Efficacy and safety of Xuebijing injection combined with phenolamine and dobutamine in the treatment of severe pneumonia complicated by heart failure / 中国基层医药

Objective:To investigate the efficacy and safety of Xuebijing injection combined with phentolamine and dobutamine for the treatment of severe pneumonia complicated by heart failure. Methods:A total of 200 patients with severe pneumonia complicated by heart failure treated in Hangzhou Ninth People's Hospital from January 2017 to December 2019 were included in this study. They were randomly allocated into the control and observation groups ( n = 100/group). The control group was treated with phentolamine and dobutamine. The observation group was treated with Xuebijing injection combined with phenolamine and dobutamine. Clinical efficacy, changes in C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), left ventricular ejection fraction (LVEF), cardiac troponin I (cTnI), and B-type natriuretic peptide (BNP) post-treatment relative to pre-treatment, and the incidence of adverse reactions were compared. Results:Total response rate was significantly higher in the observation group than in the control group [94.0% (94/100) vs. 85.0% (85/100), χ2 = 4.31, P < 0.05]. There were no significant differences in CRP, IL-6, TNF-α, LVEF, cTnI, and BNP pre-treatment between the two groups (all P > 0.05). CRP, IL-6, TNF-α post-treatment in the observation group were (56.29 ± 10.78) ng/L, (75.60 ± 13.24) ng/L, (130.42 ± 24.79) ng/L respectively, which were significantly lower than those in the control group [(70.52 ± 13.10) ng/L, (87.46 ± 15.68) ng/L, (164.51 ± 28.47) ng/L, t = 8.38, 5.77, 9.03, all P < 0.001]. LVEF post-treatment was significantly higher in the observation group than in the control group [(58.30 ± 8.65)% vs. (54.29 ± 7.9)%, t = -3.42, P < 0.05]. cTnI and BNP post-treatment in the observation group were (1.87 ± 0.52) μg/L and (218.42 ± 24.23) ng/L, respectively, which were significantly lower than those in the control group [(2.40 ± 0.65) μg/L, (325.61 ± 36.97) ng/L, t = 6.36, 24.25, both P < 0.05]. The incidence of adverse reactions in the observation group was slightly, but not significantly, higher than that in the control group [8.0% (8/100) vs. 6.0% (6/100), P > 0.05]. Conclusion:Xuebijing injection combined with phentolamine and dobutamine is effective in the treatment of severe pneumonia complicated by heart failure. The combined therapy inhibits the expression of inflammatory factors, improves cardiac function, has a low incidence of adverse reactions, and is highly safe.

Synergistic mechanism of traditional Chinese medicine based on target combination of PepT1 and PPARα / 中国中药杂志

Synergistic effect is main pharmacological mechanism of traditional Chinese medicine(TCM). The research method based on the key targets combination is an important method to explore the synergistic effect of TCM. Peptide transporter 1 (PepT1) is an essential target for drug uptake into the bloodstream, accounting for about 50% of the total transporter protein content from the small intestine. Peroxisome proliferator-activated receptor α(PPARα) is the lipid-lowering target of fibrates, which have a good hypolipidemic effect by activating PPARα. It has been reported that PPARα could activate the gene expression of PepT1s, and PPARα agonists can promote the uptake of PepT1 substrates, indicating their synergistic effect. In this paper, PepT1 substrates and PPARα agonists from TCM were discovered, and their synergistic mechanism was also been discussed based on the target combination of PepT1 and PPARα. The support vector machine(SVM) model of PepT1 substrates was first constructed and utilized to predict potential TCM components. Meanwhile, merged pharmacophore and docking model of PPARα agonists was used to screen the potential active ingredients from TCM. According to the analysis results of two groups, the TCM combination of Panax notoginseng and Ganoderma lucidum, as well as TCM combination of P. notoginseng and Salvia miltiorrhiza were identified to have the synergistic mechanism based on target combination of PepT1 and PPARα. In this study, synergistic mechanism of TCM was analyzed for absorption and hypolipidemic effect based on target combination, which provides a new way to explore the synergetic mechanism of TCM related to pharmacokinetics.

The in vitro transport mechanism of bentysrepinine:a novel anti-hepatitis B virus drug candidate / 药学学报

Bentysrepinine (Y101), a derivative of phenylalanine dipeptide, is a novel drug candidate for the treatment of hepatitis B virus (HBV) infection. Our previous preclinical pharmacokinetic study showed that its in vivo absorption and distribution characteristics were probably related to transmembrane transport after Y101 was administered intragastically in rats. In this study, Caco-2 and MDCK-MDR1 cell models were used to investigate interactions between Y101 and P-gp through the apparent permeation coefficient (Papp) and efflux ratio (RE); the results showed that Y101 was a substrate of P-gp. In addition, gene-transfected cell models, HEK293-hOATP1B1, HEK293-hOATP2B1 and CHO-PEPT1 were used to evaluate the affinity to OATP1B1,

Transport mechanism of ?-lactam antibiotics in intestine and kidney / 中国临床药理学与治疗学

Some transport systems are foun d both in intestine and kidney with functional and morphological similarities, suc h as peptide transport system, organic anion transport system, organic cation tr ansport system, and P-glycoprotein-mediated transport system. All these transp ort systems participate in the transporting process of ?-lactam antibiotics in different extent. It suggests that inhibitors of renal transport may also affec t the drug absorption of the intestine.

Interactions of intestinal H~+/oligopeptide cotransporter PEPT1 with drugs and regulation by affecting factors / 中国临床药理学与治疗学

H+/oligopeptide cotransporter PEPT1 mainly located at the brush border membrane of intestinal epithelium cell. transports dipeptide/tripeptide which is the degradation products of protein in digestive tract. Peptide-like drugs such as ?-lactam antibiotics,angiotensin-converting enzyme inhibitor (ACEI) and non-peptide drugs valaciclovir also can be transported and uptaked by PEPT1. PEPT1 is important for maintaining the homeostasis and the absorption of drugs in gastrointestinal tract. With the further research of PEPT1 gene, protein structure, and functional activity, we have known the factors about regulation of PEPT1 expression in membrane, their functional activities and substrate affinities. Some associated mechanism of regulation have been studied. As the wide substrate specificities of PEPT1, it becomes the target molecular on drug development and implication for drug delivery. Studies about interactions of PEPT1 with drugs are important for knowing the interactions of drugs, evaluating bioavailability of drug by intestinal absorption, researching the target treatment in anti-tumor drugs and individualization administration.