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PKA signaling-mediated inhibition of the AIM2 inflammasome is involved in the radioprotective effect of Eleutheroside E
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Liangliang Zhang1, 2, Changkun Hu1, 2, Zekun Wu2, 3, Ziqiao Yan2, 4, Chengrong Xiao2, Xianglin Tang2, *, Zebin Liao2, *, Yue Gao1, 2, 5, *
Acupuncture and Herbal Medicine | 2025, 5(4) : 443 - 455
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Acupuncture and Herbal Medicine | 2025, 5(4): 443-455
• Original Articles •
PKA signaling-mediated inhibition of the AIM2 inflammasome is involved in the radioprotective effect of Eleutheroside E
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Liangliang Zhang1, 2, Changkun Hu1, 2, Zekun Wu2, 3, Ziqiao Yan2, 4, Chengrong Xiao2, Xianglin Tang2, *, Zebin Liao2, *, Yue Gao1, 2, 5, *
Affiliations
  • 1Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • 2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
  • 3School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
  • 4Department of Traditional Chinese Medicine, the Sixth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
  • 5State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China
About Author:

Liangliang Zhang, Changkun Hu, and Zekun Wu contributed equally to this work.

Published: 2025-12-25 doi: 10.1097/HM9.0000000000000152
Outline
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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.

AIM2 inflammasome  /  DNA damage  /  Eleutheroside E  /  PKA signaling pathway  /  Radiation damage
Liangliang Zhang, Changkun Hu, Zekun Wu, Ziqiao Yan, Chengrong Xiao, Xianglin Tang, Zebin Liao, Yue Gao. PKA signaling-mediated inhibition of the AIM2 inflammasome is involved in the radioprotective effect of Eleutheroside E[J]. Acupuncture and Herbal Medicine, 2025 , 5 (4) : 443 -455 . DOI: 10.1097/HM9.0000000000000152
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Funding
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  • National Natural Science Foundation of China(82103776; 82192911)
  • innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207)
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Year 2025 volume 5 Issue 4
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Article Info
doi: 10.1097/HM9.0000000000000152
  • Receive Date：2024-01-26
  • Online Date：2026-11-04
  • Published：2025-12-25
Article Data
Affiliations
History
  • Received：2024-01-26
  • Accepted：2025-02-18
Funding
National Natural Science Foundation of China(82103776; 82192911)
innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207)
Affiliations
    1Tianjin University of Traditional Chinese Medicine, Tianjin, China
    2Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China
    3School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
    4Department of Traditional Chinese Medicine, the Sixth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
    5State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China

Corresponding:

* Yue Gao, E-mail: ;
Zebin Liao, E-mail: ;
Xianglin Tang, E-mail: .
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表12种不同金属材料的力学参数
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小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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