Jun-Tian Zhang
Peking Union Medical College
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Featured researches published by Jun-Tian Zhang.
Brain Research | 2011
Jin-Feng Hu; Xiu-Yun Song; Shi-feng Chu; Ji Chen; Haijie Ji; Xiao-Yu Chen; Yu-He Yuan; Ning Han; Jun-Tian Zhang; Nai-Hong Chen
Microglial activation plays a pivotal role in the pathogenesis of neurodegenerative diseases by producing various pro-inflammatory cytokines and nitric oxide (NO). In the paper, the anti-inflammatory effect of ginsenoside Rg1 was investigated in mice intracerebroventricular injected of lipopolysaccharide (LPS). NO and tumor necrosis factor (TNF)-α production in both cerebral cortex and hippocampus decreased at dose-dependent manner by oral administration with Rg1. And the expression of ionized calcium binding adaptor molecule 1 (Iba-1) increased in both cerebral cortex and hippocampus in LPS-injected group compared to that in control group. However, Rg1 inhibited microglial activation by suppressing Iba-1 expression. In addition, the expression of inducible nitric oxide synthase (iNOS) was inhibited by Rg1. Moreover, Rg1 suppressed the phosphorylation level of IκB, nuclear translocation of p65 subunit of NFκB, and phosphorylation level of p38, ERK1/2, JNK mitogen-activated protein kinase (MAPK) induced by LPS. Concluding, Rg1 inhibited the inflammation mediated by LPS by suppressing NFκB and MAPK pathway, which provided the explanation for its therapeutic effect on neurodegenerative diseases.
Neuroscience Letters | 2010
Jin-feng Hu; Shi-feng Chu; Na Ning; Yu-He Yuan; Wei Xue; Nai-Hong Chen; Jun-Tian Zhang
The neurotoxicity of aggregated beta-amyloid (Abeta) has been implicated as a critical cause in the pathogenesis of Alzheimers disease (AD). In the present study, we investigated the effect of (-)clausenamide ((-)Clau), an aqueous extract of leaves of Clausena lassium (lour) skeel, on the neurotoxicity of Abeta(25-35). The viability of differentiated PC12 cells was determined by MTT assay. Apoptosis was detected by flow cytometry. DCFH-DA was used for assessment of intracellular ROS generation, JC-1 and Rhodamine 123 for measurement of mitochondrial transmembrane potential (MMP). The intracellular calcium was determined with Fluo-3. The phosphorylation of p38 MAPK and the expression of Bcl-2, Bax, P53, Caspase 3 were examined by Western blot. The results showed that (-)Clau significantly elevated cell viability. Furthermore, (-)Clau arrested the apoptotic cascade by reversing overload of calcium, preventing ROS generation, moderated the dissipation of MMP and the misbalance of Bcl-2 and Bax, inhibiting the activation of p38 MAPK and the expression of P53 and cleaved Caspase 3. Our results suggested that (-)Clau may be a therapeutic agent for AD.
Pharmacology & Therapeutics | 2016
Shifeng Chu; Shaolin Liu; Wenzhen Duan; Yong Cheng; Xueying Jiang; Chuan-jiang Zhu; Kang Tang; Runsheng Wang; Lin Xu; Xiaoying Wang; Xiao-ming Yu; Kemei Wu; Yan Wang; Muzou Wang; Huiyong Huang; Jun-Tian Zhang
Multi-target drugs, such as the cocktail therapy used for treating AIDS, often show stronger efficacy than single-target drugs in treating complicated diseases. This review will focus on clausenamide (clau), a small molecule compound originally isolated from the traditional Chinese herbal medicine, Clausenalansium. The finding of four chiral centers in clau molecules predicted the presence of 16 clau enantiomers, including (-)-clau and (+)-clau. All of the predicted enantiomers have been successfully synthesized via innovative chemical approaches, and pharmacological studies have demonstrated (-)-clau as a eutomer and (+)-clau as a distomer in improving cognitive function in both normal physiological and pathological conditions. Mechanistically, the nootropic effect of (-)-clau is mediated by its multi-target actions, which include mild elevation of intracellular Ca(2+) concentrations, modulation of the cholinergic system, regulation of synaptic plasticity, and activation of cellular and molecular signaling pathways involved in learning and memory. Furthermore, (-)-clau suppresses the pathogenesis of Alzheimers disease by inhibiting multiple etiological processes: (1) beta amyloid protein-induced intracellular Ca(2+) overload and apoptosis and (2) tau hyperphosphorylation and neurodegeneration. In conclusion, the nature of the multi-target actions of (-)-clau substantiates it as a promising chiral drug candidate for enhancing human cognition in normal conditions and treating memory impairment in neurodegenerative diseases.
European Journal of Pharmacology | 2012
Na Ning; Jin-Feng Hu; Jian-Dong Sun; Ning Han; Jun-Tian Zhang; Nai-Hong Chen
Clausenamide is a chiral compound isolated from leaves of the traditional Chinese herb Clausena lansium (lour) Skeels. It has been shown that (-)clausenamide, but not (+)clausenamide, improved learning and memory in amnesia animal models. However, the precise mechanism of clausenamides actions remains unknown. Here we used an electrophysiological approach to observe the effect of (-)clausenamide on facilitating field excitatory postsynaptic potential (f-EPSP) in the CA1 area of hippocampal slices from rats. The results showed that (-)clausenamide enhanced synaptic transmission at doses 0.1, 1 and 10 μM. The increase of f-EPSP induced by (-)clausenamide was completely inhibited by preincubation with nimodipine (L-voltage-dependent calcium channel blocker, 10 μM), but there was no change when nimodipine was added after (-)clausenamide application. However, ryanodine (ryanodine receptors blocker, 100 μM) attenuated the slope of f-EPSP before or after (-)clausenamide incubation. The data suggested that (-)clausenamide promoted calcium influx to trigger intracellular calcium release which was responsible for potentiating synaptic transmission. Intracellular calcium release induced by (-)clausenamide promoted the activation of CaMKIIα at concentrations of 0.1, 1 and 10 μM, and pretreatment with KN93 (CaMKIIα inhibitor, 10 μM) completely blocked the enhancement of synaptic transmission induced by (-)clausenamide. cAMP response element-binding protein (CREB) was activated by (-)clausenamide and inhibited by KN93 preincubation, but H89 (PKA inhibitor, 10 μM) had no effect, indicating that (-)clausenamide facilitated synaptic transmission by a PKA-independent pathway. Collectively, (-)clausenamide facilitated synaptic transmission by promoting calcium influx to trigger intracellular calcium release, subsequently activating CaMKIIα-CREB signal pathway.
Pharmacology & Therapeutics | 2016
Guanhua Du; Lan Sun; Rui Zhao; Lida Du; Junke Song; Li Zhang; Guorong He; Yongxiang Zhang; Jun-Tian Zhang
Polyphenols, which are naturally present in plants, have been studied for their chemical and pharmacological properties. Polyphenols have been found to exhibit various bioactivities such as antioxidant, free radical scavenging and anti-inflammatory effects, in addition to regulating the intracellular free calcium levels. These bioactivities are related to the underlying mechanisms of ischaemic heart diseases. Pharmacological studies have proven polyphenols to be effective in treating cardiovascular diseases in various ways, particularly ischaemic heart diseases. Based on their mode of action, we propose that some polyphenols can be developed as drugs to treat ischaemic heart diseases. For this purpose, a strategy to evaluate the therapeutic value of drugs for ischaemic heart diseases is needed. Despite several advances in percutaneous coronary intervention (PCI), the incidence of myocardial infarction and deaths due to cardiovascular diseases has not decreased markedly in China. Due to their pleiotropic properties and structural diversity, polyphenols have been of great interest in pharmacology. In the present review, we summarize the pharmacological effects and mechanisms of polyphenols reported after 2000, and we analyse the benefits or druggability of these compounds for ischaemic heart diseases.
European Journal of Pharmaceutical Sciences | 2013
Chuan-jiang Zhu; Ling-juan Wang; Fang Hua; Xiao-ming Yu; Jun-Tian Zhang
Stereoselective differences in pharmacokinetics between clausenamide (CLA) enantiomers have been found after intravenous and oral administration of each enantiomer to rats. The differences could be associated with excretion and first-pass metabolism of two enantiomers. The data from this study demonstrated that (-)CLA was mainly excreted in feces with 13.9% of dose, whereas (+)CLA in bile with 17.2%. A large portion of CLA enantiomers could be transformed into hydroxyl metabolites. In the in vitro metabolic system using rat liver microsomes, it was found that (-)CLA was cleared more than its antipode with peak height ratios [(+)/(-)] from 1.0 to 1.8 at the corresponding substrate concentrations from 0.25 to 2mM. Further study in rabbits showed that two enantiomers underwent an intermediate degree of first-pass metabolism. (-)CLA had lower concentrations and AUC0-8h in the portal vein and heart than those of (+)CLA with rates of hepatic extraction 64.7% for (-)-isomer and 50.8% for (+)-isomer, and intrinsic metabolic clearances of (-) and (+)CLA being 186.3 and 107.2 (l/h), respectively. The first-pass metabolism was involved in CYP3A enzymes in the gut and liver, and different levels of CYP3A1 expression induced by (-)CLA or (+)CLA. Immunohistochemical analyses revealed that (-)-isomer significantly increased the expression of CYP3A1, while (+)-isomer had no obvious effects on it. Taken together, the results provided new evidence that stereoselective pharmacokinetics of CLA enantiomers could be resulted from their stereoselective excretion, first-pass metabolism and induction to metabolizing enzymes, which might be important in understanding the clinic pharmacology of active eutomer, (-)CLA, for treatment of Alzheimers disease.
Neuroscience Letters | 2012
Na Ning; Jian-Dong Sun; Guohua Du; Ning Han; Jun-Tian Zhang; Nai-Hong Chen
Effect of (+)-epi-clausenamide and (-)-epi-clausenamide on synaptic transmission in CA1 region of hippocampal slice was compared in this study. (+)-epi-Clausenamide showed more potency than (-)-clausenamide on either induction or maintenance of long term potentiation (LTP). Effect of (+)-epi-clausenamide on potentiating basic synaptic transmission was also superior to (-)-clausenamide. However, (-)-epi-clausenamide showed only slight effects on synaptic transmission, suggesting that the effect of (+)-epi-clausenamide and (-)-epi-clausenamide on synaptic transmission depended on their chirality. Calcium influx was not involved in (+)-epi-clausenamide facilitating synaptic transmission in this study. (+)-epi-Clausenamide might promote glutamate release through the activation of Synapsin I(Ser9) to activate the downstream effectors which play a key role in synaptic plasticity. Elucidating the mechanism of each optical isomer of clausenamide by electrophysiological methods provided basis for therapeutic strategies for neurological disorders.
Biomedicine & Pharmacotherapy | 2017
Zheng Mou; Qian Huang; Shi-Feng Chu; Meijin Zhang; Jin-Feng Hu; Nai-Hong Chen; Jun-Tian Zhang
BACKGROUND Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity is a well-established pathological feature of major depression, accompanied by the persistent increase of glucocorticoid level and the dysfunction of hypothalamic-pituitary-gonadal (HPG) axis. Ginsenoside Rg1 (Rg1) is one of the most active ingredients of Panax ginseng, which has various biological activity. OBJECTIVE This study aimed to investigate the antidepressive effects of Rg1 and elucidate its impact on neuroendocrine system. METHODS The antidepressive effects of Rg1 were first analysed in mice, and was further identified in the chronic-unpredictable-mild-stress (CUMS) model and the gonadectomized (GDX) model. The effects of Rg1 on depression-like behaviour were analysed by the forced swimming test (FST), tail suspension test (TST), sucrose preference test, and measurement of pentobarbital-induced sleep. The serum corticosterone and testosterone levels were detected by ELISA. The protein levels of glucocorticoid receptor (GR) and androgen receptor (AR) were analysed by western blot and immunohistochemistry analysis. RESULTS Rg1 significantly decreased the immobility time of mice in FST and TST. Furthermore, Rg1 alleviated anhedonia and hopelessness, decreased serum corticosterone level, and increased serum testosterone level, and the GR protein level in the PFC and hippocampus of the CUMS-treated rats. Moreover, Rg1 improved sleep disruption, down-regulated the serum corticosterone level, and increased AR protein level in the PFC of the GDX-treated mice. CONCLUSION Together, these studies suggest that Rg1 displayed antidepressant activity through the modulation of the HPA and the HPG axis. These findings provide new mechanism involved in the antidepressive effects of Rg1 and propose theoretical clues for clinical therapies.
Archive | 2015
Ai-Lin Liu; Yitao Wang; Guanhua Du; Xiuying Yang; Jun-Tian Zhang; Minke Tang; Ji Chen; Yonghong Chen; Zhiwei Qu; Jie Wang; Xiaoying Wang; Yan Sun; Ping Chen; Chuan Li
Early in the 1930s, studies were initiated on the material basis of pharmacological activity in Danshen. Initially, major liposoluble constituents, e.g., tanshinone I, cryptotanshinone, tanshinone IIA, and tanshinone IIB, were isolated from the root of Danshen. In the 1940s, Wang Xu et al. proved that tanshinone I structurally belongs to the tetracyclic compounds of diterpene quinone. In the 1970s, a large number of studies in China were conducted on the chemistry and pharmacology of lipo- and water-soluble constituents in Danshen. In recent years, with extensive application of new techniques and improvements in the techniques of compound isolation and analysis, more and more chemical constituents have been identified from Danshen.
Acta Pharmacologica Sinica | 2008
Jin-feng Hu; Wei Xue; Na Ning; Yu-he Yuan; Jun-Tian Zhang; Nai-Hong Chen
AbstractAim:We carried out this study to investigate the effect of ginsenoside Rg1 on the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) pathway for understanding its effect on synaptic platicity.Methods:Western blotting and immunostaining were used to examine the phosphorylation of ERK1/2, CaMKIIα and cAMP response element binding protein (CREB) in PC12 cells and synaptosomes. The confocal microscopy and fluorescent indicator Fluo-3 was applied to observe the intracellular calcium ion flux.Results:The phosphorylation of ERK1/2 in PC12 cells and synaptosomes incubated with Rg1 was increased and reached maximum at 4 min. Rg1 also promoted the transient enhancement of upstream calcium ion and activated CaMKIIα, which reached maximum at 2 min. CREB, the downstream protein, was phosphorylated within 8 min in PC12 cells after being incubated with Rg1. Moreover, KN93 partially inhibited the activation of ERK1/2, and PD98059 also partially blocked the phosphorylation of CREB.Conclusions:Rg1 activated ERK/MAPK pathway by CaMKIIα, and the activation of CREB was not only dependent on ERK induced by Rg1, which may provide an explanation for the effect of Rg1 on long-term potentiation.