Abstract
Plant-derived medicinal compounds are increasingly being used to treat acute and chronic inflammatory diseases, which are generally caused by aberrant inflammatory responses. Stephania pierrei Diels, also known as Sabu-lueat in Thai, is a traditional medicinal plant that is used as a remedy for several inflammatory disorders. Since aporphine alkaloids isolated from S. pierrei tubers exhibit diverse pharmacological characteristics, we aimed to determine the anti-inflammatory effects of crude extracts and alkaloids isolated from S. pierrei tubers against lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Notably, the n-hexane extract strongly suppressed nitric oxide (NO) while exhibiting reduced cytotoxicity. Among the five alkaloids isolated from the n-hexane extract, the aporphine alkaloid oxocrebanine exerted considerable anti-inflammatory effects by inhibiting NO secretion. Oxocrebanine also significantly suppressed prostaglandin E2, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, inducible nitric oxide synthase, and cyclooxygenase (COX)-2 protein expression by inactivating the nuclear factor κB, c-Jun NH2-terminal kinase, extracellular signal-regulated kinase 1/2, and phosphatidylinositol 3-kinase/Akt inflammatory signalling pathways. Molecular docking analysis further revealed that oxocrebanine has a higher affinity for toll-like receptor 4/myeloid differentiation primary response 88 signalling targets and the COX-2 protein than native ligands. Thus, our findings highlight the potential anti-inflammatory effects of oxocrebanine and suggest that certain alkaloids of S. pierrei could be used to treat inflammatory diseases.
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Acknowledgements
This research was supported by the Thailand Science Research and Innovation Fund (Contract No. WU-FF64102) and the new strategic research (P2P) project of Walailak University, Nakhon Si Thammarat, Thailand (grant no. CGS-P2P-2564-054). W. Chulrik expresses her gratitude to the Walailak University Graduate Research Fund (grant no. CGS-RF-2021/05) and a Walailak University Ph.D. Excellence Scholarship (grant no. 04/2020). A. Suksamrarn and W. Chaichompoo acknowledge partial support from the Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research, and Innovation. We would like to thank Editage (www.editage.com) for English language editing.
Funding
This research was supported by the Thailand Science Research and Innovation Fund (contract no. WU-FF64102) and the new strategic research (P2P) project of Walailak University, Nakhon Si Thammarat, Thailand (grant no. CGS-P2P-2564–054). W. Chulrik expresses her gratitude to the Walailak University Graduate Research Fund (grant no. CGS-RF-2021/05) and a Walailak University Ph.D. Excellence Scholarship (grant no. 04/2020).
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Conceptualization: WanC and WaranC; methodology: WanC, WaranC, and CJ; validation: WilC; formal analysis: AT and WaranC; investigation: WanC and WaralC; resources: ApsS and PY; writing—original draft preparation; WanC; writing—review and editing: WanC, WaranC and ApiS; supervision and funding acquisition: WaranC and ApiS. All authors read and approved the final manuscript.
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Chulrik, W., Jansakun, C., Chaichompoo, W. et al. Oxocrebanine from Stephania pierrei exerts macrophage anti-inflammatory effects by downregulating the NF-κB, MAPK, and PI3K/Akt signalling pathways. Inflammopharmacol 30, 1369–1382 (2022). https://doi.org/10.1007/s10787-022-01021-y
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DOI: https://doi.org/10.1007/s10787-022-01021-y