Baicalein Restores the Balance of Th17/Treg Cells via Aryl Hydrocarbon Receptor to Attenuate Colitis

Abstract

As one of the ligands of aryl hydrocarbon receptor (AhR), baicalein, isolated from Scutellaria baicalensis Georgi, has been proved to exert potential therapeutic effects on ulcerative colitis (UC), but its therapeutic mechanism remains obscure. Authentically, ulcerative colitis can be alleviated by regulating the differentiation of naïve CD4+ T cells via AhR activation. So, our study planned to prove the hypothesis that baicalein protected mice against UC by regulating the balance of Th17/Treg cells via AhR activation. Immunofluorescence and western blot results showed that baicalein could promote AhR activation and induce it to transfer to the nucleus. We further determined the effect of baicalein on naïve CD4+ T cell differentiation in vitro by magnetic cell separation and drug intervention. The results showed that baicalein could promote Treg cell differentiation by activating AhR. In vivo study, UC mice were established by free drinking of dextran sulfate sodium (DSS) for 7 days and then were orally administrated by baicalein (10, 20, and 40 mg/kg), TCDD (AhR agonist), and CH223191 (antagonist). The results demonstrated that baicalein improved the symptoms of UC mice, regulated the balance of Th17/Treg cells, and restored the balance of proinflammatory cytokines such as IL-17, IL-6, and TNF-α; anti-inflammatory cytokines such as IL-10 and TGF-β; and epithelial protective cytokine IL-22 in UC mice, and these effects were related to AhR. Taken together, our research found that baicalein might be a potential drug for UC via regulating Treg cell differentiation and maintaining immune homeostasis and attempted to shed a light on the pivotal role of AhR in these effects.

Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence

“…CH-223191 administration avoided the amelioration of symptoms of colitis associated with baicalein and abrogated the baicalein-dependent restoration in the balance between Th17 and Treg cells. Moreover, CH-223191 prevented the anti-inflammatory effect of AHR activation by precluding the decrease of the proinflammatory cytokines tumor necrosis factor ɑ (TNF-ɑ) and interleukins 6 (Il-6) and 17 (Il-17) and the increase of anti-inflammatory cytokines (transforming growth factor—TGF-β and IL-10) [ 71 ].…”

Molecular Targets and Mechanisms of Scutellariae radix-Coptidis rhizoma Drug Pair for the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

“…Baicalein is the main ingredient of Coptidis rhizoma. Studies have suggested its anti-inflammatory effect and discovered that it could improve the inflammatory state of UC and the control drugs [39][40][41]. e effect of baicalein is similar to that of the reference drug sulfasalazine and comparable to wogonin [42,43].…”

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis

“…In addition, Tregs can also promote the polarization of macrophages from an inflammatory phenotype to an anti-inflammatory phenotype ( Lui et al, 2020 ). Restoring the balance between Th17 and Tregs can reduce colitis ( Liu et al, 2020 ).…”