Novel Mechanisms of Herbal Therapies for Inhibiting HMGB1 Secretion or Action

Figure 5

TSN-SS stimulates endocytic HMGB1 uptake. TSN-SS facilitated internalization of exogenous HMGB1 possibly via clathrin- and caveolin-dependent endocytosis into cytoplasmic vesicles that eventually mature into endosomes. Consequently, it likely triggers another cellular degradation process, autophagy, during which cytoplasmic macromolecules are engulfed by double-membraned cytoplasmic vesicles termed autophagosomes. Subsequently, these HMGB1-containing endosomes could be fused with other cytoplasmic vesicles (such as autophagosomes) to form amphisomes, where the internalized HMGB1 was likely degraded via a lysosome-dependent mechanism.