Table of Content

30 March 2017, Volume 26 Issue 3

Previous Issue    Next Issue

Original articles

Synthesis of tetrahydrofuro[3,2-b]quinolin-2(3H)-one derivatives from 2-aminobenzaldehydes and α-angelica lactone via a tandem Aldol/Michael addition

Ling Ji, Dawei Yin, Xin Wang, Runtao Li

2017, 26(3):  163-172.  DOI: 10.5246/jcps.2017.03.016

Asbtract ( 222 )   HTML ( 4)   PDF (1974KB) ( 229 )  

References | Related Articles | Metrics

An efficient synthesis of tetrahydrofuro[3,2-b]quinolin-2(3H)-ones from α-angelica lactone and 2-aminobenzaldehydes via a tandem Aldol-Michael addition is described. The reactions were carried out using DBU as the base in i-PrOH at 0 °C, affording tetrahydrofuro[3,2-b]quinolin-2(3H)-ones in moderate to good yields.



Discovery of angucyclinone polyketides from marine actinomycetes with a genomic DNA-based PCR assay targeting type II polyketide synthase

Xiaoyan Yang, Jing Jin, Mengjie Zhou, Qingxia Xu, Fawang Liu, Yingtao Zhang, Ming Ma, Donghui Yang

2017, 26(3):  173-179.  DOI: 10.5246/jcps.2017.03.017

Asbtract ( 313 )   HTML ( 2)   PDF (1575KB) ( 634 )  

References | Related Articles | Metrics

Angucyclinones are aromatic polyketides produced by type II polyketide synthases (PKS) and are mainly found in terrestrial actinomycetes. To discover more angucyclinones from marine actinomycetes, a genomic DNA-based PCR assay targeting type II polyketide synthases was performed. Among the 167 marine actinomycetes strains screened, twelve strains were identified as the “positive” strains possessing type II PKS-encoding genes based on the sequencing of PCR products. One of the 12 “positive” strains, Streptomyces sp. PKU-MA00218 was selected for the large-scale fermentation based on the HPLC and TLC analysis. Four angucyclinones, 6-deoxy-8-O-methylrabelomycin (1), 8-O-methylrabelomycin (2), 8-O-methyltetrangulol (3), C-ring cleavage product of angucyclinone C (4), were isolated and their structures were elucidated based on spectroscopic analyses. The isolation of angucyclinones 1–4 highlights the power of genome mining technologies based on biosynthetic knowledge in natural products discovery.



Preparation of the nanostructured lipid carriers of artemisinin and its pharmacokinetic evaluation

Hualing Dai, Weiqi Gao, Guoshun Zhang, Ruili Wang, Shuqiu Zhang

2017, 26(3):  180-186.  DOI: 10.5246/jcps.2017.03.018

Asbtract ( 401 )   HTML ( 2)   PDF (1430KB) ( 301 )  

References | Related Articles | Metrics

Artemisinin (ART) is a widely used active drug for malaria, including severe and cerebral malaria. However, its therapeutic efficacy is affected by its lower bioavailability. In the present study, nanostructured lipid carriers (NLCs) were proposed as carrier of ART to improve pharmacokinetic properties of the drug. ART-NLC was prepared by high-pressure homogenization based on orthogonal design. The particle size, zeta potential, encapsulation efficiency (EE) and percentage of drug loading (DL) of ART-NLC were (53.06±2.11) nm, (–28.7±3.59) mV, 73.9%±0.5% and 11.23%±0.37%, respectively. ART-NLC showed the sustained release characteristics and scarcely the hemolysis effect on human red blood cells. The pharmacokinetics of ART-NLC for rats after tail intravenous injection (i.v) or intraperitoneal injection (i.p) were investigated by liquid chromatography-tandem mass spectroscopy (LC-MS/MS). And ART solution was designed as control preparation. For rats of i.v groups, the AUC0–∞ ((707.45±145.65) ng·h/mL) of ART-NLC were significantly bigger than that of ART ((368.98±139.58) ng·h/mL). The MRT ((3.38±0.46) h) of ART-NLC was longer than that of ART ((1.39±0.61) h). And similar results were observed for rats of i.p groups. The AUC0–∞ ((1233.06±235.57) ng·h/mL) and MRT ((4.97±0.69) h) of ART-NLC were both bigger than those of ART, which were (871.17±234.03) ng·h/mL) and (1.75±0.31) h), respectively. Compared with ART, ART-NLC showed a significant increase in AUC0–∞ (P<0.05) and MRT (P<0.001) for both i.p and tail i.v administrations.



Effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite in rats

Xi Tian, Ye Yuan, Ziyun Su, Deqiang Li, Weichong Dong, Xiuling Yang

2017, 26(3):  187-195.  DOI: 10.5246/jcps.2017.03.019

Asbtract ( 667 )   HTML ( 1)   PDF (1565KB) ( 191 )  

References | Related Articles | Metrics

In the present study, we aimed to examine the effects of Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule on the pharmacokinetics of clopidogrel active metabolite (CAM). The traditional Chinese medicines (TCMs) Rong Shuan capsule, Xue Zhi Kang capsule, Xin Yuan capsule and Songling Xue Mai Kang capsule are widely used to treat cardiovascular disease in China. They are often prescribed in combination with clopidogrel, a common anti-platelet Western drug. We investigated the influence of the four TCMs on CAM pharmacokinetics following administration at human dose in rats. Pharmacokinetic parameters were determined following oral (PO) administration of clopidogrel (7.5 mg/kg) with or without Rong Shuan capsule (75 mg/kg, PO), Xue Zhi Kang capsule (60 mg/kg, PO), Xin Yuan capsule (120 mg/kg, PO), or Songling Xue Mai Kang capsule (150 mg/kg, PO). Compared with the animals in the control group, Xue Zhi Kang capsule significantly decreased the area under the plasma concentration-time curve (AUC0-t) of the CAM derivative by 25.4%. However, the t1/2 and Vz/F of CAM derivative were significantly increased by 43.6% and 70.7%, respectively. It was also observed that the pharmacokinetic parameters were altered in groups pretreated with Rong shuan capsule, Xin yuan capsule or Songling Xue mai kang capsule compared with the control group, but not significant. This study indicated that Xue Zhi Kang capsule had an effect on the formation and metabolism of CAM. Therefore, in the beginning of co-administration of Xue Zhi Kang capsule and clopidogrel, the anti-platelet efficacy might be compromised because of the decreased formation of CAM. Otherwise, long-time co-administration might lead to side effects by the prolongation of the t1/2 and Vz/F increase of CAM.



Antioxidant activity of curcumine as protector on methylmercury induced-pancreas damage in mice

Sri Agus Sudjarwo, Koerniasari Eraiko, Giftania Wardani Sudjarwo, Koerniasari

2017, 26(3):  196-201.  DOI: 10.5246/jcps.2017.03.020

Asbtract ( 290 )   HTML ( 2)   PDF (1653KB) ( 236 )  

References | Related Articles | Metrics

Curcumin has been reported to have a strong antioxidant activity. In recent years, use of antioxidant in reducing heavy metal toxicities has been increased worldwide. In this study, we investigated the protective effects of curcumin on methylmercury-induced pancreas damage in mice. Briefly, 50 male mice were divided into five groups as follows: negative control (mice were given daily with aquadest); positive control (mice were orally given 2 mg/kg BW methylmercury daily for 35 d); and the treatment groups (mice were orally adminstered with curcumin 100 mg; 200 mg; 400 mg/kg BW daily for 35 d, and from 5th day, animals were given 2 mg/kg BW methylmercury daily 1 h after curcumin administration for 30 d). On day 35, levels of glucose, insulin, MDA, SOD and GPx were measured. Pancreas also was fixed in 10% neutral buffered formalin solution for histopathological examination. The results revealed that methylmercury toxicity induced a significant increase in the levels of glucose and MDA. Moreover, a significant decrease in insulin, SOD and GPx levels was observed, and pancreas tissues showed degeneration and necrotic changes in the islets of Langerhans. Treatment with curcumin (400 mg/kg BW but not 200 mg/kg BW and 100 mg/kg BW) significantly (P<0.05) decreased glucose and MDA levels in pancreas in mercury-induced mice. Treatment with curcumin 400 mg/kg BW also significantly increased insulin, SOD and GPx levels and reversed the histopathological damage in methylmercury-induced mice. Taken together, curcumin could be a potent natural herbal product, which had pancreas protective effect against methylmercury-induced pancreas damage in mice.



Effect of cytochrome P-450 inhibitors on pharmacokinetics and safety of voriconazole

Huixia Yang, Ken Chen, Shuyao Liang, Suodi Zhai, Zhanmiao Yi

2017, 26(3):  202-211.  DOI: 10.5246/jcps.2017.03.021

Asbtract ( 308 )   HTML ( 2)   PDF (2688KB) ( 504 )  

References | Related Articles | Metrics

Our objective was to systematically assess the effect of cytochrome P-450 (CYP450) inhibitors on pharmacokinetics and safety of voriconazole (VORI). Cochrane Library, PubMed, Embase, CNKI, CBM and WanFang databases and Clinicaltrials. gov were searched up to Jan. 26th 2016. Two reviewers independently identified studies, extracted data and assessed quality of studies. Meta-analysis was performed with RevMan 5.3, and risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. A total of 12 studies were included: three crossover randomized controlled trials, three single-arm before-and-after studies and six cohort studies. Compared with non-combination group, the group of VORI plus omeprazole had a significantly higher occurrence of hepatic dysfunction (RR = 4.11, 95% CI 1.12–15.08, P = 0.03). However, neurologic dysfunction and visual disturbance were not significantly different. Pantoprazole, rabeprazole, cimetidine and contraceptive significantly increased the peak concentration (Cmax) and area under the curve (AUC) of VORI, while indinavir had no significant effect on pharmacokinetics of VORI. The effects of esomeprazole, erythromycin and azithromycin on pharmacokinetic parameters of VORI presented inconsistent results. Co-administration of VORI and CYP450 inhibitors was safe except for omeprazole. Although Cmax and AUC of VORI were increased while co-administered with a couple of CYP450 inhibitors, no significant effect on clinical outcomes was observed.



Assessment of the quality of randomized controlled trials on pharmaceutical care for asthmatic patients in journals of mainland China

Liqun Wang, Xiaohui Xie, Ruirui Zhou

2017, 26(3):  212-221.  DOI: 10.5246/jcps.2017.03.022

Asbtract ( 272 )   HTML ( 0)   PDF (1248KB) ( 502 )  

References | Related Articles | Metrics

The objective of this study was to assess the quality of randomized controlled trials (RCTs) on pharmaceutical care for asthmatic patients conducted by pharmacists in mainland China, to identify the problems in current studies, and to provide some references for further studies. The China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database were searched for randomized controlled trials on pharmaceutical care for asthmatic patients, and only those studies undertaken by pharmacists were included. Information about the study design and reporting of selected studies was extracted and collected to systematically analyze these studies. Meanwhile, the Cochrane Collaboration‟s tool for assessing risk of bias was used to assess potential biases related to these studies. Ultimately, 14 articles were included in this study. No study determined the sample size in a scientific way. No article reported a scientific and detailed method of random sequence generation or allocation concealment. Two (14.3%) studies claimed to have implemented a double-blinding and a single-blinding respectively, but neither of them reported any details about how they performed the blinding. No study employed a blinding of outcome assessment. Five (35.7%) studies either stated statistical methods incompletely or used them incorrectly. One (7.1%) study reported an attrition without employing an intention-to-treat analysis. All studies reported eligibility criteria for participants to some extent, and all these criteria involved diagnosis of asthma, but only four (28.6%) of them reported patients‟ ages and three (21.4%) described the severity and the stage of asthma. Nine (64.3%) reported baseline data in the text rather than in a table, and 13 (92.9%) involved comparisons between groups with significance tests either explicitly or implicitly. No report made a distinction between primary and secondary outcomes. Two (14.3%) mentioned informed consent of subjects, while no article reported ethical approval. “Unclear risk” made up the highest percentage of the studies analyzed according to the risk of bias assessment by the Cochrane Collaboration‟s tool. Our study demonstrates that the quality of RCTs on pharmaceutical care for asthmatic patients conducted by Chinese pharmacists is suboptimal, especially with regards to study design and reporting.



Analysis of the efficacy and safety of carfilzomib and its combination in multiple myeloma

Lin Zhang, Xiaoxuan Jin, Shuting Huang, Wenyu Xu, Jiewei Ding

2017, 26(3):  222-229.  DOI: 10.5246/jcps.2017.03.023

Asbtract ( 442 )   HTML ( 2)   PDF (2597KB) ( 353 )  

References | Related Articles | Metrics

Carfilzomib has become a new choice for patients with multiple myeloma (MM). However, the use of carfilzomib single-agent or in combination with other agents in MM patients is not explicitly clarified in clinical practice. Therefore, we analyzed the effects of carfilzomib and its safety and effectiveness using available clinical trial reports in order to find out the best therapy of carfilzomib. We searched MEDLINE, Embase, PubMed and Cochrane databases as well as Chinese databases of carfilzomib trials (Jan. 2012 to Sep. 2016) for the MM treatment. Clinical characteristics and outcomes were extracted. Meta-analysis results were expressed as the overall response rate (ORR) and performed by R software. A fixed-effects model or random-effects model was applied based on the heterogeneity among studies. Based on our research standard, we identified 17 prospective studies enrolling 1960 patients. A total of 594 MM patients were enrolled in carfilzomib single-agent clinical trials, and the ORR was 32% (I² = 84.9%, P<0.0001). A total of 1366 MM patients were enrolled in clinical trials of 10 groups of carfilzomib combination regimens, 1081 patients had a therapeutic effect, and the ORR was 79% (I² = 91.0%, P<0.0001). The most frequent adverse events were fever, nausea, vomiting and other non-hematologic events. Carfilzomib was better tolerated than bortezomib, with a lower incidence of peripheral neuropathy and better therapeutic effects compared with other drugs. In this analysis, the highest ORR was achieved from combination of carfilzomib, lenalidomide and dexamethasone, which had a lower incidence of adverse events and a greater ORR compared with carfilzomib single-agent. Therefore, the combination of carfilzomib, lenalidomide and dexamethasone could be a good therapeutic agent with strong clinical effect. However, this conclusion needs to be validated in future study.



Short communication

Effects of different processing methods in Tibet on content of chebulinic acid in Terminalia chebula Retz.

Wenbo Fei, Xiaoxia Liang, Min He

2017, 26(3):  230-234.  DOI: 10.5246/jcps.2017.03.024

Asbtract ( 286 )   HTML ( 0)   PDF (1638KB) ( 533 )  

References | Related Articles | Metrics

To study the change of the content of chebulinic acid in Terminalia chebula Retz. by different processing methods in Tibet. We taking chebulinic acid as an indicator, the contents in Terminalia chebula Retz. and its processed products were analyzed by using HPLC. Also, the change rule was explored. Compared with Terminalia chebula Retz., the contents of chebulinic acid have decreased after processing, declining 50.18% for the Rubia cordifolia L. processed product, while 11.2% reduce for the Euphorbia fischeriana Steud processed product. After the specific preparation process in Tibet, the contents of chebulinic acid have reduced significantly, which may lead to different pharmacological effects.



Other

Prof. Xinshan Ye’s team makes a breakthrough in the artificial synthesis of polysaccharides

Xinshan Ye’s team

2017, 26(3):  235-236. 

Asbtract ( 260 )   HTML ( 1)   PDF (2049KB) ( 53 )  

Related Articles | Metrics

A team led by Prof. Xinshan Ye (the associate editor of this journal) at Peking University, after many years of research, has recently achieved a major breakthrough in the field of polysaccharide synthesis. Arabinogalactan was chosen as the target molecule for their research. This polysaccharide molecule is composed of a linear galactan chain (chain A) linked with two arabinan chains (chain B), forming a highly branched structure. Using simple monosaccharides as starting materials, researchers were able to produce oligosaccharide chains on the gram scale by the glycosyl donor preactivation-based one-pot oligosaccharide synthesis strategy they previously developed. The cis-1,2-glycosidic bonds were built in a highly stereoselective manner through the conformationally-constrained glycosyl donor. The one-pot protocol was used again for the rapid construction of the two chains (chain A and chain B). Finally, these chains were brought together with a [31+31+30] coupling reaction via the glycosylation promoter they developed previously, thus achieving the total synthesis of the highly branched 92-mer arabinogalactan for the first time.