the-use-piper-amalago-var-amalago-as-an-eco-friendly-insecticide

The Use of Piper amalago var. amalago as an Eco-Friendly Insecticide Synergist in the Management of Aedes Aegypti

Resistance to insecticides challenges the management of Ae. aegypti, the main vector of dengue, chikungunya, and Zika viruses in the Caribbean and Latin ...

University of The West Indies

CYP, a ubiquitous superfamily of enzymes expressed in major organs in humans, plays a key role in biosynthesis of steroids and metabolism of xenobiotics. Inhibitors of these vital enzymes provide, as tools, the opportunity to gain an insight to their role in a myriad of bioactivity and to intervene as therapeutics in disease.

A patent review on the development of human cytochrome P450 inhibitors.

The effect of apocynin on the activity of arylamine N-acetyltransferases (NATs) in excised liver samples was examined using eighteen Sprague-Dawley rats. Three groups of six animals each were fed a normal diet alone or a treatment of 50 or 100 mg/kg/day of apocynin via gavages for eight (8) weeks. Chronic in vivo administration of apocynin led to significant (p < 0.001) reduction of in vitro liver NAT activity up to 93% as compared with untreated rats (18.80 ± 2.10 μmols p-anisidine/min/μg liver protein). In vitro exposure of untreated liver homogenates to apocynin led to a dose-dependent inhibition of NAT activity with IC50 = 0.69 ± 0.02 mM. In silico modelling of apocynin tautomers and radical species into human NAT crystal structures supported the hypothesis that thiol functionalities in NAT enzymes may be crucial in apocynin binding. The involvement of human NAT enzymes in different pathological conditions, such as cancer, has encouraged the research for selective NAT inhibitors in both humans and animal models with possible chemopreventive properties.

Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver.

Quassinoids often exhibit antioxidant and antiproliferative activity. Emerging evidence suggests that these natural metabolites also display chemopreventive actions. In this study, we investigated the potential for the quassinoid glaucarubulone glucoside (Gg), isolated from the endemic Jamaican plant Castela macrophylla (Simaroubaceae), to display potent cytotoxicity and inhibit human cytochrome P450s (CYPs), particularly CYP1A enzymes, known to convert polyaromatic hydrocarbons into carcinogenic metabolites. Gg reduced the viability of MCF-7 breast adenocarcinoma cells (IC = 121 nm) to a greater extent than standard of care anticancer agents 5-fluorouracil, tamoxifen (IC >10 μm) and the tamoxifen metabolite 4-hydroxytamoxifen (IC = 2.6 μm), yet was not cytotoxic to non-tumorigenic MCF-10A breast epithelial cells. Additionally, Gg induced MCF-7 breast cancer cell death. Gg blocked increases in reactive oxygen species in MCF-10A cells mediated by the polyaromatic hydrocarbon benzo[a]pyrene (B[a]P) metabolite B[a]P 1,6-quinone, yet downregulated the expression of genes that promote antioxidant activity in MCF-7 cells. This implies that Gg exhibits antioxidant and cytoprotective actions in non-tumorigenic breast epithelial cells and pro-oxidant, cytotoxic actions in breast cancer cells. Furthermore, Gg inhibited the activities of human CYP1A according to non-competitive kinetics and attenuated the ability of B[a]P to induce CYP1A gene expression in MCF-7 cells. These data indicate that Gg selectively suppresses MCF-7 breast cancer cell growth without impacting non-tumorigenic breast epithelial cells and blocks B[a]P-mediated CYP1A induction. Taken together, our data provide a rationale for further investigations of Gg and similar plant isolates as potential agents to treat and prevent breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.

Glaucarubulone glucoside from Castela macrophylla suppresses MCF-7 breast cancer cell growth and attenuates benzo[a]pyrene-mediated CYP1A gene induction.

The emergence of novel diseases spread by the Aedes aegypti mosquito in Jamaica and the Caribbean, has prompted studies on insecticide resistance towards effective management of the vector. Though Jamaica has been using the organophosphate insecticide malathion in its vector control program for more than 30 years, resistance to the pesticide has not been tested in over a decade. We analyzed resistance to malathion and the pyrethroid insecticide, permethrin on mosquitoes collected across St. Andrew, Jamaica, and analyzed the molecular basis of resistance. The Center for Disease Control (CDC) bioassay revealed that Ae. aegypti mosquitoes from St. Andrew, Jamaica were resistant to permethrin (15 μg/bottle) with mortalities at 0-8% at 30 minute exposure time, while contact with malathion (50 μg/bottle) revealed ≤ 50% mortality at 15 minutes, which increased to 100% at 45 minutes. The standard susceptible New Orleans (NO) strain exhibited 100% mortality within15 minutes. The activities of multifunction oxidases and p-nitro phenyl-acetate esterases were significantly greater in most Jamaican populations in comparison to the NO strain, while activities of glutathione-S-transferase, acetylcholinesterase, α-esterase and ß-esterase activity were relatively equal, or lower than that of the control strain. The frequency of knockdown resistance mutations in the voltage dependent sodium channel gene were measured. All collections were fixed for Cys1,534 while 56% of mosquitoes were Ile1,016/Val1,016 heterozygotes, and 33% were Ile1,016 homozygotes. Aedes aegypti from St. Andrew Jamaica are resistant to permethrin with variations in the mode of mechanism, and possibly developing resistance to malathion. Continued monitoring of resistance is critically important to manage the spread of the vector in the country.

Insecticide resistance to permethrin and malathion and associated mechanisms in Aedes aegypti mosquitoes from St. Andrew Jamaica.

Cleome rutidosperma DC, commonly known in Jamaica as 'consumption-weed' is a plant traditionally used in folklore for treating tuberculosis and other infectious and chronic ailments. We evaluate for the first time the chemical composition and biological activities of the essential oil components of the complete aerial parts of this plant. The essential oil obtained by steam distillation (0.02%) was analyzed by a combination of gas chromatography-flame ionization detector (GC-FID), gas chromatography-mass spectroscopy (GC-MS) and retention index (RI). The volatile oil of C. rutidosperma was dominated by oxygenated diterpenes (67.6%); with (Z)-phytol (65.1%) being the single most abundant constituent. C. rutidosperma aerial essential oil exhibited moderate inhibition against the activity of recombinant arylamine N-acetyltransferase (NAT) from Mycobacterium marinum (IC 22.20 ± 1.80 μg/μL), while, racemic phytol had an inhibition with an IC of 22.33 μg/μL ± 0.50 μg/μL, thus accounting for the NAT inhibition imparted by the crude oil. Inhibition of NAT, a key enzyme in mycobacterial growth may be the pathway in which phytol, shown in this study to interact with the active site using in-silico methods, renders its previously demonstrated anti-tubercular properties. The phytol rich essential oil also demonstrated antimicrobial activity against all nine human pathogenic bacteria and the fungus strain assayed, with the most significant inhibitory activity against Bacillus cereus and justifies the need for further evaluation and development of the essential oils from this plant.

Chemical composition and biological activities of the essential oil from Cleome rutidosperma DC.

Hypertension (HTN) is responsible for a significant disease burden in Jamaica. We are reporting the results of the 2017 blood pressure (BP) screening campaign May Measurement Month in Jamaica that aimed to increase the awareness of HTN.

Blood Pressure Screening Campaign in Jamaica: May Measurement Month 2017.

Insecticide resistance has become problematic in tropical and subtropical regions, where  mosquitoes and -borne arboviral diseases thrive. With the recent occurrence of chikungunya and the Zika virus in Jamaica, the Ministry of Health and Wellness, Jamaica, partnered with the United States Agency for International Development to implement multiple intervention activities to reduce the  populations in seven parishes across the island and to assess the susceptibility of collected samples to various concentrations of temephos,  subsp.  (Bti), diflubenzuron and methoprene. Of the insecticides tested, only temephos has been used in routine larviciding activities in the island. The results showed that only temephos at concentrations 0.625 ppm and Bti at concentrations 6-8 ppm were effective at causing 98-100% mortality of local  at 24 h exposure. Surprisingly, the growth inhibitors diflubenzuron and methoprene had minimal effect at preventing adult emergence in  larvae in the populations tested. The results demonstrate the need for insecticide resistance testing as a routine part of vector control monitoring activies in order to determine useful tools that may be incorporated to reduce the abundance of .

Comparative toxicity of larvicides and growth inhibitors on  from select areas in Jamaica.

Owing to the increased reports in Aedes-borne diseases in the Caribbean and Latin America, the United States Agency for International Development assisted the Jamaican Ministry of Health and Wellness in conducting insecticide susceptibility tests on Aedes aegypti populations. Sentinel sites were established in seven parishes of Jamaica (St. Catherine, Kingston and St. Andrew, St. Thomas, Portland, St. Mary and St. Ann) and Aedes aegypti eggs were collected, reared to adults per collected population and their susceptibility to varying pyrethroids and organophosphates were tested using the World Health Organization paper bioassays for these insecticides. The Centers for Disease Control and Prevention bottle bioassay was used to assess susceptibility to the carbamate, bendiocarb. The voltage gated sodium channel gene mutations V1016I and I1011V, normally associated with pyrethroid resistance, were also analysed. The results showed that Aedes aegypti collected from all parishes exhibited resistance to pyrethroids at the following concentrations, permethrin 0.25-2.5%; deltamethrin 0.03-0.15%; lambda-cyhalothrin 0.03-0.3%; and etofenprox 0.5-2.5%. The insecticide deltamethrin at concentration 0.3% was the only pyrethroid tested that resulted in high mortality, 94.9 ± 0.34% knockdown within 1 hour of exposure and 98.95 ± 0.01% mortality (p <0.01) at 24 hours post exposure. The frequency of the voltage gated sodium channel gene mutation V1016I was high in the tested population, possibly accounting for the reduced sensitivity to pyrethroids. Organophosphate resistance was also observed in all populations tested. Mortality rates for 0.8% Malathion was 0.8 ± 0.70-60.68 ± 0.38% after 24 hour and 0.00-47.10 ± 3.02%, for pirimiphos-methyl 0.21%. Bendiocarb applied as 12.5 μg/ bottle resulted in mortality rates of 76.25 ± 4.30-100 ± 0.00% after 30 minutes of exposure. The results showed that Ae. aegypti from the seven parishes analysed demonstrated resistance to the insecticides tested. Deltamethrin and bendiocarb at concentrations 0.3% and 12.5μg respectively, were considered most effective, causing high mortality in the local populations. Routine monitoring and evaluations of Ae. aegypti populations from the included parishes are recommended. Additionally, the study results represent the most comprehensive testing to date with local Aedes aegypti populations distributed across different parishes of Jamaica and should be useful to guide national and sub national strategies for vector control and surveillance.

Screening of insecticide resistance in Aedes aegypti populations collected from parishes in Eastern Jamaica.

Melicoccus bijugatus Jacq (Mb) has been reported to have cardiovascular modulatory effects. In this study, we evaluated the antihypertensive effects and mechanism of action of Mb on N-Nitro-L-arginine Methyl Ester (L-NAME) and Deoxycorticosterone Acetate (DOCA) rat models. Aqueous extract of Mb fruit (100 mg/kg) was administered for 6 weeks to rats by gavage and blood pressure was recorded. Effects of the extract on vascular reactivity was evaluated using isolated organ baths, and tissues were collected for biochemical and histological analysis. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were significantly (P < 0.05) reduced with extract (100 mg/kg) administration and treatment compared to the hypertensive models. Mb (100 µg/mL) reduced the vascular contractility induced by phenylephrine (PE), and caused a dose-dependent relaxation of PE-induced contraction of aortic vascular rings. The vasorelaxation properties seemed to be endothelium dependent, as well as nitric oxide (NO) and guanylyl cyclase, but not prostaglandin dependent. Histomicrograph of transverse sections of the ventricles from the Mb group did not show abnormalities. The extract significantly (P < 0.05) reduced an L-NAME induced elevation of cardiac output and Creatine Kinase Muscle-Brain (CKMB), but had no significant impact on the activities of arylamine N-acetyltransferase. In conclusion, Mb significantly decreased blood pressure in hypertensive models. The extract possesses the ability to induce endothelium dependent vasodilation, which is dependent on guanylyl cyclase but not prostaglandins.

Hypotensive and antihypertensive effects of an aqueous extract from Guinep fruit (Melicoccus bijugatus Jacq) in rats.

Neglected tropical diseases (NTDs) in developing countries like the Caribbean, negatively affect multiple income-generating sectors, including the tourism industry upon which island states are highly dependent. Insect-transmitted NTDs include, but are not limited to, malaria, dengue and lymphatic filariasis. Control measures for these disease, are often ignored because of the associated cost. Many of the developing country members are thus retained in a financially crippling cycle, balancing the cost of prophylactic measures with that of controlling an outbreak.The purpose of the paper is to bring awareness to NTDs transmitted by insects of importance to humans, and to assess factors affecting such control, in the English-speaking Caribbean.

Challenges in the control of neglected insect vector diseases of human importance in the Anglo-Caribbean.

Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists.

Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae.

Article	Year
A patent review on the development of human cytochrome P450 inhibitors. Expert opinion on therapeutic patents\| PubMed ID: 24660660	2014
Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver. Scientific reports\| PubMed ID: 27242013	2016
Glaucarubulone glucoside from Castela macrophylla suppresses MCF-7 breast cancer cell growth and attenuates benzo[a]pyrene-mediated CYP1A gene induction. Journal of applied toxicology : JAT\| PubMed ID: 28138972	2017
Insecticide resistance to permethrin and malathion and associated mechanisms in Aedes aegypti mosquitoes from St. Andrew Jamaica. PloS one\| PubMed ID: 28650966	2017
Chemical composition and biological activities of the essential oil from Cleome rutidosperma DC. Fitoterapia\| PubMed ID: 29981873	2018
Blood Pressure Screening Campaign in Jamaica: May Measurement Month 2017. American journal of hypertension\| PubMed ID: 31350551	2019
Comparative toxicity of larvicides and growth inhibitors on from select areas in Jamaica. Royal Society open science\| PubMed ID: 32269812	2020
Screening of insecticide resistance in Aedes aegypti populations collected from parishes in Eastern Jamaica. PLoS neglected tropical diseases\| PubMed ID: 32716942	2020
Hypotensive and antihypertensive effects of an aqueous extract from Guinep fruit (Melicoccus bijugatus Jacq) in rats. Scientific reports\| PubMed ID: 33122667	2020
Challenges in the control of neglected insect vector diseases of human importance in the Anglo-Caribbean. One health (Amsterdam, Netherlands)\| PubMed ID: 34485673	2021
Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae. Malaria journal\| PubMed ID: 39844288	2025

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