Synergism and Subadditivity of Verbascoside-Lignans and -Iridoids Binary Mixtures Isolated from Castilleja tenuiflora Benth. on NF-κB/AP-1 Inhibition Activity

Pharmacodynamic interactions between plant isolated compounds are important to understand the mode of action of an herbal extract to formulate or create better standardized extracts, phytomedicines, or phytopharmaceuticals. In this work, we propose binary mixtures using a leader compound to found pharmacodynamic interactions in inhibition of the NF-kappa B/AP-1 pathway using RAW-Blue (TM) cells. Eight compounds were isolated from Castilleja tenuiflora, four were new furofuran-type lignans for the species magnolin, eudesmin, sesamin, and kobusin. Magnolin (60.97%) was the most effective lignan inhibiting the NF-kappa B/AP-1 pathway, followed by eudesmin (56.82%), tenuifloroside (52.91%), sesamin (52.63%), and kobusin (45.45%). Verbascoside, a major compound contained in wild C. tenuiflora showed an inhibitory effect on NF-kappa B/AP-1. This polyphenol was chosen as a leader compound for binary mixtures. Verbacoside-aucubin and verbascoside-kobusin produced synergism, while verbascoside-tenuifloroside had subadditivity in all concentrations. Verbascoside-kobusin is a promising mixture to use on NF-kappa B/AP-1 related diseases and anti-inflammatory C. tenuiflora-based phytomedicines.

Automated summary

Pharmacodynamic interactions between plant isolated compounds are crucial for understanding the mode of action of herbal extracts. In this study, eight compounds were isolated from Castilleja tenuiflora, with four new lignans showing potential inhibition of the NF-kappa B/AP-1 pathway. Verbascoside was identified as a key compound for creating synergistic mixtures with other lignans, offering promising applications for treating NF-kappa B/AP-1 related diseases and inflammation.