| Title: |
PKA signaling-mediated inhibition of the AIM2 inflammasome is involved in the radioprotective effect of Eleutheroside E |
| Authors: |
Liangliang Zhang; Changkun Hu; Zekun Wu; Ziqiao Yan; Chengrong Xiao; Xianglin Tang; Zebin Liao; Yue Gao |
| Source: |
Acupuncture and Herbal Medicine, Vol 5, Iss 4, Pp 443-455 (2025) |
| Publisher Information: |
Wolters Kluwer Health/LWW, 2025. |
| Publication Year: |
2025 |
| Collection: |
LCC:Other systems of medicine |
| Subject Terms: |
Other systems of medicine; RZ201-999 |
| Description: |
Objective:. To investigate the protective effect and underlying mechanism of Eleutheroside E (EE), derived from Acanthopanax senticosus, against γ-ray radiation-induced splenic injury. Methods:. The Cell Counting Kit-8 assay was used to determine the toxicity of the drug. Hematoxylin and eosin, terminal deoxynucleotidyl transferase dUTP nick end-labeling, and live/dead cell double staining assays were used to evaluate the protective effects of EE on the spleen. Immunofluorescence, immunohistochemical, and enzyme-linked immunosorbent assays (ELISA) were used to investigate the underlying mechanisms of EE. Cross-talk between the absent in melanoma 2 (AIM2) inflammasome and the protein kinase A (PKA) signaling pathway was clarified using selective inhibitors. Results:. EE reduced IR-induced splenic injury—the increased apoptosis rates and the levels of γ-H2AX and inflammatory factors in splenic cells were significantly alleviated. ELISA showed that EE reduced the level of interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in irradiated tissues. The radioprotective effects of EE were mediated by inhibition of the AIM2 inflammasome and stimulation of PKA signaling, in which EE inhibited the increased levels of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved caspase-1 proteins upon ionizing radiation damage but rescued the decreased protein levels in PKA signaling. Suppression of AIM2 signaling was dependent on the activation of PKA signaling by EE treatment. Conclusions:. EE exerts a significant radioprotective effect on the spleen in vitro and in vivo. Activation of the PKA signaling pathway leads to AIM2 inflammasome inhibition, thereby attenuating radiation-induced DNA damage. This was demonstrated to be the mechanism involved in the radioprotective effects of EE. Thus, EE can be used as a potential radioprotective drug in clinical practice. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2765-8619 |
| Relation: |
http://journals.lww.com/10.1097/HM9.0000000000000152; https://doaj.org/toc/2765-8619 |
| DOI: |
10.1097/HM9.0000000000000152 |
| Access URL: |
https://doaj.org/article/5f4c8e905de549e7852dfe8a8ea552e1 |
| Accession Number: |
edsdoj.5f4c8e905de549e7852dfe8a8ea552e1 |
| Database: |
Directory of Open Access Journals |