Study On The Chemical Constituents, Quality Control And Metabolism Of Cassia Obtusifolia

Cassia obtusifolia Linn, a member of the genus Cassia (Leguminosae), is a well known traditional Chinese medicinal plant. It belongs to the medically and economically important family Leguminosae (Syn. Fabaceae), subfamily Caesalpinioideae. The seed of the plant, called Juemingzi in Chinese, have been widely used for the treatments of headache and dizziness, red and tearing eyes. In previous investigations of this plant, a number of compounds were isolated, include anthraquinones, anthrones, flavonoids, and naphthopyrones. The anthraquinone derivatives, anthronic, dianthronic, and anthraquinone glycosides of Cassia are responsible for their purgative action. In the present study, the chemical constituents, pharmacokinetics and in vivo metabolism of three anthraquinone marks were studied, which is helpful in understanding the action mechanism for this therapeutic agent.By silica gel, sephadex LH-20 column chromatograpies,31 compounds were isolated from ethanol extract of C. tora.28 compounds have been identified on the basis of spectroscopic data (IR, UV, CD, MS,1H-NMR,13C-NMR, HSQC, HMBC,1H-1H COSY), including 15 anthraquinones,4 naphthopyrones,4 flavonoids,5 phenolic acids. Two new compounds of them were:(obtusifoline-2-O-β-D-6-O-acetylglucopyranoside), 2-benzyl-4,6-dihydroxy benzoic acid-6-O-β-D-glucopyranoside)。A sensitive, simple specific HPLC-DAD method has been developed to simultaneously quantify the eight major bioactive Anthraquinones in C. tora. This assay was applied to the evaluation of 15 samples from different origins in China. The results indicated that the developed assay could be readily utilized for the quality control of C. obtusifolia.Anthraquinones were well known responsible for their purgative action.. In this thesis, Aloe-emodin (1), Obtusifoline (2) chrysophanol (3) were chosen as the marker compounds for the pharmacokinetic study after oral administration of C. obtusifolia. extract. The absorption, distribution, metabolism and extraction of the three marker compounds in rats were investigated. The three anthraquinones in rat plasma, bile, urine and tissues were analyzed by HPLC-DAD. After oral administration, Aloe-emodin, Obtusifoline and chrysophanol were quickly absorbed into the blood from the gastrointestinal tract (the tmax is observed at 20-60min). The cumulative excretion of Aloe-emodin, Obtusifoline and chrysophanol was 4.87%,2.74% and 3.65% in urine samples,1.71%,7.2% and 4.9% in bile samples, respectively. The maximum urinary and biliary excretions in different intervals of Aloe-emodin, Obtusifoline and chrysophanol were observed at 12-20 and 4-8 h after oral administration, respectively.