Crofton weed derived isomers of ageraphorone as potent antifeedant against Plutella xylostella (L.).

Global agricultural production is significantly hampered by insect pests, and the demand for natural pragmatic pesticides with environmental concern remains unfulfilled. Ageratina adenophora (Spreng.) also known as Crofton weed, is an invasive perennial herbaceous plant that is known to possess multiple bioactive compounds. In our study, two isomers of ageraphorone metabolites i.e, 10 Hα-9-oxo-ageraphorone (10HA) and 10 Hß-9-oxo-ageraphorone (10HB), were identified from Crofton weed, exhibiting potent antifeedant and larvicidal activities against Plutella xylostella. For antifeedant activity, the median effective concentration (EC50) values for 10HA and 10HB in the choice method were 2279 mg/L and 3233 mg/L, respectively, and for the no choice method, EC50 values were 1721 mg/L and 2394 mg/L, respectively. For larvicidal activity, lethal concentration (LC50) values for 10HA and 10HB were 2421 mg/L and 4109 mg/L at 48 h and 2101 mg/L and 3550 mg/L at 72 h. Furthermore, both in- vivo and in-vitro studies revealed that the isomers 10HA and 10HB exhibited potent detoxifying enzymes inhibition activity such as carboxylesterase and glutathione S-transferases. Molecular docking and MD simulation analysis provide insight into the possible interaction between isomers of ageraphorone metabolites and Carboxylic Ester Hydrolase protein (Gene: pxCCE016b) of P. xylostella, which led to a finding that CarEH protein plays a significant role in the detoxification of the two compounds in P. xylostella. Finally, our findings show that the primary enzymes undergoing inhibition by isomers of ageraphorone metabolites, causing toxicity in insects, are Carboxylesterase and glutathione S-transferase.

Insecticidal and biochemical effects of Dillenia indica L. leaves against three major stored grain insect pests.

The Last four decades have witnessed the banning of several synthetic insecticides mainly due to the development of resistance to the target pests and due to hazardous effects on humans and the environment. Hence, the development of a potent insecticide with biodegradable and eco-friendly nature is the need of the hour. In the present study, the fumigant property, and biochemical effects of Dillenia indica L. (Dilleniaceae) were studied against three coleopterans stored-products insects. The bioactive enriched fraction (sub-fraction-III) was isolated from ethyl acetate extracts of D. indica leaves and found toxic to rice weevil, Sitophilus oryzae (L.) (Coleoptera); lesser grain borer Rhyzopertha dominica (L.) (Coleoptera) and red flour beetle, Tribolium castaneum (Herbst.) (Coleoptera) with the LC50 values of 101.887, 189.908 and 115.1 µg/L respectively after 24 h exposure. The enriched fraction was found to inhibit the function of acetylcholinesterase (AChE) enzyme when tested against S. oryzae, T. castaneum, and R. dominica with LC50 value of 88.57 µg/ml, 97.07 µg/ml, and 66.31 µg/ml respectively, in in-vitro condition. It was also found that the enriched fraction caused a significant oxidative imbalance in the antioxidative enzyme system such as superoxide dismutase, catalase, DPPH (2,2-diphenyl-1-picrylhydrazyl), and glutathione-S-transferase (GST). GCMS analysis of the enriched fraction indicates three major compounds namely, 6-Hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydrobenzofuran-2(4H)-one, 1,2-Benzisothiazol-3(2H)-one, and Benzothiazole, 2-(2-hydroxyethylthio)-. Finally, we concluded that the enriched fraction of D. indica has insecticidal properties and the toxicity may be due to the inhibition of the AChE enzyme in association with oxidative imbalance created on the insect's antioxidant enzyme systems.

Safety evaluation of enriched fraction from leaves of Dillenia indica L. in BALB/c mice.

The enriched fraction derived from Dillenia indica L. (Dilleniaceae), also known as elephant apple was subjected to acute and sub-acute toxicological study to document its safety issues for use as fumigant. The enriched fractions were orally administered to both sexes of BALB/c mice at doses of 200, 800 and 1600 mg/kg bw for acute toxicity, and 50 and 500 mg/kg bw for 14 days of sub-acute toxicity. Experimental results revealed that there were no signs of adverse toxicity, and mortality, with no significant treatment related effect in the percentage weight gain, daily feed and water intake, and haematological parameters. However, at higher dose in sub-acute toxicity study a patch of mild tubular injuries in kidney of female mice were observed as suggested by histopathological studies and mild abnormalities in levels of serum biochemical parameters. In general, it can be considered that the enriched fraction from D. indica leaves on oral feeding does not show any adverse effect on mice of both sexes. Hence, the highest doses 1600 mg/kg bw (acute) and 500 mg/kg bw (sub-acute) can be used as basal dose for the determination of no-observed-adverse-effect level (NOAEL) of enriched fraction from D. indica to calculate its safety margin.

Acute and sub-acute toxicity evaluation of dihydro-p-coumaric acid isolated from leaves of Tithonia diversifolia Hemsl. A. Gray in BALB/c mice.

In present study, the acute and sub-acute toxicities of Dihydro-p-coumaric acid isolated from the leaves of Tithonia diversifolia (Hemsl.) A. Gray was studied for safety issues in mammals. For acute toxicity tests, isolated compound was administered orally in both male and female BALB/c mice at the doses of 200, 800, and 1,600 mg/kg body weight for 7 days. In sub-acute toxicity study 50 and 500 mg/kg bw of the compound was orally administered for 14 days. Toxicity induced behavioural changes, haematological parameters, biochemical markers and histopathological sections were studied after Dihydro-p-coumaric acid administration. The vital organs like heart, kidney, uterus and testis revealed no adverse effects at doses of upto 1,600 mg/kg bw and 500 mg/kg bw. Slight hepatotoxicity was however demonstrated by ALT and AST assay but histopathological section did not concur as much. The study demonstrated insignificant difference in the percentage of feed intake, water intake, weight gain, haematological parameters and histopathological changes, with no toxicity signs and mortality. Dihydro-p-coumaric acid can be regarded as safe in both acute and sub-acute toxicity assay in both sexes. This indicates Dihydro-p-coumaric acid as a viable alternative to synthetic pesticides.

Biochemical efficacy, molecular docking and inhibitory effect of 2, 3-dimethylmaleic anhydride on insect acetylcholinesterase.

Evolution of resistance among insects to action of pesticides has led to the discovery of several insecticides (neonicotinoids and organophosphates) with new targets in insect nervous system. Present study evaluates the mode of inhibition of acetylchlonesterase (AChE), biochemical efficacy, and molecular docking of 2,3-dimethylmaleic anhydride, against Periplaneta americana and Sitophilus oryzae. The knockdown activity of 2,3-dimethylmaleic anhydride was associated with in vivo inhibition of AChE. At KD99 dosage, the 2,3-dimethylmaleic anhydride showed more than 90% inhibition of AChE activity in test insects. A significant impairment in antioxidant system was observed, characterized by alteration in superoxide dismutase and catalase activities along with increase in reduced glutathione levels. Computational docking programs provided insights in to the possible interaction between 2,3-dimethylmaleic anhydride and AChE of P. americana. Our study reveals that 2,3-dimethylmaeic anhydride elicits toxicity in S. oryzae and P. americana primarily by AChE inhibition along with oxidative stress.