Carvacrol as a Stimulant of the Expression of Key Genes of the Ginsenoside Biosynthesis Pathway and Its Effect on the Production of Ginseng Saponins in Panax quinquefolium Hairy Root Cultures.

The accumulation of ginsenosides (triterpenic saponins) was determined in Panax quinquefolium hairy root cultures subjected to an elicitation process using carvacrol at 5, 10, 25, 50, 100, 250, and 500 µM concentrations during 24 and 72 h exposure. This study was the first one in which carvacrol was applied as an elicitor. The content of eight ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Rg1, Rg2, and Re, was determined using HPLC analysis. Moreover, the quantitative RT-PCR method was applied to assess the relative expression level of farnesyl diphosphate synthase, squalene synthase, and dammarenediol synthase genes in the studied cultures. The addition of carvacrol (100 µM) was an effective approach to increase the production of ginsenosides. The highest content and productivity of all detected saponins were, respectively, 20.01 mg∙g-1 d.w. and 5.74 mg∙L-1∙day-1 after 72 h elicitation. The production profile of individual metabolites in P. quinquefolium cultures changed under the influence of carvacrol. The biosynthesis of most examined protopanaxadiol derivatives was reduced under carvacrol treatment. In contrast, the levels of ginsenosides belonging to the Rg group increased. The strongest effect of carvacrol was noticed for Re metabolites, achieving a 7.72-fold increase in comparison to the control. Saponin Rg2, not detected in untreated samples, was accumulated after carvacrol stimulation, reaching its maximum concentration after 72 h exposure to 10 µM elicitor.

Effects of Chronic Administration of Green Tea Ethanol Extract on Sleep Architecture in Mice: A Comparative Study with a Representative Stimulant Caffeine.

Wakefulness is defined as a state in which individuals can react to a change in situations. The number of people staying awake and compensating for lack of sleep has increased in recent years. Caffeine, a representative stimulant, is the most extensively consumed compound globally and is mainly consumed through coffee. Although green tea (Camellia sinensis L.) contains high caffeine content like coffee, its arousal-inducing effects have not yet been studied. In the present study, we aimed to identify the arousal-inducing effect of GT during a chronic administration period (three weeks) using analysis of sleep architecture. Treatment with GT (1500 mg/kg) significantly elevated the sleep latency and wakefulness throughout the treatment period, and chronic administration of GT consistently maintained an increase in wakefulness for up to 3 h. During the treatment period, the arousal-inducing effect of GT (1500 mg/kg) occurred without any change in the tolerance phenomenon or withdrawal symptoms, similar to that observed with caffeine (25 mg/kg). GT (1500 mg/kg) containing 95.6 mg/kg of caffeine did not produce a better arousal-inducing effect than caffeine at 25 mg/kg. These results indicate that the arousal-inducing effect of GT persisted for three weeks without adverse effects and that GT can control the arousal-inducing effects of caffeine due to the hypnotic effects of its other constituents.

Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2.

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.

De-risking in Tier I CNS safety assessments is the primary function of study design and technical training of laboratory staff observers.

Derisking is not a pharmaceutical industry strategy to reduce time, effort, or costs in drug development. Derisking strategies originated within the National Institutes of Health as a predicate to good science. There is a growing sentiment within drug development programs to diminish the importance of behavioral measures in toxicological studies and in the Tiered Safety assessment plans of the U.S. Regulatory Agencies and the International Commission on Harmonization. The validity and reliability of the Functional Observational Batter (FOB) is critically dependent on consistency and technical quality in each risk assessment plan. US Federal and International drug approval organizations have universally adopted the concept of principles of test construction rather than delineating specific behavioral assay endpoints for inclusion of the FOB in nonclinical safety protocols. The validity and reliability of behavioral observations in standardized neurotoxicity screening is critically dependent on the FOB developed by the Study Director with the Sponsor throughout all stages of testing.. The individual risk factors selected for observation to be included in the early Tier 1 safety program should be determined by the mechanism and mode of action of the test article. The results of Tier I testing are the basis for Tier II testing designs. Critical to the compliance with Good Laboratory Practices is the documentation of training of the operational staff scheduled to conduct all aspects of the established protocol.

Prevalence of cathinones and other new psychoactive substances in hair of parents and children of families with known or suspected parental abuse of conventional illegal drugs.

BACKGROUND: Hair analysis of parents and their children was regularly used since 2011 as a diagnostic tool in a social support project for families with known or suspected abuse of conventional illegal drugs and revealed a high incidence of cocaine, cannabinoids, amphetamines, ecstasy and heroin. In this context, the prevalence of new psychoactive substances (NPS) in these families should be important for a realistic estimate of the situation. METHODS: The extracts of 1537 hair samples from 318 children (age 1-14 years), 44 adolescents and 611 adults, which were collected and tested for conventional drugs between June 2016 and April 2021 and frozen at -20 °C, were reanalyzed by a validated LC-MS/MS method (limits of quantitation 5-24 pg/mg) for 33 cathinones, 10 phenylethylamines, 5 piperazines including the antidepressant trazodone, 2 tryptamines, 9 designer benzodiazepines, 4 synthetic opioids and 4 ketamine-like substances including phencyclidine. RESULTS: Between one and up to five from 42 of these substances were detected in 227 samples (14.8%). The most frequently detected substances were benzedrone (62x), α-pyrrolidinovalerophenone (41x), N-ethylamphetamine (29x), dimethyltryptamine (13x) and pyrovalerone (11x). The quantification was possible only for 34 results of 15 drugs and the remaining majority of the results were unambiguously identified below LLOQ. The relative frequency of conventional drugs in the 227 NPS positive samples was higher than in all 1310 NPS negative samples for cocaine (69.6% vs. 56.0%), heroin (6-acetylmorphine 8.8% vs. 4.9%), amphetamine (16.3% vs. 7.7%) and MDMA (16.3% vs. 7.0%) but was similar for THC (38.3% vs. 36.3%) and benzodiazepines (1.8% vs. 1.7%). The high prevalence of N-ethylamphetamine can be explained as a byproduct of the illicit amphetamine synthesis from benzaldehyde and nitroethane rather than as a separate drug or as a combined metabolite of amphetamine and ethanol. The isolated appearance of 3-trifluoromethylphenylpiperazine in 9 hair samples collected in January 2017 can be caused either by its use as an NPS or by its formation as a metabolite of the medical drug flibanserin. The results were compared within 17 families whose members were tested at the same time and showed positive NPS results. The detected drugs agreed between both parents only in about half of the cases whereas the drugs found in children's hair was always detected also in hair of one or both parents. CONCLUSION: The re-testing of hair extracts for NPS after long-time storage in frozen state enables an impression about the relative high prevalence in the tested population group, despite the limitation by partial degradation of the substances and the corresponding impossibility in quantitative assessments. In addition to conventional drugs, the hair test for these substances should be useful in unclear cases of child's welfare endangerment and in family law.

Screening novel CNS drug candidates for P-glycoprotein interactions using the cell line iP-gp: In vitro efflux ratios from iP-gp and MDCK-MDR1 monolayers compared to brain distribution data from mice.

Drug efflux by P-glycoprotein (P-gp, ABCB1) is considered as a major obstacle for brain drug delivery for small molecules. P-gp-expressing cell monolayers are used for screening of new drug candidates during early states of drug development. It is, however, uncertain how well the in vitro studies can predict the in vivo P-gp mediated efflux at the blood-brain barrier (BBB). We previously developed a novel cell line of porcine origin, the iP-gp cell line, with high transepithelial resistance and functional expression of human P-gp. The aim of the present study was to evaluate the applicability of the cell line for screening of P-gp interactions of novel drug candidates. For this purpose, bidirectional fluxes of 14 drug candidates were measured in iP-gp cells and in MDCK-MDR1 cells, and compared with pharmacokinetic data obtained in male C57BL/6 mice. The iP-gp cells formed extremely tight monolayers (>15 000 Ω∙cm2) as compared to the MDCK- MDR1 cells (>250 Ω∙cm2) and displayed lower Papp,a-b values. The efflux ratios obtained with iP-gp and MDCK-MDR1 monolayers correlated with Kp,uu,brain values from the in vivo studies, where compounds with the lowest Kp,uu,brain generally displayed the highest efflux ratios. 12 of the tested compounds displayed a poor BBB penetration in mice as judged by Kp,uu less than 1. Of these compounds, nine compounds were categorized as P-gp substrates in the iP-gp screening, whereas analysis of data estimated in MDCK-MDR1 cells indicated four compounds as potential substrates. The results suggest that the iP-gp cell model may be a sensitive and useful screening tool for drug screening purposes to identify possible substrates of human P-glycoprotein.

Application and advantages of zebrafish model in the study of neurovascular unit.

The concept of "Neurovascular Unit" (NVU) was put forward, so that the research goal of Central Nervous System (CNS) diseases gradually transitioned from a single neuron to the structural and functional integrity of the NVU. Zebrafish has the advantages of high homology with human genes, strong reproductive capacity and visualization of neural circuits, so it has become an emerging model organism for NVU research and has been applied to a variety of CNS diseases. Based on CNKI (https://www.cnki.net/) and PubMed (https://pubmed.ncbi.nlm.nih.gov/about/) databases, the author of this article sorted out the relevant literature, analyzed the construction of a zebrafish model of various CNS diseases，and the use of diagrams showed the application of zebrafish in the NVU, revealed its relationship, which would provide new methods and references for the treatment and research of CNS diseases.

Psychoactive Substances of Natural Origin: Toxicological Aspects, Therapeutic Properties and Analysis in Biological Samples.

The consumption of new psychoactive substances (NPSs) has been increasing, and this problem affects several countries worldwide. There is a class of NPSs of natural origin, consisting of plants and fungi, which have a wide range of alkaloids, responsible for causing relaxing, stimulating or hallucinogenic effects. The consumption of some of these substances is prompted by religious beliefs and cultural reasons, making the legislation very variable or even ambiguous. However, the abusive consumption of these substances can present an enormous risk to the health of the individuals, since their metabolism and effects are not yet fully known. Additionally, NPSs are widely spread over the internet, and their appearance is very fast, which requires the development of sophisticated analytical methodologies, capable of detecting these compounds. Thus, the objective of this work is to review the toxicological aspects, traditional use/therapeutic potential and the analytical methods developed in biological matrices in twelve plant specimens (Areca catechu, Argyreia nervosa, Ayahuasca, Catha edulis, Datura stramonium, Lophophora williamsii, Mandragora officinarum, Mitragyna speciosa, Piper methysticum Forst, Psilocybe, Salvia divinorum and Tabernanthe iboga).

Mini-Review: Induced pluripotent stem cells and the search for new cell-specific ALS therapeutic targets.

Amongst the most important discoveries in ALS pathobiology are the works demonstrating that multiple cell types contribute to disease onset and progression. However, a significant limitation in ALS research is the inability to obtain tissues from ALS patient brain and spinal cord during the course of the disease. In vivo modeling has provided insights into the role of these cell subtypes in disease onset and progression. However, in vivo models also have shortcomings, including the reliance on a limited number of models based upon hereditary forms of the disease. Therefore, using human induced pluripotent stem cells (iPSC) reprogrammed from somatic cells of ALS patients, with both hereditary and sporadic forms of the disease, and differentiated into cell subtypes of both the central nervous system (CNS) and peripheral nervous system (PNS), have become powerful complementary tools for investigating basic mechanisms of disease as well as a platform for drug discovery. Motor neuron and other neuron subtypes, as well as non-neuronal cells have been differentiated from human iPSC and studied for their potential contributions to ALS pathobiology. As iPSC technologies have advanced, 3D modeling with multicellular systems organised in microfluidic chambers or organoids are the next step in validating the pathways and therapeutic targets already identified. Precision medicine approaches with iPSC using either traditional strategies of screening drugs that target a known pathogenic mechanism as well as "blind-to-target" drug screenings that allow for patient stratification based on drug response rather than clinical characteristics are now being employed.

The potential of 1H-MRS in CNS drug development.

RATIONALE: Proton magnetic resonance spectroscopy (1H-MRS) is a cross-species neuroimaging technique that can measure concentrations of several brain metabolites, including glutamate and GABA. This non-invasive method has promise in developing centrally acting drugs, as it can be performed repeatedly within-subjects and be used to translate findings from the preclinical to clinical laboratory using the same imaging biomarker. OBJECTIVES: This review focuses on the utility of single-voxel 1H-MRS in developing novel glutamatergic or GABAergic drugs for the treatment of psychiatric disorders and includes research performed in rodent models, healthy volunteers and patient cohorts. RESULTS: Overall, these studies indicate that 1H-MRS is able to detect the predicted pharmacological effects of glutamatergic or GABAergic drugs on voxel glutamate or GABA concentrations, although there is a shortage of studies examining dose-related effects. Clinical studies have applied 1H-MRS to better understand drug therapeutic mechanisms, including the glutamatergic effects of ketamine in depression and of acamprosate in alcohol dependence. There is an emerging interest in identifying patient subgroups with 'high' or 'low' brain regional 1H-MRS glutamate levels for more targeted drug development, which may require ancillary biomarkers to improve the accuracy of subgroup discrimination. CONCLUSIONS: Considerations for future research include the sensitivity of single-voxel 1H-MRS in detecting drug effects, inter-site measurement reliability and the interpretation of drug-induced changes in 1H-MRS metabolites relative to the known pharmacological molecular mechanisms. On-going technological development, in single-voxel 1H-MRS and in related complementary techniques, will further support applications within CNS drug discovery.

Studying CNS effects of Traditional Chinese Medicine using zebrafish models.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Traditional Chinese Medicine (TCM) has a millennia-long history of treating human brain disorders, its complex multi-target mechanisms of action remain poorly understood. Animal models are currently widely used to probe the effects of various TCMs on brain and behavior. The zebrafish (Danio rerio) has recently emerged as a novel vertebrate model organism for neuroscience research, and is increasingly applied for CNS drug screening and development. AIM OF THE STUDY: As zebrafish models are only beginning to be applied to studying TCM, we aim to provide a comprehensive review of the TCM effects on brain and behavior in this fish model species. MATERIALS AND METHODS: A comprehensive search of published literature was conducted using biomedical databases (Web of Science, Pubmed, Sciencedirect, Google Scholar and China National Knowledge Internet, CNKI), with key search words zebrafish, brain, Traditional Chinese Medicine, herbs, CNS, behavior. RESULTS: We recognize the developing utility of zebrafish for studying TCM, as well as outline the existing model limitations, problems and challenges, as well as future directions of research in this field. CONCLUSIONS: We demonstrate the growing value of zebrafish models for studying TCM, aiming to improve our understanding of TCM' therapeutic mechanisms and potential in treating brain disorders.

Neurotensins and their therapeutic potential: research field study.

The natural tridecapeptide neurotensin has been emerged as a promising therapeutic scaffold for the treatment of neurological diseases and cancer. In this work, we aimed to identify the top 100 most cited original research papers as well as recent key studies related to neurotensins. The Web of Science Core Collection database was searched and the retrieved research articles were analyzed by using the VOSviewer software. The most cited original articles were published between 1973 and 2013. The top-cited article was by Carraway and Leeman reporting the discovery of neurotensin in 1973. The highly cited terms were associated with hypotension and angiotensin-converting-enzyme. The conducted analysis reveals the therapeutic potentials of neurotensin, and further impactful research toward its clinical development is warrantied.

CNS Penetration Ability: A Critical Factor for Drugs in the Treatment of SARS-CoV-2 Brain Infection.

Now, it has been evidenced that Covid19 (SARS-CoV-2) infects the brain tissues. Along with this, a challenge has been raised for research professionals to find effective drugs for its treatment since the recent spread of this virus from Wuhan, China. Targeting the treatment of brain infection, it has also been a challenge that the clinical drug should have good CNS penetration ability to cross the blood-brain barrier.

Statement of the Independent Forensic Expert Group on Conversion Therapy.

Conversion therapy is a set of practices that aim to change or alter an individual's sexual orientation or gender identity. It is premised on a belief that an individual's sexual orientation or gender identity can be changed and that doing so is a desirable outcome for the individual, family, or community. Other terms used to describe this practice include sexual orientation change effort (SOCE), reparative therapy, reintegrative therapy, reorientation therapy, ex-gay therapy, and gay cure. Conversion therapy is practiced in every region of the world. We have identified sources confirming or indicating that conversion therapy is performed in over 60 countries. In those countries where it is performed, a wide and variable range of practices are believed to create change in an individual's sexual orientation or gender identity. Some examples of these include: talk therapy or psychotherapy (e.g., exploring life events to identify the cause); group therapy; medication (including anti-psychotics, anti- depressants, anti-anxiety, and psychoactive drugs, and hormone injections); Eye Movement Desensitization and Reprocessing (where an individual focuses on a traumatic memory while simultaneously experiencing bilateral stimulation); electroshock or electroconvulsive therapy (ECT) (where electrodes are attached to the head and electric current is passed between them to induce seizure); aversive treatments (including electric shock to the hands and/or genitals or nausea-inducing medication administered with presentation of homoerotic stimuli); exorcism or ritual cleansing (e.g., beating the individual with a broomstick while reading holy verses or burning the individual's head, back, and palms); force-feeding or food deprivation; forced nudity; behavioural conditioning (e.g., being forced to dress or walk in a particular way); isolation (sometimes for long periods of time, which may include solitary confinement or being kept from interacting with the outside world); verbal abuse; humiliation; hypnosis; hospital confinement; beatings; and "corrective" rape. Conversion therapy appears to be performed widely by health professionals, including medical doctors, psychiatrists, psychologists, sexologists, and therapists. It is also conducted by spiritual leaders, religious practitioners, traditional healers, and community or family members. Conversion therapy is undertaken both in contexts under state control, e.g., hospitals, schools, and juvenile detention facilities, as well as in private settings like homes, religious institutions, or youth camps and retreats. In some countries, conversion therapy is imposed by the order or instructions of public officials, judges, or the police. The practice is undertaken with both adults and minors who may be lesbian, gay, bisexual, trans, or gender diverse. Parents are also known to send their children back to their country of origin to receive it. The practice supports the belief that non-heterosexual orientations are deviations from the norm, reflecting a disease, disorder, or sin. The practitioner conveys the message that heterosexuality is the normal and healthy sexual orientation and gender identity. The purpose of this medico-legal statement is to provide legal experts, adjudicators, health care professionals, and policy makers, among others, with an understanding of: 1) the lack of medical and scientific validity of conversion therapy; 2) the likely physical and psychological consequences of undergoing conversion therapy; and 3) whether, based on these effects, conversion therapy constitutes cruel, inhuman, or degrading treatment or torture when individuals are subjected to it forcibly2 or without their consent. This medico-legal statement also addresses the responsibility of states in regulating this practice, the ethical implications of offering or performing it, and the role that health professionals and medical and mental health organisations should play with regards to this practice. Definitions of conversion therapy vary. Some include any attempt to change, suppress, or divert an individual's sexual orientation, gender identity, or gender expression. This medico-legal statement only addresses those practices that practitioners believe can effect a genuine change in an individual's sexual orientation or gender identity. Acts of physical and psychological violence or discrimination that aim solely to inflict pain and suffering or punish individuals due to their sexual orientation or gender identity, are not addressed, but are wholly condemned. This medico-legal statement follows along the lines of our previous publications on Anal Examinations in Cases of Alleged Homosexuality1 and on Forced Virginity Testing.2 In those statements, we opposed attempts to minimise the severity of physical and psychological pain and suffering caused by these examinations by qualifying them as medical in nature. There is no medical justification for inflicting on individuals torture or other cruel, inhuman, or degrading treatment or punishment. In addition, these statements reaffirmed that health professionals should take no role in attempting to control sexuality and knowingly or unknowingly supporting state-sponsored policing and punishing of individuals based on their sexual orientation or gender identity.

Compatibility of acetaminophen with central nervous system medications during simulated Y-site injection.

BACKGROUND: The critical care patient commonly receives a lot of medications including acetaminophen and central nervous system (CNS) agents. However, research on compatibility between acetaminophen and CNS medication is still limited. METHODS: Physical compatibility was evaluated using Y-site simulation by mixing one CNS medication with 10 mg mL-1 of acetaminophen solution under aseptic conditions with a 1 : 1 ratio. The Y-site simulation mixture was subsequently kept in a clean glass tube for incompatibility investigation during 24 hours. The aliquot solutions were visually inspected with bare eyes then additionally with a Tyndall light beam, microscope, and pH at 0, 1, 4, and 24 hours. Medications were considered compatible if there was no visual change (color/gas or turbidity), and no significant particles or precipitates, which referred to United States Pharmacopeia 788 (USP 788), and pH changes less than 0.5 units. RESULTS: During 24 hours, intravenous acetaminophen was physically compatible with haloperidol, ketamine, midazolam, pethidine, rocuronium and tramadol. Meanwhile, phenytoin, and propofol showed incompatibility with acetaminophen right away. Within four hours, five medications (dexketoprofen, fentanyl, ketorolac, diazepam and phenobarbital) showed incompatibility. Two medications (atropine sulfate and metamizole) were also found to be incompatible with acetaminophen under observation for 24 hours. CONCLUSIONS: Nine of 15 common CNS medications in critical care tested with acetaminophen were physically incompatible for 24 hours.

Using Xenopus oocytes in neurological disease drug discovery.

Introduction: Neurological diseases present a difficult challenge in drug discovery. Many of the current treatments have limited efficiency or result in a variety of debilitating side effects. The search of new therapies is of a paramount importance, since the number of patients that require a better treatment is growing rapidly. As an in vitro model, Xenopus oocytes provide the drug developer with many distinct advantages, including size, durability, and efficiency in exogenous protein expression. However, there is an increasing need to refine the recent breakthroughs.Areas covered: This review covers the usage and recent advancements of Xenopus oocytes for drug discovery in neurological diseases from expression and functional measurement techniques to current applications in Alzheimer's disease, painful neuropathies, and amyotrophic lateral sclerosis (ALS). The existing limitations of Xenopus oocytes in drug discovery are also discussed.Expert opinion: With the rise of aging population and neurological disorders, Xenopus oocytes, will continue to play an important role in understanding the mechanism of the disease, identification and validation of novel molecular targets, and drug screening, providing high-quality data despite the technical limitations. With further advances in oocytes-related techniques toward an accurate modeling of the disease, the diagnostics and treatment of neuropathologies will be becoming increasing personalized.

Uncaria rhynchophylla and its Major Constituents on Central Nervous System: A Review on Their Pharmacological Actions.

BACKGROUND: Uncaria rhynchophylla (Miq.) Jacks (Rubinaceae), a common herbal medicine known as Gou-teng in Chinese, is commonly used in Chinese medicine practice for the treatment of convulsions, hypertension, epilepsy, eclampsia and other cerebral diseases. The major active components of U. rhynchophylla are alkaloids, terpenoids and flavonoids. The protective effects of U. rhynchophylla and its major components on central nervous system (CNS) have become a focus of research in recent decades. OBJECTIVE: The study aimed to systematically summarize the pharmacological activities of U. rhynchophylla and its major components on the CNS. METHODS: This review summarized the experimental findings from our laboratories, together with other literature data obtained through a comprehensive search of databases including the Pubmed and the Web of Science. RESULTS: U. rhynchophylla and its major components such as rhynchophylline and isorhynchophylline have been shown to have neuroprotective effects on Alzheimer's disease, Parkinson's disease, depression, cerebral ischaemia through a number of mechanisms including anti-oxidant, anti-inflammatory actions and regulation on neurotransmitters. CONCLUSION: U. rhynchophylla and its major components have multiple beneficial pharmacological effects on CNS. Further studies on U. rhynchophylla and its major components are warranted to fully illustrate the underlying molecular mechanisms, pharmacokinetics, and toxicological profiles of these naturally occurring compounds and their potential for clinical application.

Cytochrome P450 derived epoxidized fatty acids as a therapeutic tool against neuroinflammatory diseases.

Cytochrome P450 (CYP) metabolism of arachidonic acid (ARA) produces epoxy fatty acids (EpFAs) such as epoxyeicosatrienoic acids (EETs) that are known to exert protective effects in inflammatory disorders. Endogenous EpFAs are further metabolized into corresponding diols by the soluble epoxide hydrolase (sEH). Through inhibition of sEH, many studies have demonstrated the cardioprotective and renoprotective effects of EpFAs; however, the role of sEH inhibition in modulating the pathogenesis of neuroinflammatory disorders is less well described. In this review, we discuss the current knowledge surrounding the effects of sEH inhibition and EpFA action in neuroinflammatory disorders such as Parkinson's Disease (PD), stroke, depression, epilepsy, and Alzheimer's Disease (AD), as well as the potential mechanisms that underlie the therapeutic effects of sEH inhibition.