Modulating the polarization phenotype of microglia - A valuable strategy for central nervous system diseases.

Central nervous system (CNS) diseases have become one of the leading causes of death in the global population. The pathogenesis of CNS diseases is complicated, so it is important to find the patterns of the disease to improve the treatment strategy. Microglia are considered to be a double-edged sword, playing both harmful and beneficial roles in CNS diseases. Therefore, it is crucial to understand the progression of the disease and the changes in the polar phenotype of microglia to provide guidance in the treatment of CNS diseases. Microglia activation may evolve into different phenotypes: M1 and M2 types. We focused on the roles that M1 and M2 microglia play in regulating intercellular dialogues, pathological reactions and specific diseases in CNS diseases. Importantly, we summarized the strategies used to modulate the polarization phenotype of microglia, including traditional pharmacological modulation, biological therapies, and physical strategies. This review will contribute to the development of potential strategies to modulate microglia polarization phenotypes and provide new alternative therapies for CNS diseases.

Vegetable oils: Classification, quality analysis, nutritional value and lipidomics applications.

Lipids are widespread in nature and play a pivotal role as a source of energy and nutrition for the human body. Vegetable oils (VOs) constitute a significant category in the food industry, containing various lipid components that have garnered attention for being natural, environmentally friendly and health-promoting. The review presented the classification of raw materials (RMs) from oil crops and quality analysis techniques of VOs, with the aim of improving comprehension and facilitating in-depth research of VOs. Brief descriptions were provided for four categories of VOs, and quality analysis techniques for both RMs and VOs were generalized. Furthermore, this study discussed the applications of lipidomics technology in component analysis, processing and utilization, quality determination, as well as nutritional function assessment of VOs. Through reviewing RMs and quality analysis techniques of VOs, this study aims to encourage further refinement and development in the processing and utilization of VOs, offering valuable references for theoretical and applied research in food chemistry and food science.

Natural essential oils derived from herbal medicines: A promising therapy strategy for treating cognitive impairment.

Cognitive impairment (CI), mainly Alzheimer's disease (AD), continues to increase in prevalence and is emerging as one of the major health problems in society. However, until now, there are no first-line therapeutic agents for the allopathic treatment or reversal of the disease course. Therefore, the development of therapeutic modalities or drugs that are effective, easy to use, and suitable for long-term administration is important for the treatment of CI such as AD. Essential oils (EOs) extracted from natural herbs have a wide range of pharmacological components, low toxicity, and wide sources, In this review, we list the history of using volatile oils against cognitive disorders in several countries, summarize EOs and monomeric components with cognitive improvement effects, and find that they mainly act by attenuating the neurotoxicity of amyloid beta, anti-oxidative stress, modulating the central cholinergic system, and improving microglia-mediated neuroinflammation. And combined with aromatherapy, the unique advantages and potential of natural EOs in the treatment of AD and other disorders were discussed. This review hopes to provide scientific basis and new ideas for the development and application of natural medicine EOs in the treatment of CI.

Preparation, characterization and safety evaluation of Ligusticum chuanxiong essential oils liposomes for treatment of cerebral ischemia-reperfusion injury.

The essential oils of Ligusticum chuanxiong Hort. (CXEO) are considered to be important parts of the pharmacological action of Ligusticum chuanxiong Hort. CXEO have a wide range of applications in various fields. Despite the interesting properties of CXEO, the volatility and low solubility have limited the application. Liposomes are vesicles composed of concentric bilayer lipids arranged around the water environment. Therefore, this study aimed to prepare stable CXEO liposomes (CXEO-LP) to improve the properties. Then, CXEO-LP were prepared by thin film dispersion method and optimized. The results showed that CXEO-LP were well dispersed. Subsequently, in vitro release and antioxidant properties of CXEO-LP were researched. CXEO-LP had slow release effect and oxidation resistance, indicating CXEO-LP may be a potential drug for treating cerebral ischemia-reperfusion injury (CIRI). The nasal mucosa toxicity test and acute toxicity test showed that CXEO-LP had no obvious toxicity to nasal cavity, heart, liver, spleen, lung and kidney tissues. Pharmacodynamic studies found that CXEO-LP significantly improved neurological deficits and brain pathology in a mouse model of CIRI compared to CXEO after intranasal administration. In general, this study showed that CXEO-LP were easy to prepare and continuously released, and had an important development prospect in the treatment of CIRI.

Medicine-food herb: Angelica sinensis, a potential therapeutic hope for Alzheimer's disease and related complications.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, which has brought a huge burden to the world. The current therapeutic approach of one-molecule-one-target strategy fails to address the issues of AD because of multiple pathological features of AD. Traditionally, the herb of Angelica sinensis (AS) comes from the root of an umbrella plant Angelica sinensis (Oliv.) Diels. As a typical medicine-food herb, studies have shown that AS can alleviate AD and AD-complications by multiple targets through the various foundations of pharmaceutical material and dietary supply basis. Therefore, this review summarizes the pharmacological effects of AS for the treatment of AD and AD-complications for the first time. AS contains many effective components, such as ligustilide, z-ligustilide, n-butylidenephthalide, α-pinene, p-cymene, myrcene, ferulic acid, vanillic acid and coniferyl ferulate. It is found that AS, AS-active compounds and AS-compound recipes mainly treat AD through neuroprotective, anti-inflammation, and anti-oxidant effects, improving mitochondrial dysfunction, anti-neuronal apoptosis, regulating autophagy, regulating intestinal flora and enhancing the central cholinergic system, which shows the multi-component and multi-target effect of AS. The role of dietary supplement components in AS for AD intervention is summarized, including vitamin B12, folic acid, arginine, and oleic acid, which can improve the symptoms of AD. Besides, this review focuses on the safety and toxicity evaluation of AS, which provides a basis for its application. This review will provide further support for the research on AD and the application of medicine-food herb AS in a healthy lifestyle in the future.

Natural essential oils efficacious in internal organs fibrosis treatment: Mechanisms of action and application perspectives.

Internal organs fibrosis (IOF) is the leading cause of morbidity and mortality in most chronic inflammatory diseases, which is responsible for 45% of deaths due to disease. However, there is a paucity of drugs used to treat IOF, making it urgent to find medicine with good efficacy, low toxic side effects and good prognosis. Essential oils (EOs) extracted from natural herbs with a wide range of pharmacological components, multiple therapeutic targets, low toxicity, and broad sources have unique advantages and great potential in the treatment of IOF. In this review, we summarized EOs and their monomeric components with anti-IOF, and found that they work mainly through inhibiting TGF-ß-related signaling pathways, modulating inflammatory cytokines, suppressing NF-κB, and anti-oxidative stress. The prognostic improvement of natural EOs on IOF was further discussed, as well as the quality and safety issues in the current development of natural EOs. This review hopes to provide scientific basis and new ideas for the development and application of natural medicine EOs in anti-IOF.

Natural essential oils: A promising strategy for treating cardio-cerebrovascular diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils (EO) are volatile compounds obtained from different parts of natural plants, and have been used in national, traditional and folk medicine to treat various health problems all over the world. Records indicate that in history, herbal medicines rich in EO have been widely used for the treatment of CVDs in many countries, such as China. AIM OF THE STUDY: This review focused on the traditional application and modern pharmacological mechanisms of herbal medicine EO against CVDs in preclinical and clinical trials through multi-targets synergy. Besides, the EO and anti-CVDs drugs were compared, and the broad application of EO was explained from the properties of drugs and aromatic administration routes. MATERIALS AND METHODS: Information about EO and CVDs was collected from electronic databases such as Web of Science, ScienceDirect, PubMed, and China National Knowledge Infrastructure (CNKI). The obtained data sets were sequentially arranged for better understanding of EO' potential. RESULTS: The study showed that EO had significant application in CVDs at different countries or regions since ancient times. Aiming at the complex pathological mechanisms of CVDs, including intracellular calcium overload, oxidative stress, inflammation, vascular endothelial cell injury and dysfunction and dyslipidemia, we summarized the roles of EO on CVDs in preclinical and clinical through multi-targets intervention. Besides, EO had the dual properties of drug and excipients. And aromatherapy was one of the complementary therapies to improve CVDs. CONCLUSIONS: This paper reviewed the EO on traditional treatment, preclinical mechanism and clinical application of CVDs. As important sources of traditional medicines, EO' remarkable efficacy had been confirmed in comprehensive literature reports, which showed that EO had great medicinal potential.

Development and validation of an UHPLC-Orbitrap-HRMS method for rapid determination of endogenous L-carnitine in patients on hemodialysis/peritoneal dialysis and its application to promote rational drug use.

Background: L-carnitine is an endogenous vitamin-like amino acid derivate which plays an essential role in energy metabolism and can be easily lost via dialysis. Deficiency of L-carnitine has great effects on many aspects of bodily functions. To determine the deficiency degree and adjust the supplementation dose, a rapid, sensitive, and specific method for the detection of endogenous L-carnitine in the plasma of dialysis patients using ultra-high performance liquid chromatography-Orbitrap high resolution mass spectrometry (UHPLC-Orbitrap-HRMS) was developed and validated. Methods: The plasma samples were processed by protein precipitation and centrifugation before analysis using UHPLC-Orbitrap-HRMS. Sample separation was achieved with a hydrophilic interaction liquid chromatography (HILIC) column, using an isocratic elution with a runtime of 5 min. The separated analytes were detected by positive ionization mode in full scan mode and targeted-single ion monitoring (t-SIM) mode. Mildronate was used as the internal standard (IS). Results: All the plasma could be detected in the range of 6.169 to 197.394 µM, with adequate accuracy, precision, and recovery. The method was validated in fortified validation with relative standard deviations (RSD) 5.15-8.74%. This method was applied to the analysis of 105 dialysis patients and 39 healthy participants, the results revealed that peritoneal dialysis patients without L-carnitine supplementation should pay more attention to L-carnitine monitoring, meanwhile, all the hemodialysis patients were advised to be routinely given a full dose of L-carnitine, no matter whether they had taken L-carnitine or not. Conclusions: This study developed a simple and rapid UHPLC-Orbitrap-HRMS method for detection of endogenous L-carnitine in dialysis patients, which could be useful to promote rational drug use.

Flavonoid-Like Components of Peanut Stem and Leaf Extract Promote Sleep by Decreasing Neuronal Excitability.

SCOPE: Peanut stem and leaf (PSL), a traditional Chinese medicine, is widely used as a dietary supplement to improve sleep quality; however, the underlying mechanism is unclear. Here, the study aims to determine whether active compounds in PSL extract exert their effects by mediating neuronal excitability. METHODS AND RESULTS: Aqueous PSL extract (500 mg kg-1 BW) increases the duration of total sleep (TS), slow wave sleep (SWS) and rapid eye movement sleep (REMS) in BALB/c mice after 7 and 14 continuous days of intragastric administration. Two PSL extract components with flavonoid-like structures: 4',7-di-O-methylnaringenin (DMN, 61 µg kg-1 BW) and 2'-O-methylisoliquiritigenin (MIL, 12 µg kg-1 BW), show similar effects on sleep in BALB/c mice. Moreover, incubation with DMN (50 µM) and MIL (50 µM) acutely reduces voltage-gated sodium and potassium currents and suppresses the firing of evoked action potential in mouse cortical neurons, indicating the inhibition on neuronal excitability. Meanwhile, RNA-seq analysis predicts the potential regulation of voltage-gated channels, which is according with the molecular docking simulation that both MIL and DMN can bind to voltage gated sodium channels 1.2 (Nav 1.2). CONCLUSIONS: DMN and MIL are the active ingredients of PSL that improve sleep quality, suggesting that PSL promotes sleep by regulating the excitability of neurons.

Natural volatile oils derived from herbal medicines: A promising therapy way for treating depressive disorder.

Depression is a common global mental disorder that seriously harms human physical and mental health. With the development of society, the increase of pressure and the role of various other factors make the incidence of depression increase year by year. However, there is a lack of drugs that have a fast onset, significant effects, and few side effects. Some volatile oils from traditional natural herbal medicines are usually used to relieve depression and calm emotions, such as Lavender essential oil and Acorus tatarinowii essential oil. It was reported that these volatile oils, are easy to enter the brain through the blood-brain barrier and have good antidepressant effects with little toxicity and side effects. In this review, we summarized the classification of depression, and listed the history of using volatile oils to fight depression in some countries. Importantly, we summarized the anti-depressant natural volatile oils and their monomers from herbal medicine, discussed the anti-depressive mechanisms of the volatile oils from natural medicine. The volatile oils of natural medicine and antidepressant drugs were compared and analyzed, and the application of volatile oils was explained from the clinical use and administration routes. This review would be helpful for the development of potential anti-depressant medicine and provide new alternative treatments for depressive disorders.

Research Advances in Cardio-Cerebrovascular Diseases of Ligusticum chuanxiong Hort.

Cardio-cerebrovascular diseases (CVDs) are a serious threat to human health and account for 31% of global mortality. Ligusticum chuanxiong Hort. (CX) is derived from umbellifer plants. Its rhizome, leaves, and fibrous roots are similar in composition but have different contents. It has been used in Japanese, Korean, and other traditional medicine for over 2000 years. Currently, it is mostly cultivated and has high safety and low side effects. Due to the lack of a systematic summary of the efficacy of CX in the treatment of CVDs, this article describes the material basis, molecular mechanism, and clinical efficacy of CX, as well as its combined application in the treatment of CVDs, and has been summarized from the perspective of safety. In particular, the pharmacological effect of CX in the treatment of CVDs is highlighted from the point of view of its mechanism, and the complex mechanism network has been determined to improve the understanding of CX's multi-link and multi-target therapeutic effects, including anti-inflammatory, antioxidant, and endothelial cells. This article offers a new and modern perspective on the impact of CX on CVDs.

Sedative-hypnotic and anxiolytic effects and the mechanism of action of aqueous extracts of peanut stems and leaves in mice.

INTRODUCTION: Peanut stems and leaves (PSL) have traditionally been used as both a special food and a herbal medicine in Asia. The sedative-hypnotic and anxiolytic effects of PSL have been recorded in classical traditional Chinese literature, and more recently by many other researchers. In a previous study, four sleep-related ingredients (linalool, 5-hydroxy-4',7-dimethoxyflavanone, 2'-O-methylisoliquiritigenin and ferulic acid), among which 5-hydroxy-4',7-dimethoxyflavanone and 2'-O-methylisoliquiritigenin were newly found in Arachis species, were screened by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/QTOF-MS). In the current study, quantitative examination of the above four ingredients was conducted. Serious fundamental functional studies were done in mice, including locomotor activity, direct sleep tests, pentobarbital-induced sleeping time tests, subthreshold dose of pentobarbital tests and barbital sodium sleep incubation period tests, to determine the material base for the sedative-hypnotic and anxiolytic effects of aqueous extracts of PSL. Furthermore, neurotransmitter levels in three brain regions (cerebrum, cerebellum and brain stem) were determined using UHPLC coupled with triple-quadrupole mass spectrometry (UHPLC/QQQ-MS) in order to elucidate the exact mechanism of action. RESULTS: Aqueous extract of PSL at a dose of 500 mg kg-1 (based on previous experience), along with different concentrations of the above four functional ingredients (189.86 µg kg-1 linalool, 114.75 mg kg-1 5-hydroxy-4',7-dimethoxyflavanone, 32.4mg kg-1 2'-O-methylisoliquiritigenin and 44.44 mg kg-1 ferulic acid), had a sedative-hypnotic effect by affecting neurotransmitter levels in mice. CONCLUSION: The data demonstrate that these four ingredients are the key functional factors for the sedative-hypnotic and anxiolytic effects of PSL aqueous extracts and that these effects occur via changes in neurotransmitter levels and pathways. © 2018 Society of Chemical Industry.

Identification of chemical ingredients of peanut stems and leaves extracts using UPLC-QTOF-MS coupled with novel informatics UNIFI platform.

Peanut stems and leaves have been used traditionally as both herbal medicines and special food in Asia. In this study, the main functional compounds of peanut stems and leaves extracts were identified using UPLC separation coupled to high resolution mass spectrometry (QTOF-MS), and a traditional medicine library. Three different extraction solvents (ethyl acetate, petroleum ether and n-butanol) were evaluated to prepare the extracts of peanut stems and leaves. A total of 283 chemical compounds were identified in peanut stems and leaves extracts, of which 207 compounds are tentatively new identifications in Genus Arachis. The integration of data acquisition and processing with the traditional medicine library provides a simple, efficient process to effectively facilitate the identification of chemical ingredients in complex natural product extracts. The integrated workflow for separation, detection and identification of functional compounds in natural products using UPLC/QTOF-MS greatly improves productivity for development of traditional herbal medicines. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration.

The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified.

Ginsenoside Rg1 promotes endothelial progenitor cell migration and proliferation.

AIM: To investigate the effect of ginsenoside Rg1 on the migration, adhesion, proliferation, and VEGF expression of endothelial progenitor cells (EPCs). METHODS: EPCs were isolated from human peripheral blood and incubated with different concentrations of ginsenoside Rg1 (0.1, 0.5, 1.0, and 5.0 micromol/L) and vehicle controls. EPC migration was detected with a modified Boyden chamber assay. EPC adhesion was determined by counting adherent cells on fibronectin-coated culture dishes. EPC proliferation was analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro vasculogenesis was assayed using an in vitro vasculogenesis detection kit. A VEGF-ELISA kit was used to measure the amount of VEGF protein in the cell culture medium. RESULTS: Ginsenoside Rg1 promoted EPC adhesion, proliferation, migration and in vitro vasculogenesis in a dose- and time-dependent manner. Cell cycle analysis showed that 5.0 micromol/L of ginsenoside Rg1 significantly increased the EPC proliferative phase (S phase) and decreased the resting phase (G(0)/G(1) phase). Ginsenoside Rg1 increased vascular endothelial growth factor production. CONCLUSION: The results indicate that ginsenoside Rg1 promotes proliferation, migration, adhesion and in vitro vasculogenesis.