An activity-calibrated chemical standardization approach for quality evaluation of Salvia miltiorrhiza Bge

Due to the inherent nature of the heterogeneity and complexity in the chemical composition of medicinal plants, there are significant challenges in the characterization and quantification of all active chemical constituents of botanicals, such as those used in traditional Chinese medicines (TCMs) and botanical drugs (BDs). The selection of one or even multiple marker chemical compounds for quality control may often be inadequate, as those marker compounds may not be associated with or fully represent the clinical effects of the botanical products. In this study, we proposed a novel activity-associated chemical analysis approach, named the effect-constituents index (ECI), to evaluate the quality of TCMs, using Salvia miltiorrhiza Bge. (SM), a commonly used TCM herb, as an example. The ECI is not only a quantitative analysis of multiple chemical constituents, but also includes an effect-based calibration of the relative bioactivity coefficient of each chemical constituent to express "the whole biological/pharmacological effect" of a TCM. Our chemical assay results showed significant variations in the contents (C-i) of ninemain constituents, including cryptotanshinone and salvianolic acid B, in the SM samples. In addition, neither the concentrations of the individual constituents nor the sum of those constituents in the tested SM samples had good associations (r < 0.81) with the biopotency of SM itself, based on the activity data from an antiplatelet aggregation test. To calculate the ECI, cryptotanshinone and the other five constituents of high biopotency (above 660 U mmol(-1)) were selected, and their biopotency values were set as the calibration weight of each constituent; then, the sum of the products of content (C-i) and biopotency weight (F-i) were calculated as the ECI. By regression analysis, the ECI had either the highest correlation coefficient (r = 0.92, p < 0.001) with the biopotency of SM or the lowest residual compared to the chemical contents. Moreover, the ECI showed a good ability to distinguish and predict the biopotency-based quality grade, while the chemical markers alone did not. In conclusion, our study indicates that this effect-calibrated quantitative approach is a useful tool to associate the "quality" with the potential clinical effects of TCMs and BDs consisting of multiple active constituents or known chemical marker compounds.