Using Pharmacokinetic–Pharmacodynamic Modeling to Study the Main Active Substances of the Anticancer Effect in Mice from IPanax ginseng/I–IOphiopogon japonicus/I

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 2
• Main Authors: Liu, Lu, Lyu, Jing, Yang, Longfei, Gao, Yan, Zhao, Bonian
• Format: Journal Article
• Language: English
• Published: MDPI AG 01.01.2024
• Subjects: Cancer; Care and treatment; Drug therapy; Health aspects; Lung cancer; Medicine, Chinese; Respiratory agents; Resveratrol; Massachusetts; China
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29020334

Ginseng Radix et Rhizoma Rubra (Panax ginseng C.A. Mey, Hongshen, in Chinese) and Ophiopogonis Radix (Ophiopogon japonicus (L.f) Ker-Gawl., Maidong, in Chinese) are traditional Chinese herbal pairs, which were clinically employed to enhance the immune system of cancer patients. This study employed the pharmacokinetic and pharmacodynamic (PK–PD) spectrum-effect association model to investigate the antitumor active substances of P. ginseng and O. japonicus (PG–OJ). The metabolic processes of 20 major bioactive components were analyzed using Ultra-Performance Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (UPLC–MS/MS) in the lung tissue of tumor-bearing mice treated with PG–OJ. The ELISA method was employed to detect the levels of TGF-β1, TNF-α, and IFN-γ in the lung tissue of mice at various time points, and to analyze their changes after drug administration. The results showed that all components presented a multiple peaks absorption pattern within 0.083 to 24 h post-drug administration. The tumor inhibition rate of tumor and repair rate of IFN-γ, TNF-α, and TGF-β1 all increased, indicating a positive therapeutic effect of PG–OJ on A549 tumor-bearing mice. Finally, a PK–PD model based on the GBDT algorithm was developed for the first time to speculate that Methylophiopogonanone A, Methylophiopogonanone B, Ginsenoside Rb[sub.1], and Notoginsenoside R1 are the main active components in PG–OJ for lung cancer treatment.