Immunotoxicity and Anti-Inflammatory Characterizations of Prenylated Flavonoids—The Lipophilic 7-O-Terpenylated Wogonin

Abstract

Wogonin, one of the exceptional bioactive flavonoids found abundant in the roots of Huang-Qin (Scutellaria baicalensis Georgi), is a popular health-preserving Chinese medicine. The therapeutic applications can be expanded by improving its bioavailability. The 7-O-terpenylated wogonin consisting one to three prenyl units are chemically synthesized for increasing lipophilic nature for efficient uptake, and also an attempt in mimicry of naturally scarce terpenylated flavonoids found in limited plant families and bee propolis. Wogonin (W) and its lipophilic nature prenyl wogonin (W5), geranyl wogonin (W10), and farnesyl wogonin (W15) were comparatively studied with structure-relationship in immunotoxicity of cell livability on lymphoid, myeloid, and somatic origins cell lines. Anti-inflammatory functions characterized with nitric oxide inhibition and intracellular ROS level of LPS-activated murine macrophage RAW264.7 were assessed. Wogonin and its terpenylated derivatives have selectively influenced livability of lymphoid origin cells but not myeloid and somatic origin cells. The mitotic protein survivin gene expressions analysis further supported the selective suppressions on lymphoid origin YAC-1 cells by wogonin and geranyl wogonin, while oppositely boosted survivin expressions in LPS-activated macrophages. Moreover, wogonin exhibits dose-dependent inhibition on the nitric oxide (NO) production and iNOS gene expressions of LPS-activated RAW264.7 cells. Terpenylated wogonin exhibits profoundly superior control in intracellular ROS level and a sustained action with sound cell integrity than the wogonin. The enhanced cellular uptake with higher lipophilicity to membrane of 7-O-terpenylated wogonin may pose an important biological nature in facilitating better bioavailability and specific immunomodulatory actions of the category of terpenylated flavonoids. The 7-O-terpenylated wogonin having biological merit of fast membrane lipid bilayer integration, lower effective concentration, and better preserving immune cells functions and livability deserved further in-depth investigations and their broadly therapeutic applications.