Qing Hua Chang Yin inhibits the LPS-induced activation of the IL-6/STAT3 signaling pathway in human intestinal Caco-2 cells

Abstract

Increasing evidence indicates that the pathogenesis of ulcerative colitis (UC) is highly regulated by the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway and its negative feedback regulator, suppressor of cytokine signaling 3 (SOCS3). Therefore, modulating the signaling feedback loop of IL-6/STAT3/SOCS3 may prove to be a novel therapeutic approach for the treatment of UC. Qing Hua Chang Yin (QHCY) is a traditional Chinese formulation that has long been used in clinic for the treatment of UC. We have previously reported that QHCY ameliorates acute intestinal inflammation in vivo and in vitro through the suppression of the nuclear factor-κB (NF-κB) pathway. In the present study, in order to further elucidate the mechanisms responsible for the anti-inflammatory activities of QHCY, we stimulated human intestinal Caco-2 cells with lipopolysaccharide (LPS) to create an in vitro model of an inflamed human intestinal epithelium, and evaluated the effects of QHCY on the IL-6/STAT3/SOCS3 signaling network in inflamed Caco-2 cells. The levels of IL-6 were measured by ELISA and the levels of STAT3 and SOCS3 were measured by western blot analysis. We found that QHCY significantly inhibited the LPS-induced secretion of pro-inflammatory IL-6 in the Caco-2 cells in a dose-dependent manner. Moreover, QHCY profoundly suppressed the LPS-induced phosphorylation of Janus-activated kinase 1 (JAK1), JAK2 and STAT3. Furthermore, treatment with QHCY markedly augmented the expression of SOCS3. Taken together, the findings of the present study suggest that the modulation of the IL-6/STAT3/SOCS3 signaling network may be one of the mechanisms through which QHCY exerts its anti-inflammatory effects.

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…Furthermore, QHCY (1.4 mg/mL) treatment attenuates the LPS-induced phosphorylation of JAK1 and JAK2 in differentiated Caco-2 cells, which is in accordance with the reduced phosphorylation state of STAT3. It indicates that QHCY treatment inhibits the phosphorylation of STAT3, possibly through the inactivation of JAK1 and JAK2 in LPS-induced inflammatory responses [144].…”

“…Attenuate the levels of inflammatory markers via suppression of the PI3K/AKT/mTOR signaling pathway, in part through up-regulation of miRNA-126 [125] Astringent medicine Qing Hua Chang Yin DSS-induced colon tissue Inhibit the expression of the phosphorylation of IκB [143] Caco-2 cells Suppress the phosphorylation of JAK1, JAK2 and STAT3 [144] QingBai decoction DSS-induced colon tissue Strengthen mucus barrier through inhibiting p-ERK and Notch signaling [145] Chang-An-Shuan…”

Therapeutic effects and mechanisms of plant-derived natural compounds against intestinal mucositis

“…Enduring STAT3 activation is deemed to accelerate chronic inflammation, which elevates susceptibility of healthy cells to carcinogenesis ( Lei et al, 2021 ). When the enteric mucosa is activated, increased IL-6 can stimulate the phosphorylation of STAT3 and feedback to NF-κB ( Ke et al, 2015 ). In the present review, patchouli alcohol, thymol, puerarin, and forsythiaside A remarkably restrained intestinal mucositis in animal or cell models, which was intimately associated with the suppression of TLR2/MyD88/NF-κB, IL-6/STAT3, TGF-β/MAPK, and NLRP3 signaling pathways.…”

Huangkui Lianchang Decoction Ameliorates DSS-Induced Ulcerative Colitis in Mice by Inhibiting the NF-kappaB Signaling Pathway

“…Traditional Chinese medicine has a long history and has been widely used in Asia. An increasing number of animal experiments have confirmed that Chinese medicine monomers or compounds have good anti-inflammatory effects [14, 22, 45–47]. However, the aim of this research is to treat patients, and drugs are ultimately used on people.…”