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Mar Drugs
2014 Jun 10;126:3560-73. doi: 10.3390/md12063560.
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Acetylcholinesterase inhibitory activity of pigment echinochrome A from sea urchin Scaphechinus mirabilis.
Lee SR, Pronto JR, Sarankhuu BE, Ko KS, Rhee BD, Kim N, Mishchenko NP, Fedoreyev SA, Stonik VA, Han J.
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Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer''s disease (AD). Although EchA is clinically used to treat ophthalmic diseases and limit infarct formation during ischemia/ reperfusion injury, anti-AChE effect of EchA is still unknown. In this study, we investigated the anti-AChE effect of EchA in vitro. EchA and its exhausted form which lost anti-oxidant capacity did not show any significant cytotoxicy on the H9c2 and A7r5 cells. EchA inhibited AChE with an irreversible and uncompetitive mode. In addition, EchA showed reactive oxygen species scavenging activity, particularly with nitric oxide. These findings indicate new therapeutic potential for EchA in treating reduced acetylcholine-related diseases including AD and provide an insight into developing new AChE inhibitors.
Figure 1. The chemical structure of echinochrome A (EchA) (6-ethyl-2,3,5,7,8-pentahydroxy-1,4-naphthoquinone, FW = 266.2) comes from a class of naturally occurring polyhydroxynaphthoquinones. This compound has a red-brown color.
Figure 4. Determination of cell cytotoxicity of exhausted echinochrome A on H9c2 and A7r5 cells. Exhausted form of EchA was prepared by exposure of EchA to room air under light for at least 48 h. The exhausted form of EchA lost its H2O2-scanvenging capacity (Figure 3) but did not show any cytotoxic effect on H9c2 and A7r5 cells up to 50 μM (n = 10). Cell viability was determined by MTT assay and calculated as % of untreated control. There were no statistical significances (p > 0.05).
Figure 5. Anti-acetylcholinesterase activity of echinochrome A. (A) Representative product formation image as a function of time at different concentration of EchA (n = 9). Neostigomine was used as positive control of anti-AChE activity. The activity of AChE (100 mIU/mL) alone was used as a control for determining the anti-AChE effect of EchA; (B) Dose-dependent anti-AChE activity of EchA. The AChE inhibitory effect of EchA was calculated as % of AChE alone from Figure 5A. Values are expressed as mean ± SEM. AChE: acetylcholinesterase, EchA: echinochrome A, *
p < 0.05 vs. AChE alone.
Figure 6. Anti-acetylcholinesterase activity of echinochrome A with incubation time. Inhibitory activity of EchA was assessed based on incubation time of AChE with EchA before adding the ACh. The activity of AChE alone at different incubation time (control) was set at 100%. The inhibitory effects of EchA on AChE were expressed as % of respective control. Data are mean ± SEM (n = 5). AChE; acetylcholinesterase, EchA; echinochrome A, # p < 0.05 vs. AChE alone at different incubation time, *
p < 0.05 vs. AChE with EchA at 10 min incubation.
Figure 7. Lineweaver-Burk plot of 1/v vs. 1/[ACh] in the presence or absence of EchA. Slope indicates Km/V. The Vmax (y-intercept) and Km (x-intercept) value of AChE as plotted against [ACh] were decreased significantly in the presnec of EchA. EchA; echinochrome A.
Figure 8. Dixon plot. The Vmax value of AChE was plotted against different doses of EchA at multiple fixed Ach concentrations. The Ki value (x-intercept) could not be obtained because theslopes are parallel. ACh: acetylcholine.
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