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.
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