Immunoenhancement effect of cinobufagin on macrophages and the cyclophosphamide-induced immunosuppression mouse model

• Published in: International immunopharmacology Vol. 131; p. 111885
• Main Authors: Zhao, Yue-Zhu, Wang, Yi-Lun, Yu, Yang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.04.2024
• Subjects: Animals; Bufanolides; Cinobufagin; Cyclophosphamide - pharmacology; Immunosuppression Therapy; Immunosuppressive mice; Macrophages; Mice; Oxidative stress; Phosphatidylinositol 3-Kinases - pharmacology; PI3K/Akt/mTOR; Proto-Oncogene Proteins c-akt; RAW 264.7; TOR Serine-Threonine Kinases; Oxidative stress; RAW 264.7; Immunosuppressive mice; PI3K/Akt/mTOR; Cinobufagin
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111885

[Display omitted] •CBG restores CTX-induced immunosuppression in mice.•CBG provides better defense against CTX-induced oxidative stress damage in the spleen.•CBG improves CTX-induced peripheral blood abnormalities.•CBG is expected to be developed as a functional nutrient. Cinobufagin (CBG) is a natural active substance. Although its various pharmacological activities have been explored, the immunomodulatory activity of CBG remains unexplored. Therefore, this study aimed to investigate the anti-inflammatory and immunomodulatory activities of CBG ex vivo and in vivo. The immunomodulatory activity of CBG was investigated in RAW 264.7 cells. CBG showed no significant toxicity to cells. Additionally, 0.5–8 μg/mL CBG significantly increased the phagocytosis ability of macrophages and the secretion levels of IL-1β and TNF-α. Thus, it exerted immunomodulatory effects. We established the immunosuppressive model induced by cyclophosphamide (CTX) in mice and studied the immunomodulatory activity of CBG in vivo. The experimental results showed that the intervention of CBG alleviated the CTX-induced weight loss, restored the lymphocyte nuclear cell number, and promoted the secretion and mRNA expression of cytokines IFN-γ, IL-4, IL-6, and IL-12. Moreover, CBG increased the immune organ index, protected the growth of the spleen and thymus, and improved the pathological changes in immunosuppressed mice. Western blot results showed that different concentrations of CBG upregulated the phosphorylation level of PI3K/Akt/mTOR in the spleen of CTX-induced immunosuppressed mice. This suggests that the immunomodulatory effect of CBG may be related to the regulation of PI3K/Akt/mTOR signaling pathway. This study provides a theoretical basis for developing CBG immune enhancers and opens up new ideas for the comprehensive utilization and development of CBG in factories.