The effect of compatibility of Aconiti Radix and honey on the pharmacokinetics of five Aconitum alkaloids in rat plasma.

Aconiti Radix [Chuanwu (CW)] is widely used to treat chronic and intractable diseases due to its remarkable curative effect. CW has been combined with honey for thousands of years to reduce toxicity and enhance efficacy. This study first determined the compatibility mechanism of CW with honey using a comparative pharmacokinetic concept. We developed and validated a simple, sensitive, specific, and accurate UHPLC-MS/MS method to simultaneously determine five Aconitum alkaloids in rat plasma after the oral administration of CW decoction and CW-honey concentrated solution. Pharmacokinetic parameters were significantly different between the two groups (P < 0.01 and P < 0.05). Compared with the CW group, Cmax and AUC0 → t decreased in the CW-honey group for three diester-diterpenoid alkaloids (hypaconitine, mesaconitine, and aconitine); Tmax and T1/2 were prolonged. However, Cmax and AUC0 → t increased in the CW-honey group for two monoester-diterpenoid alkaloids (benzoylaconine and benzoylmesaconine); Tmax was shortened, and T1/2 was prolonged. These findings suggest that honey affected the pharmacokinetic behaviors of five Aconitum alkaloids. We speculate that the detoxification and synergism of honey might result from reducing the toxicity of diester-diterpenoid alkaloids and promoting the biological activity of monoester-diterpenoid alkaloids in vivo. This study provides a theoretical basis for the clinical use of CW combined with honey.

Identification of raloxifene as a novel α-glucosidase inhibitor using a systematic drug repurposing approach in combination with cross molecular docking-based virtual screening and experimental verification.

α-Glucosidase is a promising target for the treatment of diabetes. Drug repurposing can increase the chances of discovering an active inhibitor. Therefore, this study aimed to identify potential α-glucosidase inhibitor using drug repurposing and in silico strategies. We identified critical amino acid residues of the three α-glucosidase proteins. Based on cross molecular docking studies of three α-glucosidase proteins and drugs in the FDA database, we screened hits with the favorable binding affinities and modes targeting the three proteins. Subsequently, an in vitro activity assay showed that raloxifene was an excellent inhibitor of α-glucosidase. Moreover, molecular dynamics simulations of raloxifene and three proteins were performed to assess the stability of the protein-hit systems in physiological conditions and clarify protein-hit interactions. We also performed the binding free energy calculation, Hirshfeld surface and alanine scanning mutagenesis analyses. These results demonstrated that binding between raloxifene and the three proteins was stable, and the critical amino acid residues of the three proteins formed stable contacts with raloxifene. The molecular mechanisms agree well with its activity, reinforcing that raloxifene is a candidate α-glucosidase inhibitor. Our study smoothes the path for the development of novel a-glucosidase inhibitors with high efficacy and low toxicity for the treatment of diabetes.

[Analysis of the effect of sequential high-flow nasal canula oxygen therapy in post-extubation mechanically ventilated patients in intensive care unit].

OBJECTIVE: To observe the application effect of high-flow nasal canula oxygen therapy (HFNC) after extubation in patients with mechanical ventilation (MV) in the intensive care unit (ICU). METHODS: A prospective study was conducted. From January 2018 to June 2020, 163 MV patients admitted to Yijishan Hospital of Wannan Medical College were enrolled, and they were divided into HFNC group (82 cases) and traditional oxygen therapy group (81 cases) according to the oxygen therapy model. The patients included in the study were given conventional treatment according to their condition. In the HFNC group, oxygen was inhaled by a nasal high-flow humidification therapy instrument. The gas flow was gradually increased from 35 L/min to 60 L/min according to the patient's tolerance, and the temperature was set at 34-37 centigrade. The fraction of inspiration oxygen (FiO2) was set according to the patient's pulse oxygen saturation (SpO2) and SpO2 was maintained at 0.95-0.98. A disposable oxygen mask or nasal cannula was used to inhale oxygen in the traditional oxygen therapy group, and the oxygen flow was 5-8 L/min, maintaining the patient's SpO2 at 0.95-0.98. The differences in MV duration before extubation, total MV duration, intubation time, reintubation time, extubation failure rate, ICU mortality, ICU stay, and in-hospital stay were compared between the two groups, and weaning failure were analyzed. RESULTS: There was no significant differences in MV duration before extubation (days: 4.33±3.83 vs. 4.15±3.03), tracheal intubation duration (days: 4.34±1.87 vs. 4.20±3.35), ICU mortality [4.9% (4/82) vs. 3.7% (3/81)] and in-hospital stay [days: 28.93 (15.00, 32.00) vs. 27.69 (15.00, 38.00)] between HFNC group and traditional oxygen therapy group (all P > 0.05). The total MV duration in the HFNC group (days: 4.48±2.43 vs. 5.67±3.84) and ICU stay [days: 6.57 (4.00, 7.00) vs. 7.74 (5.00, 9.00)] were significantly shorter than those in the traditional oxygen therapy group, the reintubation duration of the HFNC group was significantly longer than that of the traditional oxygen therapy group (hours: 35.75±10.15 vs. 19.92±13.12), and the weaning failure rate was significantly lower than that of the traditional oxygen therapy group [4.9% (4/82) vs. 16.0% (13/81), all P < 0.05]. Among the reasons for weaning failure traditional oxygen therapy group had lower ability of airway secretion clearance than that of the HFNC group [8.64% (7/81) vs. 0% (0/82), P < 0.05], there was no statistically differences in the morbidity of heart failure, respiratory muscle weakness, hypoxemia, and change of consciousness between the two groups. CONCLUSIONS: For MV patients in the ICU, the sequential application of HFNC after extubation can reduce the rate of weaning failure and the incidence of adverse events, shorten the length of ICU stay.

[Effect of taspine hydrochloride on skin wound healing in rats and its mechanism].

OBJECTIVE: To study the effect of taspine hydrochloride (TA/HCl) on skin wound healing in rats and its mechanism. METHODS: Bilateral round wounds were made on the backs of SD rats. The effect of TA/HCl on the skin wound was evaluated through determining closure time and contracting ability of the skin wound, observing histopathological characteristics and measuring contents of hydroxyproline (Hyp) and protein in the wound tissue. RESULTS: The closure time of the skin wounds was significantly shorter in the TA/HCl-treated groups than that in the model group. The percentages of wound contraction were higher in the TA/HCl-treated groups than that in the dimethyl sulfoxide (DMSO) control group of the same group (P<0.05 or P<0.01) on the 3rd to 14th days after wounding. The content of the protein in the wound tissue in the TA/HCl-treated group (2 mg/ml) was higher than that in the model group (P<0.05) on the 3rd to 7th days after wounding, and it arrived at the peak on the 7th day and gradually decreased to the normal level in skin tissue on the 14th to 21st days after wounding. The contents of Hyp in the wound tissues in the TA/HCl-treated groups were higher than that in the model group (P<0.05 or P<0.015) on the 3rd to 21st days after wounding, and they arrived at the peak on the 14th day and at the normal level in skin tissue on the 21st day. Histopathological test results showed that TA/HCl could promote the formation of newly born capillaries in the early period of the wound healing. CONCLUSION: TA/HCl has the ability of promoting skin wound healing in rats, and it can also accelerate the growth of newly born capillaries and raise the production of protein and collagen in wound tissue.