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An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota
Zhou, J.; Li, D.; Wang, J.; Cheng, Z.; Wang, C.; Zhang, X.; Xu, X.; Gao, J. An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota. Pharmaceuticals2024, 17, 297.
Zhou, J.; Li, D.; Wang, J.; Cheng, Z.; Wang, C.; Zhang, X.; Xu, X.; Gao, J. An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota. Pharmaceuticals 2024, 17, 297.
Zhou, J.; Li, D.; Wang, J.; Cheng, Z.; Wang, C.; Zhang, X.; Xu, X.; Gao, J. An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota. Pharmaceuticals2024, 17, 297.
Zhou, J.; Li, D.; Wang, J.; Cheng, Z.; Wang, C.; Zhang, X.; Xu, X.; Gao, J. An Inulin-Type Fructan CP-A from Codonopsis pilosula Alleviated 5-Fluorouracil-Induced Intestinal Mucositis via the ERK/MLCK/MLC2 Pathway and Regulation of Gut Microbiota. Pharmaceuticals 2024, 17, 297.
Abstract
Intestinal mucositis (IM) is a common adverse effect of chemotherapy, limiting its clinical application. Edible Chinese medicine, specifically Codonopsis pilosula-derived CP-A, with anti-inflammatory and gastrointestinal protective effects. The present work was to investigate CP-A's role in ameliorating IM and its mechanism using in vitro and rat models. Western blot, immunohistochemical (IHC) and real-time PCR (RT-PCR) analyses were used to assess protein expression related to the extracellular-regulated protein kinases (ERK)/myosin light chain kinase (MLCK)/myosin light chain 2 (MLC2) signaling pathway and tight junction proteins. Enzyme-linked immunosorbent assay (ELISA) was conducted to measure inflammatory factors, and 16S rRNA Amplicon Sequencing was employed for cecum content analysis. The results indicated that CP-A could restore body weight, food intake and histopathological changes in IM rats. Besides, abnormal MLCK activation induced by 5-fluorouracil (5-FU) was attenuated by CP-A via the ERK/MLCK/MLC2 pathway. CP-A treatment improved tight junction protein levels and reduced inflammatory factor expression. On the other hand, intestinal flora experiment demonstrated that CP-A intervention could increase the abundance of lactobacillus. In conclusion, CP-A mitigates 5-FU-induced IM by inhibiting the ERK/MLCK/MLC2 pathway, reducing the expression of inflammatory factors, improving the intestinal mucosal barrier and regulating intestinal flora. This study sheds light on CP-A's therapeutic potential in IM treatment, providing insights for future research.
Medicine and Pharmacology, Medicine and Pharmacology
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