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

Abstract

‘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.

Effects of Japanese traditional medicines on circulating cytokine levels in women with hot flashes

“…Recently, the results of a randomized, placebocontrolled double-blind clinical trial showed that an herbal formula containing Chinese herbs and Cimicifuga cannot be recommended for alleviation of menopausal vasomotor symptoms. 32 Many components have been shown to be included in Japanese traditional medicines by three-dimensional high-performance liquid chromatography fingerprint analysis, 11,33 and several effects of these components have been shown in basic studies. 34,35 Further study is needed to clarify which components of keishibukuryogan and kamishoyosan have effects on cytokines.…”

Simultaneous Determination of Four Index Polar Constitutes by HILIC-ESIMS/ MS for the Quality Control of Guizhi Fuling Wan

“…GFW, prescript for treating blood disorders was compiled by Zhang Zhongjing, an outstanding physician in the Eastern Han Dynasty (150-219 AD) [2,3]. Based on a large amount of pharmacological researches, the polar active constituents of pachymic acid, albiflorin, amygdalin and cinnamic acid, were found to be responsible for the biological activities of treating gynecological diseases, uterine fibroids, pelvic inflammatory disease, ovarian cyst, dysmenorrhea [4], endometriosis [5], cervical cancer [1], hot flashes [6], improvement of blood circulation [7][8][9]. In addition, GFW was reported to prevent the progression of atherosclerosis in cholesterol-fed rabbits in vivo by limiting oxidative LDL modification [10,11].…”

Effectiveness of Keishibukuryogan on Chronic-Stage Lichenification Associated with Atopic Dermatitis

“…Matsumoto et al explored a proteomic approach for the diagnosis of blood stasis in rheumatoid arthritis patients treated with KBG [7]. In addition, KBG is used to treat symptoms of peripheral ischemia such as cold extremities [8].…”