MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

Human tissue kallikrein promoted activation of the ipsilesional sensorimotor cortex after acute cerebral infarction.

BACKGROUND/AIMS: Kallikrein, a serine proteinase, has been reported to have many functions, such as selectively dilating arterioles in the ischemic area and enhancing angiogenesis and neurogenesis. Therefore, it may promote cerebral poststroke reorganization. We observed the effect of human tissue kallikrein on the brain motor activation of acute ischemic stroke patients and evaluated patient condition severity and prognosis. METHODS: Forty-four cases suffering from cerebral infarction between 6 and 72 h of onset were randomly assigned into the kallikrein group (n = 24) and the control group (n = 20). The control group was given conventional treatment, whereas the kallikrein group was given both conventional treatment and human tissue kallikrein over the course of 12-14 days. The activation of the sensorimotor cortex (SMC) and cerebellum, the affected forefinger strength and the NIHSS scores were evaluated before and after treatment. The MBI and MRS scores were assessed at 30 and 90 days after stroke onset. RESULTS: There were no differences between the two groups in activation volume, patient condition and scores before treatment. After treatment, the ipsilesional SMC activation volume was significantly larger and the increase in the volume was significantly greater in the kallikrein group than in the control group (p < 0.05 for both). The NIHSS score was significantly smaller and the improvement in the score was significantly greater in the kallikrein group after treatment (p < 0.05 for both). Moreover, the MBI scores at 30 days were significantly higher, whereas the MRS scores at 30 days were significantly lower in the kallikrein group than in the control group (p < 0.05 for both). CONCLUSIONS: Kallikrein improved neural function effectively and quickly after stroke, and promoting cerebral reorganization might be an important mechanism for kallikrein in the treatment of acute cerebral infarction.