1. Academic Validation
  2. Berberine enhances the function of intestinal stem cells in healthy and radiation-injured mice

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

  • Int Immunopharmacol. 2024 Jul 30:136:112278. doi: 10.1016/j.intimp.2024.112278.
Siyu Tu 1 Yujun Huang 1 Hefei Tian 1 Lu Xu 2 Xi Wang 2 Lingxiao Huang 2 Xudan Lei 2 Zhenni Xu 3 Dengqun Liu 4
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China; Radiation Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
  • 2 Radiation Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
  • 3 Radiation Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China. Electronic address: xuzhenni1112@163.com.
  • 4 Radiation Oncology Key Laboratory of Sichuan Province, Department of Experimental Research, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China. Electronic address: dengqunliu@uestc.edu.cn.
Abstract

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.

Keywords

Berberine; Differentiation; Homeostasis; Intestinal stem cell; Proliferation; Radiation.

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