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1.  Wen-Dan Decoction Improves Negative Emotions in Sleep-Deprived Rats by Regulating Orexin-A and Leptin Expression 
Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and real time PCR. Open field tests showed that SD increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A and leptin levels in blood serum increased after SD but decreased in brain compared to the control group. mRNA expressions of orexin receptor 1 and leptin receptor after SD were decreased in the prefrontal cortex but were increased in hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A, leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that WDD treatment may regulate SD-induced negative emotions by regulating orexin-A and leptin expression.
PMCID: PMC4016855  PMID: 24864160
2.  Comparison of the Effects of Acarbose and TZQ-F, a New Kind of Traditional Chinese Medicine to Treat Diabetes, Chinese Healthy Volunteers 
Ethnopharmacological Relevance. TZQ-F has been traditionally used in Traditional Chinese Medicine as a formula for the treatment of diabetes. Aim of the Study. This study aims to compare the pharmacologic effects and gastrointestinal adverse events between TZQ-F and acarbose. Methods. The double-blind randomized placebo-controlled fivefold crossover study was performed in 20 healthy male volunteers. Plasma glucose, plasma IRI, and plasma C-peptide were measured to assess the pharmacologic effects. Flatus and bowel activity were measured to assess the adverse event of gastrointestinal effect. Results. 3 and 4 tablets of TZQ decreased the Cmax of plasma glucose compared with that of the previous day and with placebo. 3 tablets also decreased Cmax of plasma C-peptide compared with placebo. 4 tablets increased Cmax of plasma insulin after breakfast and the AUC of plasma C-peptide after breakfast and dinner. 2 tablets did not decrease plasma glucose and elevated the Cmax and AUC of C-peptide after breakfast and dinner, respectively. Acarbose 50 mg decreased the Cmax of plasma insulin and C-peptide after breakfast and the Cmax of plasma glucose and C-peptide after dinner. The subjects who received TZQ did not report any abdominal adverse events. Conclusions. 3 tablets of TZQ have the same effects as the acarbose.
PMCID: PMC3997856  PMID: 24808918
3.  The Use of Integrative Therapies in Patients with Amyotrophic Lateral Sclerosis in Shanghai, China 
Objective. To investigate the current use of integrative therapies (IT) in the treatment of patients with amyotrophic lateral sclerosis (ALS). Methods. A cross-sectional, multicenter clinical epidemiological survey was conducted in 12 hospitals in Shanghai. We investigated the type and frequency of IT use and determined whether the use of IT correlated with demographic, social, or disease-specific characteristics in our patient population. Results. A total of 231 (89.5%) of 258 patients with ALS were eligible for the study and 229 (99% of all) of 231 reported the use of at least one IT for the treatment of ALS. Vitamins and Chinese herb decoctions, Chinese herb compounds, massage therapy, and acupuncture were the 5 most commonly used therapies. There was a strong association between education level, income, and use of IT. A household income of more than 75,000 RMB ($49,995) correlated with multiple IT use, and married patients used IT more often than single individuals. The main reasons for using IT were to treat weakness and fatigue, muscle atrophy, the development of ALS, depression, insomnia, limb pain or numbness, and side effects associated with Riluzole. Conclusion. The use of IT is common in patients with ALS in Shanghai. Vitamins and TCM are the most used additional therapies and the widespread and largely unexamined use of IT for ALS requires more attention.
PMCID: PMC3865630  PMID: 24363770
4.  Microcirculation Perfusion Monitor on the Back of the Health Volunteers 
Objective. To observe the dermal microcirculation blood perfusion characterization of meridians channels (acupoints). Methods. 20 healthy human subjects were monitored using Pericam Perfusion Speckle Imager (PSI) for the changes in dermal microcirculation blood perfusion on governor meridian and other respective dermal regions as a control. Result. The microcirculation blood perfusion on Governor Meridian is higher than its control area. Conclusion. The dermal microcirculation blood perfusion on certain parts of Governor Meridian of healthy human subjects showed specifics.
PMCID: PMC3863559  PMID: 24371463
5.  Reconstitution of Kidney Side Population Cells after Ischemia-Reperfusion Injury by Self-Proliferation and Bone Marrow-Derived Cell Homing 
The aim of this study was to examine the contribution of side population (SP) cells from kidney and bone marrow for reconstitution of kidney SP pools after ischemia-reperfusion injury (IRI). The SP and non-SP cells in kidneys following IRI were isolated and serially assessed by fluorescence-activated cell sorting. The apoptosis, proliferation, phenotype, and paracrine actions of SP cells were evaluated in vitro and in vivo. Results indicated that the SP cells from ischemic kidney were acutely depleted within one day following renal IRI and were progressively restored to baseline within 7 days after IRI, through both proliferation of remaining kidney SP cells and homing of bone marrow-derived cells to ischemic kidney. Either hypoxia or serum deprivation alone increased apoptosis of SP cells, and a combination of both further aggravated it. Furthermore, hypoxia in vivo and in vitro induced the increase in the secretion of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte growth factor, and stromal cell-derived factor-1α in kidney SP but not non-SP cells. In summary, these results suggest that following renal IRI, kidney SP cells are acutely depleted and then progressively restored to baseline levels by both self-proliferation and extrarenal source, that is, bone marrow-derived cell homing.
PMCID: PMC3707266  PMID: 23864886
6.  Prevalence and Correlates of Discomfort and Acceptability of Acupuncture among Outpatients in Chinese Acupuncture and Moxibustion Departments: A Cross-Sectional Study 
Objective. This study aims to give a profile of discomfort and acceptability of acupuncture, including the prevalence and association with demographic and acupuncture-related factors. Methods. A cross-sectional study was conducted in Beijing, China. Outpatients of acupuncture and moxibustion departments were recruited using purposive sampling. 925 subjects were interviewed with an anonymous questionnaire. Multinomial and binary logistic regression were used to analyze factors affecting discomfort and acceptability of acupuncture. Results. The average VAS value of 925 subjects' acupuncture discomfort was 2.66 ± 2.02, within the range of mild discomfort. Acupuncture was easily accepted by 81.1% of the subjects. Results of logistic regression were as follows: (1) subjects with a better knowledge of acupuncture, or a greater fear of pain or needles, experienced more “moderate to severe discomfort” and showed a decreased acupuncture acceptance (P < 0.001 or P < 0.01); (2) Acupuncture with less discomfort or implemented by a more qualified doctor was easy to be accepted (P < 0.001); (3) subjects aged 20–29 preferred to report “moderate to severe discomfort” while those aged 40–59 preferred to report “slight discomfort” (P < 0.001). Conclusion. Acupuncture is an acceptable therapy with less discomfort, which can be greatly affected by fear of pain or needles, age, knowledge of acupuncture, and professional title of acupuncturist.
PMCID: PMC3707286  PMID: 23864895
7.  Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism 
Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg) for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day after TNBS challenge and did not recover distinctively until day 15, including an increase in macro- and microscopic scores, a colonic weight index, a decrease in colonic length, a number of functional capillaries, and blood flow. Inverted intravital microscopy and ELISA showed colonic microcirculatory disturbances and inflammatory responses after TNBS stimulation, respectively. TNBS decreased occludin, RhoA, and ROCK-I, while increasing Rac-1, PAK-1, and phosphorylated myosin light chain. In addition, ATP content and ATP5D expression in colonic mucosa decreased after TNBS challenge. Impressively, treatment with HQJZ significantly attenuated all of the alterations evoked by TNBS, promoting the recovery of colonic injury. The present study demonstrated HQJZ as a multitargeting management for colonic mucosal injury, which set in motion mechanisms involving improvement of energy metabolism.
PMCID: PMC3690262  PMID: 23840258
8.  Curcumin Protects Neuron against Cerebral Ischemia-Induced Inflammation through Improving PPAR-Gamma Function 
Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγ agonist in that it upregulated PPARγ expression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγ interacted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγ induced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.
PMCID: PMC3670515  PMID: 23762140
9.  The Pattern Element Scale: A Brief Tool of Traditional Medical Subtyping for Dementia 
Background. Syndromes are defined by traditional Chinese medicine as consisting of different pattern elements. Few scales have been designed for differentiating pattern elements of dementia and have shown major flaws. Thus, a new pattern element scale (PES) was developed. This study aimed to evaluate the utility of the PES in dementia patients. Methods. A total of 171 dementia patients were enrolled, and their pattern elements were ascertained, first by clinicians using the PES, then compared with results by two experts to be used as a standard criterion independently. Reliability of the subscales of the PES was assessed by receiver operator characteristic curves. Correlations between the subscales of the PES and cognition were calculated by canonical correlation analysis. Results. The PES consisted of 11 pattern element subscales. The area under the curves of all subscales was 0.7 or above. Phlegm muddiness, blood stasis, and yang hyperactivity subscales showed optimal sensitivity and specificity in discriminating pattern elements. Other subscales showed relatively lower sensitivity but higher specificity. Memory and language were significantly correlated to qi deficiency and the blood stasis pattern element. Conclusion. The PES can accurately and easily discriminate pattern elements and is a helpful tool for traditional medical subtyping of dementia.
PMCID: PMC3654323  PMID: 23710221
10.  Optimization on Preparation Condition of Propolis Flavonoids Liposome by Response Surface Methodology and Research of Its Immunoenhancement Activity 
The aim of this study is to prepare propolis flavonoids liposome (PFL) and optimize the preparation condition and to investigate further whether liposome could promote the immunoenhancement activity of propolis flavonoids (PF). PFL was prepared with ethanol injection method, and the preparation conditions of PFL were optimized with response surface methodology (RSM). Moreover, the immunoenhancement activity of PFL and PF in vitro was determined. The result showed that the optimal preparation conditions for PFL by response surface methodology were as follows: ratio of lipid to drug (w/w) 9.6 : 1, ratio of soybean phospholipid to cholesterol (w/w) 8.5 : 1, and speed of injection 0.8 mL·min−1. Under these conditions, the experimental encapsulation efficiency of PFL was 91.67 ± 0.21%, which was close to the predicted value. Therefore, the optimized preparation condition is very reliable. Moreover, the results indicated that PFL could not only significantly promote lymphocytes proliferation singly or synergistically with PHA, but also increase expression level of IL-2 and IFN-γ mRNA. These indicated that liposome could significantly improve the immunoenhancement activity of PF. PFL demonstrates the significant immunoenhancement activity, which provides the theoretical basis for the further experiment in vivo.
PMCID: PMC3603480  PMID: 23533491
11.  The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis 
Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale). In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 μM 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA) suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism.
PMCID: PMC3518257  PMID: 23243437
12.  Zerumbone, a Southeast Asian Ginger Sesquiterpene, Induced Apoptosis of Pancreatic Carcinoma Cells through p53 Signaling Pathway 
Pancreatic carcinoma is one common cancer with gradually increasing incidence during the past several decades. However, currently the candidate drugs to suppress pancreatic cancer remain lacking. This research was carried out to investigate if zerumbone, a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, will produce the anticancer effects on pancreatic carcinoma cell lines. The results showed that zerumbone concentration, and time, dependently produced inhibitory actions on cell viability of PANC-1 cells. In addition, Hoechst 33342, AO/EB, TUNEL staining, and caspase-3 activity assay further showed that zerumbone induced apoptosis of PANC-1 cells. The expression of p53 protein was markedly upregulated, and the p21 level was also obviously elevated in zerumbone-treated PANC-1 cells. Moreover, ROS production was increased by about 149% in PANC-1 cells treated by zerumbone 30 μM. Zerumbone also produced the same antitumor activity in pancreatic carcinoma cell lines SW1990 and AsPC-1. In summary, we found that zerumbone was able to induce apoptosis of pancreatic carcinoma cell lines, indicating to be a promising treatment for pancreatic cancer.
PMCID: PMC3290912  PMID: 22454691
13.  The Limbic-Prefrontal Network Modulated by Electroacupuncture at CV4 and CV12 
fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture's modulation effects on brain functional networks by electroacupuncture (EA) at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4) and Zhongwan (CV12) were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation.
PMCID: PMC3265182  PMID: 22291848
14.  Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats 
Flos carthami is a traditional Chinese herbal medicine. Clinically, the Flos carthami Injection has been used concomitantly with other Western drugs and may be used concomitantly with β-blockers, such as metoprolol, to treat cerebrovascular and coronary heart diseases, in China. Metoprolol is a CYP2D6 substrate and is predominantly metabolized by this isozyme. However, we do not know whether there is an effect of Flos carthami on CYP2D6 and the consequences of such an effect. Concern is raised regarding the possible herb-drug interaction. In this report, the effects of Flos carthami on the activity of CYP2D6 in vivo and in vitro and on the pharmacokinetics of metoprolol, in rats, are investigated. To assess the inhibitory potency of Flos carthami, the concentration associated with 50% inhibition (IC50) of dextromethorphan metabolism was determined based on the concentration-inhibition curves. The inhibitory effect of Flos carthami on CYP2D6 was also compared with cimetidine in vitro. Flos carthami could significantly inhibit CYP2D6 in rats both in vitro and in vivo (P < .05) and could slow down the metabolic rate of metoprolol as suggested by prolonged t1/2 (67.45%), by increased Cmax (74.51%) and AUC0−∞ (76.89%). These results suggest that CYP2D6 is a risk factor when Flos carthami is administered concomitantly with metoprolol or other CYP2D6 substrates.
PMCID: PMC2994065  PMID: 21127727
15.  Effects of Fermented Mushroom of Cordyceps sinensis, Rich in Selenium, on Uterine Cervix Cancer 
The purpose of this study was to investigate the effect of fermented mushroom of Cordyceps sinensis (CS), rich in selenium (Se-CS), on uterine cervical cancer in mice. The methylcholanthrene- (MCA-) induced tumor model was used in this paper. After the mice were administered Se-CS, the animals showed 40% tumor incidence (P < 0.05). Se-CS also enhanced the immune functions. Se-CS treatment showed significant (P < 0.05–0.01) restoration in the level of glutathione content, lipid peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+/K+-ATPase activity, and glutathione S transferase activity. This finding suggested that the concomitant use of Se and CS could be a potential therapeutic approach to improve the efficacy of therapy for uterine cervical cancer.
PMCID: PMC4058183  PMID: 24971145
16.  Acupuncture for Preventing Complications after Radical Hysterectomy: A Randomized Controlled Clinical Trial 
We aimed to investigate the preventive effects of acupuncture for complications after radical hysterectomy. A single-center randomized controlled single-blinded trial was performed in a western-style hospital in China. One hundred and twenty patients after radical hysterectomy were randomly allocated to two groups and started acupuncture from sixth postoperative day for five consecutive days. Sanyinjiao (SP6), Shuidao (ST28), and Epangxian III (MS4) were selected with electrical stimulation and Zusanli (ST36) without electrical stimulation for thirty minutes in treatment group. Binao (LI14) was selected as sham acupuncture point without any stimulation in control group. The main outcome measures were bladder function and prevalence of postoperative complications. Compared with control group, treatment group reported significantly improved bladder function in terms of maximal cystometric capacity, first voiding desire, maximal flow rate, residual urine, and bladder compliance, and decreased bladder sensory loss, incontinence, and urinary retention on fifteenth and thirtieth postoperative days. Treatment group showed significant advantage in reduction of urinary tract infection on thirtieth postoperative day. But no significant difference between groups was observed for lymphocyst formation. By improving postoperative bladder function, early intervention of acupuncture may provide a valuable alternative method to prevent bladder dysfunctional disorders and urinary tract infection after radical hysterectomy.
PMCID: PMC4009289  PMID: 24839455
17.  Suxiao Jiuxin Pill Induces Potent Relaxation and Inhibition on Contraction in Human Artery and the Mechanism 
Suxiao Jiuxin Pill, a compound Chinese traditional medicine with main components of tetramethylpyrazine and borneol, is widely used for antiangina treatment in China but its pharmacological effect on human blood vessels is unknown. We investigated the effect and possible mechanism of SJP in the human internal mammary artery (IMA, n = 78) taken from patients undergoing coronary surgery. SJP caused full relaxation in KCl- (99.4 ± 10.5%, n = 6) and U46619- (99.9 ± 5.6%, n = 6) contracted IMA. Pretreatment of IMA with plasma concentrations of SJP (1 mg/mL), calculated from the plasma concentration of its major component borneol, significantly depressed the maximal contraction to KCl (from 35.8 ± 6.0 mN to 12.6 ± 5.6 mN, P = 0.03) and U46619 (from 19.4 ± 2.9 mN to 5.7 ± 2.4 mN, P = 0.007) while SJP at 10 mg/mL abolished the subsequent contraction. Endothelium denudation and inhibition of eNOS significantly altered the SJP-induced relaxation without changes of eNOS expression. We conclude that SJP has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors in human arteries. The vasorelaxation involves both endothelium-dependent and -independent mechanisms. Thus, the effect of SJP on human arteries demonstrated in this study may prove to be particularly important in vasorelaxing therapy in cardiovascular disease.
PMCID: PMC3997901  PMID: 24808920
18.  Neuroprotective Effects of Jitai Tablet, a Traditional Chinese Medicine, on the MPTP-Induced Acute Model of Parkinson's Disease: Involvement of the Dopamine System 
Jitai tablet (JTT) is a traditional Chinese medicine used to treat neuropsychiatric disorders. We previously demonstrated that JTT treatment led to increased level of dopamine transporter (DAT) in the striatum, thus indicating that JTT might have therapeutic potential for Parkinson's disease (PD), which is characterized by dysregulated dopamine (DA) transmission and decreased striatal DAT expression. The aim of this study was to investigate the neuroprotective effect of JTT on MPTP-induced PD mice. Using locomotor activity test and rotarod test, we evaluated the effects of JTT (0.50, 0.15, or 0.05 g/kg) on MPTP-induced behavioral impairments. Tyrosine hydroxylase TH-positive neurons in the substantia nigra and DAT and dopamine D2 receptor (D2R) levels in the striatum were detected by immunohistochemical staining and/or autoradiography. Levels of DA and its metabolites were determined by HPLC. In MPTP-treated mice, behavioral impairments were alleviated by JTT treatment. Moreover, JTT protected against impairment of TH-positive neurons and attenuated the MPTP-induced decreases in DAT and D2R. Finally, high dose of JTT (0.50 g/kg) inhibited the MPTP-induced increase in DA metabolism rate. Taken together, results from our present study provide evidence that JTT offers neuroprotective effects against the neurotoxicity of MPTP and thus might be a potential treatment for PD.
PMCID: PMC3996930  PMID: 24799940
19.  Memory-Enhancing Effects of the Crude Extract of Polygala tenuifolia on Aged Mice 
Learning and memory disorders arise from distinct age-associated processes, and aging animals are often used as a model of memory impairment. The root of Polygala tenuifolia has been commonly used in some Asian countries as memory enhancer and its memory improvement has been reported in various animal models. However, there is less research to verify its effect on memory functions in aged animals. Herein, the memory-enhancing effects of the crude extract of Polygala tenuifolia (EPT) on normal aged mice were assessed by Morris water maze (MWM) and step-down passive avoidance tests. In MWM tests, the impaired spatial memory of the aged mice was partly reversed by EPT (100 and 200 mg/kg; P < 0.05) as compared with the aged control mice. In step-down tests, the nonspatial memory of the aged mice was improved by EPT (100 and 200 mg/kg; P < 0.05). Additionally, EPT could increase superoxide dismutase (SOD) and catalase (CAT) activities, inhibit monoamine oxidase (MAO) and acetyl cholinesterase (AChE) activities, and decrease the levels of malondialdehyde (MDA) in the brain tissue of the aged mice. The results showed that EPT improved memory functions of the aged mice probably via its antioxidant properties and via decreasing the activities of MAO and AChE.
PMCID: PMC3972950  PMID: 24744810
20.  Electroacupuncture Promotes Proliferation of Amplifying Neural Progenitors and Preserves Quiescent Neural Progenitors from Apoptosis to Alleviate Depressive-Like and Anxiety-Like Behaviours 
The present study was designed to investigate the effects of electroacupuncture (EA) on depressive-like and anxiety-like behaviours and neural progenitors in the hippocampal dentate gyrus (DG) in a chronic unpredictable stress (CUS) rat model of depression. After being exposed to a CUS procedure for 2 weeks, rats were subjected to EA treatment, which was performed on acupoints Du-20 (Bai-Hui) and GB-34 (Yang-Ling-Quan), once every other day for 15 consecutive days (including 8 treatments), with each treatment lasting for 30 min. The behavioural tests (i.e., forced swimming test, elevated plus-maze test, and open-field entries test) revealed that EA alleviated the depressive-like and anxiety-like behaviours of the stressed rats. Immunohistochemical results showed that proliferative cells (BrdU-positive) in the EA group were significantly larger in number compared with the Model group. Further, the results showed that EA significantly promoted the proliferation of amplifying neural progenitors (ANPs) and simultaneously inhibited the apoptosis of quiescent neural progenitors (QNPs). In a word, the mechanism underlying the antidepressant-like effects of EA is associated with enhancement of ANPs proliferation and preserving QNPs from apoptosis.
PMCID: PMC3955608  PMID: 24719647
21.  Puerarin Attenuates Cerebral Damage by Improving Cerebral Microcirculation in Spontaneously Hypertensive Rats 
Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the effective components of isoflavones isolated from the root of Pueraria lobata. Previous studies showed that extracts derived from the root of Pueraria lobata possessed antihypertensive effect. Our study is to investigate whether puerarin contributes to prevention of stroke by improving cerebral microcirculation in rats. Materials and Methods. Video microscopy and laser Doppler perfusion imaging on the pia mater were used to measure the diameter of microvessel and blood perfusion in 12-week old spontaneously hypertensive rats (SHRs) and age-matched normotensive WKY rats. Histological alterations were observed by hematoxylin and eosin staining, and microvessel density in cerebral tissue was measured by immunohistochemical analysis with anti-Factor VIII antibody. Cell proliferation was detected by [3H]-TdR incorporation, and activities of p42/44 mitogen activated protein kinases (p42/44 MAPKs) were detected by western blot analysis in cultured cerebral microvascular endothelial cells (MECs). Results. Intravenous injection of puerarin relaxed arterioles and increased the blood flow perfusion in the pia mater in SHRs. Puerarin treatment for 14 days reduced the blood pressure to a normal level in SHRs (P < 0.05) and increased the arteriole diameter in the pia mater significantly as compared with vehicle treatment. Arteriole remodeling, edema, and ischemia in cerebral tissue were attenuated in puerarin-treated SHRs. Microvessel density in cerebral tissue was greater with puerarin than with vehicle treatment. Puerarin-treated MECs showed greater proliferation and p42/44 MAPKs activities than vehicle treatment. Conclusions. Puerarin possesses effects of antihypertension and stroke prevention by improved microcirculation in SHRs, which results from the increase in cerebral blood perfusion both by arteriole relaxation and p42/44 MAPKs-mediated angiogenesis.
PMCID: PMC3971448  PMID: 24715930
22.  History and Experience: A Survey of Traditional Chinese Medicine Treatment for Alzheimer's Disease 
Traditional Chinese medicine (TCM) is practiced in the Chinese health care system for more than 2,000 years. In recent years, herbal medicines, which are used to treat Alzheimer's disease (AD) in China based on TCM or modern pharmacological theories have attracted considerable attention. In this paper, we discuss etiology and pathogenesis of AD, TCM therapy, and herbal extracts for the treatment of AD. There is evidence to suggest that TCM therapy may offer certain complementary cognitive benefits for the treatment of AD. Chinese herb may have advantages with multiple target regulation compared with the single-target antagonist in view of TCM.
PMCID: PMC3927560  PMID: 24624220
23.  Electroacupuncture at Acupoints Reverses Plasma Glutamate, Lipid, and LDL/VLDL in an Acute Migraine Rat Model: A 1H NMR-Based Metabolomic Study 
Background. The objective of this study was to identify potential biomarkers of electroacupuncture (EA) on relieving acute migraine through metabolomic study. Methods. EA treatments were performed on both acupoints and nonacupoints on the nitroglycerin (NTG)-induced migraine rat model. NMR experiments and multivariate analysis were used for metabolomic analysis. Results. The number of head-scratching, the main ethology index of migraine rat model, was significantly increased (P < 0.01) after NTG injection. The plasma metabolic profile of model group was distinct from that of the control group. Glutamate was significantly increased (P < 0.01), whereas lipids were significantly decreased (P < 0.01) in model rats. After EA at acupoints, the metabolic profile of model rats was normalized, with decreased glutamate (P < 0.05) and increased lipids (P < 0.01). In contrast, EA at nonacupoints did not restore the metabolic profile, but with six metabolites significantly different from acupoints group. Interestingly, the number of head-scratching and glutamate level were significantly decreased (P < 0.05) after receiving EA at both acupoints and nonacupoints. Conclusions. EA at acupoints may relieve acute migraine by restoring the plasma metabolic profile and plasma glutamate, while EA at nonacupoints may modestly relieve acute migraine by decreasing plasma glutamate.
PMCID: PMC3921982  PMID: 24592282
24.  Influence of Acupuncture Stimulation on Cerebral Network in Functional Diarrhea 
Acupuncture is a commonly used therapy for treating functional diarrhea (FD), although there is limited knowledge on the mechanism. The objectives of this study were to investigate the differences in brain activities elicited by acupuncture between FD patients and healthy controls (HC) so as to explore the possible mechanism. Eighteen FD patients and eighteen HC received 10 sessions of acupuncture treatment at ST25 acupoints. Functional magnetic resonance imaging (fMRI) scans were, respectively, performed before and after acupuncture. The defecation frequency, Bristol stool form scale (SBFS), and MOS 36-item Short Healthy Survey (SF-36) were employed to evaluate the clinical efficacy. After acupuncture, the FD patients showed a significant decrease in defecation frequency and BSFS score. The regional homogeneity (ReHo) map showed a decrease in the paracentral lobule and postcentral gyrus, and an increase in the angular gyrus, insula, anterior cingulate cortex (ACC), and precuneus in the FD group. Moreover, the changes in ReHo values in the ACC were correlated with the reduction in defecation frequency. Decreasing functional connectivity among the ACC, insula, thalamus, and orbital frontal cortex only existed in the FD group. Conclusively, acupuncture alleviated defecation frequency and improved stool formation in FD patients. The efficacy might result from the regulation of the homeostasis afferent processing network.
PMCID: PMC3888684  PMID: 24459533
25.  Protective Effects of Shen-Yuan-Dan, a Traditional Chinese Medicine, against Myocardial Ischemia/Reperfusion Injury In Vivo and In Vitro 
Objectives. The study was to investigate the effects and mechanisms of Shen-Yuan-Dan (SYD) pharmacological postconditioning on myocardial ischemia/reperfusion (I/R) injury. Methods. In the in vivo experiment, myocardial injury markers and histopathology staining were examined. In the in vitro experiment, cell viability and cell apoptosis were, respectively, detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and Hoechst 33342 fluorochrome staining. The protein expressions of Bcl-2 and Bax were determined by immunocytochemistry assay. Results. Both low and high doses of SYD protected myocardium against I/R injury in rat model by reducing lactic dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity and malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activity and attenuating histopathology injury. Meanwhile, in the in vitro experiment, SYD promoted cell viability and inhibited the cardiomyocyte apoptosis. The level of Bcl-2 protein was restored to the normal level by SYD pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by SYD pharmacological postconditioning. These effects of SYD were inhibited by LY294002. Conclusions. The results of this study suggested that SYD pharmacological postconditioning has protective effects against myocardial I/R injury in both in vivo and in vitro models, which are related to activating the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway.
PMCID: PMC3885196  PMID: 24454518

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