Abstract
The bark of Rhus verniciflua Stokes (RVS) has been used to treat cancer in Korean herbal medicine. When we screened for PD-1 and CTLA-4 immune checkpoint inhibitors (PD-1/PD-L1 CTLA-4/CD80) from around 800 herbal extracts using competitive Enzyme-Linked Immunosorbent Assay (ELISA), we found that RVS blocked both the PD-1/PD-L1 and the CTLA-4/CD80 interactions. To identify the active compounds from RVS, we performed bioactivity-guided fractionation, and the ethyl acetate (EtOAc) fraction of RVS proved to be the most effective at blocking the PD-1/PD-L1 and CTLA-4/CD80 interactions. In addition, we isolated and identified 20 major compounds in the EtOAc fraction of RVS and then examined the blocking effects of these 20 compounds on PD-1/PD-L1 and CTLA-4/CD80. Among them, four compounds [eriodictyol (7) > fisetin (9) > quercetin (18) > liquiritigenin (13)] blocked the interaction of PD-1/PD-L1 on competitive ELISA. In addition, four different compounds [protocatechuic acid (2) > caffeic acid (19) > taxifolin (5) > butin (6)] blocked the interaction of CTLA-4/CD80. Our findings suggest that RVS and its components could be used as a potential immune checkpoint inhibitor blockade and could be developed for immuno-oncological therapeutics.
Highlights
Rhus verniciflua Stokes (RVS) (Anacardiaceae), commonly known as Chinese lacquer tree, is distributed in Korea, Japan, and China [1]
We investigated PD-1/PD-L1 blocking effect by RVS using competition Enzyme-Linked Immunosorbent Assay (ELISA)
The EtOAc fraction of the extract showed more effective blocking efficacy than did other fractions. This observation indicates that the blocking effect of RVS on the PD-1/PD-L1 interaction was fractions
Summary
Rhus verniciflua Stokes (RVS) (Anacardiaceae), commonly known as Chinese lacquer tree, is distributed in Korea, Japan, and China [1]. RVS tissues, the bark, have been shown to contain a large number of bioactive phytochemical constituents, including alkaloids, polyphenols, and flavonoids [2,3]. The blocking effects of this plant on the immune checkpoint inhibitors, such as PD-1/PD-L1 and CTLA-4/CD80, are not currently understood. As part of an investigation of novel bioactive constituents in RVS, bioactivity-guided fractionation, and isolation from RVS bark revealed 20 secondary metabolites (1–20). Immune checkpoints, which can stimulate or inhibit T cell responses, were well known, as a result of the award of the Nobel Prize in Physiology or Medicine in 2018 to James Allison and Tasuku Honjo for their discovery of CTLA-4 and PD-1, respectively.
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