1. Academic Validation
  2. Phellodendrine promotes autophagy by regulating the AMPK/mTOR pathway and treats ulcerative colitis

Phellodendrine promotes autophagy by regulating the AMPK/mTOR pathway and treats ulcerative colitis

  • J Cell Mol Med. 2021 Jun;25(12):5707-5720. doi: 10.1111/jcmm.16587.
Shuai Su 1 Xin Wang 1 Xiaonan Xi 2 Lanping Zhu 1 Qiuyu Chen 1 Hongxia Zhang 1 Yuan Qin 3 Boli Yang 1 Na Che 4 5 Hailong Cao 1 Weilong Zhong 1 Bangmao Wang 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Disease, Tianjin, China.
  • 2 State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • 3 College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
  • 4 Department of Pathology, Tianjin Medical University, Tianjin, China.
  • 5 Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, China.
Abstract

To investigate the therapeutic effects of phellodendrine in ulcerative colitis (UC) through the AMPK/mTOR pathway. Volunteers were recruited to observe the therapeutic effects of Compound Cortex Phellodendri Liquid (Huangbai liniment). The main components of Compound Cortex Phellodendri Liquid were analysed via network pharmacology. The target of phellodendrine was further analysed. Caco-2 cells were cultured, and H2 O2 was used to stimulate in vitro cell model. Expression levels of LC3, AMPK, p-AMPK, mTOR and p-mTOR were detected via Western blotting and through immunofluorescence experiments. The therapeutic effects of phellodendrine were analysed via expression spectrum chip sequencing. The sequencing of intestinal flora further elucidated the therapeutic effects of phellodendrine. Compared with the control group, Compound Cortex Phellodendri Liquid could substantially improve the healing of intestinal mucosa. Network pharmacology analysis revealed that phellodendrine is the main component of Compound Cortex Phellodendri Liquid. Moreover, this alkaloid targets the AMPK signalling pathway. Results of animal experiments showed that phellodendrine could reduce the intestinal damage of UC compared with the model group. Findings of cell experiments indicated that phellodendrine treatment could activate the p-AMPK /mTOR signalling pathway, as well as Autophagy. Expression spectrum chip sequencing showed that treatment with phellodendrine could promote mucosal healing and reduce inflammatory responses. Results of intestinal flora detection demonstrated that treatment with phellodendrine could increase the abundance of flora and the content of beneficial bacteria. Phellodendrine may promote Autophagy by regulating the AMPK-mTOR signalling pathway, thereby reducing intestinal injury due to UC.

Keywords

AMPK/mTOR signalling pathway; autophagy; network pharmacology; phellodendrine; ulcerative colitis.

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