Inflammation is a defense mechanism in the body. The immune system recognizes harmful and external factors, and in return, projects the appropriate inflammatory responses.

Inflammation occurs through various signaling pathways such as the indoleamine 2,3- dioxygenase (IDO)/kynurenine (KYN) (IDO/KYN). Tryptophan (TRP) metabolism plays an important role in the mechanisms associated with inflammation [1]. TRP is converted to kynurenine for further metabolism. It has been shown that TRP and its metabolites such as serotonin, quinolinic acid (QUIN), and kynerunic acid (KYNA) have been linked to inflammation [2], [3]. The IDO/KYN pathway induces the production of inflammatory cytokines such as interferon-gamma (IFNγ), tumor necrosis factors (TNFs), and interleukins (ILs) (i.e. IL 6 and IL1β), which are involved in several diseases such as neurodegenerative diseases, cardiac diseases, gastric diseases, cancers, and other inflammatory disorders [4], [5], [6], [7].

The KYN pathway is mainly modulated by the IDO enzymes. IDO is predominantly presented in peripheral tissues such as macrophages, dendritic cells (DC), and the central nervous system (CNS) immune cells. This enzyme is usually evoked by an infection or inflammatory cytokines such as IFNγ, TNFs, and ILs (i.e. IL 6 and IL1β). The activation of IDO in the IFN-dependent pathway is accomplished by binding the IFNγ to a specific receptor and by activating the JAK1/2. This may activate the STAT1 transcription in tyrosine. The STAT1-STAT1 homodimers transfers to the nucleus and is connected to one of the activated parts of the IFNγ. In the IFN-independent pathway, the IDO activation occurs by B7 in DC, and the antigen-4 lymphocyte T. On the other hand, TDO is induced by corticosteroids [8].

To date, several drugs and natural products have been identified with the ability to modulate the IDO/KYN pathway like Oren-gedoku-to (OGT), Leucine, Minocycline, Honokiol, Sulfasalazine, Patchouli Alcohol (PA), Cherry juice, and Riluzole [9], [10]. This study discusses the correlation between the IDO/KYN pathway and the inflammatory-related events. Also, introduces the synthetic compounds and natural products that are able to modulate the IDO/KYN pathway, thereby are favorable for management of some inflammatory-related diseases.