Moronic acid improves intestinal inflammation in mice with chronic colitis by inhibiting intestinal macrophage polarization

Abstract

This study focuses on exploring the role and mechanism of moronic acid (MOA), a small triterpenoid molecule, against inflammatory bowel disease (IBD). Intestinal macrophages were cultured in vitro, and their M1 polarization was induced by lipopolysaccharide (LPS) and interferon gamma (IFN‐γ). After intervention with MOA, the proportion of M1 macrophages was detected, and the levels of inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β) were examined by ELISA. IFA staining was performed to determine the P50 and CD86 expressions, while DCFH‐DA was used to determine the reactive oxygen species (ROS) level, as well as the p‐P50 and NLRP3 protein levels. Additionally, we also used N‐acetylcysteine, a ROS inhibitor, to further explore the association between MOA and ROS‐NF‐κB signaling. In murine experimentation, colitis was induced in mice with DSS. After MOA intervention, we assessed the mucosal barrier damage, tissue ROS, as well as protein and inflammatory cytokine levels. MOA could inhibit the M1 polarization of intestinal macrophages, suppress the expressions of inflammatory cytokines, and reduce the level of ROS‐NF‐κB‐NLRP3 signaling. After inhibiting ROS through NAC treatment, the effect of MOA was evidently weakened. Clearly, MOA exerted its activity via ROS. In the murine model, MOA could lower the CD86 level in the intestinal tissues, inhibit the M1 polarization of macrophages, and reduce the tissue levels of inflammatory cytokines. This study finds that MOA can regulate ROS‐NF‐κB‐NLRP3 signaling by inhibiting ROS, thereby suppressing the M1 polarization of intestinal macrophages, which plays a protective role in IBD.

Chemical and cytotoxicity profiles of 11 pink pepper (Schinus spp.) samples via non-targeted hyphenated high-performance thin-layer chromatography

“…Although not yet fully understood, several studies have demonstrated that pentacyclic triterpenes can induce cell death by apoptosis (Chudzik et al, 2015 ; Coricovac et al, 2021 ; Hodoň et al, 2022 ; Mioc et al, 2022 ; Oprean et al, 2018 ; Ren & Kinghorn, 2019 ) or autophagy (El-Baba et al, 2021 ; Fogde et al, 2022 ; Wang et al, 2022b ). Also, moronic acid was shown to have cytotoxic properties (Rios et al, 2001 ) as well as other beneficial effects such as anti-viral (Chang et al, 2010 ; Yu et al, 2006 ), anti-inflammatory (Ruan & Zha, 2022 ) and anti-diabetic activity (Cerón-Romero et al, 2016 ; Estrada-Soto et al, 2022 ; Ramírez-Espinosa et al, 2013 ), indicating the potential of triterpenoic acids and the necessity of further studies for the investigation of their biological properties.…”

Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review

“…In an in vitro and in vivo study using IFN-γ-stimulated intestinal macrophages and DSS-induced C57BL/6 mice model of colitis, respectively, Ruan and Zha [ 35 ] assessed the roles of moronic acid against a triterpenoid richly found in Pistacia chinensis , against NLRP3 activation during IBD. The results showed that with treatment, the cells expressed decreased TNF-α, IL-1β, IL-6, ROS, CD11, NF-kB (P50), NLRP3, p-P50, and M1 macrophage polarization.…”