title: Biotransformation on the flavonolignan constituents of Silybi Fructus by an intestinal bacterial strain Eubacterium limosum ZL-II.
abstract: Eubacterium limosum ZL-II is an anaerobic bacterium with demethylated activity, which was isolated from human intestinal bacteria in our previous work. In this study, the flavonolignan constituents of Silybi Fructus were biotransformed by E. limosum(1) ZL-II, producing four new transformation products - demethylisosilybin B (T1), demethylisosilybin A (T2), demethylsilybin B (T3) and demethylsilybin A (T4), among which T1 and T2 were new compounds. Their chemical structures were identified by ESI-TOF/MS, (1)H NMR, (13)C NMR, HMBC and CD spectroscopic data. The bioassay results showed that the transformation products T1-T4 exhibited significant inhibitory activities on Alzheimer's amyloid-β 42 (Aβ42(2)) aggregation with IC50 values at 7.49 μM-10.46 μM, which were comparable with that of the positive control (epigallocatechin gallate, EGCG(3), at 9.01 μM) and much lower than those of their parent compounds (at not less than 145.10 μM). The method of biotransformation by E. limosum ZL-II explored a way to develop the new and active lead compounds in Alzheimer's disease from Silybi Fructus. However, the transformation products T1-T4 exhibited decreased inhibitory activities against human tumor cell lines comparing with their parent compounds.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: ydhui@bjmu.edu.cn.
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ying-Tao
authors.initials: YT
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: sqcai@bjmu.edu.cn.
authors.forename: Shao-Qing
authors.initials: SQ
authors.lastname: Cai
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001711:Biotransformation; D005051:Eubacterium / Q000378:metabolism*; D044947:Flavonolignans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005638:Fruit; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D020944:Silybum marianum / Q000737:chemistry* / Q000382:microbiology; D015394:Molecular Structure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000972:Antineoplastic Agents, Phytogenic; D044947:Flavonolignans; D010446:Peptide Fragments; D010936:Plant Extracts; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's Aβ(42); Biotransformation; Eubacterium limosum ZL-II; Flavonolignan; Isosilybin A (PubChem CID: 11059920); Isosilybin B (PubChem CID: 10885340); Silybi Fructus; Silybin A (PubChem CID: 31553); Silybin B (PubChem CID: 1548994); Silychristin (PubChem CID: 441764); Silydianin (PubChem CIcxuD: 3033957); Tumor cell