Total synthesis of dryocrassin ABBA and its analogues with potential inhibitory activity against drug-resistant neuraminidases.

The stems of Dryopteris crassirhizoma, one of the main components of Lianhua-Qingwen Formula (LQF) was traditionally used for heat-clearing and detoxifying. Dryocrassin ABBA is a key antiviral component in the herbal medicine while the compound is hard to get in large amounts with the features of homologous compounds, polyphenol groups, and low contents. Therefore, the present work aims to seek influenza H7N9 virus inhibitors from natural source by synthesis of dryocrassin ABBA and its analogues. As a result, total synthesis of the compound was achieved in nine steps with an over-all yield of 4.6%. Neuraminidases (NAs) inhibitory activities of the synthesized product and its analogues were evaluated afterward. Comparing with the positive control, OSV (9.6 µM), it was very exciting that dryocrassin ABBA and its analogues (b5 and e2) showed better NAs inhibitory activity against Anhui H7N9 with IC50 values of 3.6 µM, 2.5 µM and 1.6 µM. For the highly resistant Shanghai N9, these compounds can also show medium inhibitory activities. Docking results indicated the direct interaction of synthesized 3 hits with the key K294 by hydrogen bonds, but no direct interaction of OSV with the key K294 was observed in Shanghai N9. This study suggested that dryocrassin ABBA and its analogues especially AB, which consisted of polyphenol groups may have beneficial effects on treating avian influenza H7N9 virus.

[Effects of ulinastatin on cognitive function in patients with coronary artery bypass grafting].

OBJECTIVE: To investigate the effects of ulinastatin(UTI) on postoperative cognitive function in patients undergoing coronary artery bypass grafting. METHODS: One hundred and twenty-seven patients undergoing elective coronary artery bypass surgery were randomly divided into three groups:high-dose UTI group(16000 U/kg i.v.), low-dose UTI group(8000 U/kg i.v.) and control group(normal saline). The levels of plasma cortisol were measured before and one day after surgery. The level of IL-6, IL-10, TNF-α and S100ß were measured before operation(T0), at open chest(T1), end of operation(T2), 6 h(T3)and 24 h(T4) after operation. A neuropsychological test scale was to evaluate the cognitive function 1 day before operation, 1 week and 3 months after operation. RESULTS: Ninety-three patients completed the study. There was no significant difference in general information of patients among three groups(P>0.05). The level of plasma cortisol one day after operation was significantly higher than that before operation in control group(P<0.01). The levels of plasma cortisol in high-dose UTI group and low-dose UTI group were lower than that of control group(P<0.01). In all groups, the level of plasma IL-6, IL-10, TNF-α and S100B increased remarkably at T2, T3, T4 compared to those at T0(all P<0.05). The level of plasma IL-6, TNF-α(at T2, T3, T4)and S100ß(at T3)in high-dose UTI group and low-dose UTI group were all lower than those of control group(P<0.05),while there were no significant differences between high-dose UTI group and low-dose UTI group(P>0.05). The incidence of postoperative cognitive dysfunction in POCD 1 week after operation in high-dose UTI and low-dose UTI groups(25.8% and 23.3%)was lower than that in control group(50.0%), while there were no significant difference 1 month after operation between high-dose UTI group(12.9%) or low-dose UTI group(16.7%)and control group(28.1%). The level of plasma S100ß at T2 of POCD patients(n=31)was higher than that of non-POCD group(n=62)(P<0.05). CONCLUSION: Ulinastatin can reduce the incidence of postoperative cognitive dusfunction 1 week after coronary artery bypass surgery, which might be associated with inhibition of inflammation and S100ß expression.