Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action

Figure 3

Divergent inhibition of HMGB1 action or secretion. (a) GZA binds to the shallow cave surface of HMGB1 boxes. Computer-assisted molecular docking of HMGB1 with GZA: the blue area represents surface of HMGB1 box A, whereas the chemical structure of GZA is shown in green. (b) CBX inhibits LPS-induced HMGB1 secretion by preventing PKR activation. Prolonged stimulation with crude LPS may lead to panx-1 hemichannel-mediated ATP efflux and upregulation of PKR expression. Extracellular ATP then binds to P2X7R and activates the ATP-gated P2X7R and panx-1 hemichannels, leading to PKR phosphorylation and subsequent inflammasome-dependent HMGB1 secretion. CBX may block LPS-induced ATP efflux through panx-1, thereby impairing ATP/P2X7R-mediated PKR activation and subsequent inflammasome-dependent HMGB1 secretion.

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