Tumor necrosis factor (TNF-α) is a key regulator of the inflammatory and tissue destruc-tive pathways in rheumatoid arthritis (RA). The clinical success of anti-TNF-α and an-ti-IL-17 biologics has validated the conc...Tumor necrosis factor (TNF-α) is a key regulator of the inflammatory and tissue destruc-tive pathways in rheumatoid arthritis (RA). The clinical success of anti-TNF-α and an-ti-IL-17 biologics has validated the concept that cytokine blockade is beneficial in RA. However, as these drugs are parenterally administered, our efforts are directed at identifying a novel orally active TNF-α inhibitor with a therapeutic profile similar to that of biologics. Since plants are natural immunomodulators, we explored the immunomodulatory potential of Sphaeranthus indicus extract. In our studies, the extract dose-dependently inhibited the release of cytokines in stimulated human peripheral blood mononuclear cells (hPBMCs), and their spontaneous release in synovial cells derived from patients suffering from RA. TNF-α and IFN-γ induced release of p40 subunit of IL-12/ IL-23, and p19 subunit of IL-23 in differentiated THP-1 cells is potently blocked. The expression of endothelial cell adhesion molecules in TNF-α-stimulated HUVECs was also potently inhibited. The oral treatment significantly and dose-dependently reduced LPS-induced TNF-α and IL-1β production in mice. Disease regression was seen in collagen-induced arthritis in DBA/1J mice, which was validated along with radiological and histopathological evaluation. Therefore, the extract of Sphaeranthus indicus could be used in the management of inflammatory conditions.展开更多
文摘Tumor necrosis factor (TNF-α) is a key regulator of the inflammatory and tissue destruc-tive pathways in rheumatoid arthritis (RA). The clinical success of anti-TNF-α and an-ti-IL-17 biologics has validated the concept that cytokine blockade is beneficial in RA. However, as these drugs are parenterally administered, our efforts are directed at identifying a novel orally active TNF-α inhibitor with a therapeutic profile similar to that of biologics. Since plants are natural immunomodulators, we explored the immunomodulatory potential of Sphaeranthus indicus extract. In our studies, the extract dose-dependently inhibited the release of cytokines in stimulated human peripheral blood mononuclear cells (hPBMCs), and their spontaneous release in synovial cells derived from patients suffering from RA. TNF-α and IFN-γ induced release of p40 subunit of IL-12/ IL-23, and p19 subunit of IL-23 in differentiated THP-1 cells is potently blocked. The expression of endothelial cell adhesion molecules in TNF-α-stimulated HUVECs was also potently inhibited. The oral treatment significantly and dose-dependently reduced LPS-induced TNF-α and IL-1β production in mice. Disease regression was seen in collagen-induced arthritis in DBA/1J mice, which was validated along with radiological and histopathological evaluation. Therefore, the extract of Sphaeranthus indicus could be used in the management of inflammatory conditions.
