scholarly journals Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish

2021 ◽  
Vol 22 (21) ◽  
pp. 11420
Author(s):  
Ewelina Kozioł ◽  
Krzysztof Jóźwiak ◽  
Barbara Budzyńska ◽  
Peter A. M. de Witte ◽  
Daniëlle Copmans ◽  
...  
Keyword(s):  
Plant Secondary Metabolites ◽  
Field Potential ◽  
Coumarin Derivatives ◽  
Pharmacological Activities ◽  
Systematic Analysis ◽  
Larval Zebrafish ◽  
Power Spectral ◽  
Structural Differences ◽  
Natural Coumarin ◽  
Activity Screening

Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83–89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.

Synthesis of Isoponcimarin

1979 ◽  
Vol 34 (7) ◽  
pp. 1010-1014 ◽  
Author(s):  
P. Rodighiero ◽  
A. Guiotto ◽  
P. Manzini
Keyword(s):  
Poncirus Trifoliata ◽  
Coumarin Derivatives ◽  
Natural Coumarin

Abstract Synthesis of isoponcimarin, 7-(3'-methyl-2',3'-epoxy-butiloxy)-8-(3"-methyl-2"-oxobutyl) coumarin, a natural coumarin isolated from Poncirus trifoliata L., was obtained starting from acetyl osthenol. From the intermediate 7-acetoxy-8-(3'-methyl-2'-oxobutyl) coumarin, the coumarin derivatives isomeranzin and dihydrooroselone were also prepared

NMR spectra of natural coumarin derivatives II. Furocoumarins

1971 ◽  
Vol 7 (5) ◽  
pp. 557-562 ◽  
Author(s):  
M. E. Perel'son ◽  
Yu. N. Sheinker ◽  
G. P. Syrova
Keyword(s):  
Nmr Spectra ◽  
Coumarin Derivatives ◽  
Natural Coumarin

NMR spectra of natural coumarin derivatives

1970 ◽  
Vol 6 (1) ◽  
pp. 5-11 ◽  
Author(s):  
M. E. Perel'son ◽  
Yu. N. Sheinker ◽  
G. P. Syrova ◽  
K. F. Turchin
Keyword(s):  
Nmr Spectra ◽  
Coumarin Derivatives ◽  
Natural Coumarin

scholarly journals PO-138 Mechanism of Cortical Information Output after Exercise Fatigue Induced by D2DR

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Xiaoxin Wang ◽  
Ke Li ◽  
Lijuan Hou
Keyword(s):  
Substantia Nigra ◽  
Spectral Density ◽  
Electrical Activity ◽  
Power Spectral Density ◽  
Field Potential ◽  
Control Group ◽  
Blank Control Group ◽  
Power Spectral ◽  
Exercise Induced

Objective In this experiment, the Local field potential (LFPs) was observed in the substantia nigra compact and electrical activity change in corticostriatal pathway after D2DR intervention in exercise-induced fatigue rats. We analyzed the changes of DA neuron discharge and D2DR mediated corticostriatal pathway information transmission. To explore the mechanism of D2D2 mediated DA system in the information output of cortical M1 region. Methods Wistar rats were used to establish the model of exercise-induced fatigue. The rats were divided into control group (CG), 7 days fatigue group (7FG) and 24 hour recovery group (24RG). We used in vivo multichannel recording technology to record electrical activity in the M1, striatum and substantia nigra compact of rats and observed the electrophysiological changes after D2DR intervention. We also detected the expression of TH proteins in the dorsolateral striatum before and after exercise-induced fatigue by immunohistochemistry. Results 1) Compared with group CG, the expression of TH protein in the dorsolateral area of striatum was significantly decreased in group 7FG (P<0.05). 2) Compared with the CG group, the power spectral density of the θ, α and β band of the SNc was increased after seven days of exhaustion exercise(P < 0.05); After 24 hours of recovery, the PSD value decreased significantly compared with the 7FG group(P<0.05). 3)Compared with the CG group the power spectral density of alpha (7-13Hz) and beta (15-30Hz) bands in the M1 region and striatum was increased in 7FG after injection D2DR agonist(P < 0.05) . Conclusions After exercise-induced fatigue, the activity of substantia nigra was increased, and the activity of M1 and striatum was lower than that of the blank control group after the D2DR agonist  injection. As a key receptor for the DA signal system, D2DR regulates the electrical activity of the nigrostriatal DA pathway and affects the comprehensive information output of the cortex, which can be regarded as a target for exercise-induced fatigue (NSFC: 31401018,   SKXJX: 2014014, Corresponding [email protected]).

scholarly journals Plant Secondary Metabolites Produced in Response to Abiotic Stresses Has Potential Application in Pharmaceutical Product Development

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 313
Author(s):  
Karma Yeshi ◽  
Darren Crayn ◽  
Edita Ritmejerytė ◽  
Phurpa Wangchuk
Keyword(s):  
Abiotic Stress ◽  
Drug Discovery ◽  
Medicinal Plants ◽  
Secondary Metabolites ◽  
Natural Habitat ◽  
Plant Secondary Metabolites ◽  
Sample Collection ◽  
Pharmacological Activities ◽  
Alternative Source ◽  
Pharmaceutical Industries

Plant secondary metabolites (PSMs) are vital for human health and constitute the skeletal framework of many pharmaceutical drugs. Indeed, more than 25% of the existing drugs belong to PSMs. One of the continuing challenges for drug discovery and pharmaceutical industries is gaining access to natural products, including medicinal plants. This bottleneck is heightened for endangered species prohibited for large sample collection, even if they show biological hits. While cultivating the pharmaceutically interesting plant species may be a solution, it is not always possible to grow the organism outside its natural habitat. Plants affected by abiotic stress present a potential alternative source for drug discovery. In order to overcome abiotic environmental stressors, plants may mount a defense response by producing a diversity of PSMs to avoid cells and tissue damage. Plants either synthesize new chemicals or increase the concentration (in most instances) of existing chemicals, including the prominent bioactive lead compounds morphine, camptothecin, catharanthine, epicatechin-3-gallate (EGCG), quercetin, resveratrol, and kaempferol. Most PSMs produced under various abiotic stress conditions are plant defense chemicals and are functionally anti-inflammatory and antioxidative. The major PSM groups are terpenoids, followed by alkaloids and phenolic compounds. We have searched the literature on plants affected by abiotic stress (primarily studied in the simulated growth conditions) and their PSMs (including pharmacological activities) from PubMed, Scopus, MEDLINE Ovid, Google Scholar, Databases, and journal websites. We used search keywords: “stress-affected plants,” “plant secondary metabolites, “abiotic stress,” “climatic influence,” “pharmacological activities,” “bioactive compounds,” “drug discovery,” and “medicinal plants” and retrieved published literature between 1973 to 2021. This review provides an overview of variation in bioactive phytochemical production in plants under various abiotic stress and their potential in the biodiscovery of therapeutic drugs. We excluded studies on the effects of biotic stress on PSMs.

scholarly journals Pericardial Injection of Kainic Acid Induces a Chronic Epileptic State in Larval Zebrafish

2021 ◽  
Vol 14 ◽  
Author(s):  
Lise Heylen ◽  
Duc-Hung Pham ◽  
Ann-Sofie De Meulemeester ◽  
Éric Samarut ◽  
Adrianna Skiba ◽  
...  
Keyword(s):  
Kainic Acid ◽  
High Throughput ◽  
High Throughput Screening ◽  
Video Recording ◽  
Field Potential ◽  
Latency Period ◽  
Pharmacological Characterization ◽  
Larval Zebrafish ◽  
Zebrafish Larvae ◽  
Human Pathology

Epilepsy is a common disorder of the brain characterized by spontaneous recurrent seizures, which develop gradually during a process called epileptogenesis. The mechanistic processes underlying the changes of brain tissue and networks toward increased seizure susceptibility are not fully understood. In rodents, injection of kainic acid (KA) ultimately leads to the development of spontaneous epileptic seizures, reflecting similar neuropathological characteristics as seen in patients with temporal lobe epilepsy (TLE). Although this model has significantly contributed to increased knowledge of epileptogenesis, it is technically demanding, costly to operate and hence not suitable for high-throughput screening of anti-epileptic drugs (AEDs). Zebrafish, a vertebrate with complementary advantages to rodents, is an established animal model for epilepsy research. Here, we generated a novel KA-induced epilepsy model in zebrafish larvae that we functionally and pharmacologically validated. KA was administered by pericardial injection at an early zebrafish larval stage. The epileptic phenotype induced was examined by quantification of seizure-like behavior using automated video recording, and of epileptiform brain activity measured via local field potential (LFP) recordings. We also assessed GFP-labeled GABAergic and RFP-labeled glutamatergic neurons in double transgenic KA-injected zebrafish larvae, and examined the GABA and glutamate levels in the larval heads by liquid chromatography with tandem mass spectrometry detection (LC-MS/MS). Finally, KA-injected larvae were exposed to five commonly used AEDs by immersion for pharmacological characterization of the model. Shortly after injection, KA induced a massive damage and inflammation in the zebrafish brain and seizure-like locomotor behavior. An abnormal reorganization of brain circuits was observed, a decrease in both GABAergic and glutamatergic neuronal population and their associated neurotransmitters. Importantly, these changes were accompanied by spontaneous and continuous epileptiform brain discharges starting after a short latency period, as seen in KA rodent models and reminiscent of human pathology. Three out of five AEDs tested rescued LFP abnormalities but did not affect the seizure-like behavior. Taken together, for the first time we describe a chemically-induced larval zebrafish epilepsy model offering unique insights into studying epileptogenic processes in vivo and suitable for high-throughput AED screening purposes and rapid genetic investigations.

A review on Coumarin derivatives as potent anti-Tuberculosis agent

2021 ◽  
Vol 21 ◽  
Author(s):  
Mujeeb Samar ◽  
Singh Kuldeep ◽  
Yogi Bhoomika ◽  
Ansari Vaseem ◽  
Sinha Shweta
Keyword(s):  
Structural Changes ◽  
Mycobacterium Tuberculosis Complex ◽  
Wide Spectrum ◽  
Coumarin Derivatives ◽  
Tuberculosis Complex ◽  
Extensively Drug Resistant ◽  
Structure Activity ◽  
Mdr Tb ◽  
Cause Of Deaths ◽  
Natural Coumarin

Background: : Tuberculosis (TB) is an acute or chronic infectious disease caused by several species of Myco-bacterium, collectively called as tubercle bacilli or Mycobacterium tuberculosis complex. Around 10 million people get sick with tuberculosis (TB) each year. TB is the second leading cause of deaths today after HIV/AIDS. A serious problem in the context of MDR-TB, is the extensively drug-resistant TB which is an im-portant reason for the restricted chemotherapy in TB. Therefore, there is a need to explore new antitubercular (anti-TB) agents. Coumarin is an oxygen-containing heterocyclic compound and can be widely found in many natural products, and many of them display diverse biological activities.The wide spectrum of activities of coumarin molecules have intrigued the scientists to explore the natural coumarins and their synthetic deriva-tives for their potential as anti-TB drugs. Objective: The objective of this review is to emphasize on important coumarin analogs with anti-TB activities and their structure-activity relationships (SAR) for designing better anti-TB agents. Method: Latest, authentic and published reports on various synthetic and natural coumarin derivatives and their anti-TB activities is being thoroughly studied and analyzed. The structural requirements of coumarins as anti-TB drugs have also been studied. Results : Collection and compilation of reports on various synthetic and natural coumarin derivatives and their anti-TB activities is being done. Conclusion: The study provides latest report on coumarin derivatives synthesized as anti-TB agent and wheth-er their activity depends on structural changes or not.

scholarly journals Natural coumarin derivatives as inhibitors of mycobacterial biofilms

2018 ◽  
Vol 115 ◽  
pp. 305 ◽  
Author(s):  
C.B. Oosthuizen ◽  
N. Kishore ◽  
V. Kumar ◽  
A. Ohja ◽  
N. Lall
Keyword(s):  
Coumarin Derivatives ◽  
Natural Coumarin

scholarly journals Less efficacy of valproic acid monotherapy may be caused by neural excitatory rebound in seizures

2021 ◽  
Author(s):  
Xiang Zou ◽  
Zilu Zhu ◽  
Yu Guo ◽  
Hongmiao Zhang ◽  
Yuchen Liu ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Neural Activity ◽  
Field Potential ◽  
Multiple Wave ◽  
Focal Seizures ◽  
Power Shift ◽  
Power Spectral ◽  
Inhibitory Power ◽  
Local Field Potential Lfp ◽  
Spike Firing

Valproic acid (VPA) represents one of the most efficient antiepileptic drugs (AEDs) with either general or focal seizures, but a certain percentage of patients are not recovered or even worse, the mechanism under this phenomenon remains unclear. Here, we retrospectively reviewed 16 patients who received awake craniotomy surgery. Intro-operative high density electrocorticogram (ECoG) was used to record the local field potential (LFP) response to VPA treatment. We found the less efficacy of VPA monotherapy was associated with ECoG spectrum power shift from higher to lower frequency after VPA injection, together with increased synchronization of the LFP. Furthermore, we established the computational model to testify the hypothesis that the ineffectivity of VPA may be caused by excitatory dynamic rebound during the inhibitory power increasing. In addition to test the hypothesis, we employed the mice with Kanic Acid (KA)-induced epileptic model to confirm that it would be inhibited by VPA on behavior and neural activity. Also, the neural activity shows significant rebound on spike firing. Then we discovered that the LFP would increase the power spectral density in multiple wave bands after the VPA delivers. These findings suggest that less efficacy of valproic acid monotherapy in focal seizures may be caused by neural excitatory rebound which mediated by elevated inhibitory power.

scholarly journals Contribution of action potentials to the extracellular field potential in the nucleus laminaris of barn owl

2018 ◽  
Vol 119 (4) ◽  
pp. 1422-1436 ◽  
Author(s):  
Paula T. Kuokkanen ◽  
Go Ashida ◽  
Anna Kraemer ◽  
Thomas McColgan ◽  
Kazuo Funabiki ◽  
...  
Keyword(s):  
Spectral Power ◽  
Spectral Component ◽  
Field Potential ◽  
Barn Owl ◽  
Field Potentials ◽  
Multiple Sources ◽  
Nucleus Laminaris ◽  
Power Spectral ◽  
Spectral Components

Extracellular field potentials (EFP) are widely used to evaluate in vivo neural activity, but identification of multiple sources and their relative contributions is often ambiguous, making the interpretation of the EFP difficult. We have therefore analyzed a model EFP from a simple brainstem circuit with separable pre- and postsynaptic components to determine whether we could isolate its sources. Our previous papers had shown that the barn owl neurophonic largely originates with spikes from input axons and synapses that terminate on the neurons in the nucleus laminaris (NL) (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274–2290, 2010; Kuokkanen PT, Ashida G, Carr CE, Wagner H, Kempter R. J Neurophysiol 110: 117–130, 2013; McColgan T, Liu J, Kuokkanen PT, Carr CE, Wagner H, Kempter R. eLife 6: e26106, 2017). To determine how much the postsynaptic NL neurons contributed to the neurophonic, we recorded EFP responses in NL in vivo. Power spectral analyses showed that a small spectral component of the evoked response, between 200 and 700 Hz, could be attributed to the NL neurons’ spikes, while nucleus magnocellularis (NM) spikes dominate the EFP at frequencies ≳1 kHz. Thus, spikes of NL neurons and NM axons contribute to the EFP in NL in distinct frequency bands. We conclude that if the spectral components of source types are different and if their activities can be selectively modulated, the identification of EFP sources is possible. NEW & NOTEWORTHY Extracellular field potentials (EFPs) generate clinically important signals, but their sources are incompletely understood. As a model, we have analyzed the auditory neurophonic in the barn owl’s nucleus laminaris. There the EFP originates predominantly from spiking in the afferent axons, with spectral power ≳1 kHz, while postsynaptic laminaris neurons contribute little. In conclusion, the identification of EFP sources is possible if they have different spectral components and if their activities can be modulated selectively.

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