An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma.

PD-1/PD-L1 pathway plays a role in inhibiting immune response. Therapeutic antibodies aimed at blocking the PD-1/PD-L1 interaction have entered clinical development and have been approved for a variety of cancers. However, the clinical benefits are reduced to a group of patients. The research in combined therapies, which allow for a greater response, is strongly encouraging. We previously characterized a polyphenol-rich extract from Caesalpinia spinosa (P2Et) with antitumor activity in both melanoma and breast carcinoma, as well as immunomodulatory activity. We hypothesize that the combined treatment with P2Et and anti-PD-L1 can improve the antitumor response through an additive antitumor effect. We investigated the antitumor and immunomodulatory activity of P2Et and anti-PD-L1 combined therapy in B16-F10 melanoma and 4T1 breast carcinoma. We analyzed tumor growth, hematologic parameters, T cell counts, cytokine expression, and T cell cytotoxicity. In the melanoma model, combined P2Et and anti-PD-L1 therapy has the following effects: decrease in tumor size; increase in the number of activated CD4+ and CD8+ T cells; decrease in the number of suppressor myeloid cells; increase in PD-L1 expression; decrease in the frequency of CD8+ T cell expressing PD-1; improvement in the cytotoxic activity of T cells; and increase in the IFN γ secretion. In the breast cancer model, P2Et and PD-L1 alone or in combination show antitumor effect with no clear additive effect. This study shows that combined therapy of P2Et and anti-PD-L1 can improve antitumor response in a melanoma model by activating the immune response and neutralizing immunosuppressive mechanisms.

Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice.

Mastitis, which commonly occurs during the postpartum period, is caused by the infection of the mammary glands. The most common infectious bacterial pathogen of mastitis is Staphylococcus aureus (S. aureus) in both human and animals. Brazilin, a compound isolated from the traditional herbal medicine Caesalpinia sappan L., has been shown to exhibit multiple biological properties. The present study was performed to determine the effect of brazilin on the inflammatory response in the mouse model of S. aureus mastitis and to confirm the mechanism of action involved. Brazilin treatment was applied in both a mouse model and cells. After brazilin treatment of cells, Western blotting and qPCR were performed to detect the protein levels and mRNA levels, respectively. Brazilin treatment significantly attenuated inflammatory cell infiltration and inhibited the expressions of TNF-α, IL-1ß and IL-6 in a dose-dependent manner. Administration of brazilin in mice suppressed S. aureus-induced inflammatory injury and the production of proinflammatory mediators. This suppression was achieved by reducing the increased expression of TLR2 and regulating the NF-κB and MAPK signaling pathways in the mammary gland tissues and cells with S. aureus-induced mastitis. These results suggest that brazilin appears to be an effective drug for the treatment of mastitis and may be applied as a clinical therapy.