Preliminary clinical experience of the novel transcatheter aortic valve system Prizvalve® for the treatment of severe aortic stenosis / 中华心血管病杂志

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve® system.

Active fraction combination from Liuwei Dihuang decoction improves adult hippocampal neurogenesis and neurogenic microenvironmentin cranially irradiated mice / 中国药理学与毒理学杂志

OBJECTIVE Cranial radiotherapy is clinically used in the treatment of brain tumors;however, the conse?quent cognitive and emotional dysfunctions seriously impair the life quality of patients. LW-AFC, an active fraction combi?nation extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction, can improve cogni?tive and emotional dysfunctions in many animal models;however, the protective effect of LW-AFC on cranial irradiation-induced cognitive and emotional dysfunctions has not been reported. Recent studies indicate that impairment of adult hippocampal neurogenesis (AHN) and alterations of the neurogenic microenvironment in the hippocampus constitute crit?ical factors in cognitive and emotional dysfunctions following cranial irradiation. Here, our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation-induced cognitive and emotional dys?functions in mice. METHODS LW-AFC (1.6 g·kg-1) was intragastrically administered to mice for 14 d before cranial irra?diation (7 Gyγ-ray). AHN was examined by quantifying the number of proliferative neural stem cells and immature neu?rons in the dorsal and ventral hippocampus. The contextual fear conditioning test, open field test, and tail suspension test were used to assess cognitive and emotional functions in mice. To detect the change of the neurogenic microenvi?ronment, colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress, neurotrophic and growth factors, and inflammation in the hippocampus. RESULTS LW-AFC exerted beneficial effects on the contex?tual fear memory, anxiety behavior, and depression behavior in irradiated mice. Moreover, LW-AFC increased the num?ber of proliferative neural stem cells and immature neurons in the dorsal hippocampus, displaying a regional specificity of neurogenic response. For the neurogenic microenvironment, LW-AFC significantly increased the contents of superox?ide dismutase, glutathione peroxidase, glutathione, and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice, accompanied by the increase in brain-derived neurotrophic factor, insulin-like growth factor-1, and interleukin-4 content. Together, LW-AFC improved cognitive and emotional dysfunctions, promoted AHN preferentially in the dorsal hippocampus, and ameliorated disturbance in the neurogenic microenvironment in irradiated mice. CONCLUSION LW-AFC ameliorates cranial irradiation-induced cognitive and emotional dysfunctions, and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic micro?environment. LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.

Corticosterone induced D-serine release deficit play an important role in long-term potentiation impairment by corticosterone in perforant path-dentate gyrus pathway / 中国药理学与毒理学杂志

OBJECTIVE Previous studies showed that over activation of NMDA receptors may be a crucial cause of long-term potentiation (LTP) and cognitive impairment induced by stress or corticosterone. However, other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment. The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms. METHODS Cort was injected subcutaneously 1 h before the high-frequency stimulation (HFS) to induce LTP impairment. NMDA receptor antagonists and agonists were administrated by icv. RESULTS Hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice. Corticosterone increased the gluta?mate level in hippocampal tissues, neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP, while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone, suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticoste?rone. Further results showed that the level of D-serine and its precursor L-serine did not change. D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1 (ASC-1) in the cell membrane was decreased and increas?ing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticoste?rone. CONCLUSION Taken together, this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction, which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.

Characteristics of the traditional Liu-Wei-Di-Huang prescription reassessed in modern pharmacology / 中国天然药物

Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.

Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation / 中国天然药物

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation / 中国天然药物

Salvianolic acid A (SAA) is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier (BBB) through matrix metallopeptidase 9 (MMP-9) inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion (MCAO) for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 mg·kg. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

Research progresses in pharmacological effects of rhynchophylline and its isomers on nervous system / 药学学报

Uncaria rhynchophylla is one of the frequently used herbs in China, it is mainly used for heat-clearance, suppression of hyperactive liver, calming endogenous wind and arresting convulsion in traditional Chinese medicine (TCM). Alkaloids are the main active materials in Uncaria rhynchophylla, pharmacological studies have shown that Uncaria rhynchophylla and its alkaloids have comprehensive biological effects on the nervous system. Rhynchophylline is one of the most abundant alkaloids in Uncaria rhynchophylla. The recent studies demonstrate that rhynchophylline and its isomers (isorhynchophylline, corynoxine, corynoxine B) may be good drug candidates for treatment of Alzheimer's disease, Parkinson's disease, epilepsy, etc. Although the structures of the 4 alkaloids are very similar, they have different effects on nervous system. For example, corynoxine and corynoxine B exhibit better sedative effects than isorhynchophylline. Rhynchophylline and isorhynchophylline have been extensively studied. For development and utilization of rhynchophylline for nervous system disease, more studies are needed to unveil the structure-function relationship and the underlying mechanisms. Here, we summarizes the progresses the effects of rhynchophylline and its isomers on the nervous system.

Effect of CCL19/CCR7 on the central nervous system function / 国际药学研究杂志

The chemokine CCL19 and its receptor CCR7 are widely expressed in the body by several types of cells,including neutrophils,macrophages and glial cells.The CCL19/CCR7 signaling pathway participates in the process of inflammation,homing of lymphocytes as well as the physiological function.Recently,more and more attention has been focused on the role of CCL19/CCR7 in the nervous system and related diseases such as multiple sclerosis and cerebral ischemia.However,the effect of CCL19/CCR7 on the central nervous system(CNS)is not clear.This paper reviews the relations of CCL19/CCR7 to the CNS,in hope of sheding light on the significance of CCL19/CCR7 for the nervous system.

Effect and mechanism of LW-AFC on chronic unpredictable mild stress-induced mood and cognition impairment of mice / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect and mechanisms of LW-AFC,a new formula derived from Liuwei Dihuang decoction,on chronic unpredictable mild stress(CUMS)-induced mood and cogni-tion impairment in mice. METHODS C57BL/6J mice were randomly placed into seven groups (n=10):normal control group,CUMS group,Fluoxetine(10 mg·kg-1,once per day)group,Liuwei Dihuang de-coction group(LW,10 g·kg-1,once per day),and LW-AFC(0.8 g·kg-1,1.6 g·kg-1,3.2 g·kg-1,once per day) group. The stressed group was given CUMS for 4 weeks to set up a chronic multiple-stressed model.LW and LW-AFC was oral administered a week prior to CUMS and until the end of the study(a total of 35 d),while fluoxetine was administrated orally for 4 weeks.The anxiety behavior was analyzed using the open field test(OFT)and elevated plus maze test(EPM).The depression behavior was ana-lyzed using the sucrose preference test (SPT) and forced swimming test (FST). Spatial cognition was evaluated using Morris water maze (MWM) test and working memory was evaluated using new object recognition test(NORT). RESULTS CUMS for 28 d increased depressive-and anxiety-like behaviors. LW-AFC (1.6 g·kg-1) significantly increased the numbers of entries into the open arm and time in the open arm of CUMS mice (P<0.05). LW-AFC (3.2 g·kg-1) increased sucrose consumption and de-creased the immobility time of FST (P<0.01) of CUMS mice. The MWM test showed that spatial learning andmemory in CUMS mice were remarkably affected relative to controls,whereas LW-AFC(3.2 g·kg-1)im-proves cognitive functions(P<0.05).CONCLUSION The mood and theability of learning and memory of thestressed group can be affected after exposure to CUS.Oral administration of LW-AFC significant-ly improved CUMS-induced impairments of mood and cognition in mice.

Neural stem cells derived from sporadic Alzheimer disease iPSCs exhibit excessive cell apoptosis and premature neuronal differentiation / 中国药理学与毒理学杂志

OBJECTIVE To establish an in vitro cell model based on patient-specific human neural stem cells to study the pathomechanism of sporadic AD as well as screen candidate drugs.METHODS The peripheral blood cells from sporadic AD patients and cognitive normal controls were repro-grammed into inducedpluripotent stem cells(iPSCs),which were further induced into neural stem cells and neurons. The cell growth curve during the differentiation process was recorded by the IncuCyte ZOOM, and neural stem cells and neurons were identified by immunofluorescence. The apoptosis of neural stem cells and neurons was detected by Click-iT?Plus TUNEL Assay. RESULTS Neural stem cells derived from AD patients and cognitive normal controls can express neural stem cell markers Nes-tin,Sox1,Sox2 and Ki67.TUNEL assay results showed that the number of TUNEL-positive cells in neu-ral stem cells derived from AD patients was significantly higher than that of cognitive normal controls (P<0.01). When neural stem cells were differentiated into neurons, the percentage of MAP2 positive cells in the neural stem cell-derived culture dish of AD patients was significantly higher than the cogni-tive normal controls at day 16 of neuronal differentiation (P<0.01); the TUNEL assay showed that the number of TUNEL-positive cells in AD-derived neurons was significantly greater than that in cognitive normal controls (P<0.01) at day 16 of neuronal differentiation. CONCLUSION Our study revealed that AD-iPSC-derived neural stem cells exhibit premature neuronal differentiation and increased neural apoptosis,which might be relevant to the neuronal loss of AD,thus may provide valuable new tools to screen candidate drugs for the disease and to discover the mechanisms underlying AD pathogenesis.

Metabolism alternation of schisandra chinensis in carbon tetrachloride-intoxicated rats and patients with advanced hepatocellular carcinoma / 中国药理学与毒理学杂志

OBJECTIVE To study the pharmacokinetics change of schisandra chinensis under the pathological condition of liver dysfunction for safe and rational use of herbal medicines. METHODS The metabolism of four effective lignans from schisandra chinensis(SC), schisandrin,schisantherin A, deoxyshisandrin and γ-schisandrin was studied using microsomes from patients with advanced hepato-cellular carcinoma. In situ intestinal and hepatic perfusions were conducted to clarify the contributions from impairments of gut and liver on the pharmacokinetics of the four schisandra lignans in CCl4-intoxi-cated rats.The metabolism in rat and human liver microsomes and transport in Caco-2 monolayer cell model were studied to reveal the key factors for the in vivo disposition of the four lignans. RESULTS When SC alcoholic extract was orally administrated to CCl4-intoxicated rat for a short term (4 d), the pharmacokinetics of four active SC lignans was significantly changed while its hepatoprotective effect was not obviously observed.The plasma concentrations of the four schisandra lignans were dramatical-ly elevated compared with the control.The Cmax,AUC and MRT were all increased or prolonged signif-icantly while parameter CLz/F was obviously reduced in rat pretreated with CCl4. In hepatic perfusion study and liver microsomes incubation,it was found that the hepatic metabolism of the four lignans was markedly decreased mainly due to the activity reduction of multiple CYP450 isoenzymes involved the metabolism, which, eventually, might lead to the alternation of their pharmacokinetic profiles in CCl4-intoxicated rats or patients with advanced hepatocellular carcinoma. CONCLUSION The pharmacoki-netic studies of SC components in pathological situation of liver dysfunction are expected to provide useful data for rational and safe application of SC preparations in clinic or further pharmacological and toxicological research.

Neuroprotective effect of Liu Wei Di Huang Tang on adult hippocampal neurogenesis in mice / 中国药理学与毒理学杂志

OBJECTIVE To explore the effect and mechanisms of LW-AFC,a new formula derived from Liu Wei Di Huang Tang,on irradiation-induced reduction of mice adult hippocampal neurogenesis. METHODS C57BL/6J mice were randomly divided into seven groups (n=10): control group, LW-AFC group (1.6 g·kg-1), Liu Wei Di Huang Tang (LW) group (10 g·kg-1), brain derived neurotrophic factor (BDNF) group, irradiation group, irradiation+LW group, and irradiation+LW-AFC group. Reduction of mice adult hippocampal neurogenesis was induced by cranial irradiation.LW-AFC was administered by oral gavage for 30 d after cranial irradiation treatment. Immunofluorescence and Nissl′s staining were performed for histological morphology assessment. Bromodeoxyuridine (BrdU) staining was used in the detection of proliferation cells. The peripheral blood and hippocampal homogenate were collected to measure the content of tumor necrosis factor-α (TNF-α), interferon-gamma (INF-γ), interleukin-1β (IL-1β),IL-4 and IL-10.The hippocampal homogenate was used for Western blot to detect the BDNF-TrkB signal pathway, including extracellular regulated protein kinases1/2 (ERK1/2) and BDNF target protein. Morris water maze and new object recognition test were performed to examine the cognitive function of mice.The mice forced swimming and tail suspension test were used to assess alteration in depressive behavior. Long term potentiation was used to examine the synaptic plasticity change of mice. RESULTS Adult hippocampal neurogenesis was significantly reduced after irradiation of 20 Gray dose (10 Gray per day, total 2 d). LW-AFC treatment increased the BrdU number of irradiated mice (P<0.05). In Morris water maze test, LW-AFC group showed decreased escape latency in the learning period (P<0.05), while increased the number of crossing the platform in the memory period. LW-AFC can also reduce the immobility time of mice in the tail suspension test (P<0.01). CONCLU-SION LW-AFC modulates adult neurogenesis to ameliorate cognitive impairment and reduce depres-sive behavior in radiation injury mice.

Construction of NIM sub-network regulated by Liuwei Dihuang decoction and its characteristics / 中国药理学与毒理学杂志

OBJECTIVE To construct the neuroendocrine immunomodulation (NIM) sub-network regulated by Liuwei Dihuang decoction (LW) and analyze its characteristics. METHODS We took the GSE57273 in GEO database and screened the differentially expressed genes (DEGs)(P<0.01) by the GEO2R tool as gene expression signature of LW. The global PPI network was constructed in the context of whole PPI network through direct interaction algorithm and forest algorithm respectively.Then the enrichment and the topological characteristics of NIM signaling molecules were evaluated by permutation test. Finally, we abstracted the NIM sub-network by NIMNT, which combined the NIM molecular network and forest algorithm, and analyzed the topological characteristics of it by the Network Analyzer(release 2.7)plugin in Cytoscape v3.5.1.RESULTS We got 2468 DEGs in the gene expression signature of LW.After analyzing the global PPI network of LW got by two kinds of algorithms,we found that the NIM signaling molecules significantly enriched and located in important positions in the global PPI network. The NIM sub-network regulated by LW contained 1099 nodes and 1056 edges. We screened out 22 hub nodes (Degree>10). Among them, there were 19 NIM signaling molecules in which only ESR1 changed significantly and 3 non-DEGs(NFATC2,RARA,TP53).However,the down-stream of the hub nodes were significantly changes. CONCLUSION The results suggested that LW might mainly regulate the non-hub nodes to recovery of the network imbalance of the body in the state of disease.

LW-AFC,a new formula derived from Liuwei Dihuang decoction,ameliorates behavioral and pathological deterioration via modulating the neuroendocrine-immune system in Alzheimer disease mouse models / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer disease(AD),the most common cause of dementia among older people, could not be prevented, halted, or reversed up till now. A large body of pharmacological study has revealed that Liuwei Dihuang (LW) possesses potential therapeutic effects on AD. LW-AFC is key fractions from LW.In the present study,we investigated the effect of LW-AFC on AD mouse models. METHODS PrP-hAβPPswe/PS1ΔE9(APP/PS1) mice and senescence-accelerated mouse prone 8 strain (SAMP8), classic AD animal models, were employed. After the treatment of LW-AFC, mice were cognitively evaluated in behavioral experiments. Neuron loss, amyloid-β (Αβ) deposition, and Αβ level were analyzed using Nissl staining, immunofluorescence, and an AlphaLISA assay, respectively. Multiplex bead analysis, a radioimmunoassay, immunochemiluminometry, and an ELISA were used to measure cytokine and hormone levels.Lymphocyte subsets were detected using fl ow cytometry. RESULTS LW-AFC ameliorated the cognitive impairment observed in APP/PS1and SAMP8 mice,including the impairment of object recognition memory,spatial learning and memory,and active and passive avoidance. In addition, LW-AFC alleviated the neuron loss in the hippocampus, suppressed amyloid-β(Αβ)deposition in the brain,and reduced the concentration of Aβ1-42in the hippo-campus and plasma of APP/PS1 mice. LW-AFC treatment also significantly restored the imbalance of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis, enhanced the proliferation of splenocytes,corrected the disorder of lymphocyte subsets,and regulated the abnormal production of cytokine in APP/PS1 and SAMP8 mice. Effects of LW-AFC on pharmacodynamics and neuroendocrine immunomodulation network in APP/PS1 and SAMP8 mice were better than meman-tine and donepezil. CONCLUSION LW-AFC ameliorated the behavioral and pathological deterioration of AD mouse models via the restoration of the NIM network, which supports the use of LW-AFC as a potential agent for AD therapy.

Liuwei Dihuang Decoction improves cognitive impairments via regulating immune system in APP/PS1 transgenic mouse,a mouse model of Alzheimer disease / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect and mechanisms of Liuwei Dihuang Decoction (LW)on cognition in PrP-hAβPPswe/PS1ΔE9(APP/PS1)transgenic mice.METHODS LW was adminis-trated with oral for 3 months.The locomotor activity test was performed to investigate the spontaneous motor activity of mice. The Morris water maze test and shuttle box test were performed to investigate the spatial learning and memory and active avoidance response respectively.The Αβ deposits and neuron loss in the hippocampus was detected by immunofluorescence staining and nissl staining respectively. The flow cytometry was employed to investigate the lymphocyte subsets of the mice.The 3H-thymidine incorporation was performed to investigate the splenocytes proliferation. RESULTS The treatment of LW ameliorated the impairments of spatial learning and memory and active and passive avoidance in APP/PS1 mice. The administration of LW alleviated neuron loss in the brain, suppressed amyloid-β (Αβ) deposits in the hippocampus of APP/PS1 mice. The treatment of LW significantly increased ConA-and LPS-induced proliferation of splenocytes,increased CD3+T cells and CD19+B cells in the spleen lymphocytes and reduced Gr1+cells in APP/PS1 mice.CONCLUSION This data indicated the adminis-tration of LW ameliorated behavioral and pathological deterioration via regulating immune function.

Immunopotentiating activities and TLR4/MAPK related molecular mechanisms research of Lycium barbarum polysaccharide / 中国药理学与毒理学杂志

OBJECTIVE To observe the effect and molecular mechanisms of Lycium barbarum polysaccharide (LBP) and glycopeptides on T, B lymphocytes and macrophages. METHODS 3H-TdR incorporation method was used to compare the effects of LBP and glycopeptides on the proliferation lymphocytes. Peritoneal macrophages induced by sodium thioglycolate were used to compare the effects of LBP and glycopeptides. T and B lymphocytes were purified by immunomagnetic beads method. Using antibody blocking methods screening polysaccharide activity related receptors.C3H/HeJ mice were further used to observe the activity of LBP. Biolayer interference method was used to observe the binding kinetics of LBP with TLR4 in vitro.TLR4 level was tested by flow cytometry.Western blotting was used to observe the phosphorylation of p-38,SAPK/JNK and ERK.RESULTS The monosaccharide compo-sition of LBP is rhamnose, arabinose and galactose, and does not contain amino acids. The mixed lymphocyte proliferation experiment showed that LBP had more obvious effect on the proliferation of B cells,and glycosides induced T cells proliferation was more obvious.On the purify lymphocytes,it was found that LBP-induced B cells proliferation requires the involvement of macrophages. Further research found that anti-TLR4 antibody had significant inhibitory effect on LBP-induced macrophage release of TNF-α and IL-1β but not the anti-CR3 treatment.C3H/HeJ mice related results further demonstrated that TLR4 is necessary for LBP activity. Although biolayer interference showed no obvious binding ofTLR4/MD2 with LBP, flow cytometry confirmed that LBP could increase TLR4 expression. Western Blotexperiments showed that the effect of LBP on macrophage was related to its activation of p-38/MAPKpathway and inhibition of ERK/MAPK and JNK/MAPK pathways. CONCLUSION TLR4 is the activityrelated receptors of LBP. LBP cannot directly bind to TLR4/MD2 complex in vitro, but can increaseTLR4 expression and activate macrophage p- 38/MAPK signaling pathway, inhibiting ERK- MAPK andJNK-MAPK signaling pathways.

New situation and new strategies——research and development and internationalization of new drugs and health products of traditional Chinese medicine / 中国药理学与毒理学杂志

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

Thinking about pathogenic mechanism and therapeutic drug for Alzheimer disease / 中国药理学与毒理学杂志

Alzheimer disease (AD) is classic neurodegenerative disorders and main cause inducing dementia.The pathogenic mechanistic of AD is not yet well understood,there is no effective therapeutic target and drugs in clinical only ameliorate symptom for short term.So far,there is no success of diseasemodifying drug developed based on main pathogenesis.Facing to all these unsuccessful efforts to develop a disease-modifying treatment for AD,we have to re-examine our philosophy and strategies of drug discovery,and rethink the insights on the molecular mechanisms of AD pathogenesis.This paper reviews current situation of anti-AD drug and give some analysis,thinking and future about direction,progress and challenge of research and development.

Salvianolic acid A alleviate the brain damage in rats after cerebral ischemia-reperfusion through Nrf2/HO-1 pathway / 药学学报

The aim of present study is to investigate the protective effects and mechanism of salvianolic acid A (SAA) on cerebral ischemia-reperfusion injury in rats. The model was established with middle cerebral artery occlusion and reperfusion (MCAO/R) with ischemia for 1.5 h and reperfusion for 24 h in adult male SD rats. After the behavior assessment, TTC assay was used to calculate the infarct volume of rat brain; the distribution of Nrf2 in nuclear and cytoplasm and expression of HO-1 were detected by Western blot. The PC12 cells injury model was established with oxygen-glucose deprivation for 6 h and reintroduction for 24 h. Cell viability was determined with MTT assay, and the expression of Nrf2 and HO-1 were detected through immunofluorescence staining. The mechanisms were investigated in PC12 cells with Nrf2 knocking down by siRNA. SAA (10 and 20 mg·kg-1) significantly reduced the neuronal damage in MCAO/R model, and SAA (0.5 and 5 μmol·L-1) increased cell viability in PC12 cells injury model. Meanwhile, the nuclear translocation of Nrf-2 and the expression of HO-1 were increased in PC12 cell and rats brain. SAA exhibited anti-cerebral ischemia-reperfusion effects. The mechanism may be related to activation of Nrf2/HO-1 signaling pathway, which promotes the synthesis and nuclear translocation of Nrf2 to enhance the expression of the antioxidant protein HO-1.

Techniques of molecular network analysis in study on network pharmacology / 国际药学研究杂志

The technology of network analysis, based on a variety of disciplines theory, is the core technology in the research of network pharmacology, through which we can mine specified information from molecular networks from multi-angle and multi-level. It has been used to investigate and obtain valuable information about the ingredients/drugs with specific pharmacological effects, the key nodes, modules and motifs with specific biological function, and physiological mechanism of drug action, pathogenesis of disease, or biomarker of disease, especially for the complex disease represented by Alzheimer’s disease (AD). In this paper, the general techniques of network analysis in network pharmacology study are reviewed.