RESUMO
Bioactive fractions obtained from medicinal plants which have been used for the treatment of multiple diseases could exert their effects by targeting common pathways. Prior knowledge of their usage could allow us to identify novel molecular links. In this study, we explored the molecular basis of action of one such herbal formulation Cissampelos pareira L. (Cipa), used for the treatment of female hormone disorders and fever. Transcriptomic studies on MCF7 cell lines treated with Cipa extract carried out using Affymetrix arrays revealed a downregulation of signatures of estrogen response potentially modulated through estrogen receptor α (ERα). Molecular docking analysis identified 38 Cipa constituents that potentially bind (ΔG < - 7.5) with ERα at the same site as estrogen. The expression signatures in the connectivity map ( https://clue.io/; ) revealed high positive scores with translation inhibitors such as emetine (score: 99.61) and knockdown signatures of genes linked to the antiviral response such as ribosomal protein RPL7 (score: 99.92), which is a reported ERα coactivator. Further, gene knockdown experiments revealed that Cipa exhibits antiviral activity in dengue infected MCF7 cells potentially modulated through estrogen receptor 1. This approach reveals a novel pathway involving the ESR1-RPL7 axis which could be a potential target in dengue viral infection.
Assuntos
Antivirais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cissampelos/química , Dengue/tratamento farmacológico , Receptor alfa de Estrogênio/metabolismo , Extratos Vegetais/farmacologia , Transcriptoma/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/virologia , Dengue/metabolismo , Dengue/patologia , Dengue/virologia , Vírus da Dengue , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Células MCF-7RESUMO
BACKGROUND: Increasing rate of vector transmission of dengue has led to the exponential rise in the mortality and morbidity scales in the past five years. There are various natural and synthetic chemical agents available commercially as potent larvicides, but they are either highly toxic, difficult to obtain, have a high manufacturing cost, or show cross-resistance, hence do not suffice as ideal larvicides. The objective was to screen aqueous extracts of Bougainvillea spectabilis (B. spectabilis), Saraca asoca (S.asoca), and Chenopodium album (C. album) for larvicidal activity against Aedes aegypti (A. aegypti). METHODS: The larvae were exposed to increasing concentrations of aqueous extracts of B. spectabilis, S. asoca, and C. album under controlled laboratory environment. The mortality was checked after 24 hours, results were statistically analyzed, and LC50 and LC90 were determined. RESULTS: B. spectabilis and S. asoca were found effective as larvicides against A. aegypti with LC50 values of 0.22% and 0.26%, respectively. CONCLUSION: The aqueous extracts of B . spectabilis and S. asoca are efficient larvicides against A . aegypti and can be used as effective, accessible, and eco-friendly control options for management of A. aegypti, the vector of dengue/chikungunya.