Research Paper Volume 15, Issue 9 pp 3621—3634
Ling Zhi-8, a fungal immunomodulatory protein in Ganoderma lucidum, alleviates CPT-11-induced intestinal injury via restoring claudin-1 expression
- 1 Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan
- 2 School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- 3 Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
- 4 Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan
- 5 Yeastern Biotech Co., Ltd., New Taipei City, Taiwan
- 6 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
- 7 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- 8 Department of Clinical Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan
Received: February 27, 2023 Accepted: April 18, 2023 Published: May 5, 2023
https://doi.org/10.18632/aging.204695How to Cite
Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
CPT-11 (Irinotecan) remains an important chemotherapeutic agent against various solid tumors nowadays. Potential adverse effects, especially gastrointestinal toxicities, are the main limiting factor for its clinical utility. Ling Zhi-8 (LZ-8), a fungal immunomodulatory protein in Ganoderma lucidum mycelia, has potential for drug development due to its multiple bioactivities and functions. This study aimed to explore the influence of LZ-8 on CPT-11-treated IEC-6 cells in vitro and on mice with CPT-11-induced intestinal injury in vivo. The mechanism through which LZ-8 exerted its protective effects was also investigated. In the in vitro study, the viability and claudin-1 expression of IEC-6 cells decreased gradually with increasing concentrations of CPT-11, but LZ-8 treatment had no obvious influence on their viability, morphology, and claudin-1 expression. Pretreatment of LZ-8 significantly improved CPT-11-decreased cell viability and claudin-1 expression in IEC-6 cells. In mice with CPT-11-induced intestinal injury, LZ-8 treatment could ameliorate symptoms and mitigate intestinal damage. Meanwhile, LZ-8 restored claudin-1 expression in the intestinal membranes in CPT-11-treated mice. Collectively, our results demonstrated the protective effects of LZ-8 against CPT-11 damage in both IEC-6 cells and mice. LZ-8 can restore claudin-1 expression in intestinal cells following CPT-11 treatment, suggesting the role of claudin-1 in the scenario.
Abbreviations
CCK-8: Cell Counting Kit-8; LZ-8: Ling Zhi-8; PBS: phosphate-buffered saline; qPCR: quantitative polymerase chain reaction.