Bilobalide Alleviated Dextran Sulfate Sodium-Induced Experimental Colitis by Inhibiting M1 Macrophage Polarization Through the NF-κB Signaling Pathway

Abstract

Bilobalide, a unique Ginkgo biloba constituent has attracted significant interest as a novel therapeutic option for neuronal protection. However, there is paucity of data on its effect on colitis. This work sought to evaluate the effect of bilobalide on macrophage polarization in vitro and dextran sulfate sodium (DSS) induced colitis in vivo. Through the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/PI assay, it was shown that bilobalide has no significant toxicity on macrophage. Lipopolysaccharide (LPS) and interferon-gamma (IFN-g) induced macrophage activation and polarization were significantly suppressed by bilobalide as indicated by reduced expression of cytokine, major histocompatibility complex II (MHC-II), and CD11c. Pertinently, the signaling pathway study showed that the phosphorylation of p65 and its nuclear translocation were decreased while STAT1 was not affected. In DSS-treated mice, administration (i.g) of three doses of bilobalide na\mely 1.25 mg/kg (low dose group), 2.5 mg/kg (medium dose group), and 5 mg/kg (high dose group) was performed daily starting from day 1 to day 10. Medium and high dose bilobalide markedly reduced the inflammation of colitis proved via elevation of bodyweight, decrement in disease activity index (DAI), alleviation of colon damage as well as reduction in activity of colon tissue myeloperoxidase activity. In accordance with the in vitro results, the levels of inflammatory cytokines such as interleukin 6 (IL-6), IL-1b, and tumor necrosis factor (TNF-a) in serum as well as messenger RNA (mRNA) expression in colon were obviously reduced in the bilobalide treated groups. Also, factor nuclear factor kappa B (NF-kB) signaling pathway was decreased significantly by bilobalide treatment. Collectively, these results indicated that administration of bilobalide improved experimental colitis via inhibition of M1 macrophage polarization through the NF-kB signaling pathway. Thus, bilobalide could act as a potential drug for the treatment of inflammatory bowel disease (IBD) in the not-too-distant future.

Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota

“…However, the underlying mechanism of how lactic acid exerts its anti-inflammatory activities in colitis remains to be explored. Increasing evidence suggested that targeting macrophage polarization benefits UC treatment (33)(34)(35). The different polarization states of macrophages show diverse immunological responses.…”

“…Increasing evidence suggested that targeting macrophage polarization benefits UC treatment ( 33 – 35 ). The different polarization states of macrophages show diverse immunological responses.…”

Bilobalide Exerts Anti-Inflammatory Effects on Chondrocytes Through the AMPK/SIRT1/mTOR Pathway to Attenuate ACLT-Induced Post-Traumatic Osteoarthritis in Rats

“…Rats in the 5 mg/kg + Bilobalide and 10 mg/kg + Bilobalide groups received oral bilobalide daily for 6 weeks. The bilobalide dosage was based on previous studies ( Heng Zhang et al, 2020 ; Zhao et al, 2021 ). After 6 weeks of treatment, the rats in each group were euthanized by intraperitoneal injection of a lethal dose of ether, and their knee joints and blood samples were taken.…”

Downregulation of Macrophage-Specific Act-1 Intensifies Periodontitis and Alveolar Bone Loss Possibly via TNF/NF-κB Signaling

“…KEGG analysis revealed the activation of TNF/NF-κB signaling in LPS-treated macrophages from anti-Act1 mice. Shreds of literature had reported that the activated TNF/NF-κB signaling enhances M1-macrophage polarization ( Liu et al, 2017 ; Lu et al, 2020 ; Zhang H. et al, 2020 ). Inflammation triggers M1 macrophage polarization and M1 macrophages further release proinflammatory cytokines thereby amplifying inflammation in a vicious fashion in the periodontitis milieu.…”