Solving the puzzle: What is behind our forefathers' anti-inflammatory remedies?

Abstract

Inflammation is a ubiquitous host response in charge of restoring normal tissue structure and function but is a double-edged sword, as the uncontrolled or excessive process can lead to the injury of host cells, chronic inflammation, chronic diseases, and also neoplastic transformation. Throughout history, a wide range of species has been claimed to have anti-inflammatory effects worldwide. Among them, Angelica sinensis, Tropaeolum majus, Castilleja tenuiflora, Biophytum umbraculum, to name just a few, have attracted the scientific and general public attention in the last years. Efforts have been made to assess their relevance through a scientific method. However, inflammation is a complex interdependent process, and phytomedicines are complex mixtures of compounds with multiple mechanisms of biological actions, which restricts systematic explanation. For this purpose, the omics techniques could prove extremely useful. They provide tools for interpreting and integrating results from both the classical medical tradition and modern science. As a result, the concept of network pharmacology applied to phytomedicines emerged. All of this is a step toward personalized therapy.

Keywords: Inflammation; omics applied to phytomedicine; rational phytotherapy; traditional medicinal system.

Figure 1

Regulation of the NF-κB pathway. Polygala molluginifolia, Harpagophytum procumbens, Vitex trifolia and Calea urticifolia inhibit p50 and/or p65 phosphorylation and NF-κB translocation into the nucleus; Salvia plebeia suppresses IκBα degradation, which hinders nuclear translocation of NF-κB; and Zanthoxylum myriacanthum var. pubescens blocks the downstream IKK and I-κB phosphorylation. Xanthium strumarium diminishes NO and PGE₂ levels. Tripterygium wilfordii and Clematis pickeringii inhibit Cyclooxygenases-2. Tropaeolum majus, Castilleja tenuiflora and Kigelia africana act downregulating Cyclooxygenases-2 expression. Origanum vulgare possesses pleiotropic effects, as it is able to reduce NO and ROS species. Adapted from Leyva-López et al., 2016 and Torres-Rodríguez et al., 2016

Figure 2

Species with anti-inflammatory effect mainly based on the regulation of the NF-κB pathway

Figure 3

Activity on macrophages and other mononuclear cells. a) Magnolia spp. inhibit histamine release in mast cells, and Xanthium strumarium has the ability to downregulate IgE levels. b) Polygala sabulosa and Vitex trifolia reduce pro-inflammatory IL-1β, Citronia aromatisans, Biophytum umbraculum IL-6 and Carpobrotus rossii TNF-α, among others. Salvia plebeia inhibits Akt and MAPKs pathways, whereas Angelica sinensis does so in the TNF-α-activated NF-κB signaling pathway. c) Zataria multiflora inhibits total IL-4 and enhances IFN-γ gene expression and IFN-γ/IL-4 ratio favoring Th₁ activities and suppressing Th₂ functions. C) Salvia plebeia inhibits Akt and MAPKs pathways, whereas Angelica sinensis does so in the TNF-α-activated NF-κB signaling pathway. D) Zataria multiflora inhibits total IL-4 and enhances IFN-γ gene expression and IFN-γ/IL-4 ratio favoring Th1 activities and suppressing Th2 functions.

Figure 4

Species with anti-inflammatory effect mainly based on acting upon macrophages and other mononuclear cells

Figure 5

Toll-like receptor-mediated actions. Zanthoxylum myriacanthum var. pubescens demonstrates suppresses the expression of TLR4 in LPS-activated cells. Polygala sabulosa inhibits the activation of TLR4 by LPS. Tripterygium wilfordii affects the expression of TRAF-6, which is downstream to the MyD88 signaling pathway, and Xanthium strumarium blocks PDK1 and Akt kinase activity, inhibiting the formation of the PDK1/Akt complex. Adapted from Liao et al., 2013 and Hossen et al., 2016

Figure 6

Species with anti-inflammatory effect mainly based on a toll-like receptor-mediated action

Figure 7

Species with anti-inflammatory effect mainly based on cyclooxygenases and LOXs inhibition