Six New Phenolic Glycosides from the Seeds of Moringa oleifera Lam. and Their α-Glucosidase Inhibitory Activity.

Plant-derived phytochemicals have recently drawn interest in the prevention and treatment of diabetes mellitus (DM). The seeds of Moringa oleifera Lam. are widely used in food and herbal medicine for their health-promoting properties against various diseases, including DM, but many of their effective constituents are still unknown. In this study, 6 new phenolic glycosides, moringaside B-G (1-6), together with 10 known phenolic glycosides (7-16) were isolated from M. oleifera seeds. The structures were elucidated by 1D and 2D NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data analysis. The absolute configurations of compounds 2 and 3 were determined by electronic circular dichroism (ECD) calculations. Compounds 2 and 3 especially are combined with a 1,3-dioxocyclopentane moiety at the rhamnose group, which are rarely reported in phenolic glycoside backbones. A biosynthetic pathway of 2 and 3 was assumed. Moreover, all the isolated compounds were evaluated for their inhibitory activities against α-glucosidase. Compounds 4 and 16 exhibited marked activities with IC50 values of 382.8 ± 1.42 and 301.4 ± 6.22 µM, and the acarbose was the positive control with an IC50 value of 324.1 ± 4.99 µM. Compound 16 revealed better activity than acarbose.

Two new alkaloids from Dendrobium nobile Lindl. exhibited neuroprotective activity, and dendrobine alleviated Aß1-42 -induced apoptosis by inhibiting CDK5 activation in PC12 cells.

Dendrobium nobile Lindl. is registered in the Chinese Pharmacopoeia as a traditional medicine. Phytochemical investigation of the ethanol extract of D. nobile Lindl. stems yielded three alkaloid compounds, including two new compounds dendroxine B (2) and denrine B (3) as well as one known compound dendrobine (1). Here, we identified the structure of these compounds using spectroscopic analyses and compared them with those described in previous studies. Compounds 1-3 were found to show protective effect against amyloid-ß 1-42 (Aß1-42 )-induced neurotoxicity in rat pheochromocytoma (PC12) cells, among which dendrobine exhibited the most significant neuroprotective effect. Hoechst 33342/propidium iodide staining indicated that dendrobine ameliorated Aß1-42 -induced apoptosis. Moreover, quantitative real-time polymerase chain reaction and western blot analysis analysis demonstrated that dendrobine suppressed the activation of cyclin-dependent kinase 5 (CDK5), upregulated Bcl-2 expression, and downregulated Bax, cyto-c, and caspase-3 expression. Molecular docking analysis and surface plasmon resonance assay suggested that dendrobine directly bound to CDK5 protein with a KD value of 2.05 × 10-4 M. In summary, alkaloids are the neuroprotective constituents of D. nobile Lindl., and dendrobine protected PC12 cells against Aß1-42 -induced apoptosis by inhibiting CDK5 activation.

The Experimental Exploration of TCM Theory "Treating the Same Disease with Different Approaches" on an Ulcerative Colitis Model.

There is a relationship between lung injury and ulcerative colitis. Currently, traditional Chinese medicine (Huangqi Jiegeng (HQJGD) and Huangqi Huanglian decoctions (HQHLD)) is commonly used for UC-related lung injury; however, the mechanisms of these drugs remain unclear. In this study, UC models were established with the mucous membrane of colon allergize combined with TNBS-alcohol enteroclysis for 4 weeks. The pathological changes in the lung, intestine, liver, and kidney were observed; cytokines, chemokines, and adhesion molecules in lung tissue were detected in order to explore the immunological mechanism of UC-related lung injury and the intervention mechanism of traditional Chinese medicine in treating the lung and intestine in the immune-TNBS-ethanol rat model. Histology examinations demonstrated evident pathological changes in the lungs and intestines of the model groups. Furthermore, all groups treated with TCMs demonstrated reduced expressions of toll-like receptor 4, nuclear factor kappa-B, and macrophage migration inhibitory factor. Additionally, radioimmunoassay and immunohistochemistry showed tumor necrosis factor-α, interleukin-6, and 8 expression downregulation. The results showed that HQJGD and HQHLD could alleviate pulmonary inflammation in UC-related lung injury by obviously improving the pathology and fibrosis of the lung, inhibiting the positive feedback loop of MIF/NF-κB, and reducing lymphocyte homing to bronchial mucosa. This model revealed the immune mechanism of UC-related lung injury and the intervention mechanism of the Chinese medicine, which provided the rationale for treating ulcerative colitis clinically, so as to demonstrate the theory of "the lung and the large intestine being interior-exteriorly related" and "treating the same disease with different approaches."

Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity.

Alzheimer's disease (AD) is a neurodegenerative disorder recognized as a global public health priority. Although available treatments temporarily relieve the symptoms, they could not prevent the progression of cognitive decline. Natural compounds have been rich sources for drug discovery. Dendrobium nobile Lindl. alkaloid (DNLA) is the main active compound in Dendrobium nobile Lindl, a traditional Chinese herbal medicine. Recent studies indicated that DNLA produced neuroprotection. However, the mechanisms underlying DNLA-generated neuroprotection remain unknown. To investigate neuroprotection and the underlying mechanisms of DNLA, mouse hippocampus injection of lipopolysaccharide (LPS)-induced neuronal damage was performed. DNLA protected hippocampus neurons and working memory disorder against LPS-induced neurotoxicity. In addition, DNLA suppressed cell undergoing membrane lysis and cell swelling and inhibited the essential mediator of pyroptosis GSDMD-N expressions. Furthermore, DNLA-mediated neuroprotection was dependent on the inhibition of NLRP3 inflammasome activation, as evidenced by the fact that DNLA reduced pro-inflammatory factor (IL-18 and IL-1ß) production and inhibited the expression of related proteins. DNLA-exerted neuroprotection against LPS-induced neuronal damage, and cognitive impairment was not observed in NLRP3 knockout mice. Together, this study suggested that DNLA attenuated NLRP3-mediated pyroptosis to generate neuroprotection against LPS-induced neuronal damage and cognitive impairment.

Opposite trends of glycosides and alkaloids in Dendrobium nobile of different age based on UPLC-Q/TOF-MS combined with multivariate statistical analyses.

INTRODUCTION: Alkaloids and glycosides are the active ingredients of the herb Dendrobium nobile, which is used in traditional Chinese medicine. The pharmacological effects of alkaloids include neuroprotective effects and regulatory effects on glucose and lipid metabolism, while glycosides improve the immune system. The pharmacological activities of the above chemical components are significantly different. In practice, the stems of 3-year-old D. nobile are usually used as the main source of Dendrobii Caulis. However, it has not been reported whether this harvesting time is appropriate. OBJECTIVE: The aim of this study was to compare the chemical characteristics of D. nobile in different growth years (1-3 years). METHODS: In this study, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) was employed to analyze the constituents of D. nobile. The relative abundance of each constituent was analyzed with multivariate statistical analyses to screen the characteristic constituents that contributed to the characterization and classification of D. nobile. Dendrobine, a component of D. nobile that is used for quality control according to the Chinese Pharmacopoeia, was assayed by gas chromatography. RESULTS: As a result, 34 characteristic constituents (VIP > 2) were identified or tentatively identified as alkaloids and glycosides based on MS/MS data. Moreover, the content of alkaloids decreased over time, whereas the content of glycosides showed the opposite trend. The absolute quantification of dendrobine was consistent with the metabolomics results. CONCLUSION: Our findings provide valuable information to optimize the harvest period and a reference for the clinical application of D. nobile.

Mapping thalamic-anterior cingulate monosynaptic inputs in adult mice.

The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.

Planococcus maritimu ML1206 Strain Enhances Stress Resistance and Extends the Lifespan in Caenorhabditis elegans via FOXO/DAF-16.

The antioxidant effect of probiotics has been widely recognized across the world, which is of great significance in food, medicine, and aquaculture. There are abundant marine microbial resources in the ocean, which provide a new space for humans to explore new probiotics. Previously, we reported on the anti-infective effects of Planococcus maritimu ML1206, a potential marine probiotic. The antioxidant activity of ML1206 in C. elegans was studied in this paper. The study showed that ML1206 could improve the ability of nematodes to resist oxidative stress and effectively prolong their lifespan. The results confirmed that ML1206 could significantly increase the activities of CAT and GSH-PX, and reduce the accumulation of reactive oxygen species (ROS) in nematodes under oxidative stress conditions. In addition, ML1206 promoted DAF-16 transfer to the nucleus and upregulated the expression of sod-3, hsp-16.2, and ctl-2, which are downstream antioxidant-related genes of DAF-16. Furthermore, the expression of the SOD-3::GFP and HSP-16.2::GFP was significantly higher in the transgenic strains fed with ML1206 than that in the control group fed with OP50, with or without stress. In summary, these findings suggest that ML1206 is a novel marine probiotic with an antioxidant function that stimulates nematodes to improve their defense abilities against oxidative stress and prolong the lifespan by regulating the translocation of FOXO/DAF-16. Therefore, ML1206 may be explored as a potential dietary supplement in aquaculture and for anti-aging and antioxidant purposes.

A network pharmacological approach to investigate the pharmacological effects of CZ2HF decoction on Alzheimer's disease.

Background: Alzheimer's disease (AD) is the most common type of dementia, which brings tremendous burden to the sufferers and society. However, ideal tactics are unavailable for AD. Our previous study has shown that CZ2HF, a Chinese herb preparation, mitigates cognitive impairment in AD rats; whereas, its detailed mechanism has not been elucidated. Methods: Public databases were applied to collect and identify the chemical ingredients of eight herbs in CZ2HF. Criteria of absorption, distribution, metabolism, and excretion was used to screen oral bio-availability and drug-likeness. STITCH database and Therapeutic Target Database were applied to decipher the relationship between compounds and genes related to AD. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology term analyses were used to identify the involved signaling pathways. Cytoscape was adopted to establish the networks The molecular docking was used to validate the interactions between the candidate compounds and their potential targets. Results: 914 compounds were identified in eight herbal medicines of CZ2HF. Among them, 9 compounds and 28 genes were highly involved in the pathologic process of AD. Furthermore, the mechanism of CZ2HF to AD was based on its anti-inflammatory effects mainly through lipopolysaccharide-mediated signaling pathway and TNF signaling pathway. Core genes in this network were TNF, ICAM1, MMP9 and IL-10. Conclusion: This study predicts the active compounds in CZ2HF and uncovers their protein targets using holistic network pharmacology methods. It will provide a insight into the underlying mechanism of CZ2HF to AD from a multi-scale perspective.

Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients.

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

Pharmacokinetics of Single and Multiple Doses of Omega-3 Carboxylic Acids in Healthy Chinese Subjects: A Phase I, Open-Label Study.

In patients with coronary heart disease undergoing primary prevention, hypertriglyceridemia is a residual risk for cardiovascular events. Omega-3 carboxylic acid (OM3-CA), a mixture of the free fatty acid forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may be beneficial in reducing triglyceride levels. As part of the clinical development program of OM3-CA in China, this phase I study evaluated the pharmacokinetics, safety, and tolerability profile of OM3-CA in healthy subjects. The pharmacokinetic results of this study were also compared with those of available data for Western populations. Fourteen healthy Chinese subjects (aged 18-45 years) received once-daily oral OM3-CA 4 g for 14 consecutive days. Pharmacokinetic parameters were assessed from both baseline-uncorrected and baseline-corrected plasma concentrations vs time profile of EPA, DHA, and EPA plus DHA. Following single and multiple oral doses of OM3-CA, the absorption of EPA, DHA, and EPA plus DHA was steady with median tmax occurring at 5.5-6 hours after both single and multiple dosing. Close to steady-state concentrations in plasma were reached after 14 days of continuous once-daily dosing, and accumulation was confirmed for EPA, DHA, and EPA plus DHA. Of the 14 subjects treated with OM3-CA, 6 (42.9%) reported at least 1 adverse event (diarrhea) during the study, which was determined as mild and treatment emergent. No serious adverse events were reported. In summary, the pharmacokinetic profile of oral OM3-CA 4 g after single and multiple dosing in healthy Chinese subjects is consistent with that observed in other ethnic populations.

Dendrobium nobile Lindl. Alkaloids Ameliorate Cognitive Dysfunction in Senescence Accelerated SAMP8 Mice by Decreasing Amyloid-ß Aggregation and Enhancing Autophagy Activity.

BACKGROUND: Dendrobium nobile is a well-known traditional Chinese herbal medicine used for age-related diseases. Dendrobium nobile Lindl. alkaloid (DNLA) is the active ingredient to improve learning and memory deficits in laboratory animals. OBJECTIVE: The aim of the present study was to examine the anti-aging effects of long-term administration of DNLA and metformin during the aging process in senescence-accelerated mouse-prone 8 (SAMP8) mice. METHODS: SAMP8 mice were orally given DNLA (20 and 40 mg/kg) or metformin (80 mg/kg) starting at 6 months of age until 12 months of age. Age-matched SAMR1 mice were used as controls. DNLA and metformin treatments ameliorated behavioral deficits of 12-month-old SAMP8 mice, as determined by Rotarod, Y-maze, and Open-field tests. RESULTS: DNLA and metformin treatments prevented brain atrophy and improved morphological changes in the hippocampus and cortex, as evidenced by Nissl and H&E staining for neuron damage and loss, and by SA-ß-gal staining for aging cells. DNLA and metformin treatments decreased amyloid-ß1-42, AßPP, PS1, and BACE1, while increasing IDE and neprilysin for Aß clearance. Furthermore, DNLA and metformin enhanced autophagy activity by increasing LC3-II, Beclin1, and Klotho, and by decreasing p62 in the hippocampus and cortex. CONCLUSION: The beneficial effects of DNLA were comparable to metformin in protecting against aging-related cognitive deficits, neuron aging, damage, and loss in SAMP8 mice. The mechanisms could be attributed to increased Aß clearance, activation of autophagy activity, and upregulation of Klotho.

Chemical Composition and Anti-Alzheimer's Disease-Related Activities of a Functional Oil from the Edible Seaweed Hizikia fusiforme.

Cholinergic disorder, oxidative stress, and neuroinflammation play important roles in the pathology of Alzheimer's disease. To explore the healthy potential of the edible seaweed Hizikia fusiforme on this aspect, a functional oil (HFFO) was extracted from this alga and investigated on its constituents by gas chromatography-mass spectrometry (GC/MS) in this study. Its anti-Alzheimer's related bioactivities including acetylcholinesterase (AChE) inhibition, antioxidation, and anti-neuroinflammation were evaluated, traced, and simulated by in vitro and in silico methods. GC/MS analysis indicated that HFFO mainly contained arachidonic acid (ARA), 11,14,17-eicosatrienoic acid (ETrA), palmitic acid, phytol, etc. HFFO showed moderate AChE inhibition and antioxidant activity. Bioactivity tracing using commercial standards verified that AChE inhibition of HFFO mainly originated from ARA and ETrA, whereas antioxidant activity mainly from ARA. Lineweaver-Burk plots showed that both ARA and ETrA are noncompetitive AChE inhibitors. A molecular docking study demonstrated low CDOCKER interaction energy of -26.33 kcal/mol for ARA and -43.70 kcal/mol for ETrA when interacting with AChE and multiple interactions in the ARA (or ETrA)-AChE complex. In the anti-neuroinflammatory evaluation, HFFO showed no toxicity toward BV-2 cells at 20 µg/mL and effectively inhibited the production of nitroxide and reduced the level of reactive oxygen species in lipopolysaccharide-induced BV-2 cells. The results indicated that HFFO could be used in functional foods for its anti-Alzheimer's disease-related activities.

Dendrobium nobile Lindl alkaloid and metformin ameliorate cognitive dysfunction in senescence-accelerated mice via suppression of endoplasmic reticulum stress.

The senescence-accelerated mouse prone 8 (SAMP8) mice have many pathological features of Alzheimer's disease (AD) with aging. We previously reported that Dendrobium nobile Lindl alkaloid (DNLA) effectively improved cognitive deficits in multiple Alzheimer's disease (AD) models. This study further used SAMP8 mice to study the anti-aging effects of DNLA, focusing on endoplasmic reticulum (ER) stress. DNLA and metformin were orally administered to SAMP8 mice starting at 4-month of age for 6 months. Behavioral tests were performed in 10-month-old SAMP8 mice and age-matched SAMR1 control mice. At the end of experiment, neuron damage was evaluated by histology and transmission electron microscopy. ER stress-related proteins were analyzed with Western-blot. DNLA improved learning and memory impairments, reduced the loss of neurons and Nissl bodies in the hippocampus and cortex. DNLA ameliorated ER dilation and swelling in the hippocampal neurons. DNLA down-regulated the protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway, decreased calpain 1, GSK-3ß and Cdk5 activities and the Tau hyper-phosphorylation. The effects of DNLA were comparable to metformin. In summary, DNLA was effective in improving cognitive deficits in aged SAMP8 mice, possibly via suppression of ER stress-related PERK signaling pathway, sequential inhibition of calpain 1, GSK-3ß and Cdk5 activities, and eventually reducing the hyper-phosphorylation of Tau.

[Research progress of effect of anxiolytic traditional Chinese medicines and formulas on neurotransmitters].

Anxiety disorders are a common mental illness that seriously endangered physical and mental health of human beings. The etiology of anxiety disorders is closely related to the abnormality of monoamines neurotransmitters, amino acids neurotransmitters and neuropeptides. The long-term use of anti-anxiety chemical drugs has some adverse effects, such as constipation, muscle relaxation, lethargy, tolerance and withdrawal symptoms. However, traditional Chinese medicines have advantages of multi-component, multi-target coordination, with less adverse reactions. Therefore, it is a promising prospect to develop novel anti-anxiety drugs from traditional Chinese medicines and formulas. This article reviewed some traditional Chinese medicines and formulas that can relieve anxiety symptoms. These include traditional Chinese medicines(Panax ginseng, Lycium ruthenium, Morus alba, Bupleurum plus dragon bone oyster soup, Chailong Jieyu Pills, and Naogongtai Formulas) with the effect on monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine; traditional Chinese medicines(Rehmannia glutinosa, Ziziphus jujuba Mill. var. spinosa, Jielv Anshen Decoction, Baixiangdan Capsules, Antianxietic Compound Prescription Capsules) with the effect on amino acid neurotransmitters, such as glutamic acid, γ-aminobutyrc acid; and traditional Chinese medicines(P. ginseng, Xiaoyao San, Shuyu Ningxin Decoction)with the effect on neuropeptide Y pathway, with the aim to provide theoretical basis for the further development of some novel and more effective anti-anxiety therapeutics from traditional Chinese medicine and formulas.

Anti-hypertensive and angiotensin-converting enzyme inhibitory effects of Radix Astragali and its bioactive peptide AM-1.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypertension is one of the common chronic health problems in the world. Astragalus membranaceus root (AM), also known as Huangqi, is a popular medicinal herb traditionally used to reinforce vital energy and modulate hypertension. AIM OF THE STUDY: This study was to reveal the anti-hypertensive activities and mechanisms of AM in spontaneously hypertensive rats (SHRs). Moreover, the presence of bioactive components in AM was further identified. MATERIALS AND METHODS: We analyzed the effects of aqueous extract of AM (AME) on the regulation of blood pressure and angiotensin converting enzyme (ACE), the major target of anti-hypertensive drugs. Proteomic, bioinformatics, and docking analyses were performed to identify the anti-hypertensive bioactive peptides in AME. RESULTS: Our data showed that AME inhibited ACE activities in a dose-dependent manner, with an IC50 of 1.85 ± 0.01 µg/ml. In comparison with mock, oral administration of AME reduced systolic blood pressure (SBP) levels in SHRs, and the level of SBP was decreased by 22.33 ± 3.61 mmHg at 200 mg/kg AME. Proteomic analysis identified that an abundant 152-amino-acid putative protein kinase fragment accounted for approximately 11.7% of protein spots in AME. AM-1 (LVPPHA), a gastrointestinal enzyme-resistant peptide cleaved from putative protein kinase fragment, inhibited ACE activities, with an IC50 value of 414.88 ± 41.88 µM. Moreover, oral administration of AM-1 significantly decreased SBP levels by 42 ± 2.65 mmHg at 10 µmol/kg. Docking analysis further showed that AM-1 docked into the active site channel of ACE and interacted with Ala-354 in the active site pocket of ACE. CONCLUSIONS: the ACE inhibitory effect of AM and the presence of ACE inhibitory phytopeptide in AME supported the ethnomedical use of AM on hypertension.

Protective effects of Dendrobium nobile Lindl. alkaloids on amyloid beta (25-35)-induced neuronal injury.

Dendrobium nobile Lindl. alkaloids (DNLA), the active ingredients of a traditional Chinese medicine Dendrobium, have been shown to have anti-oxidative effects, anti-inflammatory action, and protective effect on neurons against oxygen-glucose deprivation. However, it is not clear whether DNLA reduces amyloid-beta (Aß)-induced neuronal injury. In this study, cortical neurons were treated with DNLA at different concentrations (0.025, 0.25, and 2.5 mg/L) for 24 hours, followed by administration of Aß25-35 (10 µM). Aß25-35 treatments increased cell injury as determined by the leakage of lactate dehydrogenase, which was accompanied by chromatin condensation and mitochondrial tumefaction. The damage caused by Aß25-35 on these cellular properties was markedly attenuated when cells were pretreated with DNLA. Treatment with Aß25-35 down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95, all changes were significantly reduced by pretreatment of cells with DNLA. These findings suggest that DNLA reduces the cytotoxicity induced by Aß25-35 in rat primary cultured neurons. The protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated, at least in part, through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95.

Comprehensive evaluation of gene expression signatures in response to electroacupuncture stimulation at Zusanli (ST36) acupoint by transcriptomic analysis.

BACKGROUND: Electroacupuncture (EA) has been applied to treat and prevent diseases for years. However, molecular events happened in both the acupunctured site and the internal organs after EA stimulation have not been clarified. METHODS: Here we applied transcriptomic analysis to explore the gene expression signatures after EA stimulation. Mice were applied EA stimulation at ST36 for 15 min and nine tissues were collected three hours later for microarray analysis. RESULTS: We found that EA affected the expression of genes not only in the acupunctured site but also in the internal organs. EA commonly affected biological networks involved in cytoskeleton and cell adhesion, and also regulated unique process networks in specific organs, such as γ-aminobutyric acid-ergic neurotransmission in brain and inflammation process in lung. In addition, EA affected the expression of genes related to various diseases, such as neurodegenerative diseases in brain and obstructive pulmonary diseases in lung. CONCLUSIONS: This report applied, for the first time, a global comprehensive genome-wide approach to analyze the gene expression profiling of acupunctured site and internal organs after EA stimulation. The connection between gene expression signatures, biological processes, and diseases might provide a basis for prediction and explanation on the therapeutic potentials of acupuncture in organs.

Dendrobium nobile Lindl. alkaloids regulate metabolism gene expression in livers of mice.

OBJECTIVES: In our previous studies, Dendrobium nobile Lindl. alkaloids (DNLA) has been shown to have glucose-lowering and antihyperlipidaemia effects in diabetic rats, in rats fed with high-fat diets, and in mice challenged with adrenaline. This study aimed to examine the effects of DNLA on the expression of glucose and lipid metabolism genes in livers of mice. METHODS: Mice were given DNLA at doses of 10-80 mg/kg, po for 8 days, and livers were removed for total RNA and protein isolation to perform real-time RT-PCR and Western blot analysis. KEY FINDINGS: Dendrobium nobile Lindl. alkaloids increased PGC1α at mRNA and protein levels and increased glucose metabolism gene Glut2 and FoxO1 expression. DNLA also increased the expression of fatty acid ß-oxidation genes Acox1 and Cpt1a. The lipid synthesis regulator Srebp1 (sterol regulatory element-binding protein-1) was decreased, while the lipolysis gene ATGL was increased. Interestingly, DNLA increased the expression of antioxidant gene metallothionein-1 and NADPH quinone oxidoreductase-1 (Nqo1) in livers of mice. Western blot on selected proteins confirmed these changes including the increased expression of GLUT4 and PPARα. CONCLUSIONS: DNLA has beneficial effects on liver glucose and lipid metabolism gene expressions, and enhances the Nrf2-antioxidant pathway gene expressions, which could play integrated roles in regulating metabolic disorders.

Hepatoprotective effects of ethanol extracts from Folium Syringae against acetaminophen-induced hepatotoxicity in vitro and in vivo.

BACKGROUND: The leaves of Folium Syringae (FS) have been long used as a traditional Chinese folk medicine for their anti-inflammatory effect, utilized as an antibacterial and antiviral treatment. The purpose of this study was to investigate the potential hepatoprotective effects of FS on acetaminophen-induced hepatic injury in primary hepatocytes and mice. METHODS: Hepatocytes obtained by the inverse perfusion method were divided randomly into five groups. Prior to acetaminophen exposure, 3 different doses of FS ethanol extracts were given to hepatocytes and mice, respectively. Thereafter, transaminases, glutathione S-transferase A1 (GSTA1) and some hepatic indices were determined. RESULTS: FS ethanol extracts (200 µg/mL) pretreatment prevented all of the alterations, returning their levels to nearly those levels observed in the control group in vitro. Treatment with FS ethanol extracts (200 mg/kg) significantly reduced the toxicity induced by acetaminophen in vivo, which manifested as a decrease in transaminases, and the hepatoprotective effects of FS were similar to Silymarin (positive group). GSTA1 represented the same change trend as transaminases and hepatic indices, and at a dose of 100 µg/mL FS ethanol extracts in vitro and 100 mg/kg in vivo, GSTA1 content changed significantly (p < 0.01), but transaminases were insignificant (p > 0.05). CONCLUSION: The results of our investigation suggested that FS ethanol extracts possess significant protective effects against hepatotoxicity induced by acetaminophen both in vitro and in vivo. In addition, GSTA1 could be used as an indicator assessing the extents of hepatic injury, which is more sensitive than transaminases.

Dendrobium alkaloids prevent Aß25-35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice.

BACKGROUND: Neuronal and synaptic loss is the most important risk factor for cognitive impairment. Inhibiting neuronal apoptosis and preventing synaptic loss are promising therapeutic approaches for Alzheimer's disease (AD). In this study, we investigate the protective effects of Dendrobium alkaloids (DNLA), a Chinese medicinal herb extract, on ß-amyloid peptide segment 25-35 (Aß25-35)-induced neuron and synaptic loss in mice. METHOD: Aß25-35(10 µg) was injected into the bilateral ventricles of male mice followed by an oral administration of DNLA (40 mg/kg) for 19 days. The Morris water maze was used for evaluating the ability of spatial learning and memory function of mice. The morphological changes were examined via H&E staining and Nissl staining. TUNEL staining was used to check the neuronal apoptosis. The ultrastructure changes of neurons were observed under electron microscope. Western blot was used to evaluate the protein expression levels of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex. RESULTS: DNLA significantly attenuated Aß25-35-induced spatial learning and memory impairments in mice. DNLA prevented Aß25-35-induced neuronal loss in the hippocampus and cortex, increased the number of Nissl bodies, improved the ultrastructural injury of neurons and increased the number of synapses in neurons. Furthermore, DNLA increased the protein expression of neurotrophic factors BDNF, CNTF and GDNF in the hippocampus and cortex. CONCLUSIONS: DNLA can prevent neuronal apoptosis and synaptic loss. This effect is mediated at least in part via increasing the expression of BDNF, GDNF and CNTF in the hippocampus and cortex; improving Aß-induced spatial learning and memory impairment in mice.