Jieduan-Niwan Formula Ameliorates Oxidative Stress and Apoptosis in Acute-on-Chronic Liver Failure by Suppressing HMGB1/TLR-4/NF-B Signaling Pathway: A Study In Vivo and In Vitro.

Jieduan-Niwan (JDNW) formula is a traditional Chinese medicine compound created by the famous Chinese medicine expert Professor Qian Ying, and has been used clinically for decades to treat acute-on-chronic liver failure (ACLF) and exhibits remarkable efficacy. However, the exact mechanism remains to be discovered. As an important hepatocyte damage-associated molecular patterns (DAMP) factor, high mobility group box 1 (HMGB1) is a potential therapeutic target as an accelerator of ACLF in the pathogenesis. Therefore, the present study investigated whether JDNW inhibits the overexpression and cytoplasmic translocation of HMGB1 in ACLF liver tissue and alleviates its mediated oxidative stress and apoptosis. In vivo, an immune-induced ACLF rat model was established, and then treated with JDNW for 5, 10, and 15 d. The results showed that a large number of cytoplasmic translocations of HMGB1 occurred in the ACLF group. And there was an increase in the expression of HMGB1 in the M-5 d group. After the intervention of JDNW, the overexpression and translocation of HMGB1 were inhibited. In vitro, D-GaLN caused an increase in the expression and translocation of HMGB1 in L02 cells. Similar to the inhibitor of HMGB1, JDNW serum alleviated this kind of increase. Further tests showed that JDNW attenuated ACLF-related oxidative stress and apoptosis, and the inhibition was associated with the regulation of TLR-4/NF-B signaling pathway. In conclusion, our present findings suggest that the therapeutic effect of JDNW on ACLF was associated with the inhibition of high expression and cytoplasmic translocation of HMGB1 during the acute injury phase, thus, attenuating oxidative stress injury and apoptosis induced by HMGB1/TLR-4/NF-B pathway.