Mitragyna speciosa Korth. downregulates macrophage inflammatory responses by inhibiting TLR-4 and increasing IL-10 production

Year 2024, Volume: 54 Issue: 3, 350 - 358, 30.12.2024

Anwar Salm Kalifa Kafo , Rabia Mrehil Elsalami , Masriana Hassan

https://doi.org/10.26650/IstanbulJPharm.2024.1424150

Abstract

Background and Aims: Mitragyna speciosa Korth. is a tropical plant native to Asia with various medicinal properties. This study examined the immunotherapeutic potential of M. speciosa methanolic extract (MSME) against lipopolysaccharide (LPS)- stimulated activation of macrophages via the expression of Toll-like receptor 4 (TLR-4) and CD14 and downstream signalling cascades leading to the activation of nuclear factor kappa B (NF-𝜅B), which potentially affects macrophage immune responses.
Methods: The expression of TLR-4/CD14 and NF-𝜅B genes in macrophages was determined in total RNA by qRT-PCR. Subsequently, the macrophage phagocytic activities and secretion of immune mediators such as reactive oxygen species (ROS) and cytokines were evaluated by fluorescent latex beads uptake assay, 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA), and cytometric bead array, respectively, in LPS-activated RAW264.7 cells.
Results: MSME significantly reduced macrophage-mediating inflammation by inhibiting TLR-4/CD14 signalling and subsequently suppressed the NF-𝜅B expression. Inhibition of TLR-4 by MSME attenuated macrophage phagocytic activity, which consequently reduced the production of ROS and pro-inflammatory cytokines such as IL-6, MCP-1, and TNF-α. Interestingly, MSME significantly increased the production of IL-10, which supports the anti-inflammatory properties of M. speciosa.
Conclusion: Our findings suggest the therapeutic potential of MSME through the suppression of macrophage inflammatory responses mediated by IL-10 secretion.

Keywords

Mitragyna speciosa, Macrophages; Anti-inflammatory, IL-10, TLR-4

Supporting Institution

Universiti Putra Malaysia

Project Number

GP IPS/2022/9726100

Thanks

This research was financially supported by Geran Putra Siswazah (GP IPS/2022/9726100) of Universiti Putra Malaysia

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