Research ArticleChemotherapy

The Four-Herb Chinese Medicine PHY906 Reduces Chemotherapy-Induced Gastrointestinal Toxicity

Science Translational Medicine  18 Aug 2010:
Vol. 2, Issue 45, pp. 45ra59
DOI: 10.1126/scitranslmed.3001270

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Flower Power for Intestinal Healing

Peonies and a pretty purple flower called skullcap, together with licorice and fruit from a buckthorn tree, might conjure up an enchanting still life, but this combination of plants can heal more than the spirit. These four ingredients form Huang Qin Tang, a centuries-old traditional Chinese medicine used to treat intestinal disorders such as diarrhea, nausea, and vomiting. A Western-style phase 1/2 trial confirmed that this drug reduces the intestinal side effects of chemotherapy in colon or rectal cancer patients. Now Lam et al. use a carefully prepared, consistent formulation of this medicine and show that it exerts its salutary effects by stimulating gut cell division and reducing inflammation.

Mice with colon tumors were given CPT-11, a powerful cytotoxic agent used for cancer chemotherapy, which shrank their tumors but also caused massive destruction of the intestinal lining. However, when the colon tumor–carrying mice received a combination of CPT-11 and standardized Huang Qin Tang (called PHY906), they lost less weight than did mice treated with CPT-11. Closer examination of the intestines of the doubly treated mice revealed PHY906-induced restoration of the normal architecture by 4 days after treatment, with a faster disappearance of apoptotic cells and an increase in proliferating progenitor cells, particularly at the bottom of the intestinal crypts, relative to mice that received CPT-11 only. Markers of the Wnt signaling pathway also increased, suggesting that PHY906 functioned by stimulating Wnt signaling, possibly at multiple points. So it was unexpected when the authors found that PHY906 itself did not stimulate Wnt. An explanation emerged when they discovered that, after mixing either PHY906 or the extract from skullcap alone with a bacterial enzyme common in the human gut, Wnt activity became apparent.

PHY906 has other critical actions: In addition to stimulating gut cell repopulation, it blocked the migration of inflammatory cells to the gut and inhibited inducible nitric oxide synthase and cyclooxygenase-2, two signs of inflammation, as well as the proinflammatory transcription factor NF-κB. Although all of the mechanistic details have not yet been deciphered, these effects seem to be caused by multiple actions of PHY906.

Currently, drug developers are eagerly testing combinations of agents that they hope will heal patients better than any one alone. Traditional Chinese medicine may have been the original proponent of this approach, as these results by Lam et al. reveal.


  • Citation: W. Lam, S. Bussom, F. Guan, Z. Jiang, W. Zhang, E. A. Gullen, S.-H. Liu, Y.-C. Cheng, The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci. Transl. Med. 2, 45ra59 (2010).