Berberine enhances the function of intestinal stem cells in healthy and radiation-injured mice

• Published in: International immunopharmacology Vol. 136; p. 112278
• Main Authors: Tu, Siyu, Huang, Yujun, Tian, Hefei, Xu, Lu, Wang, Xi, Huang, Lingxiao, Lei, Xudan, Xu, Zhenni, Liu, Dengqun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.07.2024
• Subjects: Berberine; Differentiation; Homeostasis; Intestinal stem cell; Proliferation; Radiation; Intestinal stem cell; Homeostasis; Berberine; Proliferation; Differentiation; Radiation
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112278

•Berberine increased intestinal length in physiology.•Berberine promoted the proliferation and differentiation of ISCs in healthy mice.•Berberine inhibited apoptosis, increased proliferation and differentiation of ISCs after radiation injury.•Berberine activated mTORC1, STAT3 and ERK signaling pathways within crypts. Intestinal stem cells (ISCs) are pivotal for the maintenance and regeneration of the intestinal epithelium. Berberine (BBR) exhibits diverse biological activities, but it remains unclear whether BBR can modulate ISCs’ function. Therefore, we investigated the effects of BBR on ISCs in healthy and radiation-injured mice and explored the potential underlying mechanisms involved. The results showed that BBR significantly increased the length of the small intestines, the height of the villi, and the depth and density of the crypts, promoted the proliferation of cryptal epithelial cells and increased the number of OLFM4+ ISCs and goblet cells. Crypts from the BBR-treated mice were more capable of growing into enteroids than those from untreated mice. BBR alleviated WAI-induced intestinal injury. BBR suppressed the apoptosis of crypt epithelial cells, increased the quantity of goblet cells, and increased the quantity of OLFM4+ ISCs and tdTomato+ progenies of ISCs after 8 Gy WAI-induced injury. Mechanistically, BBR treatment caused a significant increase in the quantity of p-S6, p-STAT3 and p-ERK1/2 positive cryptal epithelial cells under physiological conditions and after WAI-induced injury. In conclusion, BBR is capable of enhancing the function of ISCs either physiologically or after radiation-induced injury, indicating that BBR has potential value in the treatment of radiation-induced intestinal injury.