RESUMEN
BACKGROUND: Glioblastoma has been reckoned as the prime cause of death due to brain tumours, being the most invasive and lethal. Available treatment options, i.e. surgery, radiotherapy, chemotherapy and targeted therapies are not effective in improving prognosis, so an alternate therapy is insistent. Plant based drugs are efficient due to their synergistic action, multi-targeted approach and least side effects. METHODS: The anti-tumorous potential of Nardostachys jatamansi rhizome extract (NJRE) on U87 MG cell line was evaluated through various in vitro and in silico bio-analytical tools. RESULTS: NJRE had a strong anti-proliferative effect on U87 MG cells, Its IC50 was 33.73±3.5, 30.59±3.4 and 28.39±2.9 µg/mL, respectively after 24, 48 and 72 h. NJRE at 30 µg/mL induced DNA fragmentation, indicating apoptosis, early apoptosis began in the cells at 20 µg/mL, whereas higher doses exhibited late apoptosis as revealed by dual fluorescence staining. NJRE at 60 and 80 µg /mL caused a G0/G1 arrest and at 20 and 40 µg/mL showed excessive nucleation and mitotic catastrophe in the cells. Immuno-blotting validated the apoptotic mode of cell death through intrinsic pathway. NJRE was harmless to normal cells. In silico docking of NJRE marker compounds: oroselol, jatamansinol, nardostachysin, jatamansinone and nardosinone have revealed their synergistic and multi-targeted interactions with Vestigial endothelial growth factor receptor 2 (VEGFR2), Cyclin dependent kinase 2 (CDK2), B-cell lymphoma 2 (BCL2) and Epidermal growth factor receptor (EGFR). CONCLUSION: A strong dose specific and time dependent anti-tumorous potential of NJRE on U87 MG cells was seen. The extract can be used for the development of safe and multi-targeted therapy to manage glioblastoma, which has not been reported earlier.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Nardostachys/química , Extractos Vegetales/farmacología , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Ensayo Cometa , Simulación por Computador , Cumarinas/química , Cumarinas/farmacología , Quinasa 2 Dependiente de la Ciclina/química , Quinasa 2 Dependiente de la Ciclina/metabolismo , Receptores ErbB/química , Receptores ErbB/metabolismo , Glioblastoma/patología , Humanos , Simulación del Acoplamiento Molecular , Terapia Molecular Dirigida/métodos , Extractos Vegetales/química , Rizoma/química , Terpenos/química , Terpenos/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/química , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Malaria and dengue are the two most important vector-borne human diseases caused by mosquito vectors Anopheles stephensi and Aedes aegypti, respectively. Of the various strategies adopted for eliminating these diseases, controlling of vectors through herbs has been reckoned as one of the important measures for preventing their resurgence. Artemisia annua leaf chloroform extract when tried against larvae of A. stephensi and A. aegypti has shown a strong larvicidal activity against both of these vectors, their respective LC50 and LC90 values being 0.84 and 4.91 ppm for A. stephensi and 0.67 and 5.84 ppm for A. aegypti. The crude extract when separated through column chromatography using petroleum ether-ethyl acetate gradient (0-100%) yielded 76 fractions which were pooled into three different active fractions A, B and C on the basis of same or nearly similar R f values. The aforesaid pooled fractions when assayed against the larvae of A. stephensi too reported a strong larvicidal activity. The respective marker compound purified from the individual fractions A, B and C, were Artemisinin, Arteannuin B and Artemisinic acid, as confirmed and characterized through FT-IR and NMR. This is our first report of strong mortality of A. annua leaf chloroform extract against vectors of two deadly diseases. This technology can be scaled up for commercial exploitation.