The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its
in vivo
potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on
Gamma,
Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against
Gamma,
Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with
Gamma
and Delta variants substantiated
in vivo
potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against
Gamma
and Delta variants infection, hinting that CT-P59 has therapeutic
potential
for patients infected with
Gamma,
Delta and its associated variants.
Scope
Punicalagin (PCG) is one of the most abundant phytochemicals found in pomegranates. The effects and mechanistic action of PCG on obesity and obesity‐induced inflammatory and oxidant responses are investigated in vitro and in vivo.
Methods and results
The effect of PCG on adipogenesis is examined using Oil red O staining. The effects and mechanism of action of PCG on inflammatory responses are determined in adipocyte‐conditioned medium (ACM)‐cultured macrophages, a cell‐to‐cell contact system, and a transwell system. The effects of PCG on obesity and obesity‐induced inflammatory/oxidant responses are examined in high‐fat diet (HFD)‐fed mice. PCG effectively suppresses lipid accumulation in adipocytes and adipocyte‐induced inflammatory responses in adipocyte‐macrophage co‐culture systems. Small interfering RNA (siRNA) transfection indicates that the PCG‐mediated anti‐inflammatory effect is exerted via the nuclear factor erythroid 2‐related factor 2/Kelch‐like ECH‐associated protein 1(Nrf2/Keap1) pathway. PCG administration results in a significant reduction in body and white adipose tissue (WAT) weights. PCG favorably regulates pro‐ and anti‐inflammatory cytokines, downregulating nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). Immunohistochemical (IHC) analysis demonstrates that PCG differentially modulates the distribution of complement component 3 receptor 4 subunit (CD11c) and cluster of differentiation 206 (CD206). PCG regulates the level of antioxidant and oxidant molecules by activating Nrf2/Keap1 signaling.
Conclusions
PCG ameliorates obesity and obesity‐induced inflammatory responses via activation of Nrf2/Keap1 signaling, suggesting that PCG has potential as an oral agent to control obesity‐mediated diseases.
The aim of this study was to investigate the effect of brassinin (BR), a phytoalexin found in plants belonging to the Brassicaceae family, on the obesity‐induced inflammatory response and its molecular mechanism in co‐culture of 3T3‐L1 adipocytes and RAW264.7 macrophages. BR effectively suppressed lipid accumulation by down‐regulating the expression of adipogenic factors, which in turn, were regulated by early adipogenic factors such as CCAAT‐enhancer‐binding protein‐β and Kruppel‐like factor 2. Production of inflammatory cytokines and reactive oxygen species, induced by adipocyte‐conditioned medium, was significantly decreased in BR‐treated cells. This effect of BR was more prominent in contact co‐culture of adipocytes and macrophages with a 90% and 34% reduction in IL‐6 and MCP‐1 levels, respectively. BR also restored adiponectin expression, which was significantly reduced by culturing adipocytes in macrophage‐conditioned medium. In the transwell system, BR increased the protein levels of nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and its target molecule, hemoxygenase‐1 (HO‐1), by 55%–93% and 45%–48%, respectively, and also increased Nrf2 translocation into the nucleus. However, knockdown of Nrf2 or HO‐1 in RAW264.7 cells restored this BR‐mediated inhibition of IL‐6 and MCP‐1 production. These results indicated that BR inhibited obesity‐induced inflammation via the Nrf2‐HO‐1 pathway.
The aim of this study was to investigate the effects of dibenzoylmethane (1,3-diphenyl-1,3-propanedione, DBM) from licorice roots on lipid accumulation and reactive oxygen species (ROS) production in 3T3-L1 cells. DBM effectively inhibited lipid accumulation during adipogenesis, and its inhibitory effect was shown to be due to the down-regulation of adipogenic factors such as CCAAT-enhancer-binding protein-α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid-binding protein 4 (FABP4). DBM was observed to exert its inhibitory effect on lipid accumulation in the early adipogenic stage (days 0-2) by regulating early adipogenic factors including CCAAT-enhancer-binding protein-β (C/EBPβ) and Krueppel-like factor (KLF) 2. DBM significantly increased the translocation of nuclear factor (erythroid-derived 2)-like 2(Nrf2) into the nucleus, promoting the protein expression of its target gene, heme oxygenase-1 (HO-1). DBM significantly suppressed the insulin-mediated activation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt), which are components of insulin signaling. In addition, intracellular ROS production was effectively reduced by DBM treatment, which upregulated antioxidant genes such as glutathione peroxidase (Gpx), catalase (CAT), and superoxide dismutase 1 (SOD1). Furthermore, DBM significantly regulated the expression of the adipokines, resistin and adiponectin. This DBM-mediated regulation of lipid accumulation, ROS production, and adipokine production was shown to be involved in the regulation of the Nrf2 and insulin signaling.
This study was aimed to investigate the effect of red ginseng extract (RGE) on monocyte to macrophage differentiation and inflammatory signalings in THP-1 human monocytes. In HPLC analysis, RGE contained saponin level of 516 lg/mg (extract) with 14 ginsenosides. RGE effectively suppressed the monocyte-to-macrophage differentiation induced by phorbol 12-myristate 13-acetated (PMA) by inhibiting the THP-1 cell adhesion. This result is evidenced by the down-regulation of cluster of differentiation molecule b (CD11b) and CD36. RGE significantly reduced translocation of nuclear factor kappalight-chain-enhancer of activated B cells (NF-jB) (78%), while cytosolic NF-jB was increased (53%), compared with LPS group. In addition, RGE significantly increased the protein abundance of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and its target protein, hemoxygenase-1 (HO-1), but, Kelch-like ECH-associated protein 1 (KEAP1), a negative regulator of Nrf2, was greatly decreased by RGE. Furthermore, RGE effectively mediated the regulation of Nrf2 level in nucleus and cytoplasm of THP-1.
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