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The complete genome sequence of Melia azedarach Linn. (Meliaceae): a multi-purpose pesticide species.

ABSTRACT: The plant genus Melia has two or four species in the modern world, and is a natural source of a traditional pesticide, Toosendanin. In this study, we report the complete chloroplast genome of Melia azedarach, assembled from whole-genome high-throughput sequencing data, as a resource for future studies on the taxonomy and evolution of Melia. The chloroplast genome was 160,393 bp in length, with a large single-copy region of 87,598 bp, a small single-copy region of 18,709 bp, separated by two inverted repeat regions of 27,043 bp each. It was predicted to contain a total of 133 genes, with an overall GC content of 37.37%. Phylogenetic analysis placed M. azedarach closest to Azadirachta sp. in Meliaceae.

SUBMITTER: Liao B

PROVIDER: S-EPMC9225774 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Triatoma infestans is the principal vector of Trypanosoma cruzi, parasite responsible of Chagas's Disease transmission in Argentina. Pyrethroids have become common pesticides for the control of T. infestans but increasing resistance encourages the search of new alternatives and the use of natural products for biological control arises as a new strategy. Melia azedarach L. is originated from the Himalaya's region and several compounds are part of its rich phytochemistry. Folk medicine of the plant is due to its repellent and insecticidal activities. Aims of this work were to evaluate the repellent activity of methanolic and acetonic extracts from fruits of M. azedarach by means of the area preference method of fifth and first nymph stages as well as to test the acute lethal effect of the more repellent extract by means of direct application on cuticle on both stages. For repellence, qualitative filter papers were divided into two halves, one treated with methanolic (ME) or acetonic (AC) extract and the other without treatment. Controls were impregnated half with methanol or acetone and half without the solvents. One nymph was located in each Petri or well and repellence percentage was determined. For the lethal effect, fasted and fed to repletion 5th stage nymphs were topically administered with different concentrations of AC and deaths were registered after 24, 48, 72, 96, and 120 h. Phytochemical analysis of extracts was performed as well. AC demonstrated high repellent activity (100%, both stages), whereas ME extract activity was slight (10-21%). AC extract was selected for lethal assays due to early repellent activity. Fed to repletion nymphs were more sensitive to the lethal activity of the extract when compared to fasted nymphs (LD50: 11.5 vs. 23.1 μg/insect, respectively). Phytochemistry assays of extracts showed a higher concentration of flavonoids, alkaloids and triterpenes for AC. Considering these results, next assays will include the test of Melia azedarach extract on T. infestans that are resistant to pyrethroids for a possible synergism between AC and the pesticides.

Project description:BackgroundMAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available.MethodA library of compounds isolated from medicinal plants of China was screened for anti-cancer activities. Three limonoid compounds, termed A1541-43, originally isolated from the plant Melia azedarach, exhibiting strong anti-leukemic activity. The anti-neoplastic activity and the biological target of these compounds were explored using various methods, including western blotting, flow cytometry, molecular docking and animal model for leukemia.ResultsCompounds A1541-43, exhibiting potent anti-leukemic activity, was shown to induce ERK1/2 phosphorylation. In contrast, the natural product Cedrelone, which shares structural similarities with A1541-43, functions as a potent inhibitor of ERK1/2. We provided evidence that A1541-43 and Cedrelone specifically target ERK1/2, but not the upstream MAPK/ERK pathway. Computational docking analysis predicts that compounds A1541-43 bind a region in ERK1/2 that is distinct from that to which Cedrelone and EQW bind. Interestingly, both A1541-43, which act as ERK1/2 agonists, and Cedrelone, which inhibit these kinases, exerted strong anti-proliferative activity against multiple leukemic cell lines, and induced robust apoptosis as well as erythroid and megakaryocytic differentiation in erythroleukemic cell lines. These compounds also suppressed tumor progression in a mouse model of erythroleukemia.ConclusionsThis study identifies for the first time activators of ERK1/2 with therapeutic potential for the treatment of cancers driven by dysregulation of the MAPK/ERK pathway and possibly for other disorders.

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The complete genome sequence of Melia azedarach Linn. (Meliaceae): a multi-purpose pesticide species.

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