We developed a metabolomic method to evaluate the effect of pirfenidone on rats with acute paraquat (PQ) poisoning, through the analysis of various tissues (lung, liver, kidney, and heart), by gas chromatography-mass spectrometry (GC-MS). Thirty-eight rats were randomly divided into a control group, an acute PQ (20 mg kg) poisoning group, a pirfenidone (20 mg kg) treatment group, and a pirfenidone (40 mg kg) treatment group. Partial least squares-discriminate analysis (PLS-DA) revealed metabolic alterations in rat tissue samples from the two pirfenidone treatment groups after acute PQ poisoning. The PLS-DA 3D score chart showed that the rats in the acute PQ poisoning group were clearly distinguished from the rats in the control group. Also, the two pirfenidone treatment groups were distinguished from the acute PQ poisoning group and control group. Additionally, the pirfenidone (40 mg kg) treatment group was separated farther than the pirfenidone (20 mg kg) treatment group from the acute PQ poisoning group. Evaluation of the pathological changes in the rat tissues revealed that treatment with pirfenidone appeared to decrease pulmonary fibrosis in the acute PQ poisoning rats. The results indicate that pirfenidone induced beneficial metabolic alterations in the tissues of rats with acute PQ poisoning. Rats with acute PQ poisoning exhibited a certain reduction in biochemical indicators after treatment with pirfenidone, indicating that pirfenidone could protect liver and kidney function. Accordingly, the developed metabolomic approach proved to be useful to elucidate the effect of pirfenidone in rats of acute PQ poisoning.

Background: We performed the network meta-analysis (NMA) and systematic review involved all evidence from relevant trials to compare the efficiency and safety of various types of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase-5 inhibitors (PDE5i) in patients with premature ejaculation (PE).Methods: We conducted comprehensive searches of peer-reviewed and grey literature. PubMed, the Cochrane Library Central Register of Controlled Trials, Embase were searched for randomized controlled trials published up to June 1, 2017. The primary outcome was intravaginal ejaculation latency time (IVELT) and adverse effects (AEs). We performed pairwise meta-analyses by random effects model and network meta-analysis by Bayesian model. We used the GRADE framework to assess the quality of evidence contributing to each network estimate.Results: Of 3046 titles and abstracts initially identified, 17 trials reporting 5739 participants were included. Considering IVELT in the NMA, paroxetine plus sildenafil and sildenafil alone are both superior to placebo (MD: 1.75, 95% CrI: 0.05 to 3.78; MD 1.43, 95% CrI 0.003 to 2.81). Sildenafil is superior to sertraline (MD: 1.63, 95% CrI: 0.10 to 2.79). Considering AEs, placebo demonstrated obviously lower risk comparing to paroxetine, sildenafil and paroxetine plus sildenafil (OR 0.20, 95% CI: 0.05 to 0.52; OR 0.23, 95% CI: 0.04 to 0.80; OR 0.45, 95% CI: 0.01 to 0.92). Compared with tadalafil plus paroxetine, dapoxetine showed significantly less AEs (OR 0.23, 95% CI 0.02 to 0.96).Conclusions: Our study concluded that although paroxetine plus sildenafil and sildenafil alone both demonstrated significant IVELT benefit compared with placebo, significant increase of AEs risk was also observed. Furthermore, sildenafil alone was superior to sertraline in efficacy with comparable tolerability.

We developed an ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method for quantification of panasenoside pharmacokinetics in rat plasma and tissue distribution in mouse. Twelve male Sprague-Dawley rats were used for pharmacokinetics after intravenous (2 or 10 mg/kg) administration of panasenoside, six rats for each dose. Thirty mice were randomly divided into six groups (five mice for each group, one group for each time point) and received 20 mg/kg of panasenoside by intraperitoneal administration. Calibration plots were in the range of 2–2000 ng/mL for panasenoside in rat plasma and 2–3000 ng/mL in mouse tissues. The relative standard deviation (RSD) of inter-day and intra-day precision was less than 14%. The accuracy was between 89.6% and 110.0%. The AUC(0–t) was 160.8 ± 13.0 and 404.9 ± 78.0 ng/mL*h, and t1/2 of 3.2 ± 1.2 and 4.6 ± 1.7 h, CL (clearance) of 10.0 ± 2.0, and 21.4 ± 2.0 L/h/kg after intravenous administration 2 mg/kg and 10 mg/kg of panasenoside, respectively. The tissue distribution results indicated that the panasenoside diffuses rapidly and widely into major organs. The level of panasenoside was highest in mouse liver, followed by kidney, lung, and spleen. The overwhelming accumulation in liver indicated that liver was responsible for the extensive metabolism.

Background: Xuezhikang capsule, which contains cholesterol synthase inhibitors and a large number of natural statins, is put in the clinical application of lipid-lowering and so on. However, the specific use of dose, lipid-lowering effect and the relationship between metabolites are to be further studied. Introduction: Metabonomics is the study of the relationship between the change of quantity and physiological changes from metabolites. At present metabolomics has been widely used in drug development and testing. In this study, we developed a metabolomic method based on gas chromatography-mass spectrometry (GC-MS) to find out hyperlipemia-related substances, and study the lipid-lowering mechanism of Xuezhikang. Method: Fifty SD rats (220 ± 20 g) were given high-fat diet. After four-weeks modeling, they were randomly divided into semi-control group, high fat group, simvastatin intervention group and Xuezhikang intervention group (0.23, 0.69, 1.15 mg/kg, low, medium, high), each dosage in eight rats. The control group (rest eight rats) were given normal diet, and no specific treatment. The rats were sacrificed at the end of the experiment. Result: The biochemical and body weight indexes of the normal control group and the high fat group were significantly different (P <0.05), which indicated that the model of hyperlipidemia was established success. There was significant difference (P <0.05) between Xuezhikang intervention group and high fat control group (P <0.05), and hyperlipemia metabolomics related markers, oxalic acid, butyric acid, mannitol, glucose, glucuronic acid were found. Glucuronic acid and non-binding bilirubin combined with bilirubin, combined with some of the liver harmful substances, play a detoxification effect. Conclusion: The results of metabonomics showed that the high fat group and the control group were significant difference. Mannose, glucose content is relatively stable, lipid metabolism in high-fat group stearic acid, palmitic acid levels decreased, suggesting that high-fat diet disorders rat body lipid metabolism. It is worth mentioning that the experimental evaluation of rats such as biochemical indicators and pathological results are prompted to model success, Xuezhikang intervention effect is more significant, consistent with the expected.

Atractylodis exerted a variety of pharmacological effects such as anti-tumor, anti-inflammatory, anti-bacterial, and antiaging effects etc. The major ingredients of Atractylodis are atractylenolide I and II that exhibited activities in antiinflammatory and anticancer. In this work, a sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of atractylenolide I and II in rat plasma was developed. The UPLC-MS/MS method was validated for selectivity, linearity, accuracy, precision, recovery, and stability with a total run time of 4.0 min. After addition of atractylenolide III as an internal standard (IS), protein precipitation by acetonitrile was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 231.1 → 185.1 for atractylenolide I, m/z 233.1 → 91.0 for II, and m/z 249.0 → 231.1 for IS. Calibration plots were linear throughout the range 1-1000 ng/mL for atractylenolide I and II in rat plasma. Mean recoveries of atractylenolide I and II in rat plasma ranged from 86.2% to 96.3%. Relative standard deviation (RSD) of intra-day and inter-day precision was both less than 12%. The accuracy of the method was between 91.0% and 109.0%. The method was successfully applied to pharmacokinetic study of atractylenolide I and II after intravenous administration in rats.