Protective effects of Amauroderma rugosum on dextran sulfate sodium-induced ulcerative colitis through the regulation of macrophage polarization and suppression of oxidative stress - 16/06/24
, Jinming Zhang b, ⁎ , George Pak-Heng Leung c, ⁎ Abstract |
Background |
Amauroderma rugosum (AR) is a medicinal mushroom commonly used to treat inflammation, gastric disorders, epilepsy, and cancers due to its remarkable anti-inflammatory and anti-oxidative properties. This study was designed to evaluate the pharmacological effects of AR and its underlying mechanism of action against ulcerative colitis (UC) in vitro and in vivo.
Methods |
A UC mouse model was established by administration of dextran sulfate sodium (DSS). AR extract was administered intragastrically to mice for 7 days. At the end of the experiment, histopathology, macrophage phenotype, oxidative stress, and inflammatory status were examined in vivo. Furthermore, RAW 264.7, THP-1, and Caco-2 cells were used to elucidate the mechanism of action of AR in vitro.
Results |
AR extract (0.5–2 mg/mL) significantly suppressed lipopolysaccharide (LPS) and interferon-gamma (IFN-γ)-induced M1 macrophage (pro-inflammatory) polarization in both RAW 264.7 and THP-1 cells. LPS-induced pro-inflammatory mediators (nitric oxide, TNF-α, IL-1β, MCP-1, and IL-6) were reduced by AR extract in a concentration-dependent manner. Similarly, AR extract downregulated MAPK signaling activity in LPS-stimulated RAW 264.7 cells. AR extract elicited a concentration-dependent increase in the mRNA expression of M2 (anti-inflammatory) phenotype markers (CD206, Arg-1, Fizz-1, and Ym-1) in RAW 264.7 cells. Moreover, AR extract suppressed DSS-induced ROS generation and mitochondrial dysfunction in Caco-2 cells. The in vivo experiment revealed that AR extract (200 mg/kg) increased colon length compared to the DSS-treated group. In addition, disease activity index, spleen ratio, body weight, oxidative stress, and colonic inflammation were markedly improved by AR treatment in DSS-induced UC mice. Finally, AR suppressed M1 and promoted M2 macrophage polarization in UC mice.
Conclusion |
The AR extract protected against DSS-induced UC by regulating macrophage polarization and suppressing oxidative stress. These valuable findings suggest that adequate intake of AR can prevent and/or treat UC.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | AR prevents DSS-induced UC. |
• | AR regulates macrophage polarization. |
• | AR inhibits oxidative stress in UC. |
Abbreviations : 6-OHDA, AR, Arg-1, CAT, DSS, DAI, DHE, ERK, FFAR4, GO, GSH, H&E, HIF-1α, IFN-γ, IL, INOS, JNK, KEGG, LPS, MAPK, MCP-1, MDA, MTORC, NO, NLPR3, PAS, PPARγ, PPI, ROS, SOD, STAT3, TAMs, TNF-α, UC
Keywords : Amauroderma rugosum, Ulcerative colitis, Macrophage polarization, oxidative stress
Plan
Vol 176
Article 116901- juillet 2024 Retour au numéro
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