Rheinic acid ameliorates radiation-induced acute enteritis in rats through PPAR-γ/NF-κB

Background: Acute radiation enteritis (ARE), a common complication of intestinal caused by abdominal and pelvic radiation therapy. Rheinic acid is a major active ingredient derived from Rhubarb. Rhubarb could suppress inflammation, tumor, fibrosis oxidative damage. However, RA as the main active component and extract monomer of Rhubarb, the pharmacological activity and the underlying molecular mechanism on various diseases has not yet been revealed. Objective: To determine the potential role of rheinic acid (RA) in ameliorating inflammation of rats with acute radiation enteritis (ARE), and explore the underlying mechanism. Methods: ARE rat model was established by irradiated with single-dose 10 Gy X-rays at a rate of 0.62 Gy/min to the abdomen. The rats were executed after orally administered with Rheinic acid 7 days and used in the subsequent experiments. Body weight, fecal characteristics and bloody of rats were used to assess the disease activity index. Histological analysis of the jejunum and colon were evaluated using H&E staining. The pro-inflammatory cytokines levels were measured by immunohistochemistry and ELISA. The levels of nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were also determined. The mRNA and protein expression were examined by real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Results: Rheinic acid promoted intestinal functional recovery, and ameliorated intestinal damage and bloody stool in ARE rats. Rheinic acid strongly decreased the levels of tumor necrosis factor-α, interleukin-1, interleukin-6, NO, and MDA, whereas increased levels of anti-oxidants, SOD and GSH. Moreover, the expression of apoptosis-related proteins, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), were decreased with RA treatment. Further study indicated that PPAR-γ was activated and thereby NF-κB and p38 MAPK signaling pathway were suppressed after rheinic acid treatment. Conclusion: Rheinic acid could ameliorate acute radiation enteritis and the underlying molecular mechanism is, at least partially, through PPAR-γ/NF-κB and p38 MAPK/JNK pathways.