Evaluation Method Of Quality Evaluation Of Traditional Chinese Medicine

[Objectives]How to evaluate the quality of Chinese materia medica (CMM) is the key to their modern development. Multiple indexes, most of which are qualitative and isolated from each other, are applied in the current quality standard of CMM, making it difficult to reflect the clinic efficacy and evaluate the quality of medicines comprehensively.In order to deal with the contribution differences of different indexes, a novel quality evaluation method based on the chemical analysis and bioeffect detection of CMM was proposed:Effect-constituent Index (ECI). With ECI, the quality standard of CMM could be benefical to the individualized medicine administration, in an integrated and quantifiable way. In this research, the approach of ECI was elucidated by the instance analysis of Coptidis Rhizoma. Based on literature research and previous studies, major active constituents and effects including the inhibition on the growth of Shigella dysenteriae (S. dysenteriae) and the proliferation of HepG2 cells were determined. The Multi-index Evaluation Method was applied to establish ECI of inhibition on S. dysenteriae (ECIS) and ECI of inhibition on HepG2 cells(ECIH), which were used to evaluate the quality of Coptidis Rhizoma of different grades, sources and producing areas. We hope this method could be a useful attempt to improve the quality standard of CMM.[Methods]In this research, ECI Coptidis Rhizoma were established by the following steps:1. Determine the major effects and related active constituents based on literatures and previous researches.2. Prepare the water extracts of Coptidis Rhizoma and determine the levels and ranges of active constituents.3. Detect the bioactivities of constituents and assign the effect weights to different constituents with normalization processing.4. Extablish ECI of Coptidis Rhizoma with Multi-index Evaluation Method and validate it with the effect results of herbs.5. Apply ECI to evaluate the quality of Coptidis Rhizoma of different grades (classified by Delphi method), sources and producing areas.[Results]1. Based on literature researches and previous studies, the inhibiting effects on the growth of S. dysenteriae and the proliferation of HepG2 cells were chosen as effect indexes of Coptidis Rhizoma. Constituents related to the effects were berberine (BER), epiberberine (EPI), coptisine (COP), palmatine (PAL) and jatrorrhizine (JAT).2. Ten batches of Coptidis Rhizoma from different sources and producing areas were collected and prepared as the water extracts. The level range of the five constituents were from 0.00% to 24.64%. Microcalorimetry was applied to detect the inhibiting effect of constituents on the growth of Shigella dysenteriae (S. dysenteriae). The 1/IC50 values were normalized as the effect weights of the five constituents. And Multi-index Evaluation Method was used to establish ECIS as ECIS=3.1676* XBER+1.0842* XEPI+5.2062* XCOP+ 0.0164* XPAL+0.1041* XJAT.The relative inhibition rate (RT) of Coptidis Rhizoma samples of same concentration were determined to validate ECIS-The result of correlation analysis showed a significant positive correlation between RI and ECIs (Rs=0.987,**P<0.01).3. The IC50 of five constituents on the proliferation of HepG2 cells were determined. The 1/IC50 values were normalized as the effect weights of the five constituents. Multi-index Evaluation Method was used to establish ECIH as ECIH=3.7602* XBEr+0.3687* XEPI+ 0.9718* XCOP+0.3862* XPAL+0.3564* XJAT. The 1/IC50 of Coptidis Rhizoma samples were determined to validate ECIH. The result of correlation analysis showed a significant positive correlation between 1/IC50 and ECIH (RH=0.873,**P<0.01).4. Six batches of Coptidis Rhizoma were collected to enlarge the sample size, of which the ECIS and ECIH were calcutated. Delphi Evaluation Method was applied to grade Coptidis Rhizoma samples. Then ECIS and ECIH were used to evaluate the quality of Coptidis Rhizoma of different grades, sources and producing areas:superior, ECI≥0.95; good,0.85 < ECI< 0.95; inferior, ECI< 0.7.5. Compared with other evaluation method of CMM, ECI was integrated, synthetic and quantifiable.[Discussion]1. Driven by Precision Medicine and Personalized Medicine, ECI of CMM was established according to the requirement and differentiation of clinical efficacy. CMM with different ECI could be targeted using according to the clinic needs and pharmaceutical production, which would be beneficial for the effective evaluation and reasonable use of CMM resources. As a compresive index, more effects related to clinical efficacy should be included in the establishment of ECI in the future.2. As a synthetic index based on the analysis of constituents and bioactivity, ECI makes it possible to promote quality standard of CMM in an integrated, synthetic and quantifiable way, with which we can obtain the quality result by just determing the content of constituents. Therefore, ECI is mainly used for CMM with relatively clear effects and active constituents, which is not applicative to all kinds of CMM.3. Grades evaluation based on experts’experience and macroscopic observation was validated with good repeatability. While More samples with representative characters still need to be collected in the future research.