Abstract
To find novel anti-inflammatory drugs, we screened anti-inflammatory compounds from 18 different types of Artemisia argyi seed extracts. The in vitro and in vivo anti-inflammatory activities of the screened compounds and their mechanisms were characterized. We first detected the cytotoxic effect of the compounds on RAW264.7 cells and the inhibitory effect on LPS-induced NO release. It was found that sesquiterpenoids CA-2 and CA-4 had low cytotoxic and strong NO inhibitory activity with an IC50 of 4.22 ± 0.61 μM and 2.98 ± 0.23 μM for NO inhibition, respectively. Therefore, compound CA-4 was studied in depth. We found that compound CA-4 inhibited LPS-induced pro-inflammatory factor production and M1 macrophage differentiation in RAW264.7 cells. Additionally, CA-4 inhibited the expression of p-ERK1/2, p-JNK, iNOS, and COX-2 by blocking the MAPK signaling pathway. CA-4 also promoted the expression of autophagy-related proteins such as LC3 II and Beclin-1 by inhibiting activation of the PI3K/AKT/mTOR signaling pathway, and promoted the generation of autophagosomes. Finally, CA-4 significantly inhibited the degree of inflammation in mice with acute peritonitis, showing good anti-inflammatory activity in vivo. Consequently, compound CA-4 may be a promising drug for the treatment of acute inflammatory diseases and provide new ideas for the synthesis of novel anti-inflammatory compounds.
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Data availability
All data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- AKT:
-
Protein kinase B
- COX-2:
-
Cyclooxygenase 2
- DEX:
-
Dexamethasone
- ERK1/2:
-
Extracellular regulated protein kinases 1/2
- iNOS:
-
Inducible nitric oxide synthase
- JNK:
-
C-Jun N-terminal kinase
- LPS:
-
Lipopolysaccharide
- MAPK:
-
Mitogen-activated protein kinase
- MCP-1:
-
Monocyte chemoattractant protein-1
- mTOR:
-
Mammalian target of rapamycin
- NSAIDs:
-
Nonsteroidal anti-inflammatory drugs
- PI3K:
-
Phosphatidylinositol-3-kinase
- SRB:
-
Sulfonyl rhodamine
- TEM:
-
Transmission electron microscopy
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Acknowledgements
Thanks to the Key Laboratory of Advanced Pharmaceutical Preparation Technology, Ministry of Education; School of Pharmaceutical Sciences, Zhengzhou University; and State Key Laboratory of Esophageal Cancer Prevention & Treatment; School of Pharmaceutical Sciences, Zhengzhou University for providing the experimental platform.
Funding
This work was supported by the Joint Fund of Provincial Science and Technology Research and Development Plan of Henan Province (Advantageous Discipline Cultivation) (Project No. 222301420057), The Open Project of Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, (Project No. EKB202202), and The Open Project of Henan Neurodevelopment Engineering Research Center for Children (Project No. SG202201).
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YL: conceptualization, validation, and writing—original draft. YW: methodology, investigation, data curation, and writing—original draft. TL: methodology, data curation, and writing—original draft. ZL: methodology, TG: methodology. GX: conceptualization. YD: conceptualization and funding acquisition. YY: conceptualization, funding acquisition, supervision, and writing—review & editing.
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Li, Y., Wang, Y., Li, T. et al. Sesquiterpene from Artemisia argyi seed extracts: A new anti-acute peritonitis agent that suppresses the MAPK pathway and promotes autophagy. Inflammopharmacol 32, 447–460 (2024). https://doi.org/10.1007/s10787-023-01297-8
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DOI: https://doi.org/10.1007/s10787-023-01297-8