Identifying the functions and biomarkers of Codonopsis pilosula and Astragalus membranaceus aqueous extracts in hepatic cells.

Homeostasis is a crucial concept used to describe the condition of patients and the roles of herbs in traditional Chinese medicine. Qi-deficiency pattern is one of the conditions when loss of homeostasis and is usually characterized by symptoms including lassitude, spontaneous sweating, and a weak pulse, which are not easy to quantitate. Codonopsis pilosula and Astragalus membranaceus were usually prescribed for carriers with hepatitis and patients with metastatic colon cancer, because these patients tended to experience fatigue. However, crude drugs were prescribed based on the exterior symptoms of patients without controlling clinical setting, such as gender, age, and dietary habits. Limited molecular evidence of using gene expression as the guide for description is available. Therefore, the purpose of this study was to identify potential and objective biomarkers of these two qi-related drugs in a simplified cellular system.

Aqueous extracts of crude qi-tonifying herbs, C. pilosula and A. membranaceus, and that of a qi-consuming drug, Citrus reticulata, were prepared. Human liver cancer HepG2 cells were treated with the extracts of qi-tonifying herbs for 24 h. Differentially expressed genes were identified using microarrays and quantitative RT-PCR (qRT-PCR) and validated in two other hepatocellular cell lines, Huh7 and L-02.

A total of 67 differentially expressed probes that responded to both herbs were identified. A pathway analysis revealed that these genes were involved in the development, growth, movement, and viability of the liver cells.

After qRT-PCR validation and examination of clinical data from public domains, our results showed that two genes, GDF15 and HMOX1, could serve as biomarkers in liver cells for identifying responses after treatment with C. pilosula and A. membranaceus.