摘要:
Rg1 has shown multiple pharmacological activities and been considered to be evaluated for hepatic protective activity, as Rg1 could modulate different pathways in various diseases. Herein we assessed its effect and potential mechanism in a newly modified ethanol model. C57BL/6 mice were fed with Lieber-DeCarli liquid diet containing ethanol or isocaloric maltose dextrin as control diet with or without Rg1. Meanwhile, bicyclol was treated as positive drug to compare the efficacy of Rg1 against alcoholic hepatotoxicity. According to our data, Rg1 indeed improved the survival rate and lowered the abnormal high levels of serum parameters. H&E and Oil Red O staining indicated that the condition of liver damage was mitigated by Rg1 administration. Furthermore, AMPK and Nrf2 pathways were all modulated at both RNA and protein levels. In accordance with these findings, Rg1 effectively protected against alcoholic liver injury, possibly by modulating metabolism, suppressing oxidative stress, and enhancing oxidant defense systems of Nrf2 pathway. In vitro, Rg1 has no cell toxicity and promotes Nrf2 translocate into nuclear. In summary, we demonstrate that Rg1 is a potent activator of Nrf2 pathway, and could therefore be applied for prevention of hepatic damage.
期刊:
Molecular and Cellular Neuroscience,2016年71(1):102-113 ISSN:1044-7431
通讯作者:
Chen, Nai-Hong
作者机构:
[Wang, Zhen-Zhen; Mou, Zheng; Gao, Yan; Chen, Nai-Hong; Zhang, Zhao] Chinese Acad Med Sci, Peking Union Med Coll, Ctr Neurosci, Inst Mat Med,State Key Lab Bioact Subst & Funct N, Beijing 100730, Peoples R China.;[Chu, Shi-Feng] Hunan Univ Chinese Med, Coll Pharm, Collaborat Innovat Ctr Digital Tradit Chinese Med, Key Lab Diagnost Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Wei, Gui-Ning] Guangxi Inst Chinese Med & Pharmaceut Sci, Dept Pharmacol, Nanning, Peoples R China.
通讯机构:
[Chen, Nai-Hong] C;Chinese Acad Med Sci, Peking Union Med Coll, Ctr Neurosci, Inst Mat Med,State Key Lab Bioact Subst & Funct N, Beijing 100730, Peoples R China.
摘要:
Growing evidence indicates that GQ1b, one of the gangliosides members, contributes to synaptic transmission and synapse formation. Previous studies have shown that GQ1b could enhance depolarization induced neurotransmitter release, while the role of GQ1b in asynchronous release is still largely unknown. Here in our result, we found low concentration of GQ1b, but not GT1b or GD1b (which were generated from GQ1b by plasma membrane-associated sialidases), evoked asynchronous dopamine (DA) release from both clonal rat pheochromocytoma PC12 cells and rat striatal slices significantly. The release peaked at 2 min after GQ1b exposure, and lasted for more than 6 min. This effect was caused by the enhancement of intracellular Ca2+ and the activation of Pyk2. Inhibition of Pyk2 by PF-431396 (a dual inhibitor of Pyk2 and FAR) or Pyk2 siRNA abolished DA release induced by GQ1b. Moreover, Pyk2 Y402, but not other tyrosine site, was phosphorylated at the peaking time. The mutant of Pyk2 Y402 (Pyk2-Y402F) was built to confirm the essential role of Y402 activation. Further studies revealed that activated Pyk2 stimulated ERK1/2 and p-38, while only the ERK1/2 activation was indispensable for GQ1b induced DA release, which interacted with Synapsin I directly and led to its phosphorylation, then depolymerization of F-actin, thus contributed to DA release. In conclusion, low concentration of GQ1b is able to enhance asynchronous DA release through Pyk2/ERK/Synapsin I/actin pathway. Our findings provide new insights into the role of GQ1b in neuronal communication, and implicate the potential application of GQ1b in neurological disorders. (C) 2015 Elsevier Inc. All rights reserved.
作者机构:
[周兴] Department of Andrology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;[李迎秋] College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[何清湖] Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
摘要:
Jingzhaotoxin-XI (JZTX-XI) is a 34-residue peptide from the Chinese tarantula Chilobrachys jingzhao venom that potently inhibits both voltage-gated sodium channel Nav1.5 and voltage-gated potassium channel Kv2.1. In the present study, we further showed that JZTX-XI blocked Kv2.1 currents with the 1050 value of 0.39 +/- 0.06 M. JZTX-XI significantly shifted the current-voltage (I V) curves and normalized conductance-voltage (G V) curves of Kv2.1 channel to more depolarized voltages. Ala-scanning mutagenesis analyses demonstrated that mutants 1273A, F274A, and E277A reduced toxin binding affinity by 10-, 16-, and 18-fold, respectively, suggesting that three common residues (1273, F274, E277) in the Kv2.1 S3b segment contribute to the formation of JZTX-XI receptor site, and the acidic residue Glu at the position 277 in Kv2.1 is the most important residue for JZTX-XI sensitivity. A single replacement of E277 with Asp(D) increased toxin inhibitory activity. These results establish that JZTX-XI inhibits Kv2.1 activation by trapping the voltage sensor in the rested state through a similar mechanism to that of HaTxl, but these two toxins have small differences in the most crucial molecular determinant. Furthermore, the in-depth investigation of the subtle differences in molecular determinants may be useful for increasing our understanding of the molecular details regarding toxin-channel interactions. (C) 2016 Elsevier Ltd. All rights reserved.
期刊:
Journal of Acupuncture and Meridian Studies,2016年9(2):58-64 ISSN:2005-2901
通讯作者:
Jun-Feng He
作者机构:
[Du, Jia; Liu, Xia; Liu, Zhi-Jun; Guo, Sheng-Tong; Jiang, Peng-Fei] Institute of TCM Diagnostic, Hunan University of Chinese Medicine, Changsha, China;Liuyang Hospital of Traditional Chinese Medicine, Liuyang, China. Electronic address: 59421149@qq.com;[Qu, Ya-Ting; Pu, Qing-Yang] Xiangxing College of Hunan University of Chinese Medicine, Changsha, China;[He, Jun-Feng] Institute of TCM Diagnostic, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Liuyang Hospital of Traditional Chinese Medicine, Liuyang, China
通讯机构:
[Jun-Feng He] I;Institute of TCM Diagnostic, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Liuyang Hospital of Traditional Chinese Medicine, Liuyang, China
关键词:
Drug reward;Dynorphin;Kappa opioid receptor;Paraventricular nucleus of thalamus
摘要:
It has been reported that kappa opioid receptor (KOR) is expressed in the paraventricular nucleus of thalamus (PVT), a brain region associated with arousal, drug reward and stress. Although intra-PVT infusion of KOR agonist was found to inhibit drug-seeking behavior, it is still unclear whether endogenous KOR agonists directly regulate PVT neuron activity. Here, we investigated the effect of the endogenous KOR agonist dynorphin-A (Dyn-A) on the excitability of mouse PVT neurons at different developmental ages. We found Dyn-A strongly inhibited PVT neurons through a direct postsynaptic hyperpolarization. Under voltage-clamp configuration, Dyn-A evoked an obvious outward current in majority of neurons tested in anterior PVT (aPVT) but only in minority of neurons in posterior PVT (pPVT). The Dyn-A current was abolished by KOR antagonist nor-BNI, Ba2+ and non-hydrolyzable GDP analogue GDP-beta-s, indicating that Dyn-A activates KOR and opens G-protein-coupled inwardly rectifying potassium channels in PVT neurons. More interestingly, by comparing Dyn-A currents in aPVT neurons of mice at various ages, we found Dyn-A evoked significant larger current in aPVT neurons from mice around prepuberty and early puberty stage. In addition, KOR activation by Dyn-A didn't produce obvious desensitization, while mu opioid receptor (MOR) activation induced obvious desensitization of mu receptor itself and also heterologous desensitization of KOR in PVT neurons. Together, our findings indicate that Dyn-A activates KOR and inhibits aPVT neurons in mice at various ages especially around puberty, suggesting a possible role of KOR in regulating aPVT-related brain function including stress response and drug-seeking behavior during adolescence. (C) 2015 Elsevier Ltd. All rights reserved.
作者机构:
[Song, Hou-Pan; Cai, Xiong; Huang, Hui-Yong] Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410208, Hunan, Peoples R China.;[Song, Hou-Pan; Li, Ru-Liu] Guangzhou Univ Chinese Med, Spleen & Stomach Inst, Guangzhou 510405, Guangdong, Peoples R China.;[Zhou, Chi] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Guangdong, Peoples R China.;[Song, Hou-Pan] Hunan Univ Chinese Med, Inst TCM Diagnost, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Song, Hou-Pan] H;Hunan Univ Chinese Med, Inst TCM Diagnost, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词:
Atractylodes macrocephala Koidz;Intestinal epithelial cells;Cell migration;Polyamines;Rho GTPases;Non-muscle myosin II
摘要:
Ethnopharmacological relevance: Atractylodes macrocephala Koidz (AMK), a valuable traditional Chinese herbal medicine, has been widely used in clinical practice for treating patients with disorders of the digestive system. AMK has shown noteworthy promoting effect on improving gastrointestinal function and immunity, which might represent a promising candidate for the treatment of intestinal mucosa injury. The aim of this study was to investigate the efficacy of AMK on intestinal mucosal restitution and the underlying mechanisms via intestinal epithelial (IEC-6) cell migration model. Materials and methods: A cell migration model of IEC-6 cells was induced by a single-edge razor blade along the diameter of the cell layers in six-well polystyrene plates. After wounding, the cells were grown in control cultures and in cultures containing spermidine (5 mu M, SPD, reference drug), alphadifluoromethylornithine (2.5 mM, DFMO, polyamine inhibitor), AMK (50, 100, and 200 mg/L), DFMO plus SPD and DEMO plus AMK for 12 h. The polyamines content was detected by high-performance liquid chromatography (HPLC) with pre-column derivatization. The Rho mRNAs expression levels were assessed by Q-RT-PCR. The Rho and non-muscle myosin II proteins expression levels were analyzed by Western blot. The formation and distribution of non-muscle myosin II stress fibers were monitored with immunostaining techniques using specific antibodies and observed by confocal microscopy. Cell migration assay was carried out using inverted microscope and the Image-Pro Plus software. All of these indexes were used to evaluate the effectiveness of AMK. Results: (1) Treatment with AMK caused significant increases in cellular polyamines content and Rho mRNAs and proteins expression levels, as compared to control group. Furthermore, AMK exposure increased non-muscle myosin II protein expression levels and formation of non-muscle myosin II stress fibers, and resulted in an acceleration of cell migration in IEC-6 cells. (2) Depletion of cellular polyamines by DEMO resulted in a decrease of cellular polyamines levels. Rho mRNAs and proteins expression, nonmuscle myosin II protein formation and distribution, thereby inhibiting IEC-6 cell migration. AMK not only reversed the inhibitory effects of DFMO on the polyamines content, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, but also restored cell migration to control levels. Conclusions: The results obtained from this study revealed that AMK significantly stimulates the migration of IEC-6 cells through a polyamine dependent mechanism, which could accelerate the healing of intestinal injury. These findings suggest the potential value of AMK in curing intestinal diseases characterized by injury and ineffective repair of the intestinal mucosa in clinical practice. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
摘要:
Background: Poly(amidoamine) (PAMAM) dendrimers are widely used biomedical polymers, which are extensively applied in drug delivery, gene delivery, contrast agent, etc. In these biomedical applications, the bio-safety of the PAMAM dendrimers is a critical issue, which affects not only their toxicity to the host but also the expected in vivo biofunctions of the materials. To clarify the bio-safety of PAMAM dendrimers, the effects of generation 5 PAMAM dendrimers with amine, hydroxyl or carboxyl groups on immune molecules were explored in this work. Methods: Specifically, the effect of the PAMAM dendrimers on the secondary structure and conformation of immune molecule gamma-globulin was studied by using ultraviolet-visible, fluorescence, and circular dichroism spectroscopies. The effect of the PAMAM dendrimers on complement activation was determined by enzyme-linked immunosorbent assay. Further, the effect of the PAMAM dendrimers on antigen-antibody reaction was studied by using human red blood cell agglutination assay. Results: The results showed that the PAMAM dendrimers could affect the secondary structure and conformation of gamma-globulin, and inhibited complement activation. Generation 5 PAMAM dendrimer with carboxyl group at 10 mg/mL impaired red blood cell (RBC) antigen-antibody reaction. Conclusions: From these results, the effects of the PAMAM dendrimers on immune molecules depend on their bulk structure and surface groups. General significance: This work provides important information for the immunocompatibility evaluation, preclinical design, and clinical applications of PAMAM dendrimers. (C) 2014 Elsevier B.V. All rights reserved.
摘要:
The expression of Ferroportin (Fpn) was examined at different time points in rats following focal cerebral ischemia treated with or without the traditional Chinese medicine Naotaifang. Initially, rats were randomly divided into 2, 6, 12, 24 and 72 h groups following middle cerebral artery occlusion (MCAO) and the mRNA and protein level of Fpn was detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) at the above time points. Secondly, the rats were randomly divided into five groups as follows: Sham surgery group, model group, low-dose group (3 g/kg NTE), medium dose group (9 g/kg NTE) and the high-dose group (27 g/kg NTE). After 3 days of corresponding therapy by intragastric administration once a day, the regional cerebral ischemia model was reproduced by the MCAO suture method. On the third day, the neurological behavior of the rats was analyzed by neurobehavioral assessment. Fpn in the hippocampal CA2 region was measured by immunohistochemistry and the mRNA level of Fpn was detected by RT-PCR. Expression of Fpn in the hippocampal CA2 region reached a peak 12 h after surgery (P<0.05, compared with the model group). The high-dose group (27 g/kg NTE) exhibited a lower neurological behavior score (P<0.05) and a higher level of expression of Fpn at the mRNA and protein level compared with the sham surgery group and model group (P<0.05). Dysregulation of intracellular iron balance is possibly a new mechanism underlying cerebral ischemia. NTE can protect the neuronal population in the hippocampal CA2 region by adjusting the expression of Fpn to balance iron levels following cerebral ischemia.
期刊:
Journal of Acupuncture and Meridian Studies,2015年8(2):61-65 ISSN:2005-2901
通讯作者:
Huang, HY
作者机构:
[He, Junfeng; Zhang, Xing] Affiliated Hosp Hunan Univ Chinese Med, Liuyang Hosp Tradit Chinese Med, Liuyang City, Peoples R China.;[Du, Jia; Huang, Huiyong; Qu, Yating; Liu, Xia; Guo, Shengtong] Hunan Univ Chinese Med, Inst TCM Diagnost, 1 Xiangzui Rd, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Huang, HY ] ;Institute of TCM Diagnostic, Hunan University of Chinese Medicine, Hanpu Science and Education District, Number 1 Xiangzui Road, Changsha, Hunan Province, China
关键词:
acupuncture;body mass index;massage;obesity;overweight
摘要:
Obesity is one of the leading health risk factors worldwide and is associated with several other risk factors and health problems. Acupuncture is utilized to treat a variety of health problems, one of which is obesity. Fifty-six obese women with body mass index (BMI) >/=25 kg/m(2) were recruited for this trial and were randomly divided into two groups, one with combined manual acupuncture and massage therapy (MAMT), and the other with only manual acupuncture therapy (MAT). In addition, 40 overweight women with BMI 23-25 kg/m(2) were randomly divided into two groups, one with MAMT and the other with MAT. Therapy was carried out once per day for 21 days, and the body weights and the BMIs were recorded every day. The results showed that both MAMT and MAT could reduce body weight and BMI significantly, compared with the pretreatment values, for all the participants (p < 0.001); however, the differences in body weight and BMI reductions between pre- and posttreatment for the MAMT and the MAT groups were not statistically significant. The optimal periods for reductions in both body weight and in BMI were the first 4 days. Accounting for the economic strategy (time and money) in alternative therapy, MAT alone may present a reasonable option in the treatment of overweight and obesity in adults.
期刊:
International Immunopharmacology,2015年25(1):49-54 ISSN:1567-5769
通讯作者:
Wang, Haibin
作者机构:
[Wang, Haibin; Chen, Qunqun; Zhou, Chi; He, Wei] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Guangdong, Peoples R China.;[Liu, Wengang] 2nd Tradit Chinese Med Hosp Guangdong Prov, Guangzhou, Guangdong, Peoples R China.;[Song, Houpan] Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410007, Hunan, Peoples R China.;[Wang, Haibin] Guangzhou Univ Chinese Med, Affiliated Hosp 1, 16 Airport Rd, Guangzhou 510405, Guangdong, Peoples R China.
通讯机构:
[Wang, Haibin] G;Guangzhou Univ Chinese Med, Affiliated Hosp 1, 16 Airport Rd, Guangzhou 510405, Guangdong, Peoples R China.
关键词:
MAPK;NF-kappaB;Osteoclast;RANKL;Saikosaponin a
摘要:
Inflammatory cytokines play an important role in osteoclastogenesis. Saikosaponin a (SSa) possesses anti-inflammatory activity. However, the role of SSa in osteoporosis is still unclear. Therefore, the objective of this study was to investigate the effects of SSa on receptor activator of the nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and signaling pathway by in vitro assay. In mouse bone marrow monocytes (BMMs), SSa suppressed RANKL plus macrophage colony-stimulating factor (M-CSF)-induced osteodast differentiation in a dose-dependent manner. Moreover, SSa decreased osteoclastogenesis-related marker proteins expression, including NFATcl, c-fos and cathepsin K At molecular levels, SSa inhibited RANKL-induced I kappa B alpha phosphotylation, p65 phosphorylation and NF-kappa B luciferase activity in RAW264.7 cells. And SSa also suppressed RANKL-induced p-38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) phosphorylation. Taken together, these findings suggest that SSa suppresses osteoclastogenesis through inhibiting RANKL-induced p-38, ERK, JNK and NF-kappa B activation. SSa is a novel agent in the treatment of osteodast-related diseases, such as osteoporosis. (C) 2015 Elsevier B.V. All rights reserved.
作者机构:
[Zhou, Xi; Tang, Cheng; Chen, Ping; Zhang, Yunxiao; Liu, Zhonghua; Huang, Ying] Hunan Normal Univ, Coll Life Sci, Changsha 410081, Hunan, Peoples R China.;[Tao, Huai] Hunan Univ Chinese Med, Dept Biochem & Mol Biol, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Liu, Zhonghua] H;Hunan Normal Univ, Coll Life Sci, Changsha 410081, Hunan, Peoples R China.
关键词:
Jingzhaotoxin-II;Nav1.5;Action mechanism
摘要:
Jingzhaotoxin-II (JZTX-II) is a 32-residue peptide from the Chinese tarantula Chilobrachysjingzhao venom, and preferentially inhibits the fast inactivation of the voltage-gated sodium channels (VGSCs) in rat cardiac myocytes. In the present study, we elucidated the action mechanism of JZTX-II inhibiting hNav1.5, a VGSC subtype mainly distributed in human cardiac myocytes. Among the four VGSC subtypes tested, hNav1.5 was the most sensitive to JZTX-II (EC50 = 125 +/- 4 nM). Although JZTX-II had little or no effect on steady-state inactivation of the residual currents conducted by hNav1.5, it caused a 10 mV hyperpolarized shift of activation. Moreover, JZTX-II increased the recovery rate of hNav1.5 channels, which should lead to a shorter transition from the inactivation to closed state. JZTX-II dissociated from toxin-channel complex via extreme depolarization and subsequently rebound to the channel upon repolarization. Mutagenesis analyses showed that the domain IV (DIV) voltage-sensor domain (VSD) was critical for JZTX-II binding to hNav1.5 and some mutations located in S1-S2 and S3-S4 extracellular loops of hNav1.5 DIV additively reduced the toxin sensitivity of hNav1.5. Our data identified the mechanism underlying JZTX-II inhibiting hNav1.5, similar to scorpion a-toxins, involving binding to neurotoxin receptor site 3. (C) 2015 Elsevier Inc. All rights reserved.
摘要:
Intracranial multiple germ cell tumors (GCTs) are rare. In this article, we reported a case of intracranial multiple GCTs in an 18-year-old boy with symptoms of psychosis for 8 months also. Tumors in the pineal, sellar region, corpus callosum, bilateral lateral ventricles and fourth ventricle were confirmed by enhanced magnetic resonance imaging (MRI) and stereotactic biopsy. Immunohistochemical analysis results demonstrated that the tumor cells were positive for CD117 and placental alkaline phosphatase (PLAP). The patient was treated by radiotherapy and the prescribed radiation doses were 18 Gy. After near 24 months of follow-up, no local recurrence and distant metastasis has been found.
摘要:
Oxytocin (OT) was reported to affect cognitive and emotional behavior by action in ventral tegmental area (VTA) and other brain areas. However, it is still unclear how OT activates VTA and related midline nucleus. Here, using patch-clamp recording, we studied the effects of OT on neuron activity in VTA and interfascicular nucleus (IF). OT dose-dependently and selectively excited small neurons located in medial VTA and the majority of IF neurons but not large neurons in lateral VIA. We found the hyperpolarization-activated current (I-h) and the membrane capacitance of OT-sensitive neuron were significantly smaller than those of OT-insensitive neurons. The action potential width of 01-sensitive neurons was about half that of OT-insensitive neurons. The OT effect was blocked by the OT receptor antagonist atosiban and WAY-267464 but not by tetrodotoxin, suggesting a direct postsynaptic activation of OT receptors. In addition, the phospholipase C (PLC) inhibitor U73122 antagonized the depolarization by OT. Both the nonselective cation channel (NSCC) antagonist SKF96365 and the Na+-Ca2+ exchanger (NCX) blocker SN-6 attenuated OT effects. These results suggested that the PLC signaling pathway coupling to NSCC and NCX contributes to the OT-mediated activation of neurons in medial VIA and IF. Taken together, our results indicate OT directly acted on medial WA and especially IF neurons to activate NSCC and NCX via PLC. The direct activation by OT of midbrain neurons may be one mechanism underlying OT effects on social behavior. (C) 2013 Elsevier Ltd. All rights reserved.