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13-07-2022 | Alkaloids | Original Article

Oxocrebanine from Stephania pierrei exerts macrophage anti-inflammatory effects by downregulating the NF-κB, MAPK, and PI3K/Akt signalling pathways

Authors: Wanatsanan Chulrik, Chutima Jansakun, Waraluck Chaichompoo, Aman Tedasen, Pathumwadee Yotmanee, Apsorn Sattayakhom, Wilanee Chunglok, Apichart Suksamrarn, Warangkana Chunglok

Published in: Inflammopharmacology | Issue 4/2022

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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Title: Oxocrebanine from Stephania pierrei exerts macrophage anti-inflammatory effects by downregulating the NF-κB, MAPK, and PI3K/Akt signalling pathways
Authors: Wanatsanan Chulrik
Chutima Jansakun
Waraluck Chaichompoo
Aman Tedasen
Pathumwadee Yotmanee
Apsorn Sattayakhom
Wilanee Chunglok
Apichart Suksamrarn
Warangkana Chunglok
Publication date: 13-07-2022
Publisher: Springer International Publishing
Keywords: Alkaloids
Alkaloids
Published in: Inflammopharmacology / Issue 4/2022
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-022-01021-y

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Oxocrebanine from Stephania pierrei exerts macrophage anti-inflammatory effects by downregulating the NF-κB, MAPK, and PI3K/Akt signalling pathways

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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