MilliporeSigma
  • Home
  • Search Results
  • Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation.

Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation.

Journal of ethnopharmacology (2015-04-12)
Yadi Yang, Xuemei Cheng, Wei Liu, Guixin Chou, Zhengtao Wang, Changhong Wang
ABSTRACT

Seeds of Peganum harmala Linn are traditionally used as folk medical herb in Uighur medicine in China to treat disorders of hemiplegia and amnesia. Previously studies have proved that dominating alkaloids in P. harmala show significant inhibitory activities on the cholinesterase. The aim of the present study is to isolate trace ingredients from seeds of P. harmala and evaluate its inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). For sake of screening effective cholinesterase inhibitors, trace compounds were isolated from seeds of P. harmala through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The inhibitory activities on AChE and BChE were assessed using an improved Ellman method by UPLC-ESI-MS/MS to determine the common final product choline. The activity-guided fractionation led to the isolation of two new alkaloids 2-aldehyde-tetrahydroharmine (10), 2-carboxyl-3,4-dihydroquinazoline (19), one syringin structure analog 1-O-β-D-xylopyranose sinapyl alcohol (22), and along with 19 known compounds. Compounds acetylnorharmine (6), harmic acid methy ester (7), harmine N-oxide (13), 6-methoxyindoline (14), syringin (21) were first found from genus Peganum and compounds 3-hydroxylated harmine (4), 1-hydroxy-7-methoxy-β-carboline (5) were new natural products. The results showed that the 2-aldehyde-tetrahydroharmine (10) has a potential inbibitive effect on both AChE and BChE with IC50 values of 12.35 ± 0.24 and 5.51 ± 0.33 µM, respectively. Deoxyvasicine (15) and vasicine (16) showed the strongest BChE inhibitory activity with IC50 values of 0.04 ± 0.01 and 0.1 ± 0.01 µM. The analysis of the structure-activity relationship indicated that the saturation of pyridine ring and the presence of substitution at indole ring, C-1, C-3, C-7 and N-2, for β-carbolines, were essential for effective inhibition of both AChE and BChE and the five-membered ring between C-2 and N-3 as well as the substituent groups sited at C-4 and C-9, for quinazolines, were important to both the AChE/BChE-inhibitory activity. Bioassay-guided fractionation has led to the isolation of AChE and BChE inhibitors from the seeds of P. harmala. These results are in agreement with the traditional uses of the seeds of P. harmala.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, meets USP testing specifications
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, anhydrous, ≥99.5%
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Supelco
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 5 mm × 8 in.
Supelco
Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%
Sigma-Aldrich
Sodium hydroxide-16O solution, 20 wt. % in H216O, 99.9 atom % 16O
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Supelco
Ethanol standards 10% (v/v), 10 % (v/v) in H2O, analytical standard
Sigma-Aldrich
Ethanol Fixative 80% v/v, suitable for fixing solution (blood films)
Sigma-Aldrich
Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, 99.93%
Sigma-Aldrich
3-Ethyl-2,4-pentanedione, mixture of tautomers, 98%
Sigma-Aldrich
Sodium hydroxide solution, BioUltra, for molecular biology, 10 M in H2O
Sigma-Aldrich
Sodium hydroxide, BioUltra, for luminescence, ≥98.0% (T), pellets
Sigma-Aldrich
Methanol, NMR reference standard
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Sodium hydroxide, ultra dry, powder or crystals, 99.99% trace metals basis