Prediction of anti-tumor chemical probes of a traditional Chinese medicine formula by HPLC fingerprinting combined with molecular docking.

A traditional Chinese medicine formula (Fuzheng Yiliu decoction; FZYLD) has been used for many years in clinical settings to cure liver tumors; however, no empirical research has reported its chemical composition. In this paper, 21 chief constituents were distinguished from FZYLD using high-performance liquid chromatography–mass spectrometry fingerprint analysis. Molecular docking studies for B-cell lymphoma-extra large (Bcl-XL), interleukin (IL)-2, and tumor necrosis factor-α (TNF-α) were bound to evaluate their anticancer activities. 7 compounds showed potential Bcl-XL high affinity binding with a dissociate constant (Kd) < 10 μM; 7 compounds bound with IL-2 had a Kd < 10 μM; and 11 compounds showed potential TNF-α inhibition with a Kd < 10 μM. Moreover, 11 compounds showed better anticancer activity toward human HepG2 (hepatoma) cancer cell lines with IC50 values < 100 μM in vitro. The killings effects of natural killer cells can be activated by FZYLD on HepG2 cells and regulate the immune response through modulating IL-2 and TNF-α expression in vivo. In the “Fuzheng” Chinese medicine formula, many substances participate in the complex regulation of the immune network to execute the anti-tumor effect. The combination approach of chromatographic fingerprint and computer virtual docking used to explore active chemical matter of traditional Chinese medicine is extremely valuable.