title: In vitro human fecal microbial metabolism of Forsythoside A and biological activities of its metabolites.
abstract: The present study aimed to investigate the metabolism of Forsythoside A (FTA) by human fecal bacteria to clarify the relationship between its intestinal metabolism and its pharmacological activities. FTA was incubated with human fecal microflora in vitro to investigate its metabolic process, and highly sensitive and specific ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed using MetaboLynx software for metabolite analysis. Caffeic acid (CA) and hydroxytyrosol (HT) were obtained by hydrolysis of FTA, and CA was further hydrogenated to form 3,4-dihydroxybenzenepropionic acid (DCA). The anticomplementary, antimicrobial and antiendotoxin activities of FTA and its metabolites by human fecal microflora were evaluated in vitro with a hemolysis assay, the agar disc-diffusion method, the MIC value and the gel clot LAL assay, respectively. The metabolites showed higher biological activity than FTA, especially HT and DCA. Orally administered FTA may be metabolized to HT and DCA, and the pharmacological effects of FTA may be dependent on intestinal bacterial metabolism.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Xing
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Mengyue
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 200032, China.
authors.forename: Daofeng
authors.initials: D
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: xbli@sjtu.edu.cn.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry; D002109:Caffeic Acids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D051056:Complement Inactivating Agents / Q000737:chemistry; D005243:Feces / Q000382:microbiology*; D005260:Female; D006027:Glycosides / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D064307:Microbiota; D008875:Middle Aged; D015394:Molecular Structure; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D002109:Caffeic Acids; D051056:Complement Inactivating Agents; D006027:Glycosides; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol; C058049:forsythiaside; C040048:caffeic acid
keywords: 3,4-Dihydroxybenzenepropionic acid (PubChem CID: 348154); Anticomplement; Antiendotoxin; Antimicrobial; Caffeic acid (PubChem CID: 689043); Forsythoside A; Forsythoside A (PubChem CID: 45358127); Hydroxytyrosol (PubChem CID: 82755); Intestinal bacteria; Metabolite