1. Nephrotoxicity of Potential Therapeutic Agents for COVID-19 Infection with Acute Kidney Injury
Chinese Pharmaceutical Journal 2020;55(18):1481-1486
Since the outbreak of coronavirus disease 2019 (COVID-19), the National Health Commission and the expert group of the army have formulated multiple versions of diagnosis and treatment scheme, and drug therapy regimens have become a research hotspot for scholars. Meanwhile, some clinicians found that acute kidney injury (AKI) was an important risk factor in the death of patients with severe COVID 19. The mechanism of AKI in COVID-19 patients is still unclear and the causes may be related to virus infection or drug toxicity. Drug-related AKI directly affects the clinical treatment options and the patient's long-term prognosis. This article targets interferon-α, lopinavir / ritonavir, ribavirin, chloroquine phosphate, abidol and tocilizumab. This article reviewed potential novel coronavirus pneumonia treatment-related AKI, characteristics of the clinical cases, and mechanisms of renal toxicity, to provide a reference for clinical treatment.
2. Progress in Molecular Mechanisms and Cell Transplantation Therapy of Parkinson's Disease
Chinese Pharmaceutical Journal 2020;55(18):1487-1491
Neuron is the basic structure and functional unit of nervous system. Once the neurons are damaged or lost, the balance of neuroregulation will be destroyed and a series of nervous system diseases will be induced. Parkinson's disease (PD) is a kind of chronic neurodegenerative disease caused by selective loss of many dopaminergic neurons in the dense region of the substantia nigra in the ventral midbrain. At present, conventional drugs and adjuvant therapies can only relieve clinical symptoms to a certain extent, but cannot fundamentally delay the progress of the disease. With the rapid development of stem cells and reprogramming technologies around the world, cell transplantation to deal with neurodegenerative diseases including Parkinson's disease has become a new and potential therapy. This paper mainly summarizes the molecular mechanisms of Parkinson's disease, the preparation of autogenous dopaminergic neurons and the research progresses of dopaminergic neurons transplantation in the treatment of Parkinson's disease.
3. Research Progress on the Chemical Constituents and Active Constituents of Cycas revolute Thunb
Chinese Pharmaceutical Journal 2020;55(18):1492-1498
Cycas revolute Thunb is a first class protected plant in China and has high medicinal value. As early as the Qing dynasty, it was recorded that Cycas was use to treat disease. Early research on Cycas mainly focused on classification, protection and breeding. In recent years, people began to study the main chemical constituents, chemical structure and pharmacological effects of Cycas, which laid a solid theoretical foundation for the further development and utilization of Cycas. At present, most of amentoflavone derivatives and hinokiflavone derivatives found in Cycas have the therapeutic effect on tumor. In addition to the antitumor activity, the extracts of Cycas also have antibacterial, antioxidant and immunological activities.
4. Optimization of Ultrasonic-assisted Extraction of Antioxidant Compounds from Asari Radix et Rhizoma Using Response Surface Methodology
Chinese Pharmaceutical Journal 2020;55(18):1499-1504
OBJECTIVEP: To investigate ultrasonic-assisted estraction(UAE) and response surface methodology(RSM) for the extraction of asarinin from Asari Radix et Rhizoma(ARR). METHODS: The RSM was based on a three-level, four-variable Box-Behnken design (BBD). The independent variables were ultrasonic time, liquid to solid ratio, ultrasonic temperature, and ultrasonic power, the dependent variable was extraction rate of asarinin, which was used to estimate the relationship between independent and dependent variables. Box-Behnken design and RSM were used to optimize the process of extraction. The prediction was carried out through comparing the observed and predicted values. Antioxidant activity of the extract of ARR was determined by 1,1-diphenyl-2-trinitrophenylhydrazine(DPPH) and 2, 2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate(ABTS) radical scavenging assays in vitro, and good correlation between extraction rate of asarinin and antioxidant activity was observed. RESULTS: The results indicated that ultrasonic time, liquid to solid ratio, ultrasonic temperature, and ultrasonic power had a significant effect on extraction rate of asarinin. Overall process intensification was achieved with ultrasonic time of 56 min, liquid to solid ratio of 17:1 mL•g-1, ultrasonic temperature of 52℃, and ultrasonic power of 180 W by UAE method. Under optimal conditions, the yield of asarinin was (1.55±0.32) mg•g-1 (n=3), which was in accordance with the predicted yield of 1.58 mg•g-1. The IC50 values of the extract of ARR sample were 29.701 and 64.643 mg•mL-1, respectively. The antioxidant results indicate that the extract of ARR has excellent ability to scavenge free radicals and antioxidant capacity and is expected to be used as a natural antioxidant in industrial applications. CONCLUSION: The extraction technology is simple, reliable and highly predictive.The UAE method is effective for extraction of asarinin from ARR.
5. Inhibitory Effect of Cardamonin on Human Osteosarcoma Cells and Its Underlying Mechanism
Chinese Pharmaceutical Journal 2020;55(18):1505-1511
OBJECTIVEP: To analyze and confirm the inhibitory effect of cardamonin(CAR) on human osteosarcoma(OS) cells and its related mechanism. METHODS: Human osteosarcoma cells were treated with 0, 4, 12, 16 μmol•L-1 CAR and 0.08% DMSO, respectively. Cell proliferation was detected by crystal violet staining and MTT assay. Cell apoptosis was detected by Hoechst staining and flow cytometry(FCM). Cell migration ability was detected by scratch healing test. Cell invasion ability was detected by Transwell method. Western blot detects changes in cell proliferation, apoptosis, migration and invasion-associated proteins and Wnt/β-catenin signaling pathway-related proteins. RESULTS: CAR inhibits proliferation, migration and invasion of osteosarcoma cells. CAR inhibits the expression of PCNA, MMP-7 and vimentin. CAR inhibits the expression of Bcl-2, promotes the expression of apoptotic markers caspase 3 and cleaved-caspase 3. CAR inhibits the expression of the key molecule β-catenin of Wnt/β-catenin signaling and its downstream target molecules cyclin D1 and c-Myc. CONCLUSION: CAR can inhibit the proliferation, invasion and migration of osteosarcoma cells, but promote its apoptosis. Its molecular mechanism may be related to the interference of Wnt/beta-catenin signaling pathway activation.
6. Effect of Flavonoid and Triterpenoid Compounds on the Function of Organic Anion Transporting Polypeptide 1B3
Chinese Pharmaceutical Journal 2020;55(18):1512-1516
OBJECTIVEP: To investigate the effect of flavonoids and triterpenoids on the function of organic anion transporting polypeptide 1B3. METHODS: Natural products such as flavonoids and triterpenoids are widely present in traditional Chinese medicine and daily diets. In the present study, CHO cells stably expressing OATP1B3 and its fluorescent substrate fluorescein methotrexate were employed to investigate the effect of 21 natural products on the function of OATP1B3. RESULTS: Mulberrin, glycyrrhetinic acid, glycyrrhizic acid, quercitrin, quercetin, and chrysanthemum stem-leaf flavonoids showed significant inhibitory effects on OATP1B3-mediated uptake of fluorescein methotrexate, with IC50 values being of 3.6, 3.8, 7.5, 9.0, 10.1 μmol•L-1, and 4.1 μg•mL-1, respectively. The IC50 value of glycyrrhetinic acid on OATP1B3 was comparable to its blood concentration in clinics, indicating an OATP1B3-mediated drug-drug interaction could occur. CONCLUSION: Some flavonoids and triterpenoids are OATP1B3 inhibitors. When patients take medications of OATP1B3 substrates, care should be taken to avoid coadmistration of drugs or food containing these inhibitors to circumvent the occurrence of adverse drug interactions.
7. Preparation and Preliminary Stability Tests of Extemporaneously Prepared Oral Suspending Vehicle for Children
Chinese Pharmaceutical Journal 2020;55(18):1517-1523
OBJECTIVEP: To prepare the extemporaneously prepared oral suspending vehicle that can be used in divided doses for children, and preliminary stability experiments are performed. METHODS: Preparation of blank suspending vehicle by prescription screening and optimization. The preparation of suspending vehicle is based on the comprehensive scale of viscosity, redispersibility and appearance traits as the evaluation index, and signal factor study is used. The preliminary stability investigation was carried out.Using propranolole hydrochloride and spironolactone as model drugs, the drug concentration in suspension determined by ultraviolet spectrophotometry and high performance liquid chromatography(HPLC) respectively,which are methods prescribed in Chinese Pharmacopoeia. RESULTS: The dosages of CMC-Na, HPMC, xanthan gum and xylitol in the final formulation of suspension medium were 3.33% (g•mL-1), 1.67% (g•mL-1), 1% (g•mL-1) and 0.1% (g•mL-1),respectively. The extemporaneously prepared oral suspension is uniform, stable and dispersed, and the inspection conforms to the relevant regulations. Average recovery rates of propranolole hydrochloride and spironolactone are meet the relevant regulations. No stratification in the appearance of samples in centrifugal tests. Three batches of test samples remained stable at 4 and 25℃ for 10 d. CONCLUSION: The oral suspending vehicle has a simple and convenient preparation process, the drug dispersion is simple and fast, the content determination method is accurate and reliable, and the stability is good,and can be used as a drug-loading vehicle.
8. Toxicokinetics of Vitexin Injection in Beagle Dogs
Chinese Pharmaceutical Journal 2020;55(18):1524-1529
OBJECTIVEP: To investigate the toxicokinetic and tissue distribution of vitexin in Beagle dogs. METHODS: Beagle dogs were randomly divided into three groups, and received vitexin injection at small, medium and big doses of 50, 20 and 8 mg•kg-1. They were given medicine once a day for consecutive 3 months by intravenous drip. The blood samples of Beagle dogs were drawn at different time points on the first and last day of administration, and concentrations in plasma were detected by HPLC method. RESULTS: Intravenous drip the vitexin injection at the doses of 8, 20 and 50 mg•kg-1, the blood concentration of vitexin linearly metabolized in Beagle dogs when given medicine for 1, 22, 44 and 83 d. Vitexin was significantly accumulated in Beagle dogs, and the accumulation was disappeared, and the exposure decreased with the prolonged time at the dose of 50 mg•kg-1; at the dose of 8 and 20 mg•kg-1, vitexin did not accumulate in Beagle dogs, and the exposure decreased with prolonged administration time. CONCLUSION: There is no accumulation of repeated drug delivery in the Beagle dog's body by intravenous drip at the doses of 8 and 20 mg•kg-1.
9. Relationship between Multidrug Resistance Gene ABCB1 C3435T Gene Polymorphism and Serum Concentration of Levetiracetam in Children with Epilepsy in Xinjiang
Chinese Pharmaceutical Journal 2020;55(18):1530-1534
OBJECTIVEP: To explore the relationship between multidrug resistance gene ABCB1 C3435T gene polymorphism and serum concentration, clinical efficacy and adverse reactions of levetiracetam (LEV) in children with epilepsy in Xinjiang. METHODS: The serum concentration of 116 children with epilepsy of in Xinjiang were collected and determined by oral LEV. The ABCB1 C3435T genotype was detected by polymerase chain reaction-fluorescence staining in situ hybridization. The correlation between ABCB1 C3435T gene polymorphism and serum concentration, clinical efficacy and adverse reactions was analyzed. RESULTS: The C and T allele frequencies of ABCB1 C3435T in children were significantly different (χ2=12.520, P<0.01). The serum concentration of CC, CT and TT genotypes were 12.02, 13.74 and 14.53 μg•mL-1, respectively. The results of ANOVA showed that there were significant differences among the three groups (F=3.550,P<0.05). The serum concentration of LEV in children with epilepsy in Xinjiang with TT type was significantly higher than that of CC type and CT type. There was no significant difference in css between LEV effective group and ineffective group in CC type, CT type and TT type(P>0.05). The clinical effective rate of CT type was higher than that of CC type and TT type, and the incidence of adverse reactions of TT type was higher than that of CC type and CT type. There were significant differences in clinical efficacy and adverse reactions among CC type, CT type and TT type (χ2=12.870,P<0.01; χ2=19.292, P<0.01). CONCLUSION: ABCB1 C3435T gene polymorphism may has a effect on the serum concentration, clinical efficacy and adverse reactions of LEV in children with epilepsy in Xinjiang.
10. Transplacental Transfer of Glyburide in the ex vivo Human Placenta Perfusion Model
Chinese Pharmaceutical Journal 2020;55(18):1535-1539
OBJECTIVEP: To determine the ex vivo human placental transfer of glyburide from maternal circulation to the fetal circulation in Chinese Hans population. METHODS: Perfusion studies were performed on thirty-six placentas from healthy term pregnancies. The circulation of mother-placenta-fetus was set up ex vivo within minutes and accessed by studying spectrometry. Integrity and viability of the placenta were determined by measuring fetal volume loss, pH, pO2, ΔhCG, glucose consumption and lactate production during the perfusion experiments. RESULTS: Following 3 h of perfusion, the fetal transfer rate of glyburide was (1.64±0.85)%. The clearance index of glyburide was (0.05±0.03). CONCLUSION: These data suggest that tiny amount of glyburide can cross the human placenta. Glyburide could be used as a clinically effective alternative to insulin therapy.

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