Acetylcholinesterase inhibitory activity of stigmasterol & hexacosanol is responsible for larvicidal and repellent properties of Chromolaena odorata

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 3; pp. 541 - 550
• Main Authors: Gade, Sriramya, Rajamanikyam, Maheshwari, Vadlapudi, Varahalarao, Nukala, Krishna Madhav, Aluvala, Rajendar, Giddigari, Chandrasekhar, Karanam, Naga Jyothi, Barua, Nabin C., Pandey, Richa, Upadhyayula, Vijaya Saradhi V., Sripadi, Prabhakar, Amanchy, Ramars, Upadhyayula, Suryanarayana Murty
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2017
• Subjects: 1-Hexacosanol; Acetylcholinesterase; Acetylcholinesterase - metabolism; Aedes; Aedes - drug effects; Aedes - metabolism; Animals; bioactive compounds; Cholinesterase Inhibitors - pharmacology; chromatography; Chromolaena - chemistry; Chromolaena odorata; Culex quinquefasciatus; EAG; electroantennography; electrophysiology; Fatty Alcohols - pharmacology; insect repellents; Insecticides - pharmacology; Larva - drug effects; larvae; Larvicide; larvicides; mechanism of action; mortality; mosquito control; neurophysiology; neurotoxicity; Neurotoxins - pharmacology; nuclear magnetic resonance spectroscopy; Phytosterol; Phytosterols - pharmacology; plant extracts; Plant Extracts - pharmacology; Plant Leaves - chemistry; Stigmasterol; Stigmasterol - pharmacology; vector control; Stigmasterol; Stigmasterol (PubChem CID: 5280794); 1-Hexacosanol (PubChem CID: 68171); Phytosterol; 1-Hexacosanol; EAG; Larvicide; Acetylcholinesterase
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2016.11.044

Chromolaena odorata, has been traditionally known for its insect repellent property. Aim of this study was to determine larvicidal tendency of C. odorata on Culex quinquefasciatus and isolate compounds responsible for this activity and to determine the mechanism of action of these compounds. C. odorata plant extract was screened for mosquito larvicidal activity. The extract was fractionated using chromatography and the bioactive fraction showing larvicidal activity was identified. The chemical nature of the compounds in the bioactive fraction was determined using NMR and Mass spectrometry. We identified phytosterols and alkanols to be the compounds regulating larvicidal activity in the bioactive fraction of the plant extract. Stigmasterol and 1-hexacosanol were identified to be the chief orchestrators of larvicidal activity and their mode of action has been observed to be neurotoxicity. At a molecular level both stigmasterol and 1-hexacosanol were found to be inhibiting acetylcholinesterase activity in C. quinquefasciatus & A. aegypti. The acetylcholinesterase inhibitory effect was validated in vitro using recombinant acetylcholinesterase and ex vivo in larval homogenates of Culex and Aedes. Electrophysiological studies using electroantennography have shown enhanced neural response to these compounds. Neurotoxic effect of C. odorata derived stigmasterol and 1-hexacosanol, exerted through acetylcholinesterase inhibition was responsible for the mortality of C. quinquefasciatus, A. aegypti &Chironomus riparius. EAG studies pointed out hyper-excitability of the olfactory system by these compounds. These compounds are natural agents for mosquito control that can be used in vector control as larvicidal compounds, pending further investigations. [Display omitted] •Chromolaena odorata an insect repellent plant exhibited mosquito larvicidal activity.•Active compounds responsible for larvicidal activity were identified as hexacosanol and stigmasterol.•Larvicidal activity was shown in Culex, Aedes and a non-mosquito dipteran Chironomus.•Stigmasterol & hexacosanol cause uncoordinated neurological movements in mosquito larvae and adults.•Acetylcholinesterase inhibition and neurophysiology studies confirmed neurotoxic effect of stigmasterol & hexacosanol.