J Biomed Transl Res.  2023 Jun;24(2):23-40. 10.12729/jbtr.2023.24.2.23.

Anti-inflammatory and immune enhancing activities of PB203 in mouse macrophage RAW264.7 cells

• Ho SH
• Kim D
• Park SJ

• KMID: 2549238
• DOI: http://doi.org/10.12729/jbtr.2023.24.2.23

Abstract

Macrophages secrete various cytokines and inflammatory mediators, resulting in playing critical roles in inflammation and immunity. In this study, we investigated anti-inflammatory and immune enhancing properties of PB203, which is a water-soluble extract powder from the fruit of Actinidia polygama, in macrophages. A. polygama is a medicinal plant tradition-ally known to treat abdominal pain, stroke and rheumatoid arthritis. However, the molecular mechanism for the immune modulation of PB203 is still unclear. Therefore, we assessed the effects of PB203 on the lipopolysaccharide (LPS)-induced inflammation and immune activa-tion, and elucidated its action mechanism in mouse macrophage, RAW264.7 cells. PB203 significantly suppressed not only the levels of nitric oxide (NO), prostaglandin E₂ , tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), but also the mRNA expression of inducible NO synthase, cyclooxygenase-2, TNF-α and IL-1β in LPS-stimulated RAW264.7 cells. We also found that these anti-inflammatory activities of PB203 were mediated through the inhibi-tion of toll-like receptor 4 and nuclear factor kappa B (NF-κB) induced by LPS. On the other hand, in normal macrophages, PB203 dose-dependently elevated the gene expression of immunomodulators including granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1 and TNF-α in a statistically sig-nificant manner. The expression of IL-10, IL-1β, IL-6, and interferon-γ were also remarkably upregulated by the treatment of 500 μg/mL PB203. In addition, PB203-mediated produc-tion of NO and TNF-α was attenuated by NF-κB inhibition in RAW264.7 cells. Interestingly, PB203 promoted the production of nuclear factor erythroid-2-related factor 2, resulting in the increased level of heme oxygenase-1, which is a representative antioxidant enzyme, in both LPS-stimulated and normal RAW264.7 cells. Taken all together, these results suggest that PB203 may have great potential as the candidate of anti-inflammatory agent for improving inflammatory diseases or immune enhancing agent for preventing infectious diseases.

Keyword

Actinidia polygama extract (PB203); macrophages; immunomodulator; nuclear factor kappa B (NF-κB); heme oxygenase-1 (HO-1)