(±)-Vasicine

30587479

The highly oriented modern detection techniques provide a precise and definite tool for investigation in natural medicines. Current study directed the standardization of eminent biomarker Vasicine in a natural cough syrup. A highly accurate and precise method of High-performance thin layer chromatography (HPTLC) has been developed to certify the quantity of vasicine inside the syrup. Ethyl acetate, chloroform, ethanol and ammonia (6:3:1: 1 v/v) were mobile phase for the study. The TLC plate silica gel G60F254 was used with CAMAG Scanner III and CAMAG Linomate 5. The detected Rf value was 0.51 in both sample and reference standard at 254 nm. International conference of Harmonization (ICH) guidelines were followed for the validation of the developed method. Linearity was achieved in the range of 200μg to 1600μg with co-efficient correlation r2=0.9995. Accuracy was found in between 98.9 to 101.4% however precision was good at both inter and intra-day. As per the standardization of ICH, the developed method was found to be reproducible and showed sharp similar peak with high resolution.

Phytochemical standardization of Vasicinein cough syrup by high performance liquid chromatography-densitometry

Hina Rehman 1, Safila Naveed 2, Fatima Qamar 2, Sultan Ayaz 3, Sadia Jamil 4, Sakina Fatima 2, Aisha Sana 2, Khan Usmanghani 5

2018 Nov;

30077712

Vasicine (VAS) is a potential natural cholinesterase inhibitor for treatment of Alzheimer’s disease. Due to one chiral centre (C-3) presenting in molecule, VAS has two enantiomers, d-vasicine (d-VAS) and l-vasicine (l-VAS). The study was undertaken to investigate the stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic effect and acute toxicity of VAS enantiomers. In results, the glucuronidation metabolic rate of l-VAS was faster than d-VAS in human liver microsomes and isoenzymes tests, and it was proved that the UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B15 were the major metabolic enzymes for glucuronidation of l-VAS, while only UGT1A9 for d-VAS, which take responsibility of the significantly less metabolic affinity of d-VAS than l-VAS in HLM and rhUGT1A9. The plasma exposure of d-VAS in rats was 1.3-fold and 1.6-fold higher than that of l-VAS after intravenous and oral administration of d-VAS and l-VAS, respectively. And the plasma exposure of the major glucuronidation metabolite d-VASG was one of tenth of l-VASG or more less, no matter by intravenous or oral administration. Both d-VAS and l-VAS were exhibited promising acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, and the BChE inhibitory activity of d-VAS with IC50 of 0.03 ± 0.001 μM was significantly stronger than that of l-VAS with IC50 of 0.98 ± 0.19 μM. The molecular docking results indicated that d-VAS and l-VAS could bind to the catalytic active site (CAS position) either of human AChE and BChE, and the BChE combing ability of d-VAS (the score of GBI/WAS dG -7.398) was stronger than that of l-VAS (the score of GBI/WAS dG -7.135). Both d-VAS and l-VAS could improving the learning and memory on scopolamine-induced memory deficits in mice. The content of acetylcholine (ACh) after oral administration d-VAS increased more than that of l-VAS in mice cortex, through inhibiting cholinesterase (ChE) and increasing choline acetyltransferase (ChAT). In addition, the LD50 value of d-VAS (282.51 mg·kg-1) was slight lower than l-VAS (319.75 mg·kg-1). These results indicated that VAS enantiomers displayed significantly stereoselective metabolic, pharmacokinetics, anti-amnesic effect and toxic properties in vitro and in vivo. The d-VAS might be the dominant configuration for treating Alzheimer’s disease.

Anti-amnesic; Glucuronidation; Pharmacokinetics; Stereoselective; Vasicine enantiomers.

Stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic pharmacodynamics, and toxic properties of vasicine enantiomers in vitro and in vivo

Yudan Zhu 1, Wei Liu 1, Shenglan Qi 1, Hanxue Wang 1, Yuwen Wang 1, Gang Deng 1, Yunpeng Zhang 1, Shuping Li 1, Chao Ma 1, Yongli Wang 2, Xuemei Cheng 2, Changhong Wang 3

2018 Oct 15;