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Ginseng and Rhubarb combination ameliorates ferroptosis in persistent inflammation, immunosuppression, and catabolism syndrome via the CaMKII/HO-1 signaling pathway
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Yiming Wei1, 2, 3, Xiaomeng Guo1, 3, 4, Yahui Hu1, 3, Yake Li1, 3, Tengfei Chen1, Chang Liu5, Lixuan Zhang6, Qing Ye7, Qingquan Liu1, 3, 4, *, Xiaolong Xu1, 3, 4, *
Acupuncture and Herbal Medicine | 2026, 6(2) : 205 - 219
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Acupuncture and Herbal Medicine | 2026, 6(2): 205-219
• Original Article •
Ginseng and Rhubarb combination ameliorates ferroptosis in persistent inflammation, immunosuppression, and catabolism syndrome via the CaMKII/HO-1 signaling pathway
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Yiming Wei1, 2, 3, Xiaomeng Guo1, 3, 4, Yahui Hu1, 3, Yake Li1, 3, Tengfei Chen1, Chang Liu5, Lixuan Zhang6, Qing Ye7, Qingquan Liu1, 3, 4, *, Xiaolong Xu1, 3, 4, *
Affiliations
  • 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
  • 2Xiamen Traditional Chinese Medicine Hospital, Xiamen, China
  • 3Beijing Institute of Chinese Medicine, Beijing, China
  • 4Beijing Key Laboratory of Innovative Research on Removing Stasis and Detoxification Theory in Infectious Diseases, Beijing, China
  • 5Center for Health Policy and Technology Evaluation, Peking University Health Science Center, Beijing, China
  • 6Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
  • 7Beijing Changping District Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China
About Author:

Yiming Wei and Xiaomeng Guo are contributed equally to this work.

Published: 2026-06-25 doi: 10.1097/HM9.0000000000000183
Outline
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Objective:

This study aimed to investigate the therapeutic effects and underlying mechanisms of the Ginseng and Rhubarb combination (GRC) on sepsis-induced persistent inflammation, immunosuppression, and catabolism syndrome (PICS).

Methods:

The mouse model of sepsis-induced PICS was established using cecal ligation and puncture (CLP). Mice were randomly assigned to five groups: sham, model, model + GRC, model + GRC + oleic acid (OA), and model + GRC + celastrol (CELA). GRC was administered by oral gavage once daily for 7 days, whereas the agonists were injected intraperitoneally for 3 days. Additionally, KN-93 (a calcium/calmodulin-dependent protein kinase II [CaMKII] inhibitor; 5 mg/kg) was used to verify the inhibitory regulation of CaMKII signaling. Seventy-two hours after surgery, serum and tissue samples were collected to evaluate the therapeutic effects of GRC. Outcome measures included survival, body weight, splenic immune cell distribution, histopathology, inflammatory cytokine levels, and ferroptosis-related indicators. Targeted metabolomics and data-independent acquisition (DIA)-based proteomics were performed to identify differential molecules and pathways associated with GRC treatment.

Results:

Compared to the model group, GRC markedly improved the survival rate and mitigated body weight loss in septic PICS mice. GRC reduced splenic neutrophil and macrophage infiltration and increased the proportions of CD4+ and CD8+ T cells. Histopathological examination revealed attenuation of organ damage. Levels of inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor-alpha (TNF-α), IL-4, IL-13) were significantly decreased, and metabolic disturbances were ameliorated. Biochemical assays showed that GRC reduced Fe2+ and malondialdehyde (MDA) levels while increasing glutathione peroxidase (GSH-PX) and GPX4, indicating inhibition of ferroptosis. Western blot (WB) analysis demonstrated that GRC downregulated the CaMKII/heme oxygenase-1 (HO-1) pathway, and this regulatory effect was reversed by CaMKII and HO-1 agonists. Multi-omics analysis further revealed that GRC modulated metabolic and proteomic networks associated with immune regulation and ferroptosis, confirming that its therapeutic benefits were mediated through suppression of the CaMKII/HO-1/GPX4 axis.

Conclusions:

GRC exhibited significant anti-inflammatory, immunomodulatory, and organ-protective effects in the murine model of sepsis-induced PICS. These benefits were mediated through the suppression of ferroptosis via modulation of the CaMKII/HO-1 pathway, providing a novel experimental foundation and a potential therapeutic strategy for managing sepsis-associated PICS.

Ferroptosis  /  Ginseng  /  PICS  /  Rhubarb  /  Sepsis  /  CaMKII/HO-1/GPX4 axis
Yiming Wei, Xiaomeng Guo, Yahui Hu, Yake Li, Tengfei Chen, Chang Liu, Lixuan Zhang, Qing Ye, Qingquan Liu, Xiaolong Xu. Ginseng and Rhubarb combination ameliorates ferroptosis in persistent inflammation, immunosuppression, and catabolism syndrome via the CaMKII/HO-1 signaling pathway[J]. Acupuncture and Herbal Medicine, 2026 , 6 (2) : 205 -219 . DOI: 10.1097/HM9.0000000000000183
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Funding
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  • National Natural Science Foundation of China(82474428; 82505482)
  • National Major Science and Technology Project(2025ZD01903000)
  • Sanming Project of Medicine in Shenzhen(SZZYSM202411012)
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Year 2026 volume 6 Issue 2
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Article Info
doi: 10.1097/HM9.0000000000000183
  • Receive Date：2025-06-20
  • Online Date：2026-11-04
  • Published：2026-06-25
Article Data
Affiliations
History
  • Received：2025-06-20
  • Accepted：2026-01-23
Funding
National Natural Science Foundation of China(82474428; 82505482)
National Major Science and Technology Project(2025ZD01903000)
Sanming Project of Medicine in Shenzhen(SZZYSM202411012)
Affiliations
    1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
    2Xiamen Traditional Chinese Medicine Hospital, Xiamen, China
    3Beijing Institute of Chinese Medicine, Beijing, China
    4Beijing Key Laboratory of Innovative Research on Removing Stasis and Detoxification Theory in Infectious Diseases, Beijing, China
    5Center for Health Policy and Technology Evaluation, Peking University Health Science Center, Beijing, China
    6Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
    7Beijing Changping District Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China

Corresponding:

* Xiaolong Xu, E-mail: ;
Qingquan Liu, E-mail: .
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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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