Immunomodulatory effects of fermented<i>Platycodon grandiflorum</i>extract through NF-κB signaling in RAW 264.7 cells

Park, Eun-Jung; Lee, Hae‐Jeung

doi:10.4162/nrp.2020.14.5.453

Cited by 21 publications

(15 citation statements)

References 29 publications

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“…Overall, the TLR4/MyD88/NF-κB signaling pathway has attracted widespread attention in the scientific community due to their implant-related innate immune recognition and immuno-modulation [ 50 , 51 ]. In this study, it was found that LPS activated NF-κB signaling pathway and induced inflammation, as the previous study also found [ 52 ]. Meanwhile, in response to cell exposure of the prepared CH and modifiers, the cells showed regulated expression in these assessed proteins involved in the NF-κB signaling pathway, together with an inhibited nuclear translocation of p65 protein.…”

Section: Discussionsupporting

confidence: 82%

Impact of the Plastein Reaction of Casein Hydrolysates in the Presence of Exogenous Amino Acids on Their Anti-Inflammatory Effect in the Lipopolysaccharide-Stimulated Macrophages

Shi

Zhao

2022

Foods

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In this study, papain-generated casein hydrolysates (CH) with a degree of hydrolysis of 13.7% were subjected to a papain-mediated plastein reaction in the absence or presence of one of the exogenous amino acids—Gly, Pro, and Hyp—to prepare four plastein modifiers, or mixed with one of three amino acids to prepare three mixtures. The assay results confirmed that the reaction reduced free NH2 for the modifiers and caused amino acid incorporation and peptide condensation. When RAW264.7 macrophages were exposed to the CH, modifiers, and mixtures, these samples promoted macrophage growth and phagocytosis in a dose-dependent manner. In addition, the CH shared similar activity in the cells as the mixtures, while the modifiers (especially the PCH-Hyp prepared with Hyp addition) exerted higher potential than CH, the mixtures, and PCH (the modifier prepared without amino acid addition). The plastein reaction thus enhanced CH bioactivity in the cells. When RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS), the inflammatory cells produced more lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) formation, and caused more four inflammatory mediators (NO, PGE2, TNF-α, and IL-6) and two anti-inflammatory mediators (TGF-β1 and IL-10). However, the PCH-Hyp, PCH, and CH at dose levels of 100 μg/mL could combat against the LPS-induced inflammation. Overall, the PCH-Hyp was more active than the CH and PCH in reducing LDH release, ROS formation, and the secretion of these inflammatory mediators, or in increasing the secretion of the anti-inflammatory mediators. The qPCR and Western blot analysis results further confirmed that these samples had anti-inflammatory effects on the stimulated cells by suppressing the LPS-induced activation of the NF-κB signaling pathway, via regulating the mRNA/miRNA expression of iNOS, IL-6, TNF-α, IL-1β, COX-2, TLR4, IL-10, TGF-β1, miR-181a, miR-30d, miR-155, and miR-148, as well as the protein expression of MyD88, p-IKKα, p-IκBα, p-NF-κB p65, and iNOS, involved in this signaling pathway. In addition, the immunofluorescence assay results revealed that these samples could block the LPS-mediated nuclear translocation of the p65 protein and displayed the same function as the NF-κB inhibitor BAY 11-7082. It was concluded that CH could be endowed with higher anti-inflammatory activity to the macrophages by performing a plastein reaction, particularly that in the presence of exogenous Hyp.

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Section: Discussionsupporting

confidence: 82%

Impact of the Plastein Reaction of Casein Hydrolysates in the Presence of Exogenous Amino Acids on Their Anti-Inflammatory Effect in the Lipopolysaccharide-Stimulated Macrophages

Shi

Zhao

2022

Foods

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“…31 In addition, Park and Lee used Saccharomyces cerevisiae to ferment the PG extract, and the platycodin D content increased by 4 times that of the unfermented group. 32 The difference among these studies might be due to the diversity of microorganisms and fermentation methods.…”

Section: Paper Food and Functionmentioning

confidence: 99%

Platycodon grandiflorum root fermentation broth reduces inflammation in a mouse IBD model through the AMPK/NF-κB/NLRP3 pathway

Wang

et al. 2022

Food Funct.

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“…The results of the present study demonstrated that the protein expression levels of p-NF-κB were significantly increased in TGF-β1-induced MRC-5 cells, which was consistent with previous studies ( 45 , 46 ). Notably, PG or PG-derived components increase AMP-activated protein kinase (AMPK) signaling in numerous types of cell, such as macrophages and lung carcinoma cells, hepatocellular carcinoma cells ( 47 – 49 ). Moreover, AMPK activation relieves the inflammatory response via suppression of NF-κB activation and downregulation of IL-1β ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

Tang

Huang

et al. 2022

Mol Med Rep

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Platyconic acid A (PA), the active component of Platycodi radix-derived saponin, exerts ameliorating effects on liver fibrosis. Platycodon grandiflorum is used to treat lung disease. Therefore, the present study evaluated the effects of PA on pulmonary fibrosis. Transforming growth factor-β1 (TGF-β1) was used to induce MRC-5 cells to establish an in vitro pulmonary fibrosis model. The viability of MRC-5 cells in the presence or absence of TGF-β1 induction was examined using a Cell Counting Kit-8 assay and the results demonstrated that PA markedly decreased viability of TGF-β1-induced MRC-5 cells in a dose-dependent manner. Wound healing analysis, immunofluorescent staining and western blotting were performed to determine the levels of cell migration and expression of α-smooth muscle actin and extracellular matrix (ECM)-associated proteins. The results of the present study demonstrated that PA significantly suppressed the migration and ECM deposition of TGF-β1-induced MRC-5 cells. Furthermore, results obtained from ELISA and western blotting demonstrated that PA exerted suppressive effects on the inflammation of MRC-5 cells following TGF-β1 stimulation. The mRNA and protein expression levels of protein phosphatase Mg2 + /Mn2 + -dependent 1A (PPM1A) before and after transfection were assessed using reverse transcription-quantitative PCR and western blotting and the results demonstrated that the mRNA and protein expression levels of PPM1A were significantly decreased following transfection with small interfering RNA targeting PPM1A. Moreover, following PPM1A knockdown, PA significantly inhibited the proliferation, migration, inflammation and ECM deposition of TGF-β1-induced MRC-5 cells via activation of the SMAD/ β-catenin signaling pathway. In conclusion, PA activated PPM1A to ameliorate TGF-β1-elicited lung fibroblast injury via modulating SMAD/β-catenin signaling.

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Immunomodulatory effects of fermentedPlatycodon grandiflorumextract through NF-κB signaling in RAW 264.7 cells

Cited by 21 publications

References 29 publications

Impact of the Plastein Reaction of Casein Hydrolysates in the Presence of Exogenous Amino Acids on Their Anti-Inflammatory Effect in the Lipopolysaccharide-Stimulated Macrophages

Impact of the Plastein Reaction of Casein Hydrolysates in the Presence of Exogenous Amino Acids on Their Anti-Inflammatory Effect in the Lipopolysaccharide-Stimulated Macrophages

Platycodon grandiflorum root fermentation broth reduces inflammation in a mouse IBD model through the AMPK/NF-κB/NLRP3 pathway

Platyconic acid A‑induced PPM1A upregulation inhibits the proliferation, inflammation and extracellular matrix deposition of TGF‑β1‑induced lung fibroblasts

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