Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.

Clinical observation on effect of Jieyu Anshen Decoction combined with aripiprazole in treating chronic schizophrenia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the efficacy and safety of Jieyu Anshen Decoction (JAD) combined with aripiprazole in treating chronic schizophrenia.</p><p><b>METHODS</b>All 100 patients with chronic schizophrenia diagnosed according to CCMD-3 criteria were equally randomly assigned to the study group (treated with JAD combined with aripiprazole) and the control group (treated with aripiprazole alone) for 12 weeks. The efficacy and safety were evaluated by Positive and Negative Syndrome Scale (PANSS) and Treatment Emergent Side Effect Scale (TESS).</p><p><b>RESULTS</b>After 12 weeks of treatment, the clinical efficacy in the study group was significantly higher than that in the control group, the PANSS score in the study group was significantly decreased with a higher speed and range of decreasing, becoming lower than that in the control group at the same period. But the difference between the two groups in scores of TESS at corresponding times showed no significance.</p><p><b>CONCLUSION</b>JAD combined with aripiprazole has definite effect in treating chronic schizophrenia, shows advantages of quickly initiating effect, high safety and with no harm for increasing adverse reactions, so it is better than using aripiprazole alone.</p>