Oxocrebanine from Stephania Pierrei Exerts Macrophage Anti-inflammatory Effects by Downregulating the NF-κB, MAPK, and PI3K/Akt Signalling Pathways

Overview

Journal Inflammopharmacology

Specialty Pharmacology

Date 2022 Jul 13

PMID 35831735

Authors

Wanatsanan Chulrik

Chutima Jansakun

Waraluck Chaichompoo

Aman Tedasen

Pathumwadee Yotmanee

Apsorn Sattayakhom

Wilanee Chunglok

Apichart Suksamrarn

Warangkana Chunglok

Affiliations

Soon will be listed here.

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 E, 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 NH-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.

Citing Articles

Protective effects of Stephania pierrei tuber-derived oxocrebanine against LPS-induced acute lung injury in mice.

Chulrik W, Jansakun C, Chaichompoo W, Supaweera N, Tedasen A, Punsawad C Inflammopharmacology. 2023; 31(4):2023-2035.

PMID: 37129718 DOI: 10.1007/s10787-023-01231-y.

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