Journal of Chinese Pharmaceutical Sciences

Upper limb arthromyodynia can be treated with Notopterygium by down-regulating P2X3 to mediate PKC-induced inflammatory response

Yingzheng Wang, Ce Yang, Cuiping Zhu, Qianqian Zhao, Xuehua Lu, Xiaoyu Su, Yinghao Wang

2022, 31(3): 163-175. DOI: 10.5246/jcps.2022.03.014

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Rheumatoid arthritis (RA) is one of the most common refractory diseases in the world, and traditional Chinese medicine Notopterygium (NE) has been used in the treatment of upper limb pain for a long time. NE can significantly reduce the expression of inflammatory pain target P2X3 receptor in rats with upper-limb arthritis. To verify the relationship between the mechanism of NE for "upper limb paralysis" and the P2X3 receptor-mediated PKC inflammatory response pathway, UPLC was taken to measure the exact medicinal substance of ethyl acetate from NE. Sprague Dawley rats were randomly divided into a blank group, a model group, a live-action group, and a positive group. The joint cavity was removed after 21 d. Moreover, a model group, a live group, and a positive group were also set up with RA-FLS cells in our in vitro study. The expressions of P2X3 and PKC inflammation pathway indicators were detected by Western blotting analysis. A P2X3 inhibitor (A-317491) acted on RA-FLS cells, and a model group and a positive group were set. Then the protein expression of PKC was detected. NE reduced the expressions of P2X3, Rab7, PKC, and NF-κB at the protein level in both systems. NE and P2X3 receptor antagonists reduced the expressions of key proteins in the PKC pathway in RA-FLS cells to similar extents, and their effects were not additive. NE could effectively improve the "forelimb pain" of RA rats, with a mechanism closely related to the P2X3/Rab7/PKC/NF-κB pathway.

A pharmacological study of pioglitazone in the regulation of adipocyte differentiation

Chuan Qin, Qi Wan, Lei Xi, Mian Wei, Quan Du

2022, 31(3): 176-183. DOI: 10.5246/jcps.2022.03.015

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As a pathological result of the abnormal differentiation of adipocytes, the occurrence of obesity will not only lead to weight gain, abnormal energy metabolism, but also the development of the diseases such as diabetes. Early studies have focused on the discovery of protein factors that regulate this process. Recently, long noncoding RNAs (lncRNAs) are found to actively participate in the process of adipocyte differentiation. By means of literature investigation, we get to know that in the treatment of diabetes, taking pioglitazone for a long time will lead to weight gain and obesity. However, the undeerlying mechanisms are far from being clarified. To this aspect, the effects of pioglitazone treatment on adipocyte differentiation were systematically investigated, in the present study. Using an in vitro adipocyte differentiation model of 3T3-L1 cells, pioglitazone treatment was found to promot the process of differentiation. Studies were then performed with the effects on protein signaling pathway, in terms of the expressional regulation of PPARγ, C/EBPα, FABP4 and CD36. To further elucidate the effects of pioglitazone, regulation of a adipogenic lncRNA was also investigated in the study.

Research on accurate quantitation technique using liquid chromatography coupled with triple quadrupole mass spectrometry and experiment optimization—take a novel diuretic as an example

Wen Ma, Yue Xu, Shuyuan Wang, Jun Li, Baoxue Yang

2022, 31(3): 184-191. DOI: 10.5246/jcps.2022.03.016

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Liquid chromatography coupled with the triple quadrupole mass spectrometry (LC-QQQ MS) technique is the most commonly used technique for quantitative analysis. It is widely used in pharmacology, targeted metabolomics, Chinese medicine quality control, and other research fields. The technique monitors only characteristic precursors and product ions through multiple reaction monitoring (MRM) mode and can detect targeted molecules in complex matrix with high specificity and sensitivity. In the present study, a diarylamide derivative diuretic was used as an example to introduce the method establishment and parameter optimization of this liquid chromatography-mass spectrometry technique. Diuretic and its internal standard could be completely separated within a 5-min gradient, and the quantitative linear range was 1–1000 ng/mL with R²= 0.9996 in practical samples. This study showed that the key to the method development for LC-QQQ MS was the selection of the LC mobile phase, the elution gradient, the declustering potential, and the collision energy of compounds in MS.

Three previously undescribed steroidal glycoalkaloids from Solanum lyratum and their anti-tumor activities

Liangyu Liu, Yuke Yang, Xiao Du, Tong Wu, Jiannong Wang

2022, 31(3): 192-201. DOI: 10.5246/jcps.2022.03.017

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In the present study, three previously undescribed steroidal glycoalkaloids (compounds 1–3) were isolated from Solanum lyratum. Their structures were elucidated based on comprehensive spectroscopic data. Their anti-angiogenesis and anti-metastatic activities were evaluated by MTT and wound-healing assays, respectively. Tumor-derived vascular endothelial cells (TdECs), obtained by co-culture of A549 and human umbilical vein endothelial cells (HUVECs), were treated with compounds 1–3. Results showed that compounds 1–3 significantly inhibited the migration of TdECs at 25 μM despite the weak cytotoxic activities, which indicated that the compounds exerted anti-tumor activities by inhibiting metastasis, rather than directly inhibiting the proliferation of TdECs.

Sildenafil improves endometrial blood flow in patients with recurrent implantation failure

Jiajia Zhang, Hua Li, Xiumei Zhen, Lina Wang, Liying Wang

2022, 31(3): 202-211. DOI: 10.5246/jcps.2022.03.018

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Successful embryo implantation depends on a well-functioning endometrium and high-grade quality embryos. An increasing body of evidence suggests that sildenafil citrate plays an important role in endometrial receptivity and implantation. However, few studies have investigated the effects of oral sildenafil citrate on the clinical outcomes of patients with recurrent implantation failure (RIF). In the present study, we aimed to determine the impact of sildenafil citrate on improving the endometrial blood flow and pregnancy rate in RIF patients. A total of 346 frozen-thawed transfer cycles from 305 RIF patients undergoing IVF at the Center for Reproductive Medicine of Peking University Third Hospital from June 2013 to December 2017 were enrolled. Oral sildenafil citrate was given to the patients, and the related effects on endometrial blood flow, endometrial thickness, and clinical outcomes were investigated. In the 346 transferred cases, the proportion of three groups (A: undetectable blood flow; B: sub-endometrial blood flow; C: endometrial and sub-endometrial blood flow) before and after oral administration of sildenafil citrate was as follows: group A: 36.7% ( n = 127) vs. 7.5% ( n = 26); group B: 42.8% ( n = 148) vs. 24.0% ( n = 83); group C: 20.5% ( n = 71) vs. 68.5% ( n = 237). Moreover, the endometrial blood flow in 137 FET cycles was improved (61.8%). Besides, the implantation rate was 19.47% (132/678), and the clinical pregnancy rate reached 32.66% (113/346), while the endometrial blood flow of the pregnancy group was better compared with the non-pregnancy group. This study explored the improving effects of sildenafil citrate on the endometrial receptivity and clinical outcomes of RIF patients, confirming the crucial role of good endometrial blood flow in a successful pregnancy. Meanwhile, the low incidence of adverse events also supported the security and feasibility of sildenafil citrate in the clinical therapy of RIF patients.

The effects of the National Drug Pooled Procurement (NDPP) pilot program in China

Ningtai Luo, Jianying Yue, Ruojing Zhou, Bin Jiang

2022, 31(3): 212-217. DOI: 10.5246/jcps.2022.03.019

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In 2018, the Chinese government identified four municipalities and seven sub-provincial cities for the implementation of the National Drug Pooled Procurement (NDPP) pilot program (the "4 + 7" policy). In the present study, we analyzed the effects of the "4 + 7" policy with data of 25 pilot drugs from the National Healthcare Security Administration (NHSA) from the aspects of drug price, volume, and expenditure. After the implementation of the policy, the average price of total and winning drugs was decreased by 54.47% and 73.82%, respectively, while the DDDc of non-winning drugs was decreased by only 1.54%, and the DDDc of uncertificated generic drugs was increased 83.18%. The DDDs indicating the volume of total and winning drugs was increased by 21.18% and 353.98%, respectively, and the DDDs of non-winning drugs was decreased by 61.35%. The costs of total and non-winning drugs were decreased by 44.83% and 61.94%, respectively, and the cost of winning drugs was increased by 18.87%. The "4 + 7" policy reduced the price and cost of pilot drugs and improved the affordability and accessibility of drugs. However, there were also problems with unexpected excessive price increases of uncertificated generic drugs and relatively high prices of non-winning products. Therefore, we highly suggested promoting the normalization and institutionalization of pooled drug procurement, enhancing the administrative capacity of local procurement platforms, and strengthening monitoring the price of non-winning, especially for the uncertificated generic drugs.

Trends on medicine use in county public hospitals in Sanming, China from 2011 to 2017

Aichen Yu, Mengyuan Fu, Bingyu Ni, Chunxia Man, Jingyuan Zhang, Huajie Hu, Ye Tian, Yue Zhou, Sheng Han, Xiaodong Guan Guan, Luwen Shi

2022, 31(3): 218-223. DOI: 10.5246/jcps.2022.03.020

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Sanming model in healthcare reform has attracted much attention due to its comprehensive and efficient exploration, while its impact on physicians’ prescribing behavior remains unknown. In the present study, we aimed to evaluate the impact of Sanming reform on physicians’ medicine use in county-level public hospitals. We collected outpatient prescriptions in the internal medicine and pediatric departments from nine county public hospitals in Sanming from January 2011 to December 2017. We used six prescribing indicators to analyze physicians’ medicine use. The Mann-Kendall test was used to examine trends in the study outcomes. A total of 1 577 904 outpatient prescriptions were included in this study. The average prescription rate of antibiotics and combined antibiotics were 57.5% and 12.2% in 2011, respectively, which were declined to 28.2% (P = 0.007) and 2.9% (P = 0.003) in 2017, respectively. The average prescription rate of injection was 30.2% in 2011 and declined to 5.3% (P = 0.003) in 2017. As for the subgroup analysis of the internal medicine and pediatric departments, the average prescription rate of antibiotics was 39.3% and 71.4% in 2011, respectively, which was declined to 10.2% (P = 0.003) and 47.3% (P = 0.035) in 2017, respectively. The average prescription rate of combined antibiotics was 15.9% and 9.4% in 2011, respectively, which was declined to 2.9% (P = 0.003) and 2.9% (P = 0.016), respectively. The average prescription rate of injection was 17.8% and 39.6% in 2011, respectively, which was declined to 1.9% (P = 0.003) and 9.0% (P = 0.003), respectively. Our study showed a significant decreasing trend in antibiotic use in county-level public hospitals after the Sanming healthcare reform, indicating that the reform successfully promoted the appropriate use of medicine to some extent.