Atractylenolide III Ameliorates TNBS‐Induced Intestinal Inflammation in Mice by Reducing Oxidative Stress and Regulating Intestinal Flora

Abstract

The present study aimed to explore the therapeutic effects of the main active ingredients of Atractylodes macrocephala on the 2,4,6‐trinitrobenzenesulfonic acid (TNBS)‐induced mouse colitis model. TNBS‐induced colitis was established in mice, which were treated with 8‐β‐Hydroxyasterolide (Atractylenolide III) for 14 days. The body weight of the mice in the middle and high dose groups of Atractylenolide III was increased compared with that of the model group. The disease activity index score was significantly reduced. The activity levels of myeloperoxidase were significantly decreased following increase in the dosage of Atractylenolide III, as determined by histological analysis. Moreover, Atractylenolide III downregulated the expression levels of the inflammatory factors interleukin‐1β and tumor necrosis factor‐α, and greatly suppressed the levels of the pro‐oxidant markers, reactive oxygen species and malondialdehyde, while enhancing the expression levels of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. The protein expression levels of formyl peptide receptor 1 (FPR1) and nuclear respiratory factor 2 (Nrf2) were upregulated in the colonic tissues of TNBS‐treated mice. This effect was effectively reversed by Atractylenolide III treatment. In vivo studies indicated that TNBS alone induced a decrease in the abundance of lactobacilli and in the biodiversity of the colon. In conclusion, the present study suggested that Atractylenolide III attenuated TNBS‐induced acute colitis by regulating oxidative stress via the FPR1 and Nrf2 pathways and by affecting the development of intestinal flora.

Mechanisms of Atractylodes macrocephala Koidz. on therapy to diarrheal disease: A systematical review and meta-analysis of preclinical evidence

“…These reactive oxygen species can damage intestinal mucosal cells and related structures, promote inflammation, and worsen diarrhea [31]. AMK could improve diarrhea aggravated by oxidative stress factors such as MDA, GSH and SOD by regulating oxidative stress through the FPR1 and Nrf2 pathways [20] and enhancing antioxidative activities through HO-1 induction [25]. ( 4) Intestinal flora regulation: A homeostatic intestinal flora promotes nutrient absorption, resists pathogenic microorganisms, and maintains immune balance [32].…”

“…Finally, 23 papers were included for meta-analysis. [16,[17][18][19][20][21][22][23][24][25][26]. The results based on the above search strategy are shown in Fig.…”

Herbal Formula Shenling Baizhu San for Chronic Diarrhea in Adults: A Systematic Review and Meta-analysis

“… 38 Atractylenolide III helps attenuate inflammation associated with 2,4,6-trinitrobenzenesulfonic acid-induced colitis. 39 In addition, Lv et al 16 , 40 reported that SBS can enhance the richness and diversity of intestinal microbiota, increase acid metabolism, and reduce diarrhea-related intestinal, immune and infectious diseases.…”

Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review

“…Ren et al [ 64 ] carried out an in vivo study to investigate the therapeutic effects of various actives of Atractylodes macrocephala , including Atractylenolide III, in the TNBS-induced mice model of colitis. With TNBS, the animals presented increased DAI, intestinal inflammation, weight loss, colon shortening, infiltration of inflammatory cells, OS, submucosal necrosis, distortion of the mucosal structure, and ulcers, along with increased MPO, IL-1β, TNF-α, MDA, Formyl peptide receptor 1 (FPR1), NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase 1 (NOX1), and phosphorylated Nrf2, as well as reduced levels of Nrf2 activation and signaling, SOD, GSH-Px, and CAT.…”