EGb761 improves the cognitive function of elderly db/db-/- diabetic mice by regulating the beclin-1 and NF-κB signaling pathways.

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db-/- mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db-/- mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db-/- mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db-/- group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db-/- mice (P < 0.05). NF-κB levels were obviously higher in the db/db-/- group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db-/- mice (P < 0.05). There was a trend of increased autophagosomes in db/db-/- mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db-/- mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db-/- mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.

Comparison of Electroacupuncture and Mild-Warm Moxibustion on Brain-Gut Function in Patients with Constipation-Predominant Irritable Bowel Syndrome: A Randomized Controlled Trial.

OBJECTIVE: To compare the effects of electroacupuncture (EA) and mild-warm moxibustion (Mox) therapies for constipation-predominant irritable bowel syndrome (C-IBS) patients. METHODS: Sixty C-IBS patients were assigned to 2 groups by simple randomized method, i.e. EA group (30 cases) and Mox group (30 cases). Both EA and Mox treatments were performed on bilateral Tianshu (ST 25) and Shangjuxu (ST 37) for 30 min each time, 6 times per week, for 4 consecutive weeks. The gastrointestinal symptoms and psychological symptoms of the two groups were scored before and after treatment. The effects on the corresponding functional brain areas, namely the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging (fMRI) before and after treatment. RESULTS: Compared with the Mox group, greater improvements in abdominal distension, defecation frequency, diffificulty in defecation and stool features were observed in the EA group (all P<0.01), both Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores were signifificantly decreased in the EA group (all P<0.01). Finally, decreased activated voxel values were observed in the ACC, right IC and PFC brain regions of EA group with 150 mL colorectal distension stimulation (P<0.05 or P<0.01). CONCLUSIONS: Both EA and Mox could signifificantly improve some of the most intrusive symptoms of C-IBS patients, and EA was more effective than Mox. The therapeutic effect of these two therapies might through modulating of the brain-gut axis function. (Registration No. ChiCTRTRC-11001349).

Comparison of electroacupuncture and moxibustion on brain-gut function in patients with diarrhea-predominant irritable bowel syndrome: A randomized controlled trial.

OBJECTIVE: To compare the effects of electroacupuncture (EA) and moxibustion therapies on patients with diarrhea-predominant irritable bowel syndrome (D-IBS). METHODS: A total of 60 D-IBS patients were randomly allocated to the EA group (30 cases) and moxibustion group (30 cases). Before and after treatment, the gastrointestinal symptoms and psychological symptoms were scored by Visual Analogue Scale, Bristol Stool Form Scale, Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD); the expressions of 5-hydroxytryptamine (5-HT), 5-HT3 receptor (5-HT3R), and 5-HT4 receptor (5-HT4R) in the sigmoid mucosal tissue were measured by immunohistochemical staining. Additionally, the effects on the functional brain areas of the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging. RESULTS: Compared with before treatment, both EA and moxibustion groups reported significant improvements in abdominal pain and abdominal bloating after treatment (P<0.01 or P<0.05). The moxibustion group reported greater improvements in defecation emergency, defecation frequency, and stool feature than the EA group (P<0.01). Both HAMA and HAMD scores were significantly decreased in the moxibustion group than in the EA group (P<0.01). Both groups demonstrated significantly reduced expressions of 5-HT, 5-HT3R and 5-HT4R in the colonic mucosa after treatment (P<0.01), with a greater reduction of 5-HT in the moxibustion group (P<0.05). Finally, decreased activated voxel values were observed in the left IC, right IC and PFC brain regions of patients in the moxibustion group under stimulation with 150 mL colorectal distension after treatment (P<0.05 or P<0.01), while in the EA group only PFC area demonstrated a reduction (P<0.05). CONCLUSION: Moxibustion can significantly improve the symptoms of D-IBS, suggesting that moxibustion may be a more effective therapy than EA for D-IBS patients.

Acupuncture treatment of chronic low back pain reverses an abnormal brain default mode network in correlation with clinical pain relief.

BACKGROUND: Acupuncture is gaining in popularity as a treatment for chronic low back pain (cLBP); however, its therapeutic mechanisms remain controversial, partly because of the absence of an objective way of measuring subjective pain. Resting-state functional MRI (rsfMRI) has demonstrated aberrant default mode network (DMN) connectivity in patients with chronic pain, and also shown that acupuncture increases DMN connectivity in pain-modulator and affective-emotional brain regions of healthy subjects. OBJECTIVE: This study sought to explore how cLBP influences the DMN and whether, and how, the altered DMN connectivity is reversed after acupuncture for clinical pain. METHODS: RsfMRI data from 20 patients with cLBP, before and after 4 weeks of treatment, and 10 age- and gender-matched healthy controls (without treatment) were analysed using independent components analyses to determine connectivity within the DMN, and combined with correlation analyses to compute covariance between changes in DMN connectivity and changes in clinical pain. Visual analogue scale data were assessed to rate clinical pain levels. RESULTS: Less connectivity within the DMN was found in patients with cLBP than in healthy controls, mainly in the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate gyrus and precuneus. After acupuncture, patients' connectivities were restored almost to the levels seen in healthy controls. Furthermore, reductions in clinical pain were correlated with increases in DMN connectivity. CONCLUSIONS: This result suggests that modulation of the DMN by acupuncture is related to its therapeutic effects on cLBP. Imaging of the DMN provides an objective method for assessment of the effects of acupuncture-induced analgesia.

[Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: a randomized controlled trial].

BACKGROUND: Alzheimer disease (AD) is a chronic neurodegenerative disease that is characterized by its gradual progression. At present, the cause and mechanism of AD are yet unclear, and there is no effective therapy for treating it. With development of global aging, the prevalence rate of AD is increasing. The life quality of elderly people is affected severely by AD that is ultimately life-threatening. Recently, study on treating AD with traditional Chinese medicine (TCM) has deepened. OBJECTIVE: To explore the therapeutic effects of a syndrome differentiation-based TCM regime in treating patients with mild to moderate AD for improving cognition, and to evaluate the changes in brain function of AD patients observed by resting-state functional magnetic resonance imaging (fMRI) technique. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Adopting the internationally recognized criteria developed by National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association, the clinical trial was conducted on 131 patients with mild to moderate AD from 5 communities and 7 social welfare institutions. Participants were accepted after informed consent was received, and laboratory tests and a head imaging study were conducted. The patients were randomly divided into Chinese medicine group (CMG) (66 cases) or Western medicine group (WMG) (65 cases). Patients in the CMG were treated monthly with Chinese medicine according to syndrome differentiation. Patients in the WMG were treated with donepezil at a dose of 5 mg once daily. The therapeutic course lasted 48 weeks. MAIN OUTCOME MEASURES: The scores of Mini-Mental State Examination (MMSE), Fuld Object-Memory Evaluation (FOM), Block Design (BD) and Digit Span (DS) were used to evaluate the cognitive function; resting-state fMRI was used for observing brain function. The questionnaires and fMRI were performed before and after treatments. RESULTS: The cognitive functions of the patients in the CMG and WMG were improved after treatment. MMSE score was improved significantly in both groups (P<0.05 or P<0.001). After 48 weeks of treatment, 70.91% patients in the CMG had an improved MMSE score and 20% got worse, however, 55.77% patients in the WMG were improved in MMSE score and 34.62% got worse. Scores of FOM denominator and BD increased significantly in both groups; scores of FOM numerator and DS were also increased in the CMG (P<0.05 or P<0.01). The results of fMRI suggested that both Chinese medicine and donepezil treatment improved the connectivity between posterior cingulated gyrus and specific areas in the brain. The influence range of Chinese medicine primarily impacted on the left parietal lobe, being less than the influence range of donepezil, which primarily affected both sides of frontal lobes. CONCLUSION: TCM treatment based on syndrome differentiation is effective in improving cognitive function of patients with mild to moderate AD and increasing the brain function by increasing connectivity between posterior cingulated gyrus and specific areas in the brain.

fMRI study of pain reaction in the brain under state of "Qigong".

In this study, 4 male Qigong masters (aged 60 +/- 12) who had Qigong practicing experience for more than 30 years were tested. By using the technique of fMRI, the change of brain function under the state of Qigong was observed through the peripheral pain stimulation generated by potassium penetrating method. The fMRI examination was running on a GE signa VH/3.0 T MRI machine and block design was used. The test was repeated several times, which was carried out before and 15 min after Qigong practicing. The heart and respiration rate of these 4 Qigong masters were monitored during the whole test. SPM2 was used for the data analysis, and the result showed that before Qigong practicing, besides SI and SII-insula regions, many other Brodmann areas, the cigulate cortex, the thalamus, and the cerebellum were all activated, while 15 min after that, the activated areas were decreased obviously, which were mainly at the SII-insula region and some other Brodmann areas. Since the SII-insula region was activated in both of these two states, further analysis of the response curve was focused on it. Its response amplitude under the state of Qigong (3.5%) was greater than that before Qigong (1.2%). Our result indicated that the main manifestation of brain functional change under Qigong was functional suppressing, but in some particular regions such as SII-insula region in our study, the response amplitude was increased. Further study of the exact physiological mechanism of Qigong is needed.

Neuronal specificity of needling acupoints at same meridian: a control functional magnetic resonance imaging study with electroacupuncture.

The purpose of this study was to investigate the neuronal specificity of needling acupoints at same meridian by functional Magnetic Resonance Imaging (fMRI). The selected acupoints GB34 (Yanglinquan) and GB39 (Xuanzhong) were at the same gallbladder meridian based on traditional Chinese medicine. In our study we devise three distinct EA (electroacupuncture) manipulations: real EA (deep needling at acupoints), sham EA (deep needling at no-meridian points) and shallow EA (subcutaneous needling at acupoints). Twelve healthy volunteers with right-handiness were enrolled and received three different EA manipulations in counter-balanced orders. DeQi scores were used to evaluate the degree of needling sensation. We found real EA can induce significant stronger needling sensation than sham EA and shallow EA. Multisubjects group mean analysis showed that pain-related cortex including primary and secondary somatosensory cortex (SI and S II), anterior cingulated cortex (ACC), insula were involved in three EA stimulation. Bilateral activation of prefrontal gyrus and occipital cortex were exclusively found in real EA. Deactivation over the rostral segment of ACC was also shown in real and shallow EA. Further paired two difference analysis indicated that real EA induced higher activation than sham EA over bilateral prefrontal gyrus, right-side occipital gyrus and deactivation over the rostral segment of ACC. In the comparing with real EA versus shallow EA, there was right-side activation over the SI, S II, motor cortex, ACC, insula, thalamus, hippocampus, occipital cortex, and cerebellum; also activation over bilateral prefrontal gyrus, caudate and pons. Although no significant activation was found over periaqueductal gray (PAG), further analysis showed the mean and maximal signal changes were different under three EA manipulations. We concluded that EA at analgesic acupoints of same meridian maybe involved the pain-related neuromatrix especially the hypothalamus-limbic system; deep EA at meridian points could elicit stronger needling sensation and modulate the pain-related neuromatrix more effectively than EA at nonmeridian points or shallow EA at meridian points.