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

被引：19

作者：

Sahu, Roja ^{[1
]}

Kar, Rajiv Kumar ^{[2
]}

Sunita, Priyashree ^{[3
]}

Bose, Pritha ^{[1
]}

Kumari, Puja ^{[1
]}

Bharti, Salona ^{[1
]}

Srivastava, Sharad ^{[4
]}

Pattanayak, Shakti P. ^{[1
,5
]}

机构：

[1] Birla Inst Technol, Dept Pharmaceut Sci & Technol, Div Pharmacol, Ranchi 835215, Jharkhand, India

[2] Hebrew Univ Jerusalem, Fritz Haber Ctr Mol Dynam, Inst Chem, Jerusalem, Israel

[3] Govt Jharkhand, Dept Hlth Family Welf & Med Educ, Govt Pharm Inst, Ranchi 834009, Bihar, India

[4] NBRI Govt India, CSIR, Natl Bot Res Inst, Pharmacognosy & Ethnopharmacol Div, Lucknow 226001, Uttar Pradesh, India

[5] Cent Univ South Bihar Gaya, Sch Hlth Sci, Dept Pharm, Patna 824236, Bihar, India

来源：

JOURNAL OF ETHNOPHARMACOLOGY | 2021年 / 269卷

关键词：

Zanthoxylum armatum; LC-MS/MS; Breast cancer; Antioxidant; Kelch-like ECH-Associated protein 1; Nuclear factor erythroid 2; INDUCED MAMMARY CARCINOGENESIS; LIPID-PEROXIDATION; SUPEROXIDE-DISMUTASE; CRYSTAL-STRUCTURE; OXIDATIVE STRESS; ANTIOXIDANT; IDENTIFICATION; FLAVONOIDS; APOPTOSIS; DAMAGE;

D O I：

10.1016/j.jep.2020.113758

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

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.

引用

页数：16