Recent studies, however, using an endotoxemic mouse model and LPS-treated RAW 264.7 cells shed some light on this issue, showing that GLY treatment induced heme oxygenase 1 expression via a p38MAPK/Nrf2 pathway, inhibiting HMGB1 extracellular secretion and hence its extracellular cytokine activity.42 In addition, GLY has been used clinically to treat chronic hepatitis,24 allergic conjunctivitis, and blepharitis,14 while CBX was used to treat esophageal ulceration25 with no signs of adverse events or drug toxicity in patients for either agent. Here, HMGB1 is linked to chronic hepatitis.