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Life Sci. 2019 Oct 19;239:116888. doi: 10.1016/j.lfs.2019.116888. [Epub ahead of print]

Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model.

Author information

1
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
2
Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Islamabad, Pakistan.
3
School of Life Sciences, College of Natural Sciences, Kyungpook National University, 41566, Korea.
4
College of Pharmacy, Seoul National University, Seoul, South Korea.
5
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. Electronic address: skhan@qau.edu.pk.

Abstract

5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is one of the most common oncological problem. It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demonstrate the mucoprotective effects of Saikosaponin-A in 5-FU-induced intestinal mucositis in mice. Mucositis was induced in BALB/c mice by intraperitoneal injection of 5-FU (50 mg/kg/day) for three consecutive days and IM was assessed by both behavioral and histochemical analysis. While, Saikosaponin-A (1, 5, 10 mg/kg/day) was administered 1 h before 5-FU injection for consecutive seven days. Pre-treatment of Saikosaponin-A significantly ameliorated the severity of mucositis reflected as food intake, body weight loss, severity of diarrhea and mortality rate in a dose depended manner as compared to mice treated with 5-FU. Moreover, histopathological analysis furthered reinforced the mucoprotective potential of Saikosaponin-A against 5-FU-induced intestinal abnormalities referred as villus atrophy, mitotic crypt stem cells damage, inflammatory cells infiltration, vacuolization and edema. Furthermore, Saikosaponin-A administration strongly inhibited pro-inflammatory mediators (TNF-α, COX-2, IL-1β and IL-6) and apoptotic markers (p-JNK, Casp-3). Saikosaponin-A pre-treatment significantly reduced the production of nitric oxide (NO) in intestinal tissue, inhibited acetic acid-induced Evans blue vascular permeability. The Siaikosaponin-A treatment markedly enhanced the anti-oxidants enzymes (Nrf2, HO-1, SOD, GSH, GST and Catalase), while decreased the oxidative stress markers i.e. Malonaldehde (MDA). Hence, these data suggest that Saikosaponin-A maybe a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.

KEYWORDS:

5-Flourouracil; Cytokines; Intestinal mucositis; Oxidative stress; Saikosaponin-A

PMID:
31639401
DOI:
10.1016/j.lfs.2019.116888

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