A centuries‑old traditional Chinese medicine may reduce the intestinal side effects of chemotherapy in cancer patients by stimulating gut cell division and reducing inflammation, a new study in mice suggests.
The research will appear in the Wednesday, 18 August issue of Science Translational Medicine, which is published by AAAS, the nonprofit science society.
Peonies and a pretty purple flower called skullcap, together with licorice and fruit from a buckthorn tree form Huang Qin Tang (pronounced Hu-ang Chin Tong), an ancient herbal medicine used in China to treat intestinal disorders such as diarrhea, nausea and vomiting. Recently, a Western-style phase 1/2 trial confirmed that this drug reduces gut damage caused by chemotherapy in colon and rectal cancer patients.
In the new study, Yung- Chi Cheng, along with Wing Lam and colleagues from Yale University School of Medicine and a company called PhytoCeutica, Inc. use a carefully prepared, lab formulation of this medicine (called PHY906) and show that the healing effects of this blend of plants arise from its ability to target numerous biological processes in mice.
"The reductionist approach to treating multiple side effects triggered by cancer chemotherapy or complicated disease may not be sufficient. Rigorous studies of the biology of traditional herbal medicines, which target multiple sites with multiple chemicals, could lead to the development of future medicines," said Cheng.
Dr. Cheng is a scientific founder of and has equity interest in PhytoCeutica, Inc., which develops traditional Chinese medicine into drugs for the treatment of cancer and that licenses PHY906 from Yale University. Additionally, two authors of this paper own stock in PhytoCeutica, Inc. Yale University holds a patent on the herbal composition PHY906 and its use in chemotherapy.
In the study, the researchers treated cancerous mice with chemotherapy, which shrank tumors but also caused massive destruction in the intestinal lining of the animals. After a few days of treatment with PHY906, the medicine restored the damaged intestinal linings in the mice. The team found that stem cell signaling molecules (known as Wnts) were present in higher than normal levels in the guts of the treated mice. Taking a closer look, the researchers discovered that PHY906 itself did not stimulate Wnt signaling, but that mixing PHY906 with a bacterial enzyme common in the gut triggered Wnt signaling, which drives the replacement of damaged intestinal stem cells with healthy ones.
In addition to replenishing healthy gut cells, the herbal medicine blocked the migration of inflammatory cells to the gut and reduced inflammation--effects that seem to be caused by multiple actions of PHY906. These results suggest that traditional Chinese medicine may be a model approach for drug developers, who are eagerly testing combinations of agents in the hope that they hope will work better than any one alone.
"We will continue to refine these processes to better study and understand the sophisticated nature of herbal medicines. Revisiting history may lead us to discovering future medicines," said Cheng.
PHY906 is currently only available for patients enrolled in a clinical trial. The authors caution that many herbal products claiming to be Huang Qin Tang may contain harmful or ineffective substitutes and should be avoided.
This research was supported by the National Cancer Institute and the National Institutes of Health. The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society, and publisher of the journal, Science (www.sciencemag.org) as well as Science Translational Medicine (www.sciencetranslationalmedicine.org) and Science Signaling (www.sciencesignaling.org). AAAS was founded in 1848, and includes some 262 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of 1 million. The non-profit AAAS (www.aaas.org) is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy; international programs; science education; and more. For the latest research news, log onto EurekAlert!, www.eurekalert.org, the premier science-news Web site, a service of AAAS.
Science Translational Medicine