title: Comparative investigation of in vitro biotransformation of 14 components in Ginkgo biloba extract in normal, diabetes and diabetic nephropathy rat intestinal bacteria matrix.
abstract: Most herbal medicines will be metabolized by intestinal bacteria in the gastrointestinal tract before absorbed by the small intestine. Ginkgo biloba extract (GBE) possesses protective effects on the glomerulosclerosis of diabetic nephropathy (DN), but its biotransformation in diabetes and DN intestinal bacteria has not yet been recognized. In this work, a validated liquid chromatography-tandem mass spectrometry (LC-MS) method was established for the simultaneous quantification of 14 components in GBE in rat intestinal bacteria matrix, namely ginkgolides A, ginkgolides B, ginkgolides C, bilobalide, rutin, myricetin, quercitrin, quercetin, luteolin, genistein, kaempferol, apigenin, isorhamnetin and genkwanin. Chromatographic separation was performed on a Kromasil-C18 (4.6mm×250mm i.d., 5.0μm) analytical column maintained at 35°C. The mobile phase was a mixture of methanol (A) and 0.1% formic acid in water (B) with a step linear gradient at a flow rate of 1.0mlmin(-1). The calibration curves of these 14 analytes demonstrated good linearity within the test range (R>0.99). This validated method has successfully been applied into the pharmacokinetic study of the 14 components. More importantly, in the pharmacokinetic study, by comparing the time course of the biotransformation by normal, diabetes and DN rat intestinal bacteria, we found that the biotransformation speed and residence time of the 14 compounds in diabetes and DN rats differed obviously from that obtained in normal group, which provided valuable chemical information for further pharmacology and active mechanism research on GBE.
authors.affiliation: Department of Pharmaceutical Analysis, Xuzhou Medical College, Xuzhou 221004, China; Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China; Environmental Research Institute, National University of Singapore, 117411 Singapore. Electronic address: tdq993@hotmail.com.
authors.forename: Daoquan
authors.initials: D
authors.lastname: Tang
authors.affiliation: Department of Pharmaceutical Analysis, Xuzhou Medical College, Xuzhou 221004, China; Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Yinjie
authors.initials: Y
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: Jiangsu Key Laboratory of Target Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China. Electronic address: yinxx@xzmc.edu.cn.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D001711:Biotransformation; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000382:microbiology*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000382:microbiology*; D005243:Feces / Q000382:microbiology; D020441:Ginkgo biloba; D007422:Intestines / Q000382:microbiology*; D016014:Linear Models; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000493:pharmacokinetics*; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D010936:Plant Extracts
keywords: Diabetes; Diabetic nephropathy; Ginkgo biloba extract; Intestinal bacteria; LC-MS