Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments.
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ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC4782990 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Practicing "green analytical chemistry" is of great importance when profiling the chemical composition of complex matrices. Herein, a novel hybrid analytical platform was developed for direct chemical analysis of complex matrices by online hyphenating pressurized warm water extraction followed by turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry (PWWE-TFC-LC-MS/MS). Two parallel hollow guard columns acted as extraction vessels connected to a long narrow polyether ether ketone tube, while warm water served as extraction solvent and was delivered at a flow rate of 2.5?mL/min to generate considerable back pressure at either vessel. A column oven heated both the solvent and crude materials. A TFC column, which is advantageous for the comprehensive trapping of small molecular substances from fluids under turbulent flow conditions, was employed to transfer analytes from the PWWE module to LC-MS/MS. Two electronic valves alternated each vessel between extraction and elution phases. As a proof-of-concept, a famous herbal medicine for the treatment of neurodegenerative disorders, namely Polygalae Radix, was selected for the qualitative and quantitative analyses. The results suggest that the hybrid platform is advantageous in terms of decreasing time, material, and solvent consumption and in its automation, versatility, and environmental friendliness.
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Project description:Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute to other rapid-onset antidepressants known to have unacceptable side effects.
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Project description:In animal husbandry, traditional Chinese medicine (TCM) as a reasonable alternative to antibiotics has attracted more and more concerns to reduce microbial resistance. This study was aimed to investigate the effects of dietary supplementation with TCM prescriptions on serum parameters and thymus inflammation responses in finishing pigs. Thirty finishing pigs were randomly divided into three groups, which included the Con group (basal diet), the TCM1 group (basal diet supplemented with Xiao Jian Zhong prescriptions), and the TCM2 group (basal diet supplemented with Jingsananli-sepsis). The results showed that the contents of C3 and C4 in the serum were significantly increased in both the TCM1 and TCM2 groups compared to the Con group on day 30. Similarly, the levels of IgA, IgG, and IgM were increased in the TCM2 group, and only the level of IgM in TCM1 was increased on day 30. Meanwhile, the levels of classical swine fever virus (CSFV) and respiratory syndrome virus (PRRSV) antibodies had a notable increase in the TCM1 and TCM2 groups. Both TCM1 and TCM2 inhibited the levels of TLR4/MyD88/NF-κB signaling pathway-related mRNA (TLR4, MyD88, NF-κB, IL6, IL8, and TNF-α) and protein (p-IκBα and p-P65) expression levels in the thymus. In conclusion, dietary supplementation with TCM could reduce thymic inflammation levels and improve humoral immunity of finishing pigs.
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Project description:Angelicae Pubescentis Radix (APR) is a widely used antirheumatic Chinese medicinal herb known as "Duhuo" in China. It has the effects of dispelling wind and removing dampness, diffusing impediment, and relieving pain, and is mainly indicated for rheumatic arthritis with pain in the lower back and knees, and headache. To the best of our knowledge, an attempt is made to provide an up-to-date review on these aspects based on published materials, including ancient and modern books; Master's and doctoral theses; monographs on medicinal plants; the pharmacopoeia of different countries, websites for publication of patent and electronic databases, such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, CNKI, and Google Scholar. APR, which has a good clinical effect, has been used for traditional Chinese medicine more than 2000 years. Since 1957, a variety of chemical constituents have been reported from the medicinal plants of this herb, mostly coumarins and volatile oil. In the past 30 years, numerous studies have shown that the extracts and compounds isolated from APR showed effective analgesic and anti-inflammatory actions, also showing well effects on central nervous system, effects on cardiovascular system and deworming activity. In addition, we also present and discuss the botany, traditional medicinal use, pharmacokinetics, toxicity, quality control, future trends and prospects of APR. All this information suggest that future research of APR should be supplemented in the area of pharmacology and toxicology to provide further insight on the clinical use and quality control.
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Project description:ContextThe mammalian circadian clock system regulates physiological function. Crude drugs, containing Polygalae Radix, and Kampō, combining multiple crude drugs, have been used to treat various diseases, but few studies have focussed on the circadian clock.ObjectiveWe examine effective crude drugs, which cover at least one or two of Kampō, for the shortening effects on period length of clock gene expression rhythm, and reveal the mechanism of shortening effects.Materials and methodsWe prepared 40 crude drugs. In the in vitro experiments, we used mouse embryonic fibroblasts from PERIOD2::LUCIFERASE knock-in mice (background; C57BL/6J mice) to evaluate the effect of crude drugs on the period length of core clock gene, Per2, expression rhythm by chronic treatment (six days) with distilled water or crude drugs (100 μg/mL). In the in vivo experiments, we evaluated the free-running period length of C57BL/6J mice fed AIN-93M or AIN-93M supplemented with 1% crude drug (6 weeks) that shortened the period length of the PERIOD2::LUCIFERASE expression rhythm in the in vitro experiments.ResultsWe found that Polygalae Radix (ED50: 24.01 μg/mL) had the most shortened PERIOD2::LUCIFERASE rhythm period length in 40 crude drugs and that the CaMKII pathway was involved in this effect. Moreover, long-term feeding with AIN-93M+Polygalae Radix slightly shortened the free-running period of the mouse locomotor activity rhythm.Discussion and conclusionsOur results indicate that Polygalae Radix may be regarded as a new therapy for circadian rhythm disorder and that the CaMKII pathway may be regarded as a target pathway for circadian rhythm disorders.
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Project description:traditional chinese medicine Targeted loci
| PRJNA796441 | ENA
Project description:Explore Acori Tatarinowii Rhizoma (ATR) and Polygalae Radix (PR) mechanisms in Alzheimer's disease (AD) treatment through network pharmacology. ATR-PR was investigated in the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, Batman, and Traditional Chinese Medicines Integrated Database (TCMID) to gather information on its chemical components and target proteins. Target genes associated with AD were retrieved from the GeneCards and National Center for Biotechnology Information (NCBI) databases. The integration of these datasets with potential targets facilitated the construction of an AD and ATR-PR protein-protein interaction (PPI) network using the STRING database. The resulting network identified the core active ingredients and main targets of ATR-PR in AD treatment. Cluster analysis of the PPI network was performed using Cytoscape 3.7.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Metascape database. Molecular docking simulations revealed potential interactions between the main active ingredients and core targets. Our analysis identified 8 putative components and 455 targets of ATR-PR. We systematically searched for 1306 genes associated with AD, conducted Venn diagram analysis resulting in 156 common targets, and constructed a PPI network with 57 key targets. GO functional analysis highlighted the primary biological processes associated with oxidative stress. KEGG pathway enrichment analysis revealed the involvement of 64 signaling pathways, with the PI3K/Akt signaling pathway playing a key role. Molecular docking analysis indicated a high affinity between the potential targets of ATR-PR and the main compounds of AD. This study sheds light on the complex network of interactions involving ATR-PR in the context of AD. The identified targets, pathways, and interactions provide a foundation for understanding the potential therapeutic mechanisms. The involvement of oxidative stress-related processes and the crucial role of the PI3K/Akt signaling pathway suggest avenues for targeted therapeutic interventions in Alzheimer's disease treatment. Our proposition of the combined use of ATR-PR has emerged as a potential treatment strategy for AD, supported by a network pharmacology approach. This framework provides a robust foundation for future clinical applications and experimental research in the pursuit of effective Alzheimer's disease treatments.
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Project description:Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid ? (A?) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of A? plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by A?. Additionally, it prevented A?-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent A?-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.
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Project description:Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS), a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT), Poria cum Radix Pini (PRP) and Radix Polygalae (RP), is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced A? levels, retarded A? amyloidosis and reduced A?-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced A? generation, whereas AT and PRP exerted neuroprotective effects against A?. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease.
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