Astragalin identification in graviola pericarp indicates a possible participation in the anticancer activity of pericarp crude extracts: In vitro and in silico approaches

Arabian Journal of Chemistry

Xelha Araujo-Padilla¹  Eva Ramón-Gallegos¹  Francisco Díaz-Cedillo²  Rafael Silva-Torres³ 

[1] Laboratorio de Citopatología Ambiental, Departamento de Morfología, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, Ciudad de México 07738, Mexico;Laboratorio de Síntesis 2, Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, Ciudad de México 11340, Mexico;Laboratorio de anticonceptivos y antitumorales, Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, Ciudad de México 07738, Mexico;

关键词: Annona muricata;    Pericarp;    Cancerous cells;    kaempferol-3-O-glucoside;    Astragalin;    Targets prediction;   

DOI  :  

来源: DOAJ

【 摘 要 】

Graviola, soursop, or guanabana (Annona muricata L.), is an ethnomedical fruit consumed to alleviate headache, diarrhea, diabetes, and cancer. Pericarp is the inedible part of graviola least studied in comparison to seeds and leaves, even thought, it contains the highest concentration of graviola total polyphenols. Anticancer effect of graviola pericarp has been demonstrated in crude extracts attributing the effect to acetogenins, however, crude extracts contain several active molecules. Thus, the present work aimed to fractionate and purify an ethanolic crude extract from graviola pericarp. Purified graviola pericarp fraction (PGPF) was evaluated on cancerous and non-cancerous cell lines, and then was identified by NMR, TOF-MS, and HPLC. Finally, an in silico analysis was performed to predict targets cancer-related of the molecule detected. Our results revealed IC50 values for cervix adenocarcinoma (HeLa), hepatocellular carcinoma (HepG2), triple-negative breast cancer (MDA-MB-231), and non-cancerous cell line (HaCaT) of 92.85 ± 1.23, 81.70 ± 1.09, 84.28 ± 1.08, and 170.2 ± 1.12 µg PGPF/mL, respectively. In vitro therapeutic indexes estimated as quantitative relationship between safety and efficacy of PGPF were 1.83, 2.08, and 2.02 for HeLa, HepG2, and MDA-MB-231, respectively. The NMR analysis revealed astragalin (kaempferol-3-O-glucoside) in PGPF, a flavonoid not reported in graviola pericarp until now. Astragalin identity was confirmed by TOF-MS and HPLC. In silico results support previous reports about astragalin modulating proteins such as Bcl-2, CDK2, CDK4, MAPK and RAF1. Also, results suggest that astragalin may interact with other cancer-related proteins not associated previously with astragalin. In conclusion, astragalin may be contributing to the anticancer effect observed in graviola pericarp extracts.

【 授权许可】

Unknown