Lycibarbarspermidine L from the fruit of Lycium barbarum L. recovers intestinal barrier damage via regulating miR-195-3p

Abstract

Ethnopharmacological relevance: The fruit of Lycium barbarum L. is widely employed with the traditional effect of tonic properties. According to the theory of traditional Chinese medicine, Gou Qi can be distributed in the meridian of stomach, as well as the liver and kidney, indicating its effect on the digestive system. Clinical studies found that Gou Qi enhanced gastrointestinal functions. Pharmacological research showed the extract of Lycium barbarum exhibiting a repaired effect on the intestine barrier. Lycibarbarspermidine L (LBS L), which belongs to polyamines, is separated from the fruit of Lycium barbarum. However, it is unknown whether LBS L can restore damaged intestinal barrier like other polyamines such as spermidine.

Aim of the study: To elucidate the recovery effect of LBS L on damaged intestinal epithelium and its miRNA-related mechanism.

Materials and methods: IEC-6 cells were used in vitro to assess the therapeutic effect of LBS L on the injured intestine and the regulation of miR-195-3p. Spermidine (SPD) with intestinal mucosal repair effect was used as a positive control. Sprague Dawley (SD) rats were subjected to 48 h fasting to induce intestinal epithelial atrophy in vivo. To determine the therapeutic effect of LBS L on injured intestinal epithelium and explore the mechanism, the fasting model group rats were treated with LBS L (25 mg/kg) for 4 days.

Results: Results in vitro showed that LBS L (10 μM) promoted cell proliferation and migration, affecting the S phase of the cell cycle. Western blot signals showed that LBS L raised the expression level of occludin. The miR-195-3p levels were decreased following LBS L treatment, which could be inversed by transfecting miR-195-3p mimic, demonstrating that LBS L inhibited miR-195-3p to improve cell growth. Results in vivo showed that LBS L could reverse the atrophic villi and inflammatory cell infiltration in the submucosa and restore miR-195-3p, occludin, and Ki67 levels in the intestine of mice in the fasting group.

Conclusions: LBS L restores injured intestinal epithelium by reducing the expression of miR-195-3p.

Keywords: Lycium barbarum L.; dicaffeoylspermidine derivative; intestinal epithelium; lycibarbarspermidine L; miR-195-3p; occludin.