Bakkenolides and Caffeoylquinic Acids from the Aerial Portion of Petasites japonicus and Their Bacterial Neuraminidase Inhibition Ability.

Petasites japonicus have been used since a long time in folk medicine to treat diseases including plague, pestilential fever, allergy, and inflammation in East Asia and European countries. Bioactive compounds that may prevent and treat infectious diseases are identified based on their ability to inhibit bacterial neuraminidase (NA). We aimed to isolate and identify bioactive compounds from leaves and stems of P. japonicas (PJA) and elucidate their mechanisms of NA inhibition. Key bioactive compounds of PJA responsible for NA inhibition were isolated using column chromatography, their chemical structures revealed using 1 H NMR, 13 C NMR, DEPT, and HMBC, and identified to be bakkenolide B (1), bakkenolide D (2), 1,5-di-O-caffeoylquinic acid (3), and 5-O-caffeoylquinic acid (4). Of these, 3 exhibited the most potent NA inhibitory activity (IC50 = 2.3 ± 0.4 µM). Enzyme kinetic studies revealed that 3 and 4 were competitive inhibitors, whereas 2 exhibited non-competitive inhibition. Furthermore, a molecular docking simulation revealed the binding affinity of these compounds to NA and their mechanism of inhibition. Negative-binding energies indicated high proximity of these compounds to the active site and allosteric sites of NA. Therefore, PJA has the potential to be further developed as an antibacterial agent for use against diseases associated with NA.

Arousal with iv epinephrine depends on the depth of anesthesia.

PURPOSE: To investigate whether the depth of anesthesia affects the change in the bispectral index (BIS) caused by iv epinephrine during propofol anesthesia. METHODS: Forty women undergoing elective lower abdominal surgery received a propofol target controlled infusion (TCI) to maintain a modified Observer's Assessment of Alertness/Sedation (OAA/S) score of 2 (sedation period). Subsequently anesthesia was induced with propofol TCI 5 mug.mL(-1) and rocuronium 0.9 mg.kg(-1), and propofol continued so as to maintain general anesthesia at a BIS of 50 (general anesthesia period). Intravenous epinephrine at a dose of 10 mug.5 mL(-1) in normal saline (epinephrine group, n = 20) or normal saline 5 mL (control group, n = 20) was administered during both periods. The BIS, mean arterial pressure (MAP) and heart rate (HR) were measured immediately before, and one, two, three, four, six, eight, and ten minutes after injection. The modified OAA/S scale was evaluated during the sedation period. RESULTS: There was no significant change in the modified OAA/S scale, BIS, or hemodynamic variables compared to preinjection values during either sedation or general anesthesia in the control group. Intravenous epinephrine increased the BIS and modified OAA/S scale during sedation, but there was no increase in BIS during general anesthesia. Increases in HR and MAP were observed during both periods after iv epinephrine. CONCLUSION: Intravenous epinephrine 10 mug resulted in an arousal effect and an increase in BIS during sedation, but did not change the BIS during general anesthesia. These results suggest that the arousal effect of iv epinephrine during propofol anesthesia depends on anesthetic depth.