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Biomed Pharmacother ; 143: 112215, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34649346

RESUMEN

Orchids are basically ornamental, and biological functions are seldom evaluated. This research investigated the effects of Acampe ochracea methanol extract (AOME) in ameliorating the paracetamol (PCM) induced liver injury in Wistar albino rats, evaluating its phytochemical status through UPLC-qTOF-MS analysis. With molecular docking and network pharmacology, virtual screening verified the inevitable interactions between the UPLC-qTOF-MS-characterized compounds and hepatoprotective drug receptors. The AOME has explicit a dose-dependent decrease of liver enzymes acid phosphatase (ACP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin, as well as an increase of serum total protein and antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH) with a virtual normalization (p < 0.05-p < 0.001) and the values were almost equivalent to the reference drug silymarin. After pretreatment with AOME, PCM-induced malondialdehyde (MDA) levels were considerably decreased (p < 0.001). Histopathological examinations corroborated the functional and biochemical findings. The AOME upregulated the genes involved in antioxidative (CAT, SOD, ß-actin, PON1, and PFK1) and hepatoprotective mechanisms in PCM intoxicated rats. An array of 103 compounds has been identified from AOME through UPLC-qTOF-MS analysis. The detected compounds were substantially related to the targets of several liver proteins and antioxidative enzymes, according to an in silico study. Virtual prediction by SwissADME and admetSAR showed that AOME has drug-like, non-toxic, and potential pharmacological activities in hepatic damage. Furthermore, VEGFA, CYP19A1, MAPK14, ESR1, and PPARG genes interact with target compounds impacting the significant biological actions to recover PCM-induced liver damage.


Asunto(s)
Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/efectos de los fármacos , Orchidaceae , Estrés Oxidativo/efectos de los fármacos , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Acetaminofén , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacocinética , Aromatasa/genética , Aromatasa/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Regulación de la Expresión Génica , Hígado/metabolismo , Hígado/patología , Masculino , Proteína Quinasa 14 Activada por Mitógenos/genética , Proteína Quinasa 14 Activada por Mitógenos/metabolismo , Simulación del Acoplamiento Molecular , Farmacología en Red , Orchidaceae/química , Estrés Oxidativo/genética , PPAR gamma/genética , PPAR gamma/metabolismo , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacocinética , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacocinética , Mapas de Interacción de Proteínas , Ratas Wistar , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
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