title: Biotransformation of isofraxetin-6-O-β-d-glucopyranoside by Angelica sinensis (Oliv.) Diels callus.
abstract: Isofraxetin-6-O-β-d-glucopyranoside, identified from traditional medicinal herbal Xanthoceras sorbifolia Bunge, has been demonstrated to be a natural neuroinflammatory inhibitor. In order to obtain more derivatives with potential anti-neuroinflammatory effects, biotransformation was carried out. According to the characteristics of coumarin skeleton, suspension cultures of Angelica sinensis (Oliv.) Diels callus (A. sinensis callus) were employed because of the presence of diverse phenylpropanoids biosynthetic enzymes. As a result, 15 products were yielded from the suspension cultures, including a new coumarin: 8'-dehydroxymethyl cleomiscosin A (1), together with 14 known compounds. Their structures were elucidated by extensive spectroscopic analysis. Furthermore, the biotransformed pathways were discussed. Among them, compound 13 was transformed from isofraxetin-6-O-β-d-glucopyranoside, while compounds 1-6, 10-12, 14-15 were derived from the culture medium stimulated by the substrate. The biotransformation processes include hydroxylation, oxidation and esterification. Furthermore, their inhibitory effects on lipopolysaccharide (LPS)-activated nitric oxide (NO) production were evaluated in BV2 microglial cells. It is worth noting that, 1, 1'-methanediylbis(4-methoxybenzene) (3), obtucarbamates A (5), 2-nonyl-4-hydroxyquinoline N-oxide (10) and 1H-indole-3-carbaldehyde (11) exhibited significant inhibitory effect against neuroinflammation with IC50values at 1.22, 10.57, 1.02 and 0.76μM respectively, much stronger than that of the positive control minocycline (IC5035.82μM).
authors.affiliation: School of Traditional Chinese Materia Media, Shenyang Pharmaceutical University, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Wenhua Road 103, Shenyang 110016, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Yanbian University Hospital, Yanji 133000, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110004, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hou
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang 110004, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Jiao
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: ycybridge@163.com.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yan
authors.affiliation: School of Traditional Chinese Materia Media, Shenyang Pharmaceutical University, Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Wenhua Road 103, Shenyang 110016, China. Electronic address: liningsypharm@163.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001711:Biotransformation; D002460:Cell Line; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D005960:Glucosides; D008070:Lipopolysaccharides; C000620852:isofraxetin-6-O-glucopyranoside; D009569:Nitric Oxide
keywords: Angelica sinensis (Oliv.) Diels callus; Anti-neuroinflammation; Biotransformation; Isofraxetin-6-O-β-d-glucopyranoside