Insecticidal activity and mechanism of action of phenylpropanoids isolated from Piper sarmentosum against storage insect pests and mosquito vectors / Arshia Hematpoor

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

The phytochemical and biological studies were carried out on medicinal and adible \nplant known as Piper sarmentosum L. (Piperaceae). Bioassay guided study of the active \nhexane and methanol extracts from aerial parts and roots of P. sarmentosum L. lead to \nisolation of four phenylpropanoids namely, asaricin 1, isoasarone 2, trans-asarone 3 and \nasaraldehyde 4. Their insecticidal activity and mechanism of action was investigated \nagainst storage pests (Sitophilus oryzae, Rhizopertha dominica and Plodia \ninterpunctella) and mosquito vectors (Aedes albopictus, Aedes aegypti and Culex \nquinquefasciatus). Potent insecticidal activity against both species was produced by 1 \nand 2. Compounds 1 and 2 were highly toxic to S. oryzae with LC50 value of 4.7 and 5.6 \nrespectively. R. dominica was slightly more resistance, P. interpunctella had highest \nresistant to 1 and 2 with LC50 value of ≤ 17.37 μg/ml and LC95 ≤ 37.7 μg/ml. asaricin 1 \nand isoasarone 2 exhibited high repellent activity against S. oryzae, R. dominica and P. \ninterpunctella at 10 μg/ml. during the residual toxicity test it was observed that 1 and 2 \nhad consistent activity within 30 days and their activity declined after that but \ncompound 3 activity was consistent with 60 days of experiment. Likewise, 1 and 2 had \npotent larvicidal activity against Ae. albopictus, Ae. aegypti and Cx. quinquefasciatus. 1 \nand 2 similarly were highly potent against Ae. aegypti, Ae. albopictus and Cx. \nquinquefasciatus larvae with LC50 ≤ 8.9 μg/ml and LC95 ≤ 15.1 μg/ml . The ovicidal \nactivity of 1, 2 and 3 were evaluated through egg hatching. 1 and 2 showed potent \novicidal activity. Ovicidal activity for both compounds was up to 90% at 25μg/ml. \nHowever repellent and adulticide activities of 1 and 2 against tested female mosquito \nwas moderate. In all insecticidal tests compound 3 had moderate insecticidal activity \nand compound 4 did not have any insecticidal property. Biochemical investigation \nrevealed that 1, 2 and 3 inhibit the acetylcholinesterase (AChE). Although 1 and 2 inhibition was stronger than 3 but correlation study showed that the toxicity of all three \ncompounds was significantly related with their AChE inhibition activity. Further \ninvestigation for insect esterase activity showed that all insects had high GST activity \nand the level of GST was significantly higher in P. interpunchitela which had the \nhighest resistance against 1, 2 and 3. The levels of non-specific esterases and oxidases \nactivities were not significant between the tested insets. Further the docking studies \nwere done to investigate the binding mode of interaction of 1, 2 and 3 with AChE and \nGST enzyme using Autodock/Vina. Between three active sites peripheral anionic site \n(PAS), catalytic and anionic in AChE, 1, 2 and 3 interact with more residues within 3 Å \nusing a lower energy at anionic site. Compound 1 was interacted with TYR 370 pocket \nwhile 2 and 3 were more stable in THR 154, GLY 155, SER 156, TYR 162 at very low \nand stable energy level. Docking study on GST interactions with 1, 2 and 3 suggested \nthat PRO11. GLU64 and TYR105 are more essential residues in GST for 1, 2 and 3 \nbinding besides known active residues SER65 and ARG66. This can explain the high \ntoxicity of 1 and 2. Biochemical and docking clearly showed the GST activity role in \nbinding and detoxifying the 1, 2 and 3. Our result suggested that 1 and 2 were highly \ntoxic to tested insects by inhibiting AChE enzyme and computation work supported and \nclarified the binding mode of interaction. Although compound 3 activity was not as \nsignificant as 1 and 2 but there is possibility of its usage in mixture as formulation in \nfuture study since it is more stable in the environment. On the other hand understanding \nthe role of GST enzyme helped to develop knowledge on insects response to 1, 2 and 3. \nFurther studies will warrant possible applications of 1, 2 and 3 as potential natural \ninsecticide for the control of storage pests and mosquito vectors populations.