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    29 June 2021, Volume 30 Issue 6
    Review
    Recent progress of natural products in tumor prevention and treatment by regulating the reactive oxygen species level
    Zixiang Wang, Yifan Zhang, Wangchun Du, Qunli Chen, Hong Yao, Mei Zhao
    2021, 30(6):  455-467.  DOI: 10.5246/jcps.2021.06.035
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    Reactive oxygen species (ROS) is widespread in living organisms. Under normal conditions, ROS remains at low concentrations to maintain normal cell function. Studies have found that the abnormal elevation of ROS levels in normal tissues is an important mechanism underlying the tumorigenesis. However, high concentrations of ROS also have toxic, genotoxic, and even apoptotic effects on tumor cells. ROS has become one of the important targets for cancer prevention and treatment. Natural products widely exist in nature and have a wide range of pharmacological activities, which can affect the function of ROS. In the present study, we reviewed the research progress of natural products in tumor prevention and treatment by regulating ROS level in recent years.

    Original articles
    Xiao-Xu-Ming decoction extract ameliorates brain injury in rats with thrombotic focal ischemic stroke and understanding possible therapeutic targets using proteomics
    Yinglin Yang, Shanshan Zhang, Man Liu, Yuehua Wang, Guanhua Du
    2021, 30(6):  468-483.  DOI: 10.5246/jcps.2021.06.036
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    Ischemic stroke seriously threatens human health and quality of life. Xiao-Xu-Ming (XXM) decoction has been a classical prescription for stroke therapy. In our previous studies, we have found that XXM exerts neuroprotective effects, improves brain injury, and attenuates neuroinflammation in cerebral ischemia rats. In this study, we investigated the effects and possible mechanism of XXM on thrombotic focal cerebral ischemia. After treatment with XXM, the neurological function and motor abilities were improved, and cerebral infarction volume was significantly decreased compared with rats of thrombotic focal cerebral ischemia. Besides, the results of BBB integrity detected by EB leakage and tight junction (TJ) protein expression showed that XXM could maintain BBB integrity and improve the expressions of TJ proteins, including claudin-1, occluding, and ZO-1, in the ischemic ipsilateral cortex disrupted by thrombotic cerebral ischemia. Furthermore, proteomic techniques were used to identify the differentially expressed proteins (DEPs) in the ischemic cerebral cortex, and the results showed that 132 DEPs regulated by XXM were detected in the ischemic cerebral cortex. Bioinformatic analysis showed that these regulated proteins by XXM were mainly involved in complement and coagulation cascade, and lysosome, etc. Furthermore, there was an interaction among DEPs, including Lgals3, Ctsz, Capg, C1qa, S100a4, Grn, Hspb1, Aif1, and Anxa1, etc. In conclusion, XXM ameliorated brain injury of thrombotic focal ischemic stroke, and Lgals3, Ctsz, Capg, C1qa, S100a4, Grn, Hspb1, Aif1, and Anxa1 could help provide possible therapeutic targets of XXM for ischemic stroke and offer research direction for further research.

    Influence of CYP2C9*3 and CYP4F2 rs2108622 gene polymorphisms on over-anticoagulation and bleeding complications of warfarin therapy in Chinese patients: a cohort study
    Yushan Wu, Limei Yang, Xuhui Huang, Feng Huang, Tao Han
    2021, 30(6):  484-494.  DOI: 10.5246/jcps.2021.06.037
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    In this retrospective cohort study, we aimed to identify the influence of the CYP2C9*3 and CYP4F2 rs2108622 gene alleles on over-anticoagulation and bleeding complications associated with warfarin therapy. A total of 196 patients were included, including 80 males, the mean age was 50.8±10.7 years, and the average follow-up was 26.9±11.8 months. These patients underwent heart valve replacement surgery in the Cardiovascular Surgery of Fujian Provincial Hospital between January 2018 and August 2019, who took warfarin for at least 3 months and had target international normalized ratio (INR) between 1.8 and 2.5. Genotypes of CYP2C9*3 and CYP4F2 rs2108622 genes were tested by polymerase chain reaction (PCR)-gene sequencing technique. SPSS19.0 software was utilized to analyze the association between genotypes and warfarin-related over-anticoagulation and bleeding complications. Of the 434 patient-years, 18 severe bleedings and 59 mild ones occurred in 31 patients. Patients with CYP2C9 *1/*3 were associated with a higher over-anticoagulation risk compared with the *1/*1 carriers (hazard rate (HR) 7.10; 95% confidence interval (CI): 2.54–19.79, P < 0.001). The CYP4F2 rs2108622 mutant genotype did not cause significant increase in bleeding risk (HR 0.89; 95% CI: 0.43–1.82, P = 0.74) or over-anticoagulation (HR 0.43; 95% CI: 0.16–1.13, P = 0.09). Meanwhile, Kaplan-Meier survival curves showed that the time to over-anticoagulation in CYP2C9 *1/*3 carriers was significantly shorter compared with the *1/*1 carriers (log-rank test, P<0.001), while that in CYP4F2 rs2108622 mutant genotype patients was longer compared with the wild-type patients (P = 0.05). CYP2C9*3 and CYP4F2 rs2108622 might be major predictive factors of over-anticoagulation for warfarin therapy in Chinese patients.

    A new sample preparation method for the determination of acyclovir by RP-HPLC: application to a drug-drug interaction study between gefitinib and acyclovir in rats
    Ying Li, Zhou Wen, Yongling Liu, Zhibing Zhao, Lei Wang, Zeneng Cheng
    2021, 30(6):  495-504.  DOI: 10.5246/jcps.2021.06.038
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    The assay of acyclovir in plasma seems to be a challenge because of its high hydrophily. In our present study, a reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of acyclovir in rat plasma was described and validated in drug-drug interaction (DDI) between gefitinib and acyclovir in rats. The analytes were separated with gradient elution on C18 column (4.6 mm × 250 mm, 5 μm), and the peaks were recorded using ultraviolet detector at a wavelength of 254 nm. Protein precipitation followed by methyl tertiary butyl ether extraction was used for sample preparation. The calibration curve was established between 0.2 and 40 μg/mL (r2 = 0.9999). The intra- and inter-day precisions were all less than 8%, and all the biases were not more than 10%. This new method was successfully applied to a DDI study between gefitinib and acyclovir in rats. Gefitinib up-regulated the absorption of acyclovir by about three times, and our findings guided the clinical co-administration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with acyclovir.

    Chemical constituents from agarwood of Aquilaria filaria
    Chengneng Mi, Wenli Mei, Jingzhe Yuan, Wenxing Long, Haofu Dai
    2021, 30(6):  505-517.  DOI: 10.5246/jcps.2021.06.039
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    Investigations on the chemical constituents from the ethanol extract of the agarwood originating from Aquilaria filaria led to the isolation of 26 compounds by column chromatography, including silica gel, Sephadex LH-20, and semi-preparative high-performance liquid chromatography. Their structures were determined to be β-sitostenone (1), 24α-ethyl-cholestan-3α-ol (2), ergosta-4,6,8(14), 22-tetraene-3-one (3), gypsogenin (4), hederagenin (5), 17αH-trisnorhopanone (6), lupeol (7), friedelin (8), (?)-episyringaresinol (9), (?)-syringaresinol (10), 5-hydroxy-7,4′-dimethoxyflavone (11), 5,4'-dihydroxy-7,3′-dimethoxyflavone (12), 2′-hydroxy-4,3′,6′,4′′-tetramethoxy-p-terphenyl (13), scopularide A (14), 4-(4-hydroxyphenyl)butan-2-one (15), zingerone (16), coniferaldehyde (17), scopoletin (18), acetovanillon (19), isovanillin (20), vanillin (21), p-hydroxybenzaldehyde (22), p-hydroxybenzoic acid (23), protocatechuic acid (24), vanillic acid (25) and 4,5-dihydroxy-3-methoxybenzoic acid (26) by using spectroscopic techniques. All compounds were isolated from agarwood of A. filaria for the first time, and this was also the first report about the isolation of compounds 2, 4, 6, 7, 9, 10, 13?15, 17?20, 22, 24 and 26 from agarwood and Aquilaria plants.

    Two new glycoalkaloids from Solanum lyratum Thunb.
    Tong Wu, Xiao Du, Jiannong Wang, Liangyu Liu, Yuke Yang
    2021, 30(6):  518-523.  DOI: 10.5246/jcps.2021.06.040
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    To study the alkaloids of Solanum lyratum Thunb. ODS and silica gel column chromatography combined with HPLC were used to separate and purify the alkaloids. Seven alkaloids were identified via UHPLC-ESI-Q-TOF-MS, 1D and 2D NMR, respectively 15β-ethoxy-(3β,5α,25R)-16,23-epoxy-23,24-imino-cholestan-16,20,23(N)-triene-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyran-oside (1), 15β-hydroxyl-(3β,25R)-16,23-epoxy-23,24-imino-cholestan-5,16,20, 23(N)-tetraene-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactop-yranoside (2), Solalyraine A (3), Solalyraine B (4), 16,23-epoxy-22,26-imino-cholest-22(N),23,25(26)-trien-3β-ol-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside (5), N-(4-amino-butyl)-3-(3-hydroxy-4-methoxy-phenyl)-E-acrylamide (6) and magnoflorine (7). Among them, compounds 1 and 2 were two new steroidal glycoalkaloids that has not been reported in the literature, and compound 7 was isolated from S. lyratum for the first time.

    Study of β-cyclodextrin differential encapsulation of essential oil components by using mixture design and NIR: Encapsulation of α-pinene, myrcene, and 3-carene as an example
    Zhe Li, Yuan Ding, Hao Huang, Kexin Wang, Jiayi Wu, Lin Zhu, Zhenggen Liao, Liangshan Ming
    2021, 30(6):  524-537.  DOI: 10.5246/jcps.2021.06.041
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    The encapsulation of essential oil components in cyclodextrins (CDs) to form inclusion complexes (ICs) is an effective strategy for improving their stability and bioaccessibility. The aim of the present study was to obtain a deeper understanding of the encapsulation behavior of multi-components in β-CD. Guest molecules of α-pinene, myrcene, and 3-carene, having the same molecular weight, formed ICs with β-CD by a freeze-drying method. A simplex lattice mixture design with 28 experiments was carried out. Statistical analysis was applied to analyze the encapsulation behavior of guest components, and quantitative models of guest components in ICs were constructed by coupling with near-infrared (NIR) spectroscopy and chemometrics analysis. Besides, the molecular docking technique was used to obtain the optimal conformation and explain the binding behavior of inclusion. The results suggested that the spatial structure and ratio of guest molecules were the key factors affecting the encapsulation effect. A non-destructive and rapid NIR analytical model for the guest component in ICs could be obtained by second derivative (2nd der) pretreatment. Collectively, the encapsulation of guest components in β-CD was differentiated, and NIR could be used as a rapid and non-destructive tool for quantitative analysis of ICs.

    Case report
    A 61-year-old man with bloody purulent cerebrospinal fluid
    Yi Zhou, Jun Wang, Fengjuan Gao
    2021, 30(6):  538-542.  DOI: 10.5246/jcps.2021.06.042
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    Staphylococcus aureus meningitis (SAM) is a relatively uncommon but serious disease, accounting for only 1%–9% of cases of bacterial meningitis. In this report, we described a 61-year-old man, whose appearance of CSF was bloody and purulent. CSF test showed extremely elevated WBC count and protein quantification. Bacterial culture demonstrated SAM. Complications included septic shock, acute respiratory failure, and renal failure. Empiric antibiotic treatment was not effective for him. Therefore, we prescribed up to five types of antibiotics. We found that the clinical symptoms, CSF indicators, inflammatory markers, respiratory and renal function got better. The nerve function comparatively recovered well after 6 months of follow-up.

    News
    The research group of Professor Ning Jiao and Song Song made new progress in the field of electrophilic halogenation modification of drugs
    State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center
    2021, 30(6):  543-544. 
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    The research group of Professor Ning Jiao and Song Song made new progress in the field of electrophilic halogenation modification of drugs.