Abstract
Harmine, one of the natural β-carboline alkaloids extracted from Peganum harmala L., exhibits broad spectrum but limited insecticidal ability against many pests. So there is an urgent need to synthesize novel derivatives with high efficiency. In the present study, a new synthetic compound, [1-(2-naphthyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carboline] (ZC-14), showed a strong proliferation inhibition effect against the Spodoptera frugiperda Sf9 cell line in a dose-dependent manner. Simultaneously, apoptosis induced by 7.5 μg/mL ZC-14 was confirmed with physiological and biochemical evidence, including typical apoptosis characteristics with shrinkage, apoptotic bodies, nuclear condensation/fragmentation, a clear DNA ladder, and a series of apoptotic rates. In addition, mitochondria were confirmed to be involved in apoptosis induced by ZC-14 accompanied with the loss of mitochondrial membrane potential (Δψm), the release of cytochrome c from mitochondria into the cytosol and increased expression of cleaved-caspase-3. However, harmine could not induce apoptosis at the same concentration. In summary, these data indicated that compound ZC-14 has a higher cytotoxicity than harmine against Sf9 cells. Besides, it exhibited an anti-proliferative effect in Sf9 cells via inducing apoptosis in which the mitochondrial apoptotic pathway plays a crucial role.
Highlights
As the most important group of plant secondary metabolites, β-carboline alkaloids are abundant in Peganum harmala L. which is mainly distributed in northwest China and widely used for various diseases therapies due to its remarkable pharmacological effects, including anti-tumor, anti-hypertensive and anti-inflammatory activities [1,2,3]
The physiological and biochemical aspects of apoptosis induced by ZC-14 were evaluated. These results indicated that the cytotoxicity of ZC-14 was higher than harmine and it could induce apoptosis in Sf9 cells through activating mitochondrial apoptotic pathway
To evaluate the cytotoxicity of harmine and ZC-14, Sf9 cells were exposed to different concentrations of harmine and ZC-14 for 24 and 48 h
Summary
As the most important group of plant secondary metabolites, β-carboline alkaloids are abundant in Peganum harmala L. which is mainly distributed in northwest China and widely used for various diseases therapies due to its remarkable pharmacological effects, including anti-tumor, anti-hypertensive and anti-inflammatory activities [1,2,3]. The alkaloids are responsible for plant resistance to insects in plant-insect interaction [4] These plant allelochemicals could affect insect behavior as attractants, repellents or toxic substances, and regulate growth, development and other physiological processes [5,6]. A natural β-carboline alkaloid, is abundant in seeds of P. harmala [7]. Harmine was considered to be a potential candidate for Alzheimer’s disease therapy by inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity [11]. Harmine exhibited toxicity against Tribolium castaneum and Rhyzopertha dominica; but this was lower than the methanolic extract of P. harmala [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
