Advancing drug discovery and development from active constituents of yinchenhao tang, a famous traditional chinese medicine formula

Abstract

Traditional Chinese medicine (TCM) formula has been playing a very important role in health protection and disease control for thousands of years. Guided by TCM syndrome theories, formula are designed to contain a combination of various kinds of crude drugs that, when combined, will achieve synergistic efficacy. However, the precise mechanism of synergistic action remains poorly understood. One example is a famous TCM formula Yinchenhao Tang (YCHT), whose efficacy in treating hepatic injury (HI) and Jaundice syndrome, has recently been well established as a case study. We also conducted a systematic analysis of synergistic effects of the principal compound using biochemistry, pharmacokinetics and systems biology, to explore the key molecular mechanisms. We had found that the three component (6,7-dimethylesculetin (D), geniposide (G), and rhein (R)) combination exerts a more robust synergistic effect than any one or two of the three individual compounds by hitting multiple targets. They can regulate molecular networks through activating both intrinsic and extrinsic pathways to synergistically cause intensified therapeutic effects. This paper provides an overview of the recent and potential developments of chemical fingerprinting coupled with systems biology advancing drug discovery towards more agile development of targeted combination therapies for the YCHT.

Figure 1

Prepared herbal medicines of Yinchenhao Tang.

Figure 2

Chemical structure of chlorogenic acid, geniposide, 6,7-dimethylesculetin, capillarisin, and rhein. (b) Comparison of fingerprint profiles of twelve batches of YCHTE samples. Among fifteen representative general peaks, the peaks 2, 3, 6, 7, 8, 9, 10, 11, 12, and 14 originated from the flowers of Artemisia capillaries Thunb, the peaks 2, 4, and 5 originated from the fruits of Gardenia jasminoides Ellis, and the peaks 1, 13, and 15 originated from the roots of Rheum officinale Baill. The peaks 2, 5, 7, 14, and 15 are of chlorogenic acid, geniposide, 6,7-dimethylesculetin, capillarisin, and rhein, respectively. The fingerprint chromatograms of twelve batches of YCHT samples which are consisted of herbal drugs collected from different places of production, is from chromatogram a to chromatogram j. (c) HPLC chromatogram of (a), YCHTE in methanol; (b), the chemical references of five analytes in methanol: (1) chlorogenic acid; (2) geniposide; (3) 6,7-dimethylesculetin; (4) capillarisin; and (5) rhein.