In vitro biotransformation of red ginseng extract by human intestinal microflora: metabolites identification and metabolic profile elucidation using LC-Q-TOF/MS.

Ginseng is an important and widely used herbal medicine in Asia and has gained popularity in the western countries. Ginseng products are usually administered orally, after which their complicated components are brought into contact with intestinal microflora in the alimentary tract and metabolized. The metabolic investigation of ginseng in intestinal tract is necessary for elucidating its pharmacological activities. However, most of the reports about the metabolism of ginseng with intestinal microflora are focused on single ginseng saponin with the whole action of ginseng extract ignored. In the present paper, in vitro biotransformation of red ginseng extract by human intestinal microflora was conducted, and a rapid liquid chromatography with time-of-flight mass spectrometry (LC-Q-TOF/MS) method was used for rapid identification of the metabolites and metabolic profile of ginseng saponins. A total of 37 ginseng saponins in red ginseng extract were characterized, 17 of which were assessed to be metabolized by human intestinal microflora. Also, 30 metabolites, mostly deglycosylated, were detected and identified in the biotransformed red ginseng extract, including 4 original ingredients of red ginseng, 6 ginsenoside lactate esters, and 2 glycosylated metabolites. The metabolic profile of ginseng saponins biotransformed by human intestinal microflora was elucidated based on the metabolite information. The results indicated that deglycosylation was the major metabolic pathway of saponins in red ginseng. The esterification and glycosylation reaction also occurred during the biotransformation. Our study indicated that there was some differences in the biotransformation of single ginseng saponin and red ginseng extract. It must be noted that the ginsenoside lactate esters were firstly found in the metabolites of ginsenosides.

[Changes in DNA repair enzymes in rat ventroposterior nucleus of the thalamus after cerebral cortex infarction].

OBJECTIVE: To investigate the damage within the ventroposterior nucleus (VPN) of the thalamus after focal cortical infarction and its mechanism, and explore the effect of ebselen on the oxidative damage after cerebral cortex infarction in hypertensive rats. METHODS: Middle cerebral artery occlusion (MCAO) was induced in stroke-prone renovascular hypertensive rats (RHRSP), and the rats were divided into four groups by table of random number: sham operation group, model group, vehicle group and ebselen group, each group consisted of 8 rats. In animals subjected to sham surgery the middle cerebral artery was exposed only. Ebselen (5 ml/kg) or vehicle (a mixed solvent consisting of 0.5% carboxymethyl cellulose and 0.02% Tween 20, 5 ml/kg) was given by gastric gavage starting 24 hours after cerebral cortical infarction. Two weeks after the MCAO, the rats were sacrificed, and VPN from each group was sectioned and stained with hematoxylin-eosin (HE), and apurinic/apyrimidinic endonuclease (APE) and Escherichia coli MutY DNA glycosylase (MYH) were determined by immunohistochemistry. RESULTS: HE staining showed that ebselen ameliorated the VPN damage induced by ischemia. Immunohistochemical imaging analysis revealed a distinct nuclear staining of APE and nuclear and cytoplasm distribution of MYH in the entire region of the VPN. Compared with sham operation group, the number of APE and MYH positive cells decreased in model group and vehicle group (APE: 57.0±14.7, 49.4±12.5 vs. 101.0±13.6, MYH: 15.0±4.7, 10.4±2.5 vs. 56.0±13.2, all P<0.05). Compared with model group and vehicle group, the number of APE and MYH positive cells increased significantly in ebselen group (APE: 72.2±7.6 vs. 57.0±14.7, 49.4±12.5, MYH: 32.2±7.6 vs. 15.0±4.7, 10.4±2.5, all P<0.05); the difference of the number of APE and MYH positive cells between model group and vehicle group showed no statistical significance. CONCLUSION: After 2 weeks of MCAO, there is a marked decrease of APE and MYH in VPN; ebselen can obviously increase the level of APE and MYH, and ebselen may protect the VPN of the thalamus from damage after focal cortical infarction in rats.