RESUMEN
Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator. It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity, type 2 diabetes and NASH. In this study, we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator, candidusin A (CHNQD-0803). Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a KD value of 4.728 × 10-8 M and activates AMPK at both molecular and intracellular levels. We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition, LPS-stimulated inflammation, TGF-ß-induced fibrosis cell models and the MCD-induced mouse model of NASH. The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition, negatively regulated the NF-κB-TNFα inflammatory axis to suppress inflammation, and ameliorated liver injury and fibrosis. These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00168-z.
RESUMEN
Bloodletting puncture at twelve well-points is a characteristic emergency therapy in traditional Chinese medicine. This article reviewed the research advances in the clinical effect of this therapy in the treatment of acute central nervous injury and its mechanism of action over the past 30 years, and it is found that this therapy can effectively improve disturbance of consciousness, neurological defects, and cerebral edema caused by stroke, traumatic brain injury, and carbon monoxide poisoning. The mechanism involves the improvement of cerebral blood flow and tissue oxygen supply, repair of the blood-brain barrier, and regulation of local ion balance. Well-designed clinical trials and in-depth research on biological mechanisms should be performed in future to promote and guide its clinical application.