Robust optimization for the simultaneous enhancement of nitric oxide inhibition and reduction of hepatotoxicity from green tea catechins

Abstract

To provide a platform for evaluating significant interactions contributing to the enhanced physiological efficacy and reduced hepatotoxicity, we used a robust design to determine the optimal combination of six major green tea catechins, epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), gallocatechin, and catechin. Based on the mixture design, 28 experiments were performed to inhibit nitric oxide (NO) in RAW 264.7 cells and hepatotoxicity in Chang liver cells. Significant candidates, EGCG, EC, gallocatechin and catechin, were selected after optimization. The combination showing simultaneous enhancement of NO inhibition and reduction of hepatotoxicity was EGCG and gallocatechin at a ratio of 0.65 to 0.35 by surface response methodology and desirability function, through which their co-treatment was validated. Here, we describe a platform for simultaneously determining the optimized combination of natural components exerting enhanced efficacy and reduced toxicity.

Robust Optimization Approaches for a Natural Pharmaceutical Complex Product of Atractylodes Japonica Koidz and Schisandra Chinensis

“…Reference [3] showed that the coupling of the DoE approach with modern high-throughput automation systems can potentially maximize the capabilities of these systems and improve the productivity of many drug discovery procedures. Another study [6] used a robust design to determine the optimal combination of six major catechins from green tea. Besides, several optimal design processes for experimental design methods have been proposed for various industries [7,8], and other studies suggest several optimal schemes related to the field of design [9][10][11][12].…”

“…The main goal of the optimization was to identify the optimal settings of the process variables. Among the various optimization methods available, the desirability function (DF)-based optimization method was utilized to solve the simultaneous dual-objectives [6], including enhancing the significant ingredients of CKD-497 where "the nominal better (N)-type" was applied. The N-type can be defined by…”