Sanguinarine and Chelidonine Synergistically Induce Endosomal Toll-like Receptor and M1-Associated Mediators Expression

Nuchsupha Sunthamala,Surasak Khankhum,Chutimun Suebsamran,Sununta Chuncher,Janchai Janpirom,Rungruedee Thiwthong,Niramon Khruaphet,Neeranuch Sankla

doi:10.22207/jpam.14.4.13

Abstract

Natural compounds represent the great capability to stimulate several cell types. Macrophage plays an important role for an effective immune response for infection and inflammation. Isoquinoline alkaloid, sanguinarine, and chelidonine are active compounds that exhibit activity on various tumor cells and immune cells. However, the effect of these compounds on the endosomal toll-like receptor (enTLR) and type I interferon (IFN) are still unclear. The monocyte-derived macrophages (MDMs) were cultured and were determined their cell viability and phagocytic activity to Staphylococcus aureus DMST8840. The nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were also examined. The expression of enTLRs, type I IFN, and cytokines were determined by real-time PCR. Result shows that the compounds did not affect on MDM cell viability. Sanguinarine and chelidonine enhance phagocytic activity of MDM against Staphylococcus aureus DMST8840 by revealing a higher number of bacterial survival than the MDM treated by polyI:C, and the cell control after co-culture for 3 h. The production of NO has no difference amount but iNOS mRNA production was down-regulated in sanguinarine, chelidonine and their mixed treated MDM. The expressions of enTLRs and IFN-β1 mRNA were up-regulated in both compounds and their combination. Additionally, these compounds also enhance M1-liked cytokine by up-regulated IL-6 and down-regulated IL-10 and TGF-β1, respectively. Therefore, sanguinarine and chelidonine enhance enTLR and IFN-β1 expression and trend to stimulate the cell into M1-liked MDM.

Highlights

The natural product is an essential source of medical capacity
This study aims to obtain the effects of sanguinarine and chelidonine on human monocyte-derived macrophage (MDM) and their antibacterial activity on Staphylococcus aureus DMST8840 by enhancing macrophage activity, stimulating of endosomal toll-like receptor (enTLR), type I IFN, and cytokine expression toward M1 and M2-liked macrophages
The results revealed that, the monocytes were differentiated into MDM after cultured at day 6 (Fig. 1C and 1D)

Summary

Introduction

The natural product is an essential source of medical capacity. Especially medicinal plant-derived natural products, it reveals various activities such as anti-microbial, anti-oxidant, anti-tumor, and anti-inflammation[1,2,3,4,5]. The active compounds, sanguinarine and chelidonine, are isoquinoline alkaloids derived from plants including Sanguinaria canadensis, Chelidonium majus, and other poppy-Fumaria species[1,2]. These compounds have been represented several activities in both in vitro and in vivo studies, including the antiinflammatory effect of sanguinarine on murine RAW264.7 macrophage cell line and cytokine production on animal model[1,6]. Chelidonine shows the inhibition effect on nitric oxide production by murine RAW264.7 macrophage cell line[7], and anti-tumor activities on several cancer cells 2 such as head and neck cancer cell lines[5] and mouse leukemic cell line[4]. Sanguinarine and chelidonine, which exhibit activities in various cell types including cancer cells, virus-derived cancer cells, and immune cells, might stimulate a distinct mechanism in several target cells of the treatment

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