A hydroxyethyl derivative of chrysin exhibits anti-inflammatory activity in dendritic cells and protective effects against dextran sodium salt-induced colitis in mice

Song, Ha Yeon; Kim, Woo Sik; Kim, Jin Man; Bak, Dong Ho; Han, Jeong Moo; Lim, Seung Taik; Byun, Eui Baek

doi:10.1016/j.intimp.2019.105958

Cited by 21 publications

(22 citation statements)

References 45 publications

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“…Additionally, future studies using the Tollip-knockout mouse model as an inflammatory disease animal model should be performed. Specifically, we observed that CM1 had great protective efficacy against DSS-induced colitis in our previous study [23], however, it is yet unclear whether protective effects of CM1 are due to Tollip expression. Based on the present findings, further studies on whether inhibitory effects of CM1 in DSS-induced colitis are due to Tollip expression and these anti-inflammatory effects of CM1 are abolished in Tollip-knockout mice are recommended for in-depth understanding of mechanistic role of CM1 as a candidate for colitis therapy.…”

Section: Discussionmentioning

confidence: 79%

“…CM1-a new chrysin derivative produced using irradiation technology-exerts greater anti-inflammatory effect than the parent chrysin, and it is considered an attractive thera-peutic candidate for inflammatory bowel disease [23]. In this study, we investigated the mechanism underlying the anti-inflammatory effect of CM1 that is known to act as an important regulator of the early phase of inflammation in activated macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…Chrysin (C 15 H 10 O 4 ) is one of the most commonly distributed flavonoids in vegetable and fruit plants, and has been widely studied for several decades owing to its physiological properties, including anti-inflammatory, antioxidative, anticancer, and antihypertensive effects [21,22]. In our previous study, we identified a new chrysin derivative (CM1) which exhibited greater anti-inflammatory activity in dendritic cells than chrysin and exerted protective effects in a mouse colitis model [23]. We had previously identified that CM1 is a hydroxyethyl derivative of chrysin that is produced by ionizing radiation from chrysin methanolic solution (Figure 1a) [24].…”

Section: Introductionmentioning

confidence: 99%

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Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

et al. 2021

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Although our previous study revealed that gamma-irradiated chrysin enhanced anti-inflammatory activity compared to intact chrysin, it remains unclear whether the chrysin derivative, CM1, produced by gamma irradiation, negatively regulates toll-like receptor (TLR) signaling. In this study, we investigated the molecular basis for the downregulation of TLR4 signal transduction by CM1 in macrophages. We initially determined the appropriate concentration of CM1 and found no cellular toxicity below 2 μg/mL. Upon stimulation with lipopolysaccharide (LPS), CM1 modulated LPS-stimulated inflammatory action by suppressing the release of proinflammatory mediators (cytokines TNF-α and IL-6) and nitric oxide (NO) and downregulated the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, CM1 markedly elevated the expression of the TLR negative regulator toll-interacting protein (Tollip) in dose- and time-dependent manners. LPS-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II), proinflammatory cytokines (TNF-α and IL-6), COX-2, and iNOS-mediated NO were inhibited by CM1; these effects were prevented by the knockdown of Tollip expression. Additionally, CM1 did not affect the downregulation of LPS-induced expression of MAPKs and NF-κB signaling in Tollip-downregulated cells. These findings provide insight into effective therapeutic intervention of inflammatory disease by increasing the understanding of the negative regulation of TLR signaling induced by CM1.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

et al. 2021

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“…To evaluate the effects of BBPE on DC maturation, cells were stained with specifically labeled fluorescent-conjugated mAbs for 20 min at 25 °C to detect expression of CD80, CD86, MHC class I, and MHC class II in CD11c-positive cells, as previously described [ 51 ]. The expression of surface molecules was detected by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

Bombyx batryticatus Protein-Rich Extract Induces Maturation of Dendritic Cells and Th1 Polarization: A Potential Immunological Adjuvant for Cancer Vaccine

et al. 2021

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Bombyx batryticatus, a protein-rich edible insect, is widely used as a traditional medicine in China. Several pharmacological studies have reported the anticancer activity of B. batryticatus extracts; however, the capacity of B. batryticatus extracts as immune potentiators for increasing the efficacy of cancer immunotherapy is still unverified. In the present study, we investigated the immunomodulatory role of B. batryticatus protein-rich extract (BBPE) in bone marrow-derived dendritic cells (BMDCs) and DC vaccine-immunized mice. BBPE-treated BMDCs displayed characteristics of mature immune status, including high expression of surface molecules (CD80, CD86, major histocompatibility complex (MHC)-I, and MHC-II), increased production of proinflammatory cytokines (tumor necrosis factor-α and interleukin-12p70), enhanced antigen-presenting ability, and reduced endocytosis. BBPE-treated BMDCs promoted naive CD4+ and CD8+ T-cell proliferation and activation. Furthermore, BBPE/ovalbumin (OVA)-pulsed DC-immunized mice showed a stronger OVA-specific multifunctional T-cell response in CD4+ and CD8+ T cells and a stronger Th1 antibody response than mice receiving differently treated DCs, which showed the enhanced protective effect against tumor growth in E.G7 tumor-bearing mice. Our data demonstrate that BBPE can be a novel immune potentiator for a DC-based vaccine in anticancer therapy.

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“…Images (× 100 magni cation) were taken from each sample, and histopathological evaluation of the entire section was performed in a blinded manner. The injury of liver and intestine was scored using the modi ed histopathologic score described previously [17][18][19]. These criteria for histological score were shown in Table 1.…”

Section: Histologymentioning

confidence: 99%

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

Jiang¹,

Xia²,

Yang³

et al. 2020

Preprint

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Background Endotoxemia based on liver failure has been reported to be related to the worse clinical outcomes, but its management remains unsatisfactory. The addition of bone marrow mesenchymal stem cells (BMSCs) could promote the recovery of liver function and increase the survival with the liver failure. However, little is known about the potential of cell therapy with endotoxemia based on liver failure. Methods BMSCs were isolated from rats, and their morphology, differentiation potential, surface markers, and cell cycle were assayed. Thioacetamide-induced acute liver failure rats were randomized to groups with or without BMSCs. During the experiment, survival was recorded. Diamine oxidase (DAO), endotoxin, interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-α) and tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), histology, and western blot. Bromodeoxynucleoside uracil (BrdU) incorporation assay was performed to observe the migration of BMSCs. The intestinal epithelial differentiation of BMSCs was induced by co culture with small intestinal crypt in rats (IEC-6). Immunofluorescence was used to analyze the expression of intestinal endothelial markers. Western blot analysis was further performed to examine the differentiation effect when inhibiting the phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Results BrdU-traced BMSCs targeted migrate to intestinal injury sites. Mortality was significantly decreased and intestinal damage was repaired following BMSCs transplantation. Proteomics revealed higher expression of DAO, endotoxin, IL-6 and TNF-α in the model animals, but these changes were reversed after BMSCs transplantation. In the in vitro study, the intestinal epithelial differentiation of BMSCs was exhibited following co-culture. Moreover, the blocking of PI3K/AKT/mTOR signal pathway inhibited this differentiation. Conclusions These evidences indicate that BMSCs eliminate endotoxemia and reduce mortality in the animal model of acute liver failure by reducing intestine damage.

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A hydroxyethyl derivative of chrysin exhibits anti-inflammatory activity in dendritic cells and protective effects against dextran sodium salt-induced colitis in mice

Cited by 21 publications

References 45 publications

Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

Bombyx batryticatus Protein-Rich Extract Induces Maturation of Dendritic Cells and Th1 Polarization: A Potential Immunological Adjuvant for Cancer Vaccine

Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

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