Structural Analogues in Herbal Medicine Ginseng Hit a Shared Target to Achieve Cumulative Bioactivity

Overview

Journal Commun Biol

Specialty Biology

Date 2021 May 11

PMID 33972672

Citations 3

Authors

Wei Zhang

Wei-Wei Tao

Jing Zhou

Cheng-Ying Wu

Fang Long

Hong Shen

He Zhu

Qian Mao

Jun Xu

Song-Lin Li

Qi-Nan Wu

Affiliations

Soon will be listed here.

Abstract

By a pilot trial on investigating immunomodulatory activity and target of ginsenosides, the major bioactive components of ginseng, here we report that structural analogues in herbal medicines hit a shared target to achieve cumulative bioactivity. A ginsenoside analogues combination with definite immunomodulatory activity in vivo was designed by integrating pharmacodynamics, serum pharmacochemistry and pharmacokinetics approaches. The cumulative bioactivity of the ginsenoside analogues was validated on LPS/ATP-induced RAW264.7 macrophages. The potentially shared target NLRP3 involved in this immunomodulatory activity was predicted by systems pharmacology. The steady binding affinity between each ginsenoside and NLRP3 was defined by molecular docking and bio-layer interferometry assay. The activation of NLRP3 inflammasomes in LPS/ATP-induced RAW264.7 was significantly suppressed by the combination, but not by any individual, and the overexpression of NLRP3 counteracted the immunomodulatory activity of the combination. All these results demonstrate that the ginsenoside analogues jointly hit NLRP3 to achieve cumulative immunomodulatory activity.

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