Monday, 22 February 2016

Synergy in traditional Chinese medicine

Although the Lancet Oncology's call (November, 2015)1 for more research into traditional Chinese medicine (TCM) is applauded, I take issue with the paradigm that there would be “a single active component,”1 the magic bullet that hits a specific target.
Arsenic trioxide was identified as the active component of a herbal remedy and developed into a treatment for acute promyelocytic leukaemia.2 Apart from arsenic and artemisinin, however, success of the reductionist approach in TCM has been few and far between. Meanwhile, failure of monotherapies in treating cancer and infectious diseases has led increasingly to research on combination therapies and single drug capable of targeting multiple sites. In this endeavor, biomedicine could well find inspiration in an unlikely source. A holistic approach is adopted in TCM for health care, disease prevention, diagnosis, and treatment. A drug prescription (known as formula) contains herbs from four categories: the “principal” provides the main therapeutic effect, the “minister” increases the effect, the “assistant” reduces the toxicity of the principal, and the “guide” transports the drug to the desired site. A recipe is altered to suit individual conditions and environmental factors.
Despite mainstream skepticism, several studies suggest some herbal remedies might be effective, and the role of synergy should be considered. Indeed, findings from a randomised clinical trial3showed that sho-saiko-to, an extract of seven Chinese herbs, helped prevent liver cancer in patients with cirrhosis. The investigators noted that the formula showed much stronger antiproliferative effects than any one of its single components.3 A combination of tetra-arsenic tetra-sulfide, indirubin, and tanshinone IIA, three active compounds isolated from a herbal formula, was reported to show synergistic effects both in mouse models of acute promyelocytic leukaemia and in cell lines.4
PHY906 represents a case study for integrating TCM and western medicine. Equipped with competency in both medical systems, Liu and colleagues5 carefully navigated the mine field of TCM literature, which contains abundant irrelevant and false information, before reaching for useful leads. They were looking for a therapy conceptually based on a multiple component, multiple targeting principle, which might have its origin in TCM, but would be grounded on rigorous science. Mechanistic studies revealed that four herbs (PHY906) worked in concert to achieve the modulation of multiple biological activities. All four herbs were required to maximally enhance the therapeutic activity of the cancer drug irinotecan in vivo, and any single herb had much lower activity than full formulation.5 The magic bullet approach probably would have missed this valuable finding.
Beyond cancer, findings from clinical trials in the UK showed that a TCM formulation was effective in treating atopic eczema that was resistant to conventional therapies. Preliminary investigations indicate that there was no single active herb and that the complete combination of ten herbs was needed to achieve the desired clinical results.6
The above-mentioned examples, albeit preliminary in nature, point to the need for us to rethink limitations of the existing research methods, which were developed for the mono-agent model. A holistic or integrated approach that treats herbal remedies as a whole system might complement the former.
I declare no competing interests.


  1. The Lancet Oncology. Rethinking traditional Chinese medicines for cancer. Lancet Oncol201516:1439
  2. Shen, Z, Chen, G, Ni, J et al. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood199789:3354–3360
  3. Oka, H, Yamamoto, S, Kuroki, T et al. Prospective study of chemoprevention of hepatocellular carcinoma with sho-saiko-to (TJ-9). Cancer199576743–749
  4. Wang, L, Zhou, G, Liu, P, Song, J et al. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci USA20081054826–4831
  5. Liu, S and Cheng, Y. Old formula, new Rx: the journey of PHY906 as cancer adjuvant therapy. J Ethnopharmacol2012140614–623
  6. Phillipson, J. A matter of some sensitivity. Phytochemistry1995381319–1343