2. Academic Validation
  3. Molecular Mechanism Study of Dietary Fiber Lignin Intervention in Ulcerative Colitis through GPR37

Molecular Mechanism Study of Dietary Fiber Lignin Intervention in Ulcerative Colitis through GPR37

  • J Agric Food Chem. 2024 Jun 7. doi: 10.1021/acs.jafc.4c01452.
Hanhan Xie 1,  Ji Yang 2,  Tong Liu 3,  Xinyue Zhang 4,  Shan Zuo 4,  Yingjie Gao 4,  Xi Kuang 5,  Tao Zhang 1 4
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital of Chengdu Medical College, China Nation Nuclear Corporation 416 Hospital, Chengdu 610057, China.
  • 2 School of Laboratory Medicine, Chengdu Medical College, Chengdu 610500, China.
  • 3 Anaesthesiology department, Pidu Distriet People's Hospital, Chengdu 611730, China.
  • 4 School of Biological Sciences and Technology, Chengdu Medical College, Chengdu 610500, China.
  • 5 Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
PMID: 38845410 DOI: 10.1021/acs.jafc.4c01452
Abstract

Lignin is dietary fiber from plant cell walls with multiple biological antioxidant and anti-inflammatory activities. However, whether lignin protects from ulcerative colitis (UC) and underlying mechanisms is unclear. Herein, UC mouse modeling was established with dextran sulfate sodium (DSS) and treatment with lignin for 1 week. Results showed that lignin inhibited the disease activity index (DAI), histological damage, and cell death in UC mice. We also found that lignin reversed the alterations of ferroptotic features in DSS-induced mice and ferroptotic cells, as evidenced by increased expression of GPX4 and 4-HNE and decreased transferrin expression, ameliorating the phenomenon of iron overload, GSH depletion, and ROS and MDA production. Furthermore, the increased expression of NRF2 was observed in IECs under lignin treatment. Also, the upstream regulatory molecule ERK of NRF2 was activated. Further research revealed that lignin can bind GPR37. Meanwhile, lignin was able to alleviate colitis by improving the composition of the intestinal flora in DSS mice and its effect was similar to that of 5-ASA. Taken together, these findings suggest that lignin protects against Ferroptosis in UC by combining GPR37 and activating the ERK-NRF2-GPX4 signaling axis, which provides new ideas for clinical intervention in the treatment of UC.

Keywords

GPR37; ferroptosis; inflammation; lignin; ulcerative colitis.

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