Acetylcholinesterase inhibitive activity-guided isolation of two new alkaloids from seeds of Peganum nigellastrum Bunge by an in vitro TLC- bioautographic assay

Abstract

Acetylcholinesterase inhibitors (AChEIs) currently form the basis of the newest drugs available for the treatment of Alzheimer's disease. For the aim of screening effective AChEIs, the methanol extracts of the seeds of genus Peganum were found to show significant inhibitory activity of acetylcholinesterase enzyme (AChE) using an in vitro TLC-bioautographic assay. In further studies to seed of P. nigellastrum Bunge, activity-guided fractionation led to the isolation of two new alkaloids nigellastrine I (9) and nigellastrine II (10), and along with eight known alkaloids, vasicinone (1), vasicine (2), harmine (3), deoxyvasicinone (4), deoxyvasicine (5), harmaline (6), harmol (7), harman (8), in which harmol and harman were first isolated from species P. nigellastrum Bunge. As active constituents, all compounds showed good inhibitory activities against AChE. The results of in vitro semi-quality TLC-bioautographic assay showed that harmine, harmaline and harmol displayed a similar AChE inhibitive activities comparing to galanthamine. These results indicated that these alkaloids in P. nigellastrum Bunge could be a potent class of AChEIs.

Characterization and determination of trace alkaloids in seeds extracts fromPeganum harmalalinn. Using LC-ESI-MS and HPLC

“…Former research of our group revealed that harmaline and harmine, accounting for more than 70% in composition, were the main alkaloids in extracts. Both of them exhibited strong AChE inhibitive activity remarkably superior to other alkaloids in P. harmala [20]. More attention, however, should be paid to the other alkaloids which would be favorable or unfavorable to the efficacy and safety of the products.…”

“…Harmine and harmaline showed special affinity to the central nervous system (CNS) and exhibited extensive bioactivities such as multi-enzymes inhibitions including monoamine oxidaze type-A [7,8], cyclin-dependent kinases [9], N-acetyltransferase [10] and Na-K ATPase [11], cytotoxicity and antitumour activities [12,13], anti-bacterial activity [14], antiplasmodial activity [15], antileishmanial activity [16], immunomodulator properties [17], temperature-lowering effect [18], cardiovascular actions [19] and so on. Recent research reported that the alkaloids showed potential inhibitory effects on the acetylcholinesterase (AChE) activity using an in vitro thin-layer chromatography (TLC)-bioautographic assay, and ten alkaloids isolated were evaluated based on their inhibitory ability [20]. Considering its potential effect on the treatment of Alzheimer's disease (AD), ten batches of total alkaloids extracts from seeds of P. harmala were prepared for pharmacologic research.…”

“…For example, vasicine was a promising uterotonic abortifacient [22]. In contrast, some trace alkaloids like harmalol and harmol also showed certain inhibitory effects on the AChE activity [20], which might increase the efficacy of the extracts. In addition, the variance in the content and sorts of alkaloids in extracts owing to fluctuation of technological parameters and qualities of raw plant material might influence the quality and safety of the raw extracts.…”

Therapeutic potential of harmaline, a novel alkaloid, against cervical cancer cells in vitro: Apoptotic induction and DNA interaction study

“…Recently, they have also been proved to cause oxidative modification of low-density lipoprotein particles, which can reduce severe atherosclerosis [10]. Harmaline [ Figure 1], a di-hydro beta carboline alkaloid, is such a plant alkaloid isolated from the seeds and roots of Peganum harmala (Syrian rue) [11] and have wide range of biological actions including anti-leishmanial [12], insecticidal [13], acetylcholinesterase inhibition [14], central monoamine oxidase inhibition [15], and in vitro human topoisomerase I inhibition effects [16] and in vitro cytotoxic effects [17]. Another beta carboline alkaloid harmine and its derivatives were also proved to be cytotoxic against different cancer cell lines [18].…”

Establishment of an effective TLC bioautographic method for the detection ofMycobacterium tuberculosisH37Ra phosphoglucose isomerase inhibition by phosphoenolpyruvate

“…In our opinion, there is a clear trend towards the use of the TLC bioautography technique as a method for screening active compounds against microorganisms rather than a method for the detection of enzyme activities or inhibitors. The use of TLC (bio)autography was reported for the screening of inhibitors of acetylcholinesterase [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] , butyrylcholinesterase 12,16,22,23,27 , dipeptidyl peptidase IV 28 , glucose-6-phosphate dehydrogenase 29 , a-and b-glucosidases [30][31][32][33][34] , lipase [35][36][37] , monoamine oxidases A and B 38,39 , DNA topoisomerase I 40 , tyrosinase [41][42][43] and xanthine oxidase 44 . To date, the use of the TLC-based autographic method for the detection of PGI inhibition has only been developed for a biocatalyst isolated from the reference E. coli strain ATCC (American Type Culture Collection) 25922 45 .…”