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.
Highlights
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
One study revealed that the combination of three components in a traditional Chinese medicines called RealgarIndigo naturalis formula synergistically treats acute promyelocytic leukaemia (APL) by hitting different targets involved in the induction of APL cell differentiation[17]
Serum expressions of cytokines IL-2, IL-6, IFN-γ and antibodies IgG, IgM were greatly elevated, while proliferation of splenic lymphocytes was significantly inhibited in the model group compared to the control group (Fig. 1a–i)
Summary
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. One study revealed that the combination of three components in a traditional Chinese medicines called RealgarIndigo naturalis formula synergistically treats acute promyelocytic leukaemia (APL) by hitting different targets involved in the induction of APL cell differentiation[17]. These studies focused on chemicals belonging to different structural types; how structural analogues in herbal medicines work together remains unexplained so far.
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