ruiqiang Zhang Siyue Zhu Dongli Li Denggao Zhao Yanyan Ma Chi-Tang Ho Qingrong Huang |
| author_facet | Yanping Xin Ting Zheng Man Zhang Ruiqiang Zhang Siyue Zhu Dongli Li Denggao Zhao Yanyan Ma Chi-Tang Ho Qingrong Huang |
| author_sort | Yanping Xin |
| collection | DOAJ |
| description | 5-Demethylnobiletin (5-DMN), a hydroxylated polymethoxyflavone (OH-PMF) identified in aged citrus peels, has demonstrated health benefiting effects in previous studies. 5-DMN undergoes biotransformation in vivo, yielding 5,3'-didemethylnobiletin (5,3'-DDMN), 5,4'-didemethylnobiletin (5,4'-DDMN) and 5,3',4'-tridemethylnobiletin (5,3',4'-TDMN). However, the anti-cancer effects of 5-DMN and its in vivo metabolites against HepG2 cells remain unclear. In this study, an efficient chemical synthetic method was developed to obtain 5-DMN and its 3 metabolites, and their molecular structures were confirmed by 1H NMR and LC-MS. Cytotoxicity, cell cycle arrestment, apoptosis and caspase-3 expression were investigated to evaluate the anti-liver cancer effects of these OH-PMFs on HepG2 cells. The results showed that all 4 compounds inhibited the proliferation of HepG2 cells in a concentration-dependent manner. Their anti-proliferative activity was exerted through inducing G2/M phase arrestment, cell apoptosis and promoting expression of a key apoptotic protein called cleaved caspase-3. Our results indicated that 5,3'-DDMN and 5,3',4'-TDMN showed a stronger inhibitory activity on cell proliferation than 5-DMN, followed by 5,4'-DDMN. The expression of cleaved caspase-3 was the highest in cells treated with 5,4'-DDMN, implying that the apoptosis induced by other OH-PMFs might be mediated by other apoptotic execution proteins. Our research reveals the application potential and scientific evidence for the production and functionality of OH-PMFs. |
| format | Article |
| id | doaj-art-cf9b4e11d8c44ff8afdfa7980a92f407 |
| institution | Kabale University |
| issn | 2213-4530 |
| language | English |
| publishDate | 2022-09-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-cf9b4e11d8c44ff8afdfa7980a92f4072025-02-03T02:27:47ZengTsinghua University PressFood Science and Human Wellness2213-45302022-09-0111511911200Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cellsYanping Xin0Ting Zheng1Man Zhang2Ruiqiang Zhang3Siyue Zhu4Dongli Li5Denggao Zhao6Yanyan Ma7Chi-Tang Ho8Qingrong Huang9School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, China; Department of Food Science, Rutgers University, New Jersey 08901, USADepartment of Food Science, Rutgers University, New Jersey 08901, USADepartment of Food Science, Rutgers University, New Jersey 08901, USASchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, ChinaDepartment of Food Science, Rutgers University, New Jersey 08901, USASchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, China; Corresponding authors.School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, ChinaDepartment of Food Science, Rutgers University, New Jersey 08901, USADepartment of Food Science, Rutgers University, New Jersey 08901, USA; Corresponding authors.5-Demethylnobiletin (5-DMN), a hydroxylated polymethoxyflavone (OH-PMF) identified in aged citrus peels, has demonstrated health benefiting effects in previous studies. 5-DMN undergoes biotransformation in vivo, yielding 5,3'-didemethylnobiletin (5,3'-DDMN), 5,4'-didemethylnobiletin (5,4'-DDMN) and 5,3',4'-tridemethylnobiletin (5,3',4'-TDMN). However, the anti-cancer effects of 5-DMN and its in vivo metabolites against HepG2 cells remain unclear. In this study, an efficient chemical synthetic method was developed to obtain 5-DMN and its 3 metabolites, and their molecular structures were confirmed by 1H NMR and LC-MS. Cytotoxicity, cell cycle arrestment, apoptosis and caspase-3 expression were investigated to evaluate the anti-liver cancer effects of these OH-PMFs on HepG2 cells. The results showed that all 4 compounds inhibited the proliferation of HepG2 cells in a concentration-dependent manner. Their anti-proliferative activity was exerted through inducing G2/M phase arrestment, cell apoptosis and promoting expression of a key apoptotic protein called cleaved caspase-3. Our results indicated that 5,3'-DDMN and 5,3',4'-TDMN showed a stronger inhibitory activity on cell proliferation than 5-DMN, followed by 5,4'-DDMN. The expression of cleaved caspase-3 was the highest in cells treated with 5,4'-DDMN, implying that the apoptosis induced by other OH-PMFs might be mediated by other apoptotic execution proteins. Our research reveals the application potential and scientific evidence for the production and functionality of OH-PMFs.http://www.sciencedirect.com/science/article/pii/S2213453022000568Hydroxylated polymethoxyflavonesChemical synthesisHepG2Cell cycleApoptosis |
| spellingShingle | Yanping Xin Ting Zheng Man Zhang Ruiqiang Zhang Siyue Zhu Dongli Li Denggao Zhao Yanyan Ma Chi-Tang Ho Qingrong Huang Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells Food Science and Human Wellness Hydroxylated polymethoxyflavones Chemical synthesis HepG2 Cell cycle Apoptosis |
| title | Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells |
| title_full | Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells |
| title_fullStr | Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells |
| title_full_unstemmed | Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells |
| title_short | Demethylnobiletin and its major metabolites: Efficient preparation and mechanism of their anti-proliferation activity in HepG2 cells |
| title_sort | demethylnobiletin and its major metabolites efficient preparation and mechanism of their anti proliferation activity in hepg2 cells |
| topic | Hydroxylated polymethoxyflavones Chemical synthesis HepG2 Cell cycle Apoptosis |
| url | http://www.sciencedirect.com/science/article/pii/S2213453022000568 |
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