Diterpenoids from Tripterygium Glycosides Tablets and their anti-inflammatory activity

Renowned in traditional medicine, Tripterygium wilfordii is historically recognized for its efficacy against inflammatory and autoimmune disorders. The modern clinical preparation, Tripterygium Glycosides Tablets (TGTs), is derived from this plant. Despite its proven clinical efficacy, the precise bioactive constituents underlying TGTs' anti-inflammatory effects remain incompletely characterized.

This paper aimed to identify the phytochemical constituents in the raw material of TGTs and to examine their potential cytotoxicity and anti-inflammatory activities.

Phytochemical investigation was performed by several column chromatographic techniques. Through comprehensive spectroscopic analysis and quantum chemical calculations, the structures were elucidated. All isolates from TGTs were tested for cytotoxicity alongside anti-inflammatory effects in LPS-induced RAW264.7 cells via CCK-8, Griess, ELISA, and high-content cell painting assays.

Ten diterpenoids were obtained, including three new abietane diterpenoids (1-3), along with seven known analogues (4-10). Compound 1 markedly suppressed NO, IL-6, and TNF-α production (IC₅₀ = 2.12 ± 0.23, 3.36 ± 0.22, and 4.86 ± 0.53 μM, respectively). Compounds 2, 5, and 7 exhibited moderate inhibitory activity. High-content phenotypic screening further delineated the potential anti-inflammatory mechanisms of 1.

This study validates the anti-inflammatory basis of TGTs' clinical efficacy and identifies diterpenoids, particularly compound 1, as promising lead compounds for novel anti-inflammatory drug development. These well-characterized compounds also serve as potential chemical markers for the quality assessment of T. wilfordii preparations.