Identification of a predictive biomarker for the beneficial effect of a Kampo (Japanese traditional) medicine keishibukuryogan in rheumatoid arthritis patients.

OBJECTIVES: Kampo (Japanese traditional herbal) medicines are now ethically used in Japan as pharmaceutical grade prescription drugs. However, there are distinct groups of responders and non-responders to Kampo medicines. We searched for biomarker candidates to discriminate responders from non-responders to keishibukuryogan (KBG); one of the most frequently used Kampo medicines. DESIGN AND METHODS: A combination of SELDI technology and a decision tree analysis with proprietary developed bioinformatics tools was applied to 41 (32 for tree construction and 9 for validation test) plasma samples obtained from rheumatoid arthritis (RA) patients. A candidate biomarker protein was identified using LC-MS/MS. RESULTS: The constructed tree with measurable reliability contained only a single peak which was identified as haptoglobin alpha 1 chain (Hpalpha1). CONCLUSION: Hpalpha1 is a biomarker candidate for discriminating responders from non-responders to KBG treatment for RA. The present results may open the way to the establishment of "evidence-based" complementary and alternative medicine.

A Proteomic Approach for the Diagnosis of 'Oketsu' (blood stasis), a Pathophysiologic Concept of Japanese Traditional (Kampo) Medicine.

'Oketsu' is a pathophysiologic concept in Japanese traditional (Kampo) medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for 'Oketsu'. Sixteen rheumatoid arthritis (RA) patients were treated with keishibukuryogan (KBG), a representative Kampo medicine for improving 'Oketsu'. Plasma samples were diagnosed as either having an 'Oketsu' (n = 19) or 'non-Oketsu' (n = 29) state according to Terasawa's 'Oketsu' scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the 'Oketsu' scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the 'Oketsu' and 'non-Oketsu' states. Hierarchical clustering gave three major clusters (I, II, III). The majority (68.4%) of 'Oketsu' samples were clustered into one cluster as the principal component of cluster I. The remaining 'Oketsu' profiles constituted a minor component of cluster II and were all derived from patients cured of the 'Oketsu' state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for 'Oketsu'. A reduction in measurement/pre-processing conditions (from 55 to 16) gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine 'Oketsu' has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing 'Oketsu' using a combination of proteomic and bioinformatics-based classification methods.