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LC-MS characterized methanolic extract of zanthoxylum armatum possess anti-breast cancer activity through Nrf2-Keap1 pathway: An in-silico, in-vitro and in-vivo evaluation.

Abstract：

ETHNOPHARMACOLOGICAL RELEVANCE:Zanthoxylum armatum DC (Rutaceae) containing flavonoids, alkaloids, coumarins, lignans, amides and terpenoid is well-known for its curative properties against various ailments including cancer. In the current research, phytochemicals present in the methanolic extract of Zanthoxylum armatum bark (MeZb) were characterized by LC-MS/MS analysis and chemotherapeutic potential of this extract was determined on DMBA-induced female Sprague Dawley rats. MATERIALS AND METHODS:A simple and fast high-performance liquid chromatography-mass spectroscopy (LC-MS/MS) of MeZb was established followed by in-vitro antioxidant assays. This was followed by in-silico docking analysis as well as cytotoxicity assessment. Successively in-vivo study of MeZb was performed in DMBA-induced Sprague Dawley rats possessing breast cancer along with detailed molecular biology studies involving immunofluorescence, RT-qPCR and Western blot analysis. RESULTS:LC-MS/MS investigation revealed the presence of compounds belonging to flavonoid, alkaloid and glycoside groups. MeZb revealed potential antioxidant activity in in-vitro antioxidant assays and strong binding energy of identified compounds was seen from the in-silico study with both HO1 and Keap1 receptor. Furthermore, the antioxidant action of MeZb was proven from the in-vivo analysis of antioxidant marker enzymes (lipid peroxidation, enzymic and non-enzymic antioxidants). This study also revealed upregulation of protective Nrf-2 following downregulation of Keap1 after MeZb treatment with respect to untreated cancerous rats. CONCLUSION:These results exhibited anti-breast-cancer potential of MeZb through Nrf2-Keap1 pathway which may be due to the flavonoids, alkaloids and glycosides present in it.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

Sahu R,Kar RK,Sunita P,Bose P,Kumari P,Bharti S,Srivastava S,Pattanayak SP

doi

10.1016/j.jep.2020.113758

subject

Has Abstract

pub_date

2021-04-06 00:00:00

pages

113758

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(20)33646-1

journal_volume

269

pub_type

杂志文章

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LC-MS characterized methanolic extract of zanthoxylum armatum possess anti-breast cancer activity through Nrf2-Keap1 pathway: An in-silico, in-vitro and in-vivo evaluation.