The Attenuation of Chronic Ulcerative Colitis by (R)-salbutamol in Repeated DSS-Induced Mice

Abstract

Racemic salbutamol ((RS)-sal), which consist of the same amount of (R)-sal and (S)-sal, has been used for asthma and COPD due to its bronchodilation effect. However, the effect of (R)-sal on repeated dextran sulfate sodium (DSS)-induced chronic colitis has not yet been investigated. In this study evaluated the potential effect of (R)-, (S)-, and (RS)-sal in mice with repeated DSS-induced chronic colitis and investigated the underlying mechanisms. Here, we verified that chronic colitis was significantly attenuated by (R)-sal, which was evidenced by notably mitigated body weight loss, disease activity index (DAI), splenomegaly, colonic lengths shortening, and histopathological scores. (R)-sal treatment noticeably diminished the levels of inflammatory cytokines (such as TNF-α, IL-6, IL-1β, and IFN-γ). Notably, the efficacy of (R)-sal was better than that of (RS)-sal. Further research revealed that (R)-sal mitigated colonic CD4 leukocyte infiltration, decreased NF-κB signaling pathway activation, improved the Nrf-2/HO-1 signaling pathway, and increased the expression of ZO-1 and occludin. In addition, (R)-sal suppressed the levels of TGF-β1, α-SMA, and collagen in mice with chronic colitis. Furthermore, the 16S rDNA sequences analyzed of the intestinal microbiome revealed that (R)-sal could mitigate the intestinal microbiome structure and made it more similar to the control group, which mainly by relieving the relative abundance of pathogens (such as Bacteroides) and increasing the relative abundance of probiotics (such as Akkermansia). Therefore, (R)-sal ameliorates repeated DSS-induced chronic colitis in mice by improving inflammation, suppressing oxidative stress, mitigating intestinal barrier function, relieving intestinal fibrosis, and regulating the intestinal microbiome community. These results indicate that (R)-sal maybe a novel treatment alternative for chronic colitis.

Yiyi Fuzi Baijiang Powder Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Rats via Inhibiting the TLR4/NF-κB/NLRP3 Inflammasome Signaling Pathway to Repair the Intestinal Epithelial Barrier, and Modulating Intestinal Microbiota

“…It has been demonstrated that IL-1 β and TNF- α induced increase in intestinal TJ permeability which was regulated by the activation of NF- κ B [ 55 , 56 ]. Significant downregulation of ZO-1, occludin, and claudin-1 has been observed in UC patients and UC mice [ 57 , 58 ]. In this study, we also found that the expressions of ZO-1, occludin, and claudin-1 in the colon tissue of UC rats were significantly decreased, while their expressions were significantly increased after YFBP treatment.…”

Therapeutic effects of sulforaphane in ulcerative colitis: effect on antioxidant activity, mitochondrial biogenesis and DNA polymerization

“…One of the elements of the antioxidant system in the body is Nrf2. When the body suffers from oxidative stress, Nrf2 is activated and translocated inside the nucleus, leading to the expression of downstream antioxidant enzymes [ 32 ]. In addition, the overexpression of Nrf2 was previously reported to improve UC [ 33 ].…”

Curative effects of fucoidan on acetic acid induced ulcerative colitis in rats via modulating aryl hydrocarbon receptor and phosphodiesterase-4

“…Nrf2 is a remarkable antioxidant transcription factor. Under oxidative stress, Nrf2 is activated and transfer inside nucleus, and elevated the expression of downstream antioxidant enzymes making Nrf2 as a critical player in activity of antioxidant system [ 32 ]. Overexpression of Nrf2 was reported to improve UC [ 33 ].…”