Bioactive Equivalent Combinatorial Compounds contributing to the holistic effect of traditional Chinese medicine Bupleuri chinense DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR, also known as Chaihu) is a well-established traditional Chinese medicine (TCM) used for inflammation and fever with a history spanning over two millennia. BR is integral to the production of various patented TCM formulations and traditional prescriptions. Nevertheless, the previous pharmacological evaluations of BR are limited to extracts or isolated saikosaponins. The lack of understanding of the holistic efficacy of BR has become significant obscure for the development of BR-based therapy in clinical settings.

AIM OF THE STUDY: We aim to identify the pharmacologically active compounds in combination that collectively represent the overall efficacy of BR particularly for anti-inflammatory and anti-pyretic effects. The strategy of "bioactive equivalent combinatorial components (BECCs)" was employed using bioactive equivalence-oriented feedback screening method.

MATERIALS AND METHODS: The operations employed chemical profiling with HPLC-MS, followed by preparation of candidate BECCs by preparative HPLC, and evaluation of BECCs on the in-vitro anti-inflammation and in-vivo anti-pyretic activities in LPS-induced models.

RESULTS: A combination of 18 compounds was discovered and demonstrated to be as bioactive equivalent as original BCH on anti-inflammatory effect in LPS-induced RAW264.7 cell and on antipyretic activity in LPS-indued rats.

CONCLUSIONS: This work offers evidence-based data to answer the key questions of which are real bio-active components for BR that have been used in clinics for thousands of years. This work demonstrates a promising approach for clinical benefits-associated quality control of BR and other multi-originated HMs.