Clinical research progress on drugs for non-alcoholic steatohepatitis treatment / 药学学报

Nonalcoholic steatohepatitis (NASH) is the leading chronic liver disease worldwide. NASH is commonly associated with metabolic risk factors, including obesity, hypertension, and diabetes. Hepatic glucose and lipid metabolism disorder, bile acid toxicity, oxidative stress, inflammation, fibrosis, intestinal dysbacteriosis, and susceptibility gene variation are involved in the pathogenesis of NASH. Drug development for NASH has been slow, this article focuses on the clinical research and development of several promising NASH drugs and their mechanisms, such as drugs targeting gut-liver axis, improving metabolism, inhibiting inflammation and fibrosis.

Effect of Gualou Xiebai Banxiatang on Expression of Gal-3 in Rats After Myocardial Infarction / 中国实验方剂学杂志

Objective:To observe the effect of Gualou Xiebai Banxiatang（GXBT） on cardiac function and myocardial fibrosis in rats after myocardial infarction. Method:The 36 male SD rats were randomly divided into blank group, sham group and surgical group, and 6 males in blank group and sham operation group. The model of phlegm obstruction in myocardial infarction of rats was replicated by ligation of left anterior descending coronary artery and high fat diet, and the successful rats were randomly divided into 3 groups: model group, GXBT group and acertil group. In the sham group, only the threading was not ligated. The blank group and the sham group and the model group were given 10 mL·kg-1·d-1 of normal saline, and 2.68 g·kg-1·d-1 of the GXBT group were given intragastric administration，and 0.36 mg·kg-1·d-1 was given intragastrically in acertil group. After 4 weeks of model, the heart function was detected by heart ultrasound to verify the success of the model. After 8 weeks, the heart function of the heart of the rat was detected by heart ultrasound again, and then the samples were sacrificed. The pathological changes of the myocardial cells of the rats were observed with hematoxylin-eosin(HE) staining， and the degree of myocardial fibrosis in the rats was observed by Masson staining. The changes of serum B-type natriuretic peptide (BNP) and galectin-3 (Gal-3) in rat serum were detected by enzyme-linked immunosorbent assay（ELISA） method, and the expression of Gal-3, Collagen Ⅰ (Col-Ⅰ) and Collagen Ⅲ (Col-Ⅲ) was detected by Western blot. Result:Compared with blank group and sham group, the left ventricular ejection fraction (EF) and short-axis shortening rate (FS) of model group were significantly decreased (P<0.01)， the infiltration of inflammatory cells, the increase of the myocardial collagen fibers, the contents of BNP and Gal-3 in the serum were increased (P<0.05). The expression of Gal-3,Col-Ⅰ and Col-Ⅲ in the myocardial tissue increased significantly (P<0.01). Compared with the model group, EF and FS of GXPD were significantly increased (P<0.05), the morphological structure of myocardial cells was improved, the collagen fiber was decreased. The expression of BNP and Gal-3 in serum decreased significantly (P<0.05), and the content of Gal-3, Col-Ⅰ and Col-Ⅲ in myocardial tissue was decreased (P<0.05). Conclusion:Gualou Xiebai Banxiatang can improve cardiac function, reduce myocardial fibrosis and slow down the process of heart failure after myocardial infarction in rats with myocardial infarction. Its mechanism may be related to the decrease of Gal-3 expression.

Quantitative structure activity relationship models based on heuristic method and gene expression programming for the prediction of the pK(a) values of sulfa drugs / 药学学报

Quantitative structure-property relationships (QSPR) were developed to predict the pK(a) values of sulfa drugs via heuristic method (HM) and gene expression programming (GEP). The descriptors of 31 sulfa drugs were calculated by the software CODESSA, which can calculate constitutional, topological, geometrical, electrostatic, and quantum chemical descriptors. HM was also used for the preselection of 4 appropriate molecular descriptors. Linear and nonlinear QSPR models were developed based on the HM and GEP separately and two prediction models lead to a good correlation coefficient (R) of 0.90 and 0.95. The two QSPR models are tseful in predicting pK(a) during the discovery of new drugs and providing theory information for studying the new drugs.

Tumstatin185-191 increases the sensitivity to cisplatin in a cisplatin-resistant human lung adenocarcinoma cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects and related mechanisms of Tumstatin 185-191 as a single agent or in combination with cisplatin on proliferation and apoptosis in a cisplatin-resistant human lung adenocarcinoma cell line A549-DDP cells.</p><p><b>METHODS</b>A549-DDP cells were treated with Tumstatin185-191 and cisplatin at varying concentrations. Cell viability was assessed by a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 50% inhibiting concentration (IC(50)) values of the chemotherapeutic drugs were analyzed by MTT assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and ERK was evaluated by Western blotting.</p><p><b>RESULTS</b>Tumstatin185-191 inhibited the proliferation of A549-DDP cells and its IC(50) value was 80.25 micromol/L. After cotreatment with 20 micromol/L Tum185-191, the IC(50) value of cisplatin in A549-DDP cells reduced from 77.16 micromol/L to 57.97 micromol/L, the reverse index was 1.33, while with 40 micromol/L Tumstatin185-191 the IC(50) was reduced from 77.16 to 26.40 micromol/L and the reverse index was 2.92. The early apoptosis rate was 19.5% +/- 1.1% in the cotreatment group, while 13.3% +/- 1.5% in cisplatin group and 10.2% +/- 2.0% in Tum185-191 group (F = 4.09, P < 0.05). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549-DDP cells were remarkably lower after treatment with Tumstatin 185-191. The Tumstatin 185-191 treatment alone or in combination with cisplatin had a similar effect on the protein levels of p-Akt and p-ERK in A549-DDP cells.</p><p><b>CONCLUSION</b>Our data suggest that Tumstatin185-191 may promote apoptosis, downregulate proliferation and partly reverse the drug resistance of A549-DDP cells to cisplatin. The effects induced by Tum185-191 may be mediated through inactivation of the Akt and ERK pathways.</p>

Determination of tetrandrine and fangchinoline in Radix Stephaniae tetrandrae and its preparation by nonaqueous capillary chromatography / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a new method for the determination of fangchinoline and tetrandrine in Stephania tetrandra and Fengtongan capsule by noanqueous capillary electrophoresis.</p><p><b>METHOD</b>Separation was carried out in an uncoated fused capillary (50 cm x 75 microm i.d.) with a running buffer containing 50 mmol x L(-1) ammonium acetate, 1.0% acetic acid and 20% acetonitrile in methanol. A separation voltage of 20 kV and a UV detector wavelength at 214 nm were adopted. Sample was introduced from the anode.</p><p><b>RESULT</b>The calibration ranges were 1.00, 500 mg x L(-1) for both analytes. Under the optimum conditions, the relative standard deviation (RSD, n = 6) for the migration time of each analyte were 0.09%, 1.9% (intra-day) and 0.63%, 1.9% (inter-day); The RSD for the peak area of each analyte were 0.45%, 5.9% (intra-day) and 2.3%, 5.6% (inter-day), respectively. The contents of the analytes were determined easily with average recoveries 102% for fangchinoline and 105% for tetrandrine in S. tetrandra and 94.6% for fangchinoline and 98.7% for tetrandrine in Fengtongan capsules, respectively.</p><p><b>CONCLUSION</b>The proposed method is simple, rapid, accurate and higher repeatable, and can be used to control of the quality of S. tetrandra and Fengtongan capsules.</p>