The Role and Mechanism of Berberine as a Candidate Drug for the Treatment of Radiation-Induced Intestinal Injury

Abstract

Radiation-induced intestinal injury (RIII) is among the most common complications of radiotherapy in patients with abdominaltumours. At present, there are no effective methods for reducing the occurrence or severity of RIII. Berberine (BBR) is a quaternary ammonium alkaloid extracted from Coptis chinensis that has antioxidant, anti-inflammatory, and protective effects on the intestine. A RIII model was established using 10 Gy of X-ray total abdominal irradiation (TAI). The effects of BBR on mice exposed to 10 Gy of X-ray TAI were determined by analysing pathological sections of the mouse intestine. TUNEL staining was used to detect apoptosis of intestinal epithelial cells in mice. Immunohistochemistry was applied to detect the expression of proliferation indicators PCNA and Ki-67, and immunofluorescence staining was used to quantify BrdU-positive proliferative cells. BBR stimulates crypt formation ex vivo after irradiation and upregulates the expression of FXR. The expression of goblet cell and intestinal stem cell markers was quantified by qRT-PCR. The expression of farnesoid X receptor (FXR) in RIII was detected via qRT-PCR and Western blot. Additionally, a Western blot was performed to detect the protein levels of NF-κB, p-p38, total p38, and β-catenin, and qRT-PCR was used to measure the mRNA expression levels of pro-inflammatory factors TNF-α, IL-1β, and IL-6. BBR alleviated RIII, mainly manifested as body weight loss, longer colons, greater numbers of villi, and greater numbers of crypts. BBR also maintained the regeneration ability and promoted the proliferation of crypt cells, reduced the apoptosis rate, and alleviated intestinal injury. Importantly, BBR rescued radiation-induced dysregulation of these key signalling proteins and pro-inflammatory factors. BBR failed to promote the repair of RIII when FXR was inhibited. BBR treatment increased the expression of FXR in crypts and was at least protective against radiation-induced intestinal damage in mice through the modulation of FXR. BBR may be a potential drug for the treatment of radiation-induced intestinal damage.