Table 1.

Tryptophan metabolites as AHR ligands in CKD

Ligands	Compounds	Origin	Biological effects	Molecular mechanism	References
Agonist	Indole	Indolic pathway	Alleviate inflammation and oxidative stress	Decreased IL-1β, IL-6, and chemokine ligand 2 levels	[58]
Agonist	IS	Indolic pathway	Induce podocyte injury	Increased CYP1A1 expression	[97]
Agonist	IS	Indolic pathway	Inhibit neovascularization, cause peripheral arterial disease	Inhibit TF ubiquitination, down-regulate HIF/IL-10/VEGF signaling pathway	[62, 68]
Agonist	IS	Indolic pathway	Induce inflammation	Increased expression of SOCS2 and TNF-α	[75, 77]
Agonist	IAA	Indolic pathway	Accelerate vascular dysfunction	Increased TF level via AHR/p38 MAPK/NF-κB pathway	[47, 48]
Agonist	IAA	Indolic pathway	Induce oxidative stress and inflammation	Increased CYP1A1,ROS and COX-2 expression	[50, 51, 56]
Agonist	Tryptamine	Indolic pathway	Regulate intestinal immune response	Increased CYP1A1 expression	[78, 79]
Agonist	Indole-3-aldehyde	Indolic pathway	Reduce mucosal inflammation, protect the intestinal epithelial barrier	Increased IL-22 level and STAT3 phosphorylation, decreased levels of TNF-α and IL-1β	[81, 82]
Agonist	Kynurenine	Kynurenine pathway	Accelerate arteriovenous thrombosis	Increased levels of TF and PAI-1 via AHR-TF/PAI-1 axis	[98, 99]
Agonist	Kynurenine	Kynurenine pathway	Induce chronic inflammation and oxidative stress	Increased HIF, IL-1β, and IL-6 levels, decreased EPO expression	[100, 101]
Antagonist	Indolo[3,2-b] carbazole	Dietary	Protect against oxidative DNA damage	Increased an antioxidant enzyme expression	[102]
Antagonist	6-formylindolo-[3,2-b]-carbazole	UV light	Reduce inflammation	Decreased levels of IL-6 and claudin-2	[103, 104]
Antagonist	5,7,3′,4′,5′-pentahydroxy flavanone	Semen Plantaginis	Ameliorate CKD and renal fibrosis	Inhibit profibrotic protein expression expression	[21]
Antagonist	Barleriside A	Semen Plantaginis	Ameliorate CKD and renal fibrosis	Inhibit profibrotic protein expression expression	[21]
Antagonist	Rhoifolin	Semen Plantaginis	Ameliorate CKD and renal fibrosis	Inhibit profibrotic protein expression expression	[21]
Antagonist	Baicalein	Scutellaria baicalensis	Alleviate aristolochic acid I (AAI)-mediated kidney toxicity	Induce CYP1A1 and CYP1A2 expression	[95]
Antagonist	Tanshinone I	Salvia miltiorrhiza	Alleviate AAI-mediated kidney injury	Increased CYP1A1 and CYP1A2 expression	[96]