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Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 μmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 μmol·L-1, respectively.
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Flavonoids/chemistry , SARS-CoV-2 , Rhizome , COVID-19 , Peptide Hydrolases , Antiviral Agents/chemistryABSTRACT
OBJECTIVE：To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS ：Totally 32 rats were randomly divided by random number table method into normal control group ，yunacotine low-dose and high-dose groups （0.09，0.14 mg/kg），aconitine group （positive control ，0.88 mg/kg），with 8 rats in each group. Administration groups were given the corresponding drugs once a day ，and normal control group was given the constant volume of normal saline ，for consecutive 7 d. After last intragastric administration ，the changes of electrocardiogram （ECG） were observed. The contents of adenosine triphosphate（ATP）in myocardial tissue and Ca 2+ in myocardial cells ，the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2（RyR2）and Ca 2+-ATPase（SERCA2）in myocardial tissue were determined. RESULTS：Compared with normal control group ，time limit of QRS wave and QTc intervals of rats were prolonged significantly in yunaconitine low-dose group （P＜0.01）. The content of Ca 2 + in myocardial cells ， the ATP contents ， the activities of Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly （P＜0.05 or P＜0.01）. The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly （P＜ 0.05 or P＜0.01），and time limit of QRS wave and QTc intervals were significantly prolonged （P＜0.01）；the content of Ca 2+ in myocardial cells was increased significantly （P＜0.01）；ATP content ，the activities of Ca 2+-Mg2+-ATPase and Na +-K+-ATPase，and protein expression of RyR 2 and SERCA 2 in myocardial tissue were decreased significantly （P＜0.01）. CONCLUSIONS ： Yunaconitine can induce arrhythmia in rats ，the mechanism of which may be associated with Ca 2+ overload that resulted from reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.
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OBJECTIVE：To study the effect of isofla vaspidicacid PB （called PB for short ）on the biofilm adhesion and the gene expression of ergosterol metabolism related enzymes in Trichophyton rubrum . METHODS ：M38-A2 method was adopted to determine MIC of PB to T. rubrum . MTT assay was used to screen the biolfilm condition and initial adhesion period of T. rubrum . The effects of different concentrations of PB （40，80，160 µg/mL）on the adhesion duration of T. rubrum （growth control group without PB was set up ，similarly hereinafter ）were evaluated and the adhesion rate was calculated by using XTT assay ；the effects of different concentrations of PB （20，40，80 µg/mL）on the biofilm formation of T. rubrum at different initial adhesion periods （3，5，9 h）were observed and the adhesion rate was calculated by using XTT assay combined with inverted microscope ；qRT-PCR method was used to detect the effects of PB （320 µg/mL）on the mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11 in biofilm of T. rubrum . RESULTS ：MIC of PB to T. rubrum was 20 µg/mL. The biofilm of T. rubrum in RPMI-1640 medium containing 10％ FBS was the most metabolism activity at 6 h of initial adhesion. Compared with growth control group ，after treated with different concentrations of PB ，adhesion rate and mRNA expression of ERG6 and ERG11 in biofilm were decreased significantly （P＜0.01）. Hyphae decreased or even disappeared ，and the adhesion inhibition rate （at 5 and 9 h of initial adhesion ）increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：PB can inhibit the adhesion of T. rubrum and reduce the hyphae ；the mechanism may be associated with the inhibition of the biofilm adhesion and mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11.
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OBJECTIVE：To study the effects of different penetration enhancers on in vitro transdermal permeation of Flavaspidic acid BB cream. METHODS ：Flavaspidic acid BB cream was prepared ，containing 11 kinds of different penetration enhancers as 1％ azone，2％ azone，3％ azone，4％ azone，1％ menthol，1％ propylene glycol ，1％ oleic acid ，1％ azone+1％ menthol，1％ azone+1％ propanediol，1％ azone+1％ oleic acid or 1％ menthol+1％ propanediol. Modified Franz diffusion cell was adopted using abdominal skin of isolated male rat as transdermal barrier. The content of flavaspidic acid BB was determined by UPLC. The accumulative transdermal amount （Q24 h）and percutaneous permeability （Jss）within 24 h were calculated ；and compared with Flavaspidic acid BB cream without transdermal enhancer ，the enhancement ratio （ER）was calculated. RESULTS ： Q24 h of Flavaspidic acid BB cream with above 11 kinds of transdermal enhancers were （82.96±7.15），（80.17±0.66），（78.22± 1.87），（73.53±1.24），（35.65±2.23），（34.02±1.73），（42.68±2.66），（33.94±1.37），（34.16±1.54），（46.78±1.21），（43.66±1.69） μg/cm2，respectively. Jss value were （5.26±0.10），（4.69±0.12），（4.45±0.45），（4.00±0.06），（3.74±0.33），（3.23±0.18）， （3.73±0.53），（3.14±0.47），（3.54±0.11），（3.98±0.34），（4.34±0.14）μg（/ cm2·h），respectively. ER were 2.055，1.831，1.738， 1.564，1.462，1.263，1.456，1.227，1.385，1.557，1.698，respectively. CONCLUSIONS ：All of the above transdermal absorption enhancers can enhance the percutaneous absorption of Flavaspidic acid BB cream ，among which ，1％ azone is the best.
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Traditional Chinese Medicine (TCM) is an important reservoir for bioactive natural products. TCM extraction methods by water decoction and wine tincture are an integral part of TCM and essential for their widely acknowledged efficacy. In this study, we selected 6 common TCMs that are rich in chemistry to investigate whether the TCM extraction methods deliver molecules with drug-like physical chemical properties. Six TCM herbal materials were extracted by water, 95% ethanol, and sequential hexane, dichloromethane and methanol. The extracts were analyzed by HPLC and H NMR. Isolation on one of the extracts yielded 32 compounds, their physical chemical properties were analyzed by Instant JChem. Our results showed that ethanol extraction, which mimics TCM wine tincture, delivered compounds with physical chemical properties compliant to Lipinski's rule of 5.
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Objective To investigate the effects of four interior-warming drugs( galangal,cinnamon,evodia rutaecarpa,and dried ginger)on the tension of ileum smooth muscle and Ca2+-ATPase on the cell membrane in rabbits. Methods The effects of galangal,cinnamon,evodia rutaecarpa,and dried ginger were examined on normal ileum smooth muscle,in vitro intestinal muscle contraction caused by acetylcholine(ACh),barium chloride(BaCl2 )and histamine(His), and ACh-induced calcium release by using BL-420E+ biological signal collection and processing system.The average tension was measured within 1 min before delivery and within 3 minutes after the treatment,and the inhibition rate was calculated according to the average tension value.The effects of sera containing galangal,cinnamon,evodia rutaecarpa,and dried ginger on Ca2+-ATPase activity on the cell membrane of the intestinal smooth muscle were examined by phosphorus method. Results Galangal,cinnamon,evodia rutaecarpa,and dried ginger at high concentrations could restrain in vitro intestinal contraction in normal circumstances(P<0.05 or P<0.01).Significant inhibitory effects on intestinal contraction caused by ACh,His and BaCl2 were found in low,medium and high concentration groups(P<0.01).There was a dose-effectiveness relationship between the inhibition rate and final drug concentrations.The ACh-induced intracellular and extracellular calcium dependent contraction were significantly inhibited by the four interior-warming drugs( P < 0. 05 or P < 0. 01). The Ca2+-ATPase activities were( 0. 384 ± 0.070),(0.302±0.016),(0.307±0.016),(0.296±0.016),(0.313±0.003)U·mg-1 ,respectively,in intestinal smooth muscle in normal control group and high concentration groups of galangal,cinnamon,evodia rutaecarpa,and dried ginger(P<0.01). Conclusion Interior-warming drugs may relax intestinal smooth muscle by reducing the intracellular calcium release and the extracellular calcium inflow via receptor-controlled calcium channels,and inhibiting the Ca2+-ATPase activity in smooth muscle.
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Objective To investigate the efficacy of dual plating internal fixation with olecranon osteotomy approach for the emergency surgery of complex distal humeral fractures (intereondylar and supracondylar fracture).Methods Forty-seven cases of complex distal humeral fractures were treated with emergency surgery from May 2002 to May 2007.The dual plating internal fLxation was implemented with olecranon osteotomy approach in a posteubital slight arc shaped median incision.Early postoperative rehabilitation was necessary.Results The follow-up period differed from 5 to 50 months,averaged 18 months.All fractures healed in 3-6 months after surgery.The Cassebaum scoring system was used for the assessment of cubital joint function,36 cases were excellent,4 cases were good,5 cases were common,and 2 cases were bad.The excellent and good rate was 85.1%.Conclusions For complex distal humeral fractures,dual plating internal fixation emergency surgery with olecranon osteotomy approach ensures the early postoperative rehabilitation of the cubital joint and the maximum possible functional recovery.It shows the efficacy is satisfactory.
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OBJECTIVE: To study the effect of total flavonoids from Alpinia officinarum on gastrointestinal motility.METHODS: Gastric emptying method was applied to observe the effect of total flavonoids from A.officinarum on gastric emptying of normal mice and sthenic gastric emptying induced by pyridostigmine bromide.Effect of total flavonoids from A.officinarum on gastric smooth muscle of rats was observed through in vitro test and small intestine advancement was used to observe the influence of total flavonoids from A.officinarum on intestinal motility.RESULTS: Total flavonoids from A.officinarum had no significant influence on gastric emptying of normal mice,but distinctly inhibited sthenic gastric emptying induced by pyridostigmine bromide(P
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Objective To investigate the features of brainstem auditoryresponses (BAR) in patients with attention deficit and hyperactive disorder (ADHD), mental retardation and conduct disorder. Methods BAR in children with ADHD ( n =37), mental retardation (MR, n =24) and conduct disorder (CD, n =22), and in normal children ( n =30) were measured by use of Nicolet Spirit electrophysiological instrument delivering stimulation of Clicks. Results The absolute latencies (AL) of wave Ⅲ、Ⅴ recorded from Fz region (WⅢ、Ⅴ/Fz) and wave Ⅲ from Pz region (WⅢ/Pz) as well as the absolute amplitudes (AA) of WⅢ/Fz and WⅤ/Pz were significantly different ( P
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Aim To probe into the best conditions for the establishment of endometriosis model in rats by the orthogonal experiment method.Methods Autotransplantation was used to establish the endometriosis model in rats by the orthogonal experiment method in which four main factors were considered to optimize the condition of model,according to the volume of heterotopic endometrium.Results The para ligament of uterus was the best place for transplanting.Both dissecting muscular layer and injecting estrin played an important role in the establishment of endometriosis model in rats. The value of four factors decreased progressively according to the injection of estrin,the dissection of muscular layer,the direction of endometrium implantation and oestrus.Conclusions By optimizing the condition for the establishment of endometriosis model in rats by orthogonal experiment,the volume of heterotopic endometrium was improved.A technology platform for pharmacodynamics research was thus offered.
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Objective To investigate the clinical application of various parameters of visual evoked potential (VEP) and auditory evoked potential (AEP) in patients with attention deficit and hyperactive disorder (ADHD), mental retardation (MR) and conduct disorder (CD). Methods Thirty-seven ADHD patients, 24 MR patients, 22 CD patients and 36 normal subjects were included in this study. The VEP and AEP were recorded from every subject and analyzed. Results A significant difference was found among 4 subject groups, with both latencies (Oz/N_1, P_2) and amplitudes of VEP (Cz/P_2, P_3 and Oz/P_3 ) (P
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AIM: The bacteriostatic effects of Shenning suppository in the treatment of vaginitis were investigated in vivo and in vitro. METHODS: The minimal inhibitory concentration(MIC)against ten clinical pathogens isolates was determined by tube dilution method,minimal bactericide concentration(MBC) was measured by the agar dilution method.The model of vaginitis from Candida albicans in the rabbit was investigated. RESULTS: Shenning suppository could inhibit and/or destroy Staphylococcus aureus,Candida albicans,ect in virto.It also improved the pathological change in the model of vaginitis from Candida albicans in the rabbit. CONCLUSION: Shenning Suppository could treat bacterial and mycotic vaginitis
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AIM To investigate the effect of oral roxithromycin on serum concentrations at steady state and its pharmacokinetics of aminophylline in New Zealand rabbits. METHODS The experiment was divided into 2 stages: (Ⅰ) The subjects only received a four-day course of oral aminophylline until steady-state; (Ⅱ) aminophylline and roxithromycin were coadministrated from the d 5～10. After the last dose of aminophylline at the end of each study stage, serum theophylline concentrations were determined with HPLC. RESULTS Compared to stage Ⅰ, AUC、CL/Fs、 K a、 K e、 T 1/2(ka) 、 T max had significantly changed or very significantly changed at stage Ⅱ ( P