Skimmianine, a furoquinoline alkaloid from Zanthoxylum nitidum as a potential acetylcholinesterase inhibitor

Abstract

Skimmianine (1), a newly discovered strong acetylcholinesterase (AChE) inhibitor, along with nine weakly or no active compounds, toddalolactone (2), dictamnine (3), c-fagarine (4), magnolone (5), (-)-(S)-edulinine (6), zanthodioline (7), edulitine (8), 5,6,7-trimethoxycoumarin (9), and haplopine (10) have been isolated from Zanthoxylum nitidum (Z. nitidum). Skimmianine (1) inhibited 50% of AChE activity at the concentrations of 8.6 ± 0.7 lg/ml when the IC 50 value of Physostigmine as a standard was 0.013 ± 0.002 lg/ml. Antiacetylcholinesterase activity of skimmianine (1) was also supported by TLC bioautographic assay. The structure activity relationship on the anti-acetylcholinesterase activity of the quinoline moiety is also discussed in this article.

Biologically active quinoline and quinazoline alkaloids part II

“…In the same study, other quinoline alkaloids, inclucing dictamnine, γ‐fagarine, (−)‐(S)‐edulinine, zanthodioline, edulitine, and haplopine, were weakly active or inactive. TLC bioautographic assay also supported skimmianine's inhibitory activity, which was enhanced by the presence of a methoxy group at C‐7 . In other studies, skimmianine, another furoquinoline kokusaginine, and the quinolin‐4‐one leiokinine A, inhibited AChE inhibition with IC 50 values of 1.4 mM, 46 μM, and 0.21 mM, respectively .…”

“…The newest drugs to treat Alzheimer's disease are acetylcholinesterase inhibitors (AChEIs). As a newly discovered AChEI, the furoquinoline alkaloid skimmianine from Zanthoxylum nitidum inhibited 50% of AChE activity at a concentration of 8.6 μg/mL, while the IC 50 value of the standard physostigmine was 0.013 μg/mL . In the same study, other quinoline alkaloids, inclucing dictamnine, γ‐fagarine, (−)‐(S)‐edulinine, zanthodioline, edulitine, and haplopine, were weakly active or inactive.…”

Natural AChE Inhibitors from Plants and their Contribution to Alzheimer’s Disease Therapy

“…The isolation of skimmianine ( 11 ), a furoquinoline alkaloid with very low AChE inhibitory activity, was also reported by the same authors. This alkaloid was observed in another Rutaceae, Zanthoxylum nitidum , exhibiting a moderate AChE inhibitory activity (IC 50 = 8.6 µg/ml) [13]. …”

Metabolite Profiling by Hyphenated Liquid Chromatographic Mass Spectrometric Technique (HPLC‐DAD‐ESI‐Q‐TOF‐MS/MS) and Neurobiological Potential of Haplophyllum sahinii and H. vulcanicum Extracts

“…Among plant secondary metabolites, alkaloids are proven to possess a marked level of anticholinesterase effect . For instance, the alkaloids, skimmianine, γ ‐fagarine, and dictamnine isolated from the roots of Zanthoxylum nitidum and also found in Haplophyllum species, only skimmianine (91.3±2.0 %, IC 50 =8.6±0.7 μg/mL) showed a strong AChE inhibitory activity at concentration of 100 μg/mL as compared to the reference drug; physostigmine (IC 50 =0.013±0.002 μg/mL), which was later confirmed in another study for skimmianine (58.63±1.22 %, IC 50 =8.52±0.64 μg/mL) . On the other hand, skimmianine obtained from the leaves of Evodia lepta was reported to demonstrate a weak level of AChE and BChE inhibition (IC 50 =69.1 μ m and 5.6 μ m against AChE and IC 50 =130.2 μ m and 26.3 μ m against BChE for skimmianine and galantamine, respectively) .…”

“…[26] For instance, the alkaloids, skimmianine, γfagarine, and dictamnine isolated from the roots of Zanthoxylum nitidum and also found in Haplophyllum species, only skimmianine (91.3 � 2.0 %, IC 50 = 8.6 � 0.7 μg/mL) showed a strong AChE inhibitory activity at concentration of 100 μg/mL as compared to the reference drug; physostigmine (IC 50 = 0.013 � 0.002 μg/mL), [27] which was later confirmed in another study for skimmianine (58.63 � 1.22 %, IC 50 = 8.52 � 0.64 μg/mL). [28] On the other hand, skimmianine obtained from the leaves of Evodia lepta was reported to demonstrate a weak level of AChE and BChE inhibition (IC 50 = 69.1 μM and 5.6 μM against AChE and IC 50 = 130.2 μM and 26.3 μM against BChE for skimmianine and galantamine, respectively). [29] The moderate inhibition of AChE by skimmianine (67.213 � 0.298 %) as well as dictamnine plus γ-fagarine (52.002 � 0.203 %) was also shown by Cabral et al, [30] as well as Cardoso-Lopez et al [31] Since presence of these alkaloids was exhibited in Haplophyllum species including H. vulcanicum and H. sahinii screened herein, skimmianine in particular could be considered to contribute ChE inhibitory effect of these species.…”