Advances in research of novel coronavirus related drugs and biological products / 药学学报

The novel coronavirus pneumonia was first discovered in December 2019. By February 21, 2020, the virus had spread to 27 countries, and the total number of patients were nearly 80 thousands. In order to effectively prevent and control the epidemic, countries around the world are organizing scientific research, especially in screening of therapeutic drugs, researching and developing of vaccine, which is the key point and difficulty of epidemic control. On the basis of a large number of relevantly collected information about drugs and biological products in the academia and the press of various countries, this paper focus on the research status and development of antiviral chemical drugs, Chinese traditional medicines and biological products, aiming to provide reference for relevant departments, units and scientists.

Global gene expression analysis in liver of db/db mice treated with catalpol / 中国天然药物

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.

Global gene expression analysis in liver of db/db mice treated with catalpol / 中国天然药物

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.

The swelling behavior of choline fenofibrate hydrogel matrix tablets using dynamic image analysis / 药学学报

The purpose of this study is to investigate the effects of formulation on the swelling behavior of choline fenofibrate hydrogel matrix tablets and reveal the relation between swelling property and release profile using dynamic image analysis. The volume swelling ratio (SR) and height/width (k) could evaluate the swelling behavior of matrix tablets well. The mount of hydroxypropyl methylcellulose (HPMC) and the ratio between K15M and K4M affected the volume swelling ratio, while PVP didn't. The three factors all impacted k, which was an indicator of the strength of the gel formed by HPMC. The accumulative release ratio and SR, the rate of swelling and the rate of release were compared. The proper model equations were established for the results with an excellent correlation. The results prove that there is a strong relevance between the swelling behavior and release property. This study provides a guideline in the study design for hydrogel matrix tablets.

Preparation and properties of thermosensitive in situ gel for ophthalmic formulation containing pearl hydrolyzate / 药学学报

The study was designed to generate an ophthalmic thermosensitive in situ gel with improved mechanical and mucoadhesive properties that may prolong the retention time to enhance the bioavalability of pearl hydrolyzate. The gene was comprised of poloxamer 407, poloxamer188 and Carbopol 934, which were optimized by central composite design and response surface methodology. The rheological properties, transcorneal permeability, retention time and in vitro release behaviors of the optimal gel formulation were investigated. The gel was Newtonian liquid at 25℃ and performed as a semisolid gel with non-Newtonian liquid property with a gelation time of 13 s at 35℃. Compared with a conventional eye drops, the ophthalmic in situ gel exhibited a sevenfold increase in retention with a sustained release behavior, which was observed with suitable permeability coefficient at 5.58 cm·s-1. In conclusion, the new gel of pearl hydrolyzate prolonged the release duration of drug, which may decrease the frequency of administration of pearl hydrolyzate. kilometers with ecological similarity between 20% and 40%, mainly in Yunnan, Guangxi, Guangdong, Guizhou, Hainan, Sichuan, Fujian and Chongqing. The climate factors mainly affecting the distribution of Panax notoginseng (Burk.) F. H. Chen were precipitation of warmest quarter, SD of temperature seasonality, altitude, isothermality, coefficient of variation of precipitation seasonality, mean temperature of monthly, precipitation of driest month, reference bulk density of soil and soil texture.

Isoflavonoids from Caragana changduensis and their nitric oxideinhibitory activities / 中国中药杂志

Ten isoflavonoids were isolated from the heartwoods of Caragana changduensis Lion f. by means of various column chromatographic techniques. Based on the detailed spectral data analysis (MS and NMR), as well as comparison with the literatures, their chemical structures were determined as 7,2'-dihydroxy-8,4'-dimethoxyisoflavone (1), 4'-hydroxy-7,3'-dimethoxyisoflavone (2), 5, 7, 4'-trihydroxy-2',5'-dimethoxyisoflavone (3), prunetin (4), afrormosin (5), odoratin (6), genistein (7), texasin (8), pratensein (9), and 6,7,3'-trihydroxy-4'-methoxyisoflavone (10). Among them, compounds 1-3 and 9-10 were isolated from the Caragana genus for the first time. All the compounds were obtained from this species for the first time. In the preliminary assays, compounds 1, 2, 6, and 7 possessed significant inhibitory effects on NO production, with IC50 values of 48.12, 25.32, 62.71, 43.59 μmol x L(-1), respectively.

Determination of contact angle of pharmaceutical excipients and regulating effect of surfactants on their wettability / 药学学报

To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose <magnesium stearate. In addition, surfactants both in droplets and mixed in excipients significantly reduced the contact angle of excipients, and their abilities to lower contact angle varied. The results of the present study offer a guideline in the formulation design of tablets.

Songling Xuemaikang Capsule () for primary hypertension: A systematic review of randomized controlled trials / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness and safety of Songling Xuemaikang Capsule (, SXC) for the treatment of primary hypertension.</p><p><b>METHODS</b>An extensive search including Cochrane Library, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), KoreaMed, Japanese database, and online clinical trial registry websites was performed up to February 2013. Randomized controlled trials (RCTs) regarding SXC for the treatment of primary hypertension were searched without no language restrictions. The quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0, and RevMan 5.0 provided by the Cochrane Collaboration.</p><p><b>RESULT</b>A total of 17 RCTs involving 1,778 patients were included. Meta-analysis showed that there was no significant difference between SXC and antihypertensive agents on systolic blood pressure [mean difference (MD): -0.10 [-4.83, 4.63]; P=0.97] and diastolic blood pressure (MD: 1.00 [-1.16, 3.16]; P=0.36), but SXC combined with antihypertensive drugs was more effective in lowering systolic blood pressure (MD: -6.17 [-7.86, -4.49]; P<0.00001) and diastolic blood pressure (MD: -7.24 [-8.62, -5.85]; P<0.00001) compared with the antihypertensive drugs alone.</p><p><b>CONCLUSIONS</b>SXC used alone or combined with antihypertensive drugs appear to be an effective treatment for lowering elevated blood pressure and improving symptoms in patients with primary hypertension. However, the conclusion cannot be drawn definitely due to the poor quality of the included studies. There is still an urgent need for well-designed, long-term studies to address the benefits of SXC for treating primary hypertension.</p>

A high-performance liquid chromatography with circular dichroism detector for determination of stereochemistry of 6, 9-oxygen bridge dibenzocyclooctadiene lignans from kadsura coccinea / 中国天然药物

The stereochemistry of two 6, 9-oxygen bridge dibenzocyclooctadiene lignans from Kadsura coccinea, are difficult to separate and very unstable. The present study was designed to develop a high-performance liquid chromatography using circular dichroism detection for the analysis of the stereochemistry. A new 6, 9-oxygen bridge dibenzocyclooctadiene lignans named Kadsulignan Q was firstly found with an S-biphenyl configuration. The other compound was identified as Kadsulignan L with an R- biphenyl configuration. In order to obtain kinetic data on their reversible interconversion, the stability was measured at different deuterated solvents such as deuterated methanol, deuterated chloroform and deuterated dimethylsulfoxide. The lignans were more unstable and converted more easily in deuterated methanol than in deuterated chloroform and deuterated dimethylsulfoxide.

Effects of ultrahigh pressure extraction on yield and antioxidant activity of chlorogenic acid and cynaroside extracted from flower buds of Lonicera japonica / 中国天然药物

The present study was designed to establish and optimize a new method for extracting chlorogenic acid and cynaroside from Lonicera japonica Thunb. through orthogonal experimental designl. A new ultrahigh pressure extraction (UPE) technology was applied to extract chlorogenic acid and cynaroside from L. japonica. The influential factors, including solvent type, ethanol concentration, extraction pressure, time, and temperature, and the solid/liquid ratio, have been studied to optimize the extraction process. The optimal conditions for the UPE were developed by quantitative analysis of the extraction products by HPLC-DAD in comparison with standard samples. In addition, the microstructures of the medicinal materials before and after extraction were studied by scanning electron microscopy (SEM). Furthermore, the extraction efficiency of different extraction methods and the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of the extracts were investigated. The optimal conditions for extracting chlorogenic acid and cynaroside were as follows: ethanol concentration, 60%; extraction pressure, 400 MPa; extraction time, 2 min; extraction temperature, 30 °C; and the solid/liquid ratio, 1 : 50. Under these conditions, the yields of chlorogenic acid and cynaroside were raised to 4.863% and 0.080%, respectively. Compared with other extraction methods, such as heat reflux extraction (HRE), ultrasonic extraction (UE), and Sohxlet extraction (SE), the UPE method showed several advantages, including higher extraction yield, shorter extraction time, lower energy consumption, and higher purity of the extracts. This study could help better utilize L. japonica flower buds as a readily accessible source of natural antioxidants in food and pharmaceutical industries.

The rheology properties of common hydrophilic gel excipients / 药学学报

To investigate theological properties of common hydrophilic gel excipients such as Carbopol based on viscosity, the viscosity was determined by rotation method and falling-ball method. Linear regression was made between ln(eta) and concentration, the slope of which was used to explore the relation between viscosity and concentration of different excipients. The viscosity flow active energy (E(eta)) was calculated according to Arrhenius equation and was used to investigate the relation between viscosity and temperature of different excipients. The results showed that viscosities measured by two methods were consistent. Concentration of guargum (GG) and hydroxypropylmethyl cellulose (HPMC) solution had a great influence on the viscosity, k > 5; while concentration of polyvinylpyrrolidone-K30 (PVP-K30) and polyethylene glycol 6000 (PEG6000) exerted a less effect on viscosity, k < 0.2; viscosity flow active energy of different excipients were close, which ranged from 30 to 40 kJ x mol(-1). Therefore, theological properties study could provide the basis for application of excipients and establish a foundation for the research of relation between excipients structure, property and function.

Role of opioid receptors in protective effects of isoflurane- induced delayed preconditioning against myocardial ischemia-reperfusion injury in rabbits / 中华麻醉学杂志

Objective To investigate the role of opioid receptors in the protective effects of isoflurane-induced delayed preconditioning against myocardial ischemia-reperfusion (I/R) injury in rabbits. Methods Forty male New Zealand white rabbits weighing 2.0-2.5 kg were randomly assigned into 4 groups ( n = 10 each) : group I sham operation (S); group II I/R; group Ⅲ isoflurane + I/R (Iso) and group IV Iso + naloxone + I/R (Nal). Myocardial I/R was induced by 40 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 120 min reperfusion. In group Ⅲ (Iso) 2% isoflurane in 100% O2 was inhaled for 2 h and I/R was produced 24 h later. In group IV (Nal) naloxone 6 mg/kg was given iv 10 min before 2 h of 2% isoflurane inhalation and I/R was produced 24 h later. At the end of 120 min reperfusion, infarct size (IS) and area at risk (AAR) were determined by Evan's blue and TTC staining. Myocardial ultrastructure was examined by electron microscopy. The phosphorylated p38MAPK protein expression in myocardium was determined by Western blot. Results The IS was significantly smaller in group Iso ( Ⅲ ) ( 19.7% ± 2.8%) than in I/R group ( II ) (37.8% ±1.7%) (P<0.05). The phosphorylated p38MAPK protein expression in myocardium was significantly lower in group Iso than in group I/R. Microscopic examination showed less myocardial damage in Iso group than in group I/R. The protective effects of delayed preconditioning by isoflurane was prevented by naloxone pretreatment. ConclusionOpioid receptors may be involved in the protective effects of delayed preconditioning by isoflurane against myocardial I/R injury.

Adenovirus mediated gene transfer of tyrosinase gene on HepG2 cell by magnetic resonance imaging / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the transfect results of recombinant adenovirus vector carrying tyrosinase gene (Ad-tyr) in vitro by magnetic resonance imaging (MRI) after the Ad-tyr was transfected into HepG2 cell.</p><p><b>METHODS</b>The Ad-tyr which carried the full-length cDNA of tyrosinase gene was transfected into HepG2 cell. The transfected cells were scan by MRI sequences of T1 weighted image (T1WI) , T2 weighted image (T2WI) , and short time inversion recovery (STIR) to observe the MRI signals of expressed melanin. Masson-Fontana staining was performed to search for melanin granules in transfected cells. Real-time PCR method was used to search for cDNA of tyrosinase gene.</p><p><b>RESULTS</b>Ad-tyr was transfected into HepG2 cells and synthesized a large amount of melanin inside. The synthesized melanin of 1 x 10(6) cells which had been transfected by Ad-tyr with the 50, 150, and 300 multiplicity of infection separately were all sufficient to be detected by MRI and showed high signals in MRI T1WI, T2WI, and STIR sequences. The signal intensities of MRI were positively correlated to the amounts of transfected Ad-tyr. The melanin granules were found in HepG2 cells in Masson-Fontana staining. The cDNA amount of tyrosinase gene in transfected HepG2 cells, which was detected by real-time PCR, was remarkably higher than that in nontransfected cells.</p><p><b>CONCLUSION</b>The synthesized melanin of HepG2 cells, which controlled by expression of exogenous gene, can be detected by MRI, indicating that the adenovirus vector can efficiently carry the tyrosinase gene into HepG2 cells.</p>