Naoxin'an capsules protect brain function and structure in patients with vascular cognitive impairment.

Introduction: Vascular cognitive impairment (VCI) is one of the most common types of dementia. Naoxin'an capsule (NXA), a traditional Chinese medicine compound, has been used to treat VCI for a long time in the clinic. Previous studies proved that the NXA capsules could ameliorate the cerebral mitochondrion deficits of VCI animals. This study aimed to investigate the protectiveness of NXA on human brain structure and function in patients with VCI. Methods: In total, 100 VCI patients were enrolled in this 24-week trial and randomly divided into the NXA capsules group (n = 50) and the ginkgo biloba capsules control group (n = 50). Before and after the treatment, cognitive behavior tests and multimodal brain magnetic resonance imaging were analyzed to comprehensively evaluate the effectiveness of NXA treatment on VCI patients after 24 weeks. Results: We found that the NXA group significantly improved overall cognitive ability (Alzheimer's Disease Assessment Scale-Cognitive section, p = 0.001; Mini-Mental Status Examination, p = 0.003), memory (Rey-Osterrieth Complex Figure test, p < 0.001) and executive function (Trail Making Test-A, p = 0.024) performance after treatment compared with the control group. For brain function, the degree of centrality in the left middle frontal gyrus, right postcentral gyrus, and left supplementary motor area increased in the NXA group and decreased in the ginkgo biloba group after treatment. The fractional amplitude of low-frequency fluctuation (fALFF) of the left precentral and right superior parietal gyrus increased, and the fALFF of the right parahippocampal and left inferior temporal gyrus decreased in the NXA group after treatment. For brain structure, the gray matter density of the left postcentral gyrus increased in the NXA group after treatment, and the total volume of white matter hyperintensity showed a decreasing trend but was not statistically significant. Furthermore, the improvement effect of NXA on executive function was associated with changes in brain function. Conclusion: These findings suggest that the NXA capsules improved cognitive performance and multiregional brain function, as well as gray matter structure in the postcentral gyrus.

Network Pharmacology and Molecular Docking-Based Strategy to Investigate the Multitarget Mechanisms of Shenqi Yizhi Granule on Alzheimer's Disease.

Background: Traditional Chinese herbal medicine draws more attention to explore an effective therapeutic strategy for Alzheimer's disease (AD). Shenqi Yizhi granule (SQYG), a Chinese herbal recipe, has been applied to ameliorate cognitive impairment in mild-to-moderate AD patients. However, the overall molecular mechanism of SQYG in treating AD has not been clarified. Objective: This study aimed to investigate the molecular mechanism of SQYG on AD using an integration strategy of network pharmacology and molecular docking. Methods: The active compounds of SQYG and common targets between SQYG and AD were screened from databases. The herb-compound network, compound-target network, and protein-protein interaction network were constructed. The enrichment analysis of common targets and molecular docking were performed. Results: 816 compounds and 307 common targets between SQYG and AD were screened. KEGG analysis revealed that common targets were mainly enriched in lipid metabolism, metal ion metabolism, IL-17 signaling pathway, GABA receptor signaling, and neuroactive ligand-receptor interaction. Molecular docking analysis showed high binding affinity between ginsenoside Rg1 and Aß 1-42, tanshinone IIA and BACE1, baicalin, and AchE. Conclusions: The therapeutic mechanisms of SQYG on AD were associated with regulating lipid metabolism, metal ion metabolism, IL-17 signaling pathway, and GABA receptor signaling. Ginsenoside Rg1, tanshinone IIA, baicalin, astragaloside IV, and folic acid may play an important role in AD treatment.

Identification of miRNAs and their target genes in genic male sterility lines in Brassica napus by small RNA sequencing.

BACKGROUND: Brassica napus is the third leading source of edible oil in the world. Genic male sterility (GMS) lines provide crucial material for harnessing heterosis for rapeseed. GMS lines have been used successfully for rapeseed hybrid production in China. MicroRNAs (miRNAs) play crucial regulatory roles in various plant growth, development, and stress response processes. However, reports on miRNAs that regulate the pollen development of GMS lines in B. napus are few. RESULTS: In this study, 12 small RNA and transcriptome libraries were constructed and sequenced for the flower buds from the fertile and sterile lines of two recessive GMS (RGMS) lines, namely, "6251AB" and "6284AB". At the same time, 12 small RNA and transcriptome libraries were also constructed and sequenced for the flower buds from the fertile and sterile lines of two dominant GMS (DGMS) lines, namely, "4001AB" and "4006AB". Based on the results, 46 known miRNAs, 27 novel miRNAs on the other arm of known pre-miRNAs, and 44 new conserved miRNAs were identified. Thirty-five pairs of novel miRNA-3p/miRNA-5p were found. Among all the identified miRNAs, fifteen differentially expressed miRNAs with over 1.5-fold change between flower buds of sterile and fertile lines were identified, including six differentially expressed miRNAs between "4001A" and "4001B", two differentially expressed miRNAs between "4006A" and "4006B", four differentially expressed miRNAs between "6251A" and "6251B", and ten differentially expressed miRNAs between "6284A" and "6284B". The correlation analysis of small RNA and transcriptome sequencing was conducted. And 257 candidate target genes were predicted for the 15 differentially expressed miRNAs. The results of 5' modified RACE indicated that BnaA09g48720D, BnaA09g11120D, and BnaCnng51960D were cleaved by bna-miR398a-3p, bna-miR158-3p and bna-miR159a, respectively. Among the differentially expressed miRNAs, miR159 was chosen to analyze its function. Overexpression of bna-miR159 in Arabidopsis resulted in decreased seed setting rate, and shortened siliques, illustrating that miR159 may regulate the fertility and silique development in rapeseed. CONCLUSIONS: Our findings provide an overview of miRNAs that are potentially involved in GMS and pollen development. New information on miRNAs and their related target genes are provided to exploit the GMS mechanism and reveal the miRNA networks in B. napus.

Nanosized Cu-In spinel-type sulfides as efficient sorbents for elemental mercury removal from flue gas.

Mercury emitted from human activities has received increasing attention because of its extreme toxicity, persistence and bioaccumulation. The development of highly-efficient sorbent with abundant active sites that exhibit high affinity toward Hg0 is the key challenge for elemental mercury capture at low temperature. Herein, Cu-In spinel-type sulfides were synthesized through a hydrothermal synthesis. The Hg0 removal performance of CuxIn2-xS2 sorbents was evaluated in the temperature range of 75 °C to 175 °C. The synthesized CuxIn2-xS2 sorbents showed excellent performance for Hg0 removal at low temperatures, which perfectly matches the optimal temperature of flue gas at the downstream of desulfurization system. Hg0 removal efficiency of CuxIn2-xS2 sorbents significantly improved as the Cu proportion increased. CuInS2 sorbent showed superior mercury removal performance, the mercury removal efficiency reached 99.6% at 125 °C. O2 and NO showed a slight inhibition on Hg0 capture. The coexistence of SO2 and H2O showed no obvious negative effects on Hg0 removal. The CuInS2 sorbent displayed a superior tolerance to SO2 and H2O. TPD and XPS analyses demonstrated that the adsorbed mercury mainly existed in the form of mercuric sulfides (HgS). Hg0 adsorption over CuInS2 sorbent occurred via the Mars-Maessen mechanism. In this mechanism, Hg0 vapor was physically adsorbed on CuInS2 sorbent and then converted to HgS. This study provides future potential for applying CuxIn2-xS2 sorbents to capture gaseous mercury at low temperature.

Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism.

Acute liver failure (ALF) is a serious clinical disorder with high fatality rates. Mahuang decoction (MHD), a well-known traditional Chinese medicine, has multiple pharmacological effects, such as anti-inflammation, anti-allergy, anti-asthma, and anti-hyperglycemia. In this study, we investigated the protective effect of MHD against ALF. In the lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced ALF mouse model, the elevated activities of the serum alanine and aspartate transaminases as well as the liver pathological damage were markedly alleviated by MHD. Subsequently, a metabolomics study based on the ultrahigh performance liquid chromatograph coupled with Q Exactive Orbitrap mass spectrometry was carried to clarify the therapeutic mechanisms of MHD against ALF. A total of 36 metabolites contributing to LPS/D-GalN-induced ALF were identified in the serum samples, among which the abnormalities of 27 metabolites were ameliorated by MHD. The analysis of metabolic pathways revealed that the therapeutic effects of MHD are likely due to the modulation of the metabolic disorders of tricarboxylic acid (TCA) cycle, retinol metabolism, tryptophan metabolism, arginine and proline metabolism, nicotinate and nicotinamide metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan synthesis, as well as cysteine and methionine metabolism. This study demonstrated for the first time that MHD exerted an obvious protective effect against ALF mainly through the regulation of TCA cycle and amino acid metabolism, highlighting the importance of metabolomics to investigate the drug-targeted metabolic pathways.

Shenqi Yizhi granules protect hippocampus of AD transgenic mice by modulating on multiple pathological processes.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) draws more attention to explore effective therapeutic strategy for Alzheimer's disease (AD). CHM usually uses combinations of herbs or herbal ingredients to treat diseases, with the components targeting different disease processes. CHM might improve cognition in AD and MCI patients by optimizing network activity, promoting neural plasticity and repairing damaged neurons. Shenqi Yizhi granules (SQYG), a CHM prescription, are mainly consists of Panax ginseng C.A.Mey, Astragalus membranaceus (Fisch.) Bunge, and Scutellaria baicalensis Georgi and have been used to ameliorate cognitive impairment in mild-to-moderate dementia patients. AIM OF THE STUDY: To investigate the neuroprotection effect and pharmacological mechanism of SQYG in the hippocampus of 5XFAD transgenic mice. MATERIALS AND METHODS: The immunofluorescence detection, 2DE-gels, mass spectrum identification, biological information analysis and Western blot were performed after SQYG treatment. RESULTS: SQYG treatment significantly decreased the fluorescence intensities of anti-GFAP and anti-Iba1 in the hippocampus of 5XFAD mice. The expression levels of 31 proteins in the hippocampus were significantly influenced by SQYG, approximately 65% of these proteins are related to energy metabolism, stress response and cytoskeleton, whereas others are related to synaptic transmission, signal transduction, antioxidation, amino acid metabolism, and DNA repair. The expression of these proteins were increased. The changes in the expression levels of malate dehydrogenase (cytoplasmic) and pyruvate kinase M were confirmed by Western blot. CONCLUSIONS: The pharmacological mechanism of SQYG on the hippocampus may be related to modulation of multiple pathological processes, including energy metabolism, stress response, cytoskeleton, synaptic transmission, signal transduction, and amino acid metabolism in 5XFAD mice.

Evaluation of Mogroside V as a Promising Carrier in Drug Delivery: Improving the Bioavailability and Liver Distribution of Silybin.

The objective of this work was to investigate the capacity of mogroside V (MOG-V), a food additive, as a novel carrier to improve the bioavailability and liver distribution of silybin (SLY). Solid dispersion particles (SDPs) of SLY/MOG-V were prepared utilizing the solvent evaporation method. The physicochemical characterizations of SDPs were evaluated by using dynamic light scattering (DLS), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) measurements. DLS results demonstrated the formation of nanoparticles (206 nm) of SDPs in water. DSC and PXRD analysis revealed that SLY was in amorphous form or molecularly dispersed in SDPs. SDPs also exhibited a major increase in both dissolution rate and saturation solubility, as evidenced by a 1931-fold improvement (2201 µg/mL) in solubility compared with pure SLY (1.14 µg/mL). The pharmacokinetic study in rats showed that oral absorption of SLY/MOG-V SDPs was dramatically increased. The mean value of AUC until 12 h for SLY/MOG-V SDPs (27,481 ng·min/mL) was 24.5-fold higher than that of pure SLY (1122 ng·min/mL). In vivo tissue distribution experiment in mice confirmed that the major distribution tissue was changed from lungs to liver after SLY was loaded into MOG-V. In addition, even orally administrated to mice at a high dose (4.2 g/kg), MOG-V exhibited no undesirable effect on the plasma glucose concentrations. Thus, MOG-V may have the applicability to serve as an ideal excipient for solubilization or as a novel liver targeting carrier for the delivery of SLY.

Network topology and machine learning analyses reveal microstructural white matter changes underlying Chinese medicine Dengzhan Shengmai treatment on patients with vascular cognitive impairment.

With the increasing incidence of cerebrovascular diseases and dementia, considerable efforts have been made to develop effective treatments on vascular cognitive impairment (VCI), among which accumulating practice-based evidence has shown great potential of the traditional Chinese medicine (TCM). Current randomized double-blind controlled trial has been designed to evaluate the 6-month treatment effects of Dengzhan Shengmai (DZSM) capsules, one TCM herbal preparations on VCI, and to explore the underlying neural mechanisms with graph theory-based analysis and machine learning method based on diffusion tensor imaging (DTI) data. A total of 82 VCI patients were recruited and randomly assigned to drug (45 with DZSM) and placebo (37 with placebo) groups, and neuropsychological and neuroimaging data were acquired at baseline and after 6-month treatment. After treatment, compared to the placebo group, the drug groups showed significantly improved performance in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog) score (p < 0.001) and the other cognitive domains. And with the reconstruction of white matter structural network, there were more streamlines connecting the left thalamus and right hippocampus in the drug groups (p < 0.001 uncorrected), with decreasing nodal efficiency of the right olfactory associated with slower decline in the general cognition (r = -0.364, p = 0.048). Moreover, support vector machine classification analyses revealed significant white matter network alterations after treatment in the drug groups (accuracy of baseline vs. 6-month later, 68.18 %). Taking together, the present study showed significant efficacy of DZSM treatment on VCI, which might result from white matter microstructure alterations and the topological changes in brain structural network.

A proton-coupled organic cation antiporter is involved in the blood-brain barrier transport of Aconitum alkaloids.

ETHNOPHARMACOLOGICAL RELEVANCE: The herbs of Aconitum are the essential Traditional Chinese medicine and have played an indispensable role in many Asian countries for thousands of years to treat critical illnesses, and chronic, stubborn diseases. However, Aconitum may induce severe neurotoxicity and even death. So far the mechanism of Aconitum penetrating the blood-brain barrier (BBB) is still unclear. AIM OF THE STUDY: To determine whether influx transporters contribute to the brain uptake of the highly toxic alkaloids in Aconitum including aconitine (AC), mesaconitine (MA) and hypaconitine (HA). MATERIALS AND METHODS: The uptake of AC, MA and HA was characterized using in vitro hCMEC/D3 model and in situ mouse brain perfusion. In hCMEC/D3 cells, the effect of incubation temperature, time, initial drug concentration, energy (NaN3), extracellular and intracellular pH (FCCP and NH4Cl), the prototypical substrates/inhibitors of known organic cation transporting carriers and trans-stimulation (pre-incubating with pyrilamine and diphenhydramine) on the cellular uptake were studied. In addition, the effect of silencing OCTN1, OCTN2 and PMAT by specific siRNA was investigated. In mice, the contribution of the proton-coupled antiporter on the brain uptake of Aconitum was investigated by chemical inhibition. RESULTS: In hCMEC/D3 cells, AC, MA and HA were each taken up in a temperature-, time- and concentration-dependent manner, which were reduced by NaN3 and FCCP. Regulation of extracellular and intracellular pH as well as trans-stimulation studies showed that AC, MA and HA were transported by a proton-coupled antiporter expressed at the plasma membrane that could also transport pyrilamine and diphenhydramine. Each uptake was markedly inhibited by various cationic drugs, but insensitive to the prototypical substrates/inhibitors of identified organic cation transporting carriers, such as OCTs, PMAT, MATEs and OCTNs. In addition, silence of OCTN1, OCTN2 and PMAT had no significant inhibitory effect on the uptake of AC, MA and HA. In mice, the brain uptake of each alkaloid measured by in situ brain perfusion was suppressed by diphenhydramine when the transport capacity of P-gp/Bcrp at the BBB was chemically inhibited. CONCLUSIONS: A novel proton-coupled organic cation antiporter plays a predominant role in the blood to brain influx of AC, MA and HA at the BBB, and thus affect the safety of Aconitum species.

Hypoglycemic activity of CPU2206: A novel peptide from sika (Cervus nippon Temminck) antler.

Previous work had extracted and purified an antidiabetic peptide named CPU2206 with 7,127.6 Da. In this work, the toxicity of CPU2206 was first evaluated by daily administration to ICR mice, and after 28 days of administration, the body weight and lipid metabolism of the mice did not change significantly, which proved its safety and reliability. Second, further studies have focused on its hypoglycemic effects by daily intraperitoneal injection to alloxan-induced diabetic mice and KK-Ay mice, showing that CPU2206 effectively decreased the blood glucose and corresponding indicators of diabetic mice. Daily administration of CPU2206 nearly normalized the lipid metabolic parameters in diabetic mice. Histological examination also validated that CPU2206 ameliorated the pancreas injuries induced by alloxan or alleviated islet hypertrophy caused by insulin resistance in KK-Ay mice. To sum up, a totally new bioactive peptide CPU2206 obtained from sika antler showed significantly antidiabetic as well as lipid-lowering effects in diabetic mice. PRACTICAL APPLICATIONS: Antler has been used as a traditional Chinese medicine to invigorate primordial energy, enrich the blood, strengthen bones, and improve both male and female sexual functions for thousands of years. Traditionally, velvet antler can be grinded directly and taken orally, or used in porridge, wine and meat stew. Our experiment enriches the research on the function of edible antlers, provides the basis for developing it into functional health food, and on the other hand, provides an idea for finding new antidiabetic drugs.

Long-term efficacy of Chinese medicine Bushen Capsule on cognition and brain activity in patients with amnestic mild cognitive impairment.

Mild cognitive impairment (MCI), regarded as the prodromal stage before the clinical phase of Alzheimer's disease (AD), has been considered for early intervention. Unfortunately, many trials in this stage with drugs with single-target turned out to be little or no effect. Multi-targeting in nature based on the theory of Traditional Chinese Medicine (TCM) offers another prospect for intervention. Together with advanced functional magnetic resonance imaging (fMRI) technique for more sensitive and objective evaluation, we investigated the long-term therapeutic effects of a TCM compound on cognition and task-related neuronal activity. Sixty amnestic MCI (aMCI) participants from randomly divided into drug (30 with Bushen capsules (BSC)) and placebo (30 with placebo capsules) groups for this 2-years trial. Neuropsychological and N-back task-fMRI data were acquired at baseline and two follow-ups to assess, via linear mixed effect models, the changes of cognitive ability and brain activation over treatments. The drug group, compared with placebo group, exhibited improvement or stabilization in memory measures over time. Analyses of fMRI revealed that the placebo group exhibited higher activation magnitude and spatial extents at left superior parietal lobule; importantly, the greater activation identified in placebo group was related to more decline in the digit span. BSC showed long-term ameliorative effects on cognitive performances in aMCI patients, which might result from the regulation of abnormal brain activities. Our study provided evidence for the potential of TCM in early prevention of AD, as well as the feasibility of neuroimaging biomarkers in clinical trials.

Distinguishable brain networks relate disease susceptibility to symptom expression in schizophrenia.

Disease association studies have characterized altered resting-state functional connectivities describing schizophrenia, but failed to model symptom expression well. We developed a model that could account for symptom severity and meanwhile relate this to disease-related functional pathology. We correlated BOLD signal across brain regions and tested separately for associations with disease (disease edges) and with symptom severity (symptom edges) in a prediction-based scheme. We then integrated them in an "edge bi-color" graph, and adopted mediation analysis to test for causality between the disease and symptom networks and symptom scores. For first-episode schizophrenics (FES, 161 drug-naïve patients and 150 controls), the disease network (with inferior frontal gyrus being the hub) and the symptom-network (posterior occipital-parietal cortex being the hub) were found to overlap in the temporal lobe. For chronic schizophrenis (CS, 69 medicated patients and 62 controls), disease network was dominated by thalamocortical connectivities, and overlapped with symptom network in the middle frontal gyrus. We found that symptom network mediates the relationship between disease network and symptom scores in FEP, but was unable to define a relationship between them for the smaller CS population. Our results suggest that the disease network distinguishing core functional pathology in resting-state brain may be responsible for symptom expression in FES through a wider brain network associated with core symptoms. We hypothesize that top-down control from heteromodal prefrontal cortex to posterior transmodal cortex contributes to positive symptoms of schizophrenia. Our work also suggests differences in mechanisms of symptom expression between FES and CS, highlighting a need to distinguish between these groups.

CuS nanoagents for photodynamic and photothermal therapies: Phenomena and possible mechanisms.

Photodynamic therapy (PDT) and photothermal therapy (PTT) have been emerging as attractive and promising methods for tumor treatment in clinical approaches. CuS nanoparticles are effective and cost-effective agents for PTT. Recently, it was observed that CuS nanoparticles are also excellence candidates for PDT. However, the mechanisms for CuS nanoparticles as PDT agents have never been discussed. The goal here is to explore the killing mechanisms of CuS nanoparticles as PTT and PDT agents. CuS nanoparticles were synthesized by a simple wet chemistry method by coating with amphiphilic polymer and examined for their therapeutic potential on lung adenocarcinoma cell line SPC-A-1 in vitro and in vivo using a murine cancer model. The CuS nanoparticles produce heat as well as reactive oxygen species (ROS) when excited by 808nm laser and show strong anticancer effects both in vitro and in vivo. The heating effects and release of copper ions from CuS upon heating in the tumor acidic environments are the main mechanisms for the generation of reactive oxygen species which are lethal bullets for cancer destruction. As a dual-function agent for PTT and PDT, CuS nanoparticles are promising phototherapy agents for cancer treatment.

Polydopamine-Functionalized Graphene Oxide Loaded with Gold Nanostars and Doxorubicin for Combined Photothermal and Chemotherapy of Metastatic Breast Cancer.

Breast cancer is the leading cancer type diagnosed in the female population, and cancer metastasis is the main reason for cancer-caused mortality. A novel nanoplatform is herein presented integrating polydopamine-functionalized nanosized reduced graphene oxide (NRGO), gold nanostars (GNS), and doxorubicin (DOX) (denoted as NRGO-GNS@DOX) for combinational treatment of metastatic breast cancer. Upon localized near infrared (NIR) laser irradiation, the NRGO-GNS@DOX nanocomposites induce significant cytotoxicity in 4T1 breast cancer cells due to a cumulative therapy effect of NRGO-GNS-elicited hyperthermia and DOX-induced cytotoxicity. Antitumor studies in orthotopic 4T1 breast tumor-bearing nude mice demonstrate that NRGO-GNS@DOX in combination with NIR laser irradiation inhibit the tumor growth and suppress the lung metastasis. Contribution of DOX-caused apoptosis of the cancer cells and hyperthermia-induced deconstruction of the tumor-associated blood vessels may account for the superior antitumor performance of the NRGO-GNS@DOX nanocomposites. These results imply a good potential of NRGO-GNS@DOX for combined photothermal and chemotherapy of the metastatic cancer.

A Two-Year Treatment of Amnestic Mild Cognitive Impairment using a Compound Chinese Medicine: A Placebo Controlled Randomized Trial.

We aimed to investigate the long-term therapeutic effects of a compound Chinese medicine, the Bushen capsule, on cognition and brain connectivity in patients with amnestic mild cognitive impairment (aMCI). Thus, sixty aMCI participants were recruited to this 24-month study and were randomly divided into treatment (30 with a Bushen capsule) and placebo (30 with a placebo capsule) groups. Neuropsychological tests with MMSE and episodic memory as the primary outcomes and resting-state functional magnetic resonance imaging (fMRI) were analyzed before and after the treatment over 24 month period. In contrast to the placebo group, the drug group presented improved or stable general cognitive function, memory, language and executive function especially the primary outcomes MMSE and episodic memory with Bushen capsule treatment. FMRI results showed increased connectivity in the right precuneus and the global connectivity indexed with goodness of fit (GOF) of the default mode network (DMN) in the drug group and decreased GOF in the placebo group. More importantly, we found the GOF change was positively correlated with changes in MMSE and memory scores after 24 months in the drug group. Over 24 months, treatment with the compound Chinese medicine Bushen capsule can improve multiple domains of cognition and increase the functional local (right precuneus) and global connectivity within the DMN, which are associated with better performance.

The Effects of Bushen Capsule on Episodic Memory in Amnestic Mild Cognitive Impairment Patients: A Pilot Placebo Controlled fMRI Study.

BACKGROUND: Observing the effects of a drug on episodic memory and the underlying brain function has extreme significance in evaluating its therapeutic value in treating amnestic mild cognitive impairment (aMCI). OBJECTIVE: To observe the effects of Bushen capsule (BSC), a Chinese herbal medicine, on episodic memory in aMCI and further explore the underlying mechanism. METHODS: 44 aMCI patients from hospitals and local communities in Beijing were randomly divided into the BSC treatment group (22 patients orally treated with BSC) and the placebo group (22 patients treated with placebo). The duration of intervention lasted for 3 months. Before and after the 3 months treatment, neuropsychological tests and fMRI examinations were carried out to assess cognitive ability and brain activation changes, respectively. RESULTS: Compared to the placebo group, the BSC group presented a significant increase in the AVLT(N5) (p = 0.003) and Stroop (C-B) time (p = 0.002). fMRI results showed a reduction of brain negative activation in the right middle temporal gyrus and a positive activation enhancement in the right putamen among the BSC group after treatment. Meanwhile, the variation in activation values in the right middle temporal gyrus was significantly correlated with the improvement in test values of AVLT(N5), and the variation in deactivation values in the right putamen was significantly correlated with the improvement in test values of Stroop (C-B) time. CONCLUSIONS: BSC can improve the behavioral performances of episodic memory in aMCI; this effect may be related to its modulation on the activations of the temporal lobe and the putamen under episodic memory encoding task.

The effects of CCRC on cognition and brain activity in aMCI patients: a pilot placebo controlled BOLD fMRI study.

OBJECTIVE: To investigate effects and functional mechanism of compound Congrongyizhi Capsule (CCRC), a Chinese medicine, on cognitive functions against amnestic mild cognitive impairment (aMCI) patients with functional magnetic resonance imaging (fMRI) based on n-back task. METHODS: Forty-one aMCI participants from hospital and local communities in Beijing and randomly divided into treatment (16 patients with CCRC capsule treatment), placebo (12 patients with placebo capsules) and control group (13 patients with no treatment). The duration of intervention lasted for 3 months. Neuropsychological tests and fMRI were applied to assess cognitive ability and brain activation changes after three months treatment. RESULTS: Drug group (n=16) presented increased significance in the MMSE (P=0.008) and digit span (P<0.001) tests, while other scores of neuropsychological tests showed no statistical significance. fMRI results showed an increased brain negative activation in drug group during performing the n-back working-memory task in posterior cingulate (PCC), inferior frontal gyrus and lingual gyrus regions after 3 months; placebo and control group did not show the same effect. Meanwhile, there were negative correlations between left PCC activation levels and changed values of MMSE and digit span separately since increased negative activation was associated with better performance on the scores of MMSE and Digit Span tests. CONCLUSIONS: CCRC can increase negative activation degree of PCC under performing working memory tasks while this modulation are associated with better performance on the MMSE and Digit Span.

Ameliorative effects of a combination of baicalin, jasminoidin and cholic acid on ibotenic acid-induced dementia model in rats.

AIMS: To investigate the therapeutic effects and acting mechanism of a combination of Chinese herb active components, i.e., a combination of baicalin, jasminoidin and cholic acid (CBJC) on Alzheimer's disease (AD). METHODS: Male rats were intracerebroventricularly injected with ibotenic acid (IBO), and CBJC was orally administered. Therapeutic effect was evaluated with the Morris water maze test, FDG-PET examination, and histological examination, and the acting mechanism was studied with DNA microarrays and western blotting. RESULTS: CBJC treatment significantly attenuated IBO-induced abnormalities in cognition, brain functional images, and brain histological morphology. Additionally, the expression levels of 19 genes in the forebrain were significantly influenced by CBJC; approximately 60% of these genes were related to neuroprotection and neurogenesis, whereas others were related to anti-oxidation, protein degradation, cholesterol metabolism, stress response, angiogenesis, and apoptosis. Expression of these genes was increased, except for the gene related to apoptosis. Changes in expression for 5 of these genes were confirmed by western blotting. CONCLUSION: CBJC can ameliorate the IBO-induced dementia in rats and may be significant in the treatment of AD. The therapeutic mechanism may be related to CBJC's modulation of a number of processes, mainly through promotion of neuroprotection and neurogenesis, with additional promotion of anti-oxidation, protein degradation, etc.

Chemical composition and anti-inflammatory and antioxidant activities of eight pear cultivars.

The contents of total phenolics, total flavonoids, total anthocyanins, and total triterpenes of eight pear samples were determined, and the monomeric compounds were identified and quantitated using high-performance liquid chromatography. The in vitro antioxidant and in vivo anti-inflammatory activities of the different pear cultivars were compared. Arbutin and catechin were the dominant polyphenol compounds in the eight pear varieties, followed by chlorogenic acid, quercetin, and rutin. In addition, Xuehua pear and Nanguo pear had significantly higher total phenolics and flavonoids contents, while Dangshansu pear had the largest total triterpenes value (209.2 mg/100 g). Xuehua pear and Nanguo pear also were the highest in total anthocyanins. The pears with high total phenolics and total flavonoids contents had significantly higher antioxidant and anti-inflammatory abilities than those of other species. Anthocyanins were correlated to antioxidant capacity in pears, whereas total triterpenoids were strongly correlated to anti-inflammatory activity.

Study on chemical composition, anti-inflammatory and anti-microbial activities of extracts from Chinese pear fruit (Pyrus bretschneideri Rehd.).

Pyrus bretschneideri Rehd. belongs to the genus Pyrus, a member of Rosaceae family. It is a routine edible fruit, and also used as a folk medicine to treat cough, eliminate constipation, and relieve alcoholism. In order to clarify the active compounds of P. bretschneideri, the phytochemical study were performed. Five compounds were isolated and identified as 2ß,19α-dihydroxy ursolic acid, quercitrin, dibutyl phthalate, diisobutyl phthalate and α-amyrin. Additionally, we investigate the anti-inflammatory and anti-microbial effects of the fractions of P. bretschneideri partitioned with petroleum ether, ethyl acetate and n-butanol, respectively. In the carrageenan-induced rat paw edema test, the EtOAc fraction showed the strongest inhibition of edema formation 0.5-5 h after edema induction, followed by n-butanol. EtOAc also displayed potent anti-inflammatory activity against xylene-induced ear edema (22.03% and 43.69%, respectively) and acetic acid-induced extravasation of Evan's blue dye (39.58% and 49.92%, respectively) at the dose of 200 and 400 mg/kg. While, the anti-microbial results showed that ethyl acetate and n-butanol fractions exhibited strong activity against the bacteria strains. Moreover, 2ß,19α-dihydroxy ursolic acid, α-amyrin and quercitrin could significantly inhibit the ear edema induced by xylene at the dose of 20 mg/kg, and exhibited moderate anti-microbial activities against the bacteria strains.