Chemical Constituents of Rhododendron lepidotum
Two new coumarin glycosides, 7-O-β-D-glucopyranosyl-8-methoxybenzopyranone (1) and 7-hydroxy-8-O-β-glycosylbenzopyranone ((2), are reported along with the isolation of 7,8-dihydroxy coumarin (daphnetin) from Rhododendron lepidotum (aerial part).
Chemical constituents from Phyllanthus emblica and the cytoprotective effects on H2O2-induced PC12 cell injuries
Two new compounds (1–2), including a bisabolane-type sesquiterpenoid (1), one new diphenyl ether derivative (2), together with 23 known compounds (3–25), were isolated from the fruits of Phyllanthus emblica. Their structures were elucidated by detailed spectroscopic analysis. All the isolated compounds were screened for the DPPH scavenging effects and cytoprotective effects against H2O2 induced PC12 cells injury. Compounds 12–15 showed significant DPPH scavenging effects with the IC50 values in the range of 3.25–4.18 μM. Among these potential antioxidants, compound 14 improved the survival of PC12 cells after H2O2 exposure without showing any cytotoxicity at the tested concentrations.
Pharmacokinetics and Metabolism of 14C-Brivaracetam, a Novel SV2A Ligand, in Healthy Subjects
This study was designed to investigate the human absorption, disposition, and mass balance of 14C-brivaracetam, a novel high affinity SV2A ligand with potent anticonvulsant activity. Six healthy male subjects received a single p.o. dose of 14C-brivaracetam (150 mg, 82 μCi, or 3.03 MBq). Serial blood and complete urine and feces were collected until 144 h postdose. Expired air samples were obtained until 24 h. Brivaracetam was rapidly absorbed, with Cmax of 4 μg/ml occurring within 1.5 h of dosing. Unchanged brivaracetam amounted to 90% of the total plasma radioactivity, suggesting a modest first-pass effect. Plasma protein binding of radioactivity was low (17.5%). Urinary excretion exceeded 90% after 2 days, and the final mass balance reached 96.8% of the radioactivity in urine and 0.7% in feces. Only 8.6% of the radioactive dose was recovered in urine as unchanged brivaracetam, the remainder being identified as non–cytochrome P450 (P450)- and P450-dependent biotransformation products resulting from hydrolysis of the amide moiety (M9, 34.2%), hydroxylation of the n-propyl side chain (M1b, 15.9%), and a combination of these two pathways leading to the hydroxy acid (M4b, 15.2%). Minor amounts of taurine and glucuronic acid conjugates and other oxidized derivatives were also identified. Brivaracetam is completely absorbed, is weakly bound to plasma proteins, extensively biotransformed through several metabolic pathways, and eliminated renally.