The neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/reperfusion in rats / 中国药理学通报

Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

Research advances on dihydrofolate reductase inhibitors in the treatment of tumors and bacterial infections / 药学学报

Dihydrofolate reductase (DHFR) is a well-known key target in the treatment of tumors, bacterial infections, and parasitic infections; and it plays a critical role in the biosynthesis of cellular DNA. DHFR inhibitors interfere with one-carbon metabolism by inhibiting substrate binding to DHFR, thereby inhibiting cell proliferation. Research on DHFR inhibitors has continued since the 1940s. To date, a variety of DHFR inhibitors have come into the market, primarily used for anti-tumor, antibacterial, antiparasitic, and anti-inflammatory therapy. This review summarizes the research progress of DHFR inhibitors with antitumor or antibacterial effects in recent years based on the classification of single-target and dual-target and looks forward to the opportunities and challenges faced by the work in this field.

Effects of salidroside on cerebral vascular endothelial cells in MCAO rats / 中国药理学通报

Aim To study the effect of salidroside (SAL) on cerebral vascular endothelial cells of rats with ischemic brain injury and its mechanism of action. Methods Twenty-four healthy adult SD male rats were prepared by bolt plugging method to prepare MCAO models,and randomly divided into sham surgery group ( Sham ) , model group ( MCAO ) , and SAL administration group (MCAO + SAL) ,and the concentration of SAL was 50 mg • kg ~ , with a continuous administration for six days. Western blot was used to detect the protein expression of ICAM-1, VCAM-1 , E-se-lectin,and P-selectin in injured brain tissue of rats. In vitro cell experiments using HUVECs were subjected to different concentrations of salidroside (0. 1,1,10 jjunol • L ) and LPS (100

Pharmacokinetics and blood-brain barrier penetration of a novel salidroside derivative pOBz in rats / 中国药理学通报

Aim To develop a ultra-high performance liquid chromatography electrospray-ionization tandem mass spectrometry ( UPLC-MS/MS ) method for the simultaneous determination of salidroside derivative pOBz in rat plasma and brain tissue, and to study the pharmacokinetic profile and penetration of the blood-brain barrier in rats after a single dose intravenous administration of pOBz. Methods SD rats were administered pOBz at a dose of 50 mg • kg

The neuroprotective effect of salidroside prophylactic administration on MCAO model rats / 中国药理学通报

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

The neuroprotective effect of p-benzoyl salidroside, a derivative of salidroside, on MCAO model rats / 中国药理学通报

Aim To study the neuroprotective effect of p-benzoyl salidroside (pOBz), a derivative of salidroside, on MCAO model rats.Methods ( 1 ) Thirty healthy adult male SD rats were randomly divided into Sham group, MCAO group and MCAO + pOBz group (25, 50, 1(X) mg • kg"1).MCAO model was made by suture-embolus method.The rats were scored for neurological function impairment and weighed every day.pOBz was intraperitoneally injected and administered continuously for two days after preparation of MCAO model.The cerebral infarction volume of rats was detected by MRI.( 2 ) Twenty-four healthy adult male SD rats were randomly divided into Sham group, MCAO group, MCAO + pOBz group (50 mg • kg"1 ) and MCAO + Sal group (50 mg • kg 1 ).The model was made by the suture-embolus method.pOBz was in-traperitoneally injected and administered continuously for one day.Western blot was used to detect the ex pression of NeuN, EGR1 , Bcl-2 and Bax.(3) Eighteen healthy adult male SD rats were randomly divided j j into Sham group, MCAO group and MCAO + pOBz group ( 50 mg • kg 1 ).Administration continued for 2 days.Immunofluorescence staining was used to detect the expression of NeuN.Results Intraperitoneal injection of pOBz for 2 days could reduce the cerebral infarction volume of MCAO rats, improve neurological impairment and increase the expression of NeuN and EGR1 , and the effect was better than that of Sal.pOBz improved Bcl-2/Bax in brain tissues of MCAO rats to the same extent as Sal did.Conclusions pOBz can reduce the volume of cerebral infarction in MCAO rats and has better neuroprotective effect than that of salidroside.

Advances in anti-tumor research of HDAC inhibitors and combination with PI3K inhibitors / 药学学报

Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.

Research Advances of Genetics, Diagnosis and Treatment of T-cell Prolymphocytic Leukemia--Review / 中国实验血液学杂志

T-cell prolymphocytic leukemia (T-PLL) is a rare but highly aggressive and malignant mature T-lymphoid tumor. The diagnosis of T-PLL mainly depend on genetic characteristics, clinical manifestations, cell morphology and immunophenotype. At present, clinical treatment is mainly aimed at improving the response rate and prolonging the remission period. With the development of new molecular biology technologies, researchers have gained a deeper understanding of the pathogenesis and related genetics of T-PLL, targeted drugs, including HDAC inhibitors, JAK/STAT inhibitors, AKT inhibitors and BCL-2 inhibitors, are also under evolution and providing the new opportunities to improve the efficacy of therapy. In this review, the advances in genetics and treatment of T-PLL were summarized briefly.

The neuroprotective effect of rhubarb on MCAO model rats / 中国药理学通报

Aim To study the neuroprotective effect of rhubarb extract on MCAO model rats and explore its mechanism of action. Methods Forty-five SPF male Sprague-Dawley rats were randomly divided into sham group, MCAO group, and MCAO + rhubarb group. MCAO model was prepared by silk plug method, and rhubarb extract was administered at a concentration of 200 mg · kg

The therapeutic effect of salidroside on rats with permanent cerebral ischemia through regulating PDK/Akt signaling pathway / 中国药理学通报

Aim To investigate the neuroprotective effect and mechanism of salidroside (Sal) on rats with permanent middle cerebral artery occlusion model (pMCAO) by regulating the PI3 K/AKT signaling pathway. Methods A total of 80 healthy adult SPF male SD rats were randomly divided into sham operation group (sham group), model group (pMCAO group), drug administration group (pMCAO + Sal group) and inhibitor group (pMCAO + Sal + YL group). After the pMCAO model rats were prepared by the line bolt method, salidroside (50 mg · kg

Research Progress on Chemical Constituents and Pharmacological Effects of Asari Radix et Rhizoma / 中国实验方剂学杂志

Asari Radix et Rhizoma （ARR） is a traditional Chinese medicine for relieving exterior syndrome， and its roots and stems contain rich chemical components， including volatile oils （terpenoids， aromatics and aliphatics）， lignans， flavonoids， etc. Clinically， it has been traditionally used for the treatment of diseases such as phlegm and cough， anemofrigid cold， rheumatic arthralgia due to its ability to spread cold. Modern pharmacological studies have shown that ARR played beneficial roles in analgesic， anti-inflammatory， antitussive， antiasthmatic， antiviral， antibacterial， sedative， antioxidative， and antidepressant responses， antihypertension， as well as tumor suppression. The current studies on the chemical composition of ARR mainly focused on volatile components， and little information is available for the occurrence and pharmacological effects of non-volatile components. In addition， there is a lack of clear classification of chemical components and the distribution of chemical components in medicinal parts and the origin of species. Therefore， in this study， the authors reviewed a large number of literature on the chemical compositions and pharmacological effects of ARR， and hoping to provide a reference for further pharmacological research and the new drug development of ARR.

Synthesis and biological evaluation of phosphoinositide 3-kinase (PI3K) inhibitors based on a quinoxaline scaffold / 药学学报

Based on the structure of inhibitors XL765 and WR23, the quinoxaline scaffold was selected as an attractive structure for drug design. In this protocol, the 2-position of quinoxaline was modified with a substituted phenoxy fragment. Meanwhile, the linking chain at the 3-position was changed to a sulfonyl hydrazine or was removed. A series of substituent groups were added at the 6-position of the quinoxaline scaffold. Twenty-two quinoline derivatives were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, and ESI-MS. All compounds were screened for anti-tumor activity in vitro in A549, MCF-7, HCT-116 and HepG2 cancer cells. The results showed that P6b was effective, P6e and P6f had better activity against HCT116 (IC50 = 3.24, 4.78 and 4.50 μmol·L-1), and P6d had strong inhibitory effect on MCF-7 (IC50 = 0.228 7 μmol·L-1).

Influence of different prompt measures on the quality of cardiopulmonary resuscitation chest compressions in the first year standardized training of residents in Chinese medicine hospitals / 中国中西医结合急救杂志

Objective To investigate the influence of different prompt measures on the quality of cardiopulmonary resuscitation (CPR) chest compressions in the standardized training of residents in Chinese medicine hospitals. Methods There were 84 participants who were the first year standardized training residents recruited from Guangdong Provincial Hospital of Chinese medicine during July to August 2016, and eleven of them were excluded because of incomplete chest compression data collected from the feedback system. Finally, 73 participants being volunteers were enrolled. They were divided randomly into phone metronome group (n = 16), music metronome group (n = 15), depth display group (n = 22), and blank control group (n = 20). In phone metronome group, a mobile phone metronome was applied in the duration of CPR, with a frequency of 110 beats per minute, beat 2/4; in the music metronome group, it was accompanied by the music Staying Alive during the compression period, with frequency of 107 beats per minute, beat 4/4; in depth display group, a model electronic displayer was used in the duration of the compressions to feedback the real time compression depth and its rebound situation in CPR; there was no any intervention measure in blank control group. Each participant performed 5 cycles of CPR on a manikin. A chest compression feedback device was placed on the pressing point, on which the participants places the hand for CPR. The chest compression fraction 1 (CCF1), compression depth, compression rate, too slow frequency, too fast frequency, too shallow frequency, the total times of compressions, the correct times of compressions, correct rate, and the rate of compression retention were record as preliminary evaluation data by using the dual sensor and the pressure sensor built in the chest compression feedback device. At the same time, the correct compression ratio, correct ventilation ratio, the chest compression fraction 2 (CCF2) displayed on the human electronic displayer of the manikin were used as the review criteria. The quality of chest compression among the four groups of volunteers was compared. Results The compression rate and the too fast frequency in the depth display group were significantly higher than those in the music metronome group [compression rate (bpm): 140.59±17.90 vs. 124.27±21.43, the too fast frequency (times): 134.18±49.88 vs. 95.40±53.76, both P < 0.05], and the total compression times in depth display group were significantly higher than either in music metronome group or in blank control group (times: 152.73±27.05 vs. 135.60±10.38, 144.60±12.56, all P < 0.05), the rate of compression retention in depth display group was significantly higher than that in blank control group [37.50% (4.75%, 88.25%) vs. 12.00% (2.75%, 47.00%)]. Consistency detection of two sets of feedback systems for chest compression showed that the chest compression ratio in music metronome group evaluated by the chest compression feedback device was obviously lower than that assessed by the analog human electronic displayer [(53.60±9.87)% vs. (58.20±28.17)%], and it was suggested that the chest compression ratio in depth display group evaluated by the chest compression feedback device be markedly higher than that assessed by the analog human electronic displayer [(56.32±7.77)% vs. (43.86±27.63)%, P < 0.05], and it was shown that the correct rates of chest compression assessed by the chest compression feedback device were significantly lower than those evaluated by the analog human electronic displayer in metronome, music, depth and blank control groups [phone metronome group: 0.00% (0.00%, 60.75%) vs. 38.50% (24.25%, 92.00%), music metronome group: 0.00% (0.00%, 7.00%) vs. 60.00% (32.00%, 89.00%), depth display group: 0.00% (0.00%, 0.25%) vs. 34.00% (20.75%, 68.25%), blank control group: 0.00% (0.00%, 1.75%) vs. 61.50% (30.75%, 84.25%), all P < 0.05], suggesting that the consistency of this two feedback systems be poor and their degrees of reliability low. Conclusion The effects of intervention measures on the quality of chest compressions vary from person to person, and the quality of chest compressions can be really elevated only by systematic training and repeated practice.

The effects of different stimulators on the activation of human lymphocytes / 药学学报

The research aims to study the effects of different stimulants on the activation of human lymphocytes. Human peripheral blood mononuclear cells were prepared by density centrifugation. The blood's sample was provided by National Institutes for Food and Drug Control and approved by its Ethics Committee. The expressions of CD69 in CD3+CD4+ and CD3+CD8+ human T cells were detected by flow cytometry after administrated with CD3/CD28 antibody, phytohaemagglutinin (PHA), Staphylococcus auresus enterooxin B (SEB), interleukin (IL27) and PMA plus ionomycin for 24 h. The proliferation of lymphocyte was detected by CellTiter-Glo kit. The secreted IFNγ in supernatant of medium was examined by ELISA kit. The proliferation of lymphocytes had no change after exposed of CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin for 24 h. However, the CD69 expressions in CD3+CD4+ and CD3+CD8+ T cells and IFNγ productions were significantly increased by CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin at 24 h, indicating that CD3+CD4+ and CD3+CD8+ T cells were activated under above-mentioned stimulated condition. CD3/CD28 antibody, SEB, IL27 and PMA plus ionomycin were valid stimulants for T cell activation.

Establishment and optimization of an enzyme-cell based high-throughput screening platform for IDO1 inhibitors / 药学学报

In this study, we used the tumor immunotherapy protein indoleamine 2,3-dioxygenase 1 (IDO1) as the target, and proposed an enzyme-cell-based tertiary IDO1 inhibitor high throughput screening platform. Firstly, the recombinant human IDO1 protein was expressed by genetic engineering and efficient IDO enzymatic screening system was established. Secondly, A172 cells stimulated with interferon-γ (IFNγ) or constructed plasmid which could highly express human IDO1 protein in HEK293 cells with transient transfection were used to construct the specific IDO1 cell based screening system. Finally, the effect of the compound on kynurenine and tryptophan in mouse plasma was determined by LC/MS/MS method on C57 mice, which could further verify the inhibitory effect of the selected compounds on IDO1 in vivo. The established and optimized enzyme-cell based screening model in this study can efficiently and effectively obtain IDO1 inhibitors in vitro, which lays a good foundation for the rapid development of clinical drugs. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College.

Pien Tze Huang promotes HepG2 apoptosis via regulating ANXA1/VEGF signaling pathway / 中国药理学通报

Aim To explore the effect of Pien Tze Huang (PZH) on inhibiting HepG2 cells via regulating ANXA1/VEGF signaling pathway and the underlying mechanism. Methods HepG2 cells were treated with different concentrations (1, 1 0, 100 mg • L ~ l ) of PZH. MTT assay and colony formation assay were used to calculate cell viability and cell survival. Western blot was used to determine the expression of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, and ANXA1/VEGF signaling pathway protein, such as ANXA1, VEGF, VEGFR, NF-KB P 5 0 . Results Compared with normal group, different concentrations of PZH inhibited HepG2 cells in a dose-dependent manner, inhibited the colony formation, promoted the expression of apoptotic expression, promoted the expression of ANXA1 protein, inhibited the expression of VEGF, VEGFR, and N F - K B P 5 0 as well. Conclusions PZH can inhibit the activity of HepG2 cells in vitro. Its main mechanism is related to the promotion of apoptotic protein in HepG2 cells, the promotion of cell ANXA1 protein, and the inhibition of VEGF/VEGF receptor and NF-KB signaling pathway.

Antitumor activity of a novel PARP1/2 inhibitor YHP-743 / 药学学报

Poly(ADP-ribose) polymerase (PARP)-1 and PARP2 function as ADP-ribosylases involved in DNA repair. PARP1/2 is highly expressed in cancers and emerged as an attractive target for antitumor drug. In this study, we investigated the antitumor activity of a novel PARP1/2 inhibitor YHP-743 in vitro and in vivo. The results showed that YHP-743 had potent enzymatic inhibitory activity against PARP1 and PARP2 to down-regulate the PAR level. YHP-743 not only inhibited breast cancer cells with genes deficiency of homologous recombination repair, but also potentiated chemotherapy agent's cytotoxicity, such as temozolomide, topotecan, cisplatin and doxorubicin. YHP-743 elicited good antitumor activity in combination with temo-zolomide in vivo.

Research progress of indoleamine 2,3-dioxygenase 1 in tumor immunotherapy / 药学学报

IDO1 (indoleamine 2,3-dioxygenase 1) is one of the most significant checkpoint in tumor immunology. Numerous studies indicates that IDO1 is abnormally expressed in breast cancer, colorectal cancer, liver cancer and other tumor tissues, participating in tumor immune escape through multiple pathways. This review is prepared to elucidate the biological function of IDO1, highlight its pivotal role in tumor evasion, and summarize IDO1 inhibitors in the clinical trials.

Optimize dropping process of Ginkgo biloba dropping pills by using design space approach / 中国中药杂志

In this paper, a design space approach was applied to optimize the dropping process of Ginkgo biloba dropping pills. Firstly, potential critical process parameters and potential process critical quality attributes were determined through literature research and pre-experiments. Secondly, experiments were carried out according to Box-Behnken design. Then the critical process parameters and critical quality attributes were determined based on the experimental results. Thirdly, second-order polynomial models were used to describe the quantitative relationships between critical process parameters and critical quality attributes. Finally, a probability-based design space was calculated and verified. The verification results showed that efficient production of Ginkgo biloba dropping pills can be guaranteed by operating within the design space parameters. The recommended operation ranges for the critical dropping process parameters of Ginkgo biloba dropping pills were as follows: dropping distance of 5.5-6.7 cm, and dropping speed of 59-60 drops per minute, providing a reference for industrial production of Ginkgo biloba dropping pills.

Clinical observation of Xuanfeitongfu method in cluster treatment of severe pneumonia / 实用医学杂志

Objective To observe the clinical efficacy of Xuanfeitongfu method in treatment of severe pneumonia and to explore its clinical value in the management of severe pneumonia. Methods Totally,62 patients with severe pneumonia were randomly divided into the control group (n = 30) and the treatment group (n = 32). The control group was given cluster treatment,including oxygen cure,anti-infection and nutrition support and maintaining a stable internal environment and etc. The treatment group was treated with Tongfu decoction orally(one dose a day,a total of 5 days)on a basis of cluster treatment. The comparison was conducted in the 2 groups in the levels of C reaction protein,calcitonin,the change of blood gas analysis,the time of mechanical ventilation and the mortality of severe pneumonia in ICU at baseline and 3,5 days after treatment. Results The level of C-reactive protein,calcitonin,the change of blood gas analysis were statistically significant (P < 0.05). The time of mechanical ventilation and the mortality were better in the treatment group (P < 0.05). Conclusion Xuanfeitongfu method can effectively improve oxygenation ,assist the anti-infection effect ,reduce the time of mechanical ventilation and ICU retention time ,ultimately improve the outcome of severe pneumonia.