To evaluate the bioequivalence of domestic duloxetine hydrochloride enteric-coated tablets and original enteric-coated capsules in Chinese healthy subjects.

In a random, open, two periods, two sequence, self-crossover study, 40 cases healthy subjects in fasting test and 48 cases healthy subjects in fed test were given single oral test preparation and reference preparation 20 mg of duloxetine hydrochloride. The concentrations of duloxetine hydrochloride in plasma were determined by high performance liquid chromatography tandem mass spectrometry. The pharmacokinetic parameters were calculated using Phonenix WinNolin 8.0 software, and the bioequivalence of the test and the reference duloxetine hydrochloride was evaluated.

The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fasting test were as follows: C_max were (16.70±5.94) and (16.70±7.10) ng·mL^-1; AUC_0-t were (217.28±98.82) and (222.42±117.98) ng·h·mL^-1; AUC_0-∞ were (225.91±100.35) and (229.40±119.34) ng·h·mL^-1. The main pharmacokinetic parameters of the test and the reference duloxetine hydrochloride in fed test were as follows: C_max were (20.10±9.56) and (21.30±10.90) ng·mL^-1; AUC_0-t were (266.99±146.66) and (273.22±168.09) ng·h·mL^-1; AUC_0-∞ were (277.83±154.73) and (283.51±174.63) ng·h·mL^-1. The 90% confidence intervals of the main pharmacokinetic parameters of the test and reference preparations in fasting and fed tests were between 80.00%-125.00%.

The test and the reference duloxetine hydrochloride were bioequivalent under fasting and fed conditions.

To explore the underlying mechanism of TanshinoneⅡA (TanⅡA) exerted in myocardial infarction (MI) through nuclear factor E2-related factor 2 (NRF2)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/pyroptosis axis.

SD rats were randomly divided into sham operation group [only exposed the heart without left anterior descending (LAD) ligation], model group (LAD ligation) and experimental group (LAD ligation and 10 mg·kg^-1 TanⅡA). 2,3,5-Triphenyte-trazoliumchloride (TTC) staining was used to detect the area of infarction; Western blot was utilized to investigate the expression level of NRF2, NLRP3 and gasdermin D (GSDMD) in myocardial tissue. The H9c2 cells were divided into blank group (normal culture), model group [oxygen-glucose deprivation (OGD) culture], control group (normal culture and 40 μmol·L^-1 TanⅡA) and combined group (OGD culture and 40 μmol·L^-1 TanⅡA). Western blot was utilized to investigate the expression level of NRF2, GSDMD in cardiomyocyte. Creatine kinase MB (CK-MB) in cell culture supernatant were detected by automatic biochemical analyzer.

The proportion of myocardial infarction area in the sham operation group, model group and experimental group were 0, (58.64±13.41)% and (41.69±8.73)%, respectively; the relative expression of NLRP3 protein were 1.01±0.10, 2.12±0.26 and 1.48±0.11, respectively; the relative expression of GSDMD protein were 1.03±0.17, 2.22±0.20 and 1.40±0.17, respectively; the relative expression of NRF2 protein were 1.12±0.29, 0.51±0.02 and 0.96±0.10, respectively; the indicators of the model group compared with the sham operation group, and the indicators of the experimental group were compared with the model group, the differences were statistically significant (all P<0.05). The CK-MB in blank group, model group, control group and combined group were (54.30±19.24), (208.60±38.19), (46.76±13.63) and (126.10±42.87) U·L^-1, respectively; the relative expression of NRF2 protein were 1.37±0.14, 0.44±0.08, 1.34±0.17 and 0.79±0.11, respectively; the relative expression of GSDMD protein were 0.95±0.26, 1.97±0.17, 1.04±0.20 and 1.16±0.16, respectively. The indicators of the model group compared with the blank group, and the indicators of the combined group were compared with the model group, the differences were statistically significant (all P<0.05).

TanⅡA can alleviate myocardial infarction-induced myocardial injury through regulation NRF2/NLRP3/pyroptosis axis.

To evaluate the bioequivalence of montelukast sodium chewable tablets test formulation and reference formulation in Chinese healthy subjects.

A single-center, single-dose, two-period, randomized, open-label, self-cross-over design was designed. A single oral dose of montelukast sodium chewable tablets 5 mg was administered under fasting or fed conditions in each period. The blood concentration of montelukast in plasma was determined by liquid chromatography-mass spectrometry, and pharmacokinetic parameters were calculated by SAS 9.4 software.

Twenty-six and 30 cases healthy subjects were included in the fasting and fed groups, respectively. The main pharmacokinetics (PK) parameters of the test formulation and reference formulation in the fasting group: C_max were (331.00±86.00) and (327.08±76.03) ng·mL^-1; AUC_0-t were (2 265.12±560.34) and (2 318.56±589.51) ng·mL^-1·h; AUC_0-∞ were (2 352.60±591.43) and (2 409.12±636.79) ng·mL^-1·h, respectively. The main PK parameters of the test formulation and reference formulation in the fed group: C_max were (262.07±52.94) and (256.73±63.07) ng·mL^-1; AUC_0-t were (2 014.43±356.47) and (2 071.53±462.56) ng·mL^-1·h; AUC_0-∞ were (2 072.30±384.30) and (2 138.57±509.46) ng·mL^-1·h, respectively. The 90% confidence intervals of the geometric mean ratios of the main PK parameters of montelukast in the test formulation and reference formulation in fasting and fed groups were all within 80.00%-125.00%. In the fasting test, a total of 8 cases (32.00%) subjects had 11 adverse reactions, and in the fed test, a total of 11 cases (36.67%) subjects had 18 adverse reactions.

The test and reference montelukast sodium chewable tablets were bioequivalent under fasting and fed conditions.

To investigate the protective effect of Danzhi Jiangtang capsule on kidney of db/db mice with diabetic kidney disease (DKD) and its effects on the autophagy-lysosomal pathway.

The db/db mice were randomly divided into model group (0.2 mL·d^-1 0.9% NaCl), positive control group (45 mg·kg^-1·d^-1 irbesartan) and experimental-H, -M, -L groups (1 800, 900 and 450 mg·kg^-1·d^-1 Danzhi Jiangtang capsule), and another db/m mice were taken as blank group (0.2 mL·d^-1 0.9% NaCl), which were continuously infused for 8 weeks. The expression levels of sequestosome1 (P62), microtubule-associated protein light chain 3 (LC3), transcription factor EB (TFEB), lysosomal associated membrane protein 1 (LAMP-1) and cathepsin D (CTSD) were detected in renal tissues by Western blot.

The relative expression levels of P62 protein in blank group, model group, positive control group and experimental-H,-M,-L groups were 1.00±0.04, 7.66±0.27, 3.52±0.11, 2.21±0.09, 2.86±0.10 and 4.05±0.16; the LC3Ⅱ/Ⅰ levels were 1.00±0.02, 0.17±0.01, 0.71±0.08, 0.86±0.05, 0.80±0.04 and 0.73±0.06; the TFEB protein levels were 1.00±0.01, 0.17±0.01, 0.30±0.01, 0.63±0.01, 0.45±0.01 and 0.42±0.01; the LAMP-1 protein levels were 1.00±0.01, 0.28±0.02, 0.42±0.01, 0.77±0.00, 0.55±0.03 and 0.40±0.02; the CTSD protein levels were 1.00±0.04, 0.27±0.03, 0.47±0.04, 0.73±0.02, 0.63±0.01 and 0.52±0.02. The differences between the above indexes in the experimental-H, -M, -L groups and the model group were statistically significant (all P<0.01).

Danzhi Jiangtang capsule can improved renal damage in db/db mice, which may be related to the repair of autophagy-lysosome pathway, accelerate clearance of abnormal proteins and degradation of organelles.

To investigate the protective effects of monosialotetrahexosylganglioside (GM1) on hypoxic-ischemic brain damage (HIBD) in neonatal rats based on the ubiquitin C-terminal hydrolase L1 (UCH-L1)/brain-derived neurotrophic factor (BDNF) signaling pathway.

Twenty-day-old SD rats were randomly divided into model group, sham group and experimental group, with 10 rats in each group. Rats in model group and experimental group were lapped with left common carotid artery and placed in anoxic chamber with a certain oxygen to nitrogen ratio (8∶92) for 2 h to construct HIBD model. After the successful construction of the model, the experimental group was intraperitoneally injected with 20 mg·kg^-1·d^-1GM1, and the model group and sham group were injected with 0.9 % NaCl (0.25 mL·kg^-1). The modified neurological severity score (mNSS) was used to evaluate the degree of neurological damage in the treated rats. Cerebral infarction was detected by 2,3,5-triphenyte-trazoliumchloride staining method; cerebral water content was determined by wet and dry weight method; cognitive ability was assessed by Morris water maze test; apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; inflammatory factors were detected by enzyme-linked immunosorbent assay; UCH-L1 and BDNF protein levels were detected by Western blot.

After different treatments, the mNSS scores of sham group, model group and experimental group were (0.10±0.02), (2.60±0.45) and (1.50±0.20) points; the cerebral infarction rates were (0.89±0.11)%, (32.56±4.12)% and (18.56±2.52)%; the cerebral water content were (68.25±7.05)%, (88.87±9.26)% and (71.11±8.11)%; the latent period were (22.60±2.86), (38.60±4.11) and (25.50±3.33) s; the platform residence time were (125.50±17.68), (80.60±9.68) and (115.80±13.89) s; the platform crossing times were (2.80±0.35), (0.70±0.09) and (1.80±0.30) times; the apoptosis rates were (6.65±0.74)%, (21.88±3.05)% and (13.62±2.62)%; the tumor necrosis factor-α levels were (30.05±3.85), (121.61±18.85) and (82.14±11.65) pg·mL^-1; the levels of interleukin-1 beta were (92.55±12.15), (321.25±41.24) and (212.32±25.61) pg·mL^-1; interleukin-6 levels were (184.32±20.54), (275.62±31.12) and (208.65±22.65) pg·mL^-1; UCH-L1 protein levels were 1.00±0.22, 1.75±0.34 and 1.40±0.28; BDNF protein levels were 1.00±0.21, 1.68±0.38 and 2.54±0.41. There were statistically significant differences between sham group and model group (P<0.01, P<0.001). There were statistically significant differences between model group and experimental group (P<0.05, P<0.001).

GM1 can improve nerve cell apoptosis and inflammatory response by activating UCH-L1/BDNF signaling pathway, and play a protective role in neonatal rat HIBD.