Berberine alleviates Alzheimer's disease by regulating the gut microenvironment, restoring the gut barrier and brain-gut axis balance.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Intestinal flora and its metabolism play a significant role in ameliorating central nervous system disorders, including AD, through bidirectional interactions between the gut-brain axis. A naturally occurring alkaloid compound called berberine (BBR) has neuroprotective properties and prevents Aß-induced microglial activation. Additionally, BBR can suppress the synthesis of Aß and decrease BACE1 expression. However, it is still unclear if BBR therapy can alleviate AD by changing the gut flora. PURPOSE: In this study, we examined whether a partial alleviation of AD could be achieved with BBR treatment and the molecular mechanisms involved. METHODS: We did this by analyzing alterations in Aß plaques, neurons, and related neuroinflammation-related markers in the brain and the transcriptome of the mouse brain. The relationship between the intestinal flora of 5xFAD model mice and BBR treatment was investigated using high-throughput sequencing analysis of 16S rRNA from mouse feces. RESULTS: The findings demonstrated that treatment with BBR cleared Aß plaques, alleviated neuroinflammation, and ameliorated spatial memory dysfunction in AD. BBR significantly alleviated intestinal inflammation, decreased intestinal permeability, and could improve intestinal microbiota composition in 5xFAD mice.

Oral, Nasal, and Gut Microbiota in Parkinson's Disease.

Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease. The purpose of this study was to investigate the link between microbiota composition in important mucosal interfaces (oral, nasal, and intestinal) and PD. Sequencing was undertaken of the V4-V5 region of the 16S ribosomal RNA (rRNA) gene of the microbiome from the oral cavity, nasal cavity, and gut of 91 PD patients and 91 healthy controls. Significant differences were found in microbiota composition in the oral cavity and gut, but not the nasal cavity, between PD patients and healthy controls after adjusting for age, gender, and body mass index (BMI). More genera in the oral cavity were significantly positively correlated with clinical characteristics, such as the HAMA and HAMD rating scales. The taxa c_Clostridia, o_Clostridiales, and f_Ruminococcaceae in the gut microbiota were associated with weight and MMSE score. Furthermore, as a result of dysbiosis, there was an enrichment of ion channel-, oxidative phosphorylation-, and carbohydrate metabolism-related pathways in the oral cavity and glycolysis/gluconeogenesis- and propanoate metabolism-related pathways in the intestine. Changes in these pathways can influence metabolism and inflammation, thereby contributing to PD pathogenesis. In addition, several subnetworks containing differentially abundant microbiota in the oral cavity and gut samples from PD patients may regulate microbial composition and function in PD. Overall, our results indicate that oral and gut dysbiosis may affect PD progression and provide a basis for understanding the pathogenesis of PD and identifying potential therapeutic targets for the treatment of this disease.

Altered Actinobacteria and Firmicutes Phylum Associated Epitopes in Patients With Parkinson's Disease.

Recent evidence suggests that inflammation was participated in the pathogenesis of PD, thus, to understand the potential mechanism of gut microbiota in the pathogenesis of Parkinson's disease (PD), we performed a metagenomic analysis of fecal samples from PD patient and controls. Using a two-stage metagenome-wide association strategy, fecal DNA samples from 69 PD patients and 244 controls in three groups (comprising 66 spouses, 97 age-matched, and 81 normal samples, respectively) were analyzed, and differences between candidate gut microbiota and microbiota-associated epitopes (MEs) were compared. In the study, 27 candidate bacterial biomarkers and twenty-eight candidate epitope peptides were significantly different between the PD patients and control groups. Further, enriched 4 and 13 MEs in PD were positively associated with abnormal inflammatory indicators [neutrophil percentage (NEUT.1), monocyte count/percentage (MONO/MONO.1), white blood cell count (WBC)] and five candidate bacterial biomarkers (c_Actinobacteria, f_Bifidobacteriaceae, g_Bifidobacterium, o_Bifidobacteriales, p_Actinobacteria) from Actinobacteria phylum, and they were also positively associated with histidine degradation and proline biosynthesis pathways, respectively. Additionally, enriched 2 MEs and 1 ME in PD were positively associated with above inflammatory indicators and two bacteria (f_Lactobacillaceae, g_Lactobacillus) from Firmicutes phylum, and they were also positively associated with pyruvate fermentation to propanoate I and negatively associated with isopropanol biosynthesis, respectively. Of these MEs, two MEs from GROEL2, RPSC were derived from Mycobacterium tuberculosis, triggered the T cell immune response, as previously reported. Additionally, other candidate epitope peptides derived from Mycobacterium tuberculosis and Mycobacterium leprae may also have potential immune effects in PD. In all, the altered MEs in PD may relate to abnormalities in immunity and glutamate and propionate metabolism, which furthers our understanding of the pathogenesis of PD.

[Effect of electroacupuncture on mitochondrial function in mice with Parkinson's disease].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on behavior, tyrosine hydroxylase (TH), mitochondrial complexes Ⅰ-Ⅳ, mitochondrial membrane potential and mitochondrial ultrastructure of Parkinson's disease (PD) mice, so as to explore its mechanism underlying improvement of PD. METHODS: C57BL/6 mice were randomly divided into normal, model, medication (Madopar) and EA groups (n=11 in each group). PD model was duplicated by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP, 30 mg·kg-1·d-1) for consecutively 5 d. EA was performed on the chorea tremor areas on both sides of the head of mice for 15 min, once a day for 14 d. The behavioral changes of mice were observed. The expression of TH in substantia nigra compacta of midbrain was detected by immunohistochemistry. The activities of mitochondrial complexes Ⅰ-Ⅳ were measured. The changes of mitochondrial membrane potential were detected by JC-1 staining method. The ultrastructural changes of striatum mitochondria were observed by transmission electron microscope. RESULTS: After modeling, the mice showed obvious behavioral abnormalities such as tremor, vertical hair and tail warping, and the pole test time in the model group was significantly longer than that in the normal group (P<0.01). After 7 and 14 days of the treatment, the pole test time in the EA and medication groups was shorter than that in the model group (P<0.05，P<0.01). Compared with the normal group, the number of TH positive cells of the substantia nigra, the mitochondrial membrane potential and the activity of mitochondrial complex I were decreased significantly in the model group (P<0.01), and EA and medication intervention reversed these changes (P<0.01). The mitochondrial structure of mice in the model group was obviously damaged, and the damage of mitochondrial structure was alleviated and the number of damaged mitochondria was decreased in the EA and medication groups. CONCLUSION: EA can protect and promote the recovery of mitochondrial structure and function in MPTP-induced PD mice, which may play a neuroprotective effect on PD mice by improving mitochondrial dysfunction, balancing cell homeostasis and reducing dopaminergic neuron damage.

Neuroprotective effect of the traditional Chinese herbal formula Tongxinluo: a PET imaging study in rats.

Tongxinluo has been widely used in China for the treatment of acute stroke and for neuroprotection. However, there are few positron emission tomography (PET) studies on the neuroprotective effect of Tongxinluo on cerebral ischemia/reperfusion in small animals. In the present study, Tongxinluo superfine powder suspension or its vehicle was administered intragastrically to rats for 5 successive days before middle cerebral artery occlusion. (18)F-fluorodeoxyglucose (FDG) small animal PET imaging showed that at 1 and 2 weeks after cerebral ischemia/reperfusion, glucose metabolism in the ischemic area was greater in rats that had received Tongxinluo than in those that had received the vehicle. Nissl staining showed that 2 weeks after cerebral ischemia/reperfusion, there was less neuronal loss in the prefrontal cortex in Tongxinluo-treated rats than in controls. In addition, Tongxinluo-treated animals showed better neurologic function and lower cerebral infarct volume than rats that received the vehicle. These findings suggest that Tongxinluo exhibits neuroprotective effects in cerebral ischemia/reperfusion injury and demonstrates that (18)F-FDG small animal PET imaging is a useful tool with which to study the molecular pharmacology of traditional Chinese medicine.

[Establishing a concise disease-syndrome differentiation and treatment system--the primary work for the modernization of Chinese medicine].

The priority of the modernization of Chinese medicine at present is the standardization of Chinese medicine practice, including syndrome differentiation, disease diagnosis, standardized therapeutic program, etc. For this reason, the primary work is to establish a concise disease-syndrome differentiation and treatment system (CDSDTS) under the guidance of Chinese medicine theory, holding the core advantages and effectiveness of Chinese medicine, and aiming at creating a simplified theoretical and practical program facilitating for operation and spreading. It is not a mere simplification or careless reduction, but a normalized program of treatment according to the essence of Chinese medicine. Although the therapeutic effect might be somewhat lost, it can be widely approved, thereby, it would make contributions for the inheritance and development of Chinese medicine.

[Effects of scalp penetration acupuncture on plasma endothelin (ET) and calcitonin related peptide (CGRP) contents in the patient of acute intracerebral hemorrhage].

OBJECTIVE: To study the mechanism of scalp penetration acupuncture treating acute cerebral hemorrhage (ACH). METHODS: The treatment group (n = 30) and the control group (n = 30) were treated with the same basic therapy, but scalp penetration acupuncture was added to the treatment group. Changes of plasma ET and CGRP contents were compared. RESULTS: After treatment for 14 days, the content of plasma ET in the treatment group was significantly lower than that in the control group (P < 0.01). Moreover, the content of plasma CGRP was significantly higher than that in the control group (P < 0.01). CONCLUSION: Scalp penetration acupuncture is able to improve the prognosis of the patient with ACH by means of regulating the contents of plasma ET and CGRP.