Anxiolytic - like properties of Hallea ciliata in mice

Background: The aim of the present study was to evaluate the anxiolytic properties of the decoction of stem bark of Hallea ciliate in mice. The decoction of Hallea ciliata is used in traditional medicine in Cameroon to treat diseases like anxiety disorders, fever, infantile convulsions and malaria.Materials and Methods: Stress induced hyperthermia, elevated plus maze, open field and hole-board tests were used. Four different doses of the decoction were administered to mice and their effects were compared to the effects of diazepam and vehicle. Phytochemical characterization of the decoction revealed the presence of alkaloids, flavonoids, tannins and saponins.Results: Administration of Hallea ciliata resulted in a significant decrease of stress induced hyperthermia in mice at the doses of 29.5, 59 and 118 mg/kg. In the elevated plus maze test, Hallea ciliata increased the number of entries and the percentages of entries and time into the open arms, and reduced the number of entries and the percentages of entries and time into the closed arms. In the  hole-board test, Hallea ciliata increased the number of both head-dipping and crossing and decreased the latency to the first head-dips and rearing. The decoction of Hallea ciliata and diazepam increased locomotion in the open field test.Conclusion: The number of rearing and the mass of fecal boli produced were decreased in mice treated with decoction and diazepam. In conclusion, the results indicated that decoction of Hallea ciliata has anxiolytic-like properties in mice and could potentially be used for anxiety treatment.Key words: anxiety, herbs, pharmacology, diazepa

ANXIOLYTIC - LIKE PROPERTIES OF HALLEA CILIATA IN MICE

Background: The aim of the present study was to evaluate the anxiolytic properties of the decoction of stem bark of Hallea ciliata in mice. The decoction of Hallea ciliata is used in traditional medicine in Cameroon to treat diseases like anxiety disorders, fever, infantile convulsions and malaria. Materials and Methods: Stress induced hyperthermia, elevated plus maze, open field and hole-board tests were used. Four different doses of the decoction were administered to mice and their effects were compared to the effects of diazepam and vehicle. Phytochemical characterization of the decoction revealed the presence of alkaloids, flavonoids, tannins and saponins. Results: Administration of Hallea ciliata resulted in a significant decrease of stress induced hyperthermia in mice at the doses of 29.5, 59 and 118 mg/kg. In the elevated plus maze test, Hallea ciliata increased the number of entries and the percentages of entries and time into the open arms, and reduced the number of entries and the percentages of entries and time into the closed arms. In the hole-board test, Hallea ciliata increased the number of both head-dipping and crossing and decreased the latency to the first headdips and rearing. The decoction of Hallea ciliata and diazepam increased locomotion in the open field test. Conclusion: The number of rearing and the mass of fecal boli produced were decreased in mice treated with decoction and diazepam. In conclusion, the results indicated that decoction of Hallea ciliata has anxiolytic-like properties in mice and could potentially be used for anxiety treatment

Anxiolytic and Antiepileptic Properties of the Aqueous Extract of Cissus quadrangularis (Vitaceae) in Mice Pilocarpine Model of Epilepsy

Cissus quadrangularis (C. quadrangularis) is a plant of the Vitaceae family known for its anticonvulsant effects in traditional medicine. The objective of this study was to elucidate the anxiolytic and antiepileptic effects of aqueous extract of C. quadrangularis. The mice were divided into different groups and treated for seven consecutive days as follows: a negative control group that received distilled water, po, four test groups that received four doses of the plant (37.22, 93.05, 186.11, and 372.21 mg/kg, po), and a positive control group that received sodium valproate (300 mg/kg, ip). One hour after the first treatment (first day), epilepsy was induced by intraperitoneal administration of a single dose of pilocarpine (360 mg/kg). On the seventh day, the anxiolytic effects of the extract were evaluated in the epileptic mice using the elevated plus maze (EPM) and open field (OP) paradigms. Antioxidant activities and the involvement of gabaergic neurotransmission were determined by measuring the levels of malondialdehyde, reduced glutathione (GSH), GABA, and GABA-transaminase (GABA-T) in the hippocampus of sacrificed epileptic mice. The results show that the extract of C. quadrangularis significantly and dose-dependently increased the latency to clonic and generalized tonic–clonic seizures and decreased the number and duration of seizures. In the EPM, the extract of C. quadrangularis significantly increased the number of entries and the time spent into the open arms and reduced the number of entries and the time spent into the closed arms as well as the number of rearing. The extract of C. quadrangularis also increased the number of crossing, and the time spent in the center of the OP. The level of MDA and the activity of GABA-T were significantly decreased by the extract of C. quadrangularis while reduced GSH and GABA levels were increased. The results suggest that the anticonvulsant activities of C. quadrangularis are accompanied by its anxiolytics effects. These effects may be supported by its antioxidant properties and mediated at least in part by the GABA neurotransmission

ANTIOXIDANT PROPERTIES OF DICHROCEPHALA INTEGRIFOLIA (ASTERACEAE) IN A MOUSE MODEL OF MONOSODIUM GLUTAMATE-INDUCED NEUROTOXICITY

Background: In Africa, neurodegenerative diseases in the elderly have become a major health concern due to the increase in live expectancy. Glutamate mediated neurotoxicity is involved in neurodegenerative diseases such as Ischemia, Epilepsy, Alzheimer’s and Parkinson diseases. Plants with antioxidant properties are reported to protect vital organs against glutamate toxicity. This study aims to assess the effect of Dichrocephala integrifolia against monosodium glutamatemediated neurotoxicity and oxidative stress. Methodology: The decoction prepared from the leaves of Dichrocephala integrifolia was evaluated against monosodium glutamate-induced neurotoxicity in mice. The animals were grouped in seven groups of 6 animals each. The animals received daily; distilled water (p.o) for the distilled water and the negative control groups, one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o) for the tests groups and memantine (20 mg/kg p.o) for the positive control group. Monosodium glutamate (2.5 g/kg ip) was injected daily to animals except those of the normal control group all the seven days of the experimentation. Animals were observed for aggressiveness, locomotor and forepaws muscle grip activities 30 min after monosodium injections. Brain reduced glutathione and malondialdehyde levels were also assessed following the behavioral tests on day 8. Results: The decoction of Dichrocephala integrifolia at the doses of 87.5 and 175 mg/kg significantly (

The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis

Synthèse de cyclopentènes et d'époxydiynes fonctionnalisés, vers la synthèse de diènediynes naturels

Les diènediynes sont une famille de substances naturelles aux propriétés biologiques d intérêt clinique, essentiellement des activités antitumorales ou antibiotiques. Parmi cette famille s est particulièrement démarqué la néocarzinostatine (NCS), utilisée en clinique pour traiter essentiellement les cancers du foie. Le chromophore de la NCS est une molécule hautement réactive stabilisée par une protéine à l état naturel, qui n a, à ce jour, fait l objet que d une seule synthèse totale. La N1999-A2 possède une structure fort similaire et a fait l objet de deux synthèses totales.Ce travail traite de la synthèse de ces deux composés selon une stratégie reposant sur la formation finale du cycle diènediyne par couplages successifs de deux fragments de complexité équivalente : un fragment cyclopentanique (CyP) et un fragment époxydiyne (EdY). La synthèse du fragment CyP a été étudiée et certains points clés de la synthèse telles que la réaction de Baylis-Hillman ou la formation stéréosélective d éthers d énols de triflate à partir d un céto-aldéhyde ont été développés. Cette réaction a été étendue à d autres systèmes b-dicarbonylés ainsi qu aux céto-sulfones et céto-phosphonates avec un contrôle total de la stéréochimie Z du triflate de vinyle formé. La synthèse du fragment EdY a également été réalisée impliquant notamment l addition d un anion oxiranique sur un carbonyle ainsi que la réduction diastéréosélective de l a,b-époxycétone ainsi formée. Une version asymétrique de la synthèse des fragments CyP et EdY a été réalisée suivant une stratégie de résolution enzymatique. Des essais préliminaires de couplage de précurseurs des fragments CyP et EdY ont été effectués.Dienediynes consist in a series of natural compounds exhibiting similar structures and antitumor and antibiotic activites. One of these compounds, neocarzinostatin (NCS), a protein stabilized compound, was extensively studied for its antitumor properties and even applied to clinical use. Due to its unstability, only a single synthesis has so far been achieved. Another dienediyne, N1999-A2, structurally similar to NCS, exhibit similar antibiotic activities and was synthesized twice.This work deals with the total synthesis of both natural compounds according to a strategy that relies on the final formation of the dienediyne core by successive cross-coupling of two fragments: a cyclopentane fragment (CyP) and an epoxydiyne fragment (EdY). The synthesis of the CyP fragment was studied and several key reactions were specifically developed, such as the Baylis-Hillman reaction or the stereocontrolled formation of Z vinyl triflate from a keto-aldehyde. The latter reaction was extended to several b-dicarbonylated systems and to keto-sulfones and keto-phosphonates with a full Z control of the so-formed vinyl triflate. The synthesis of the EdY fragment was performed following a new sequence including a new reaction i.e. oxirane anion acylation and diastereoselective reduction of the so-formed a,b-epoxyketone. Asymmetric versions of both CyP and EdY syntheses were achieved, based on enzymatic resolution strategy. Furthermore, preliminary results were obtained for the cross-coupling of CyP and EdY fragments precursors.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

HDTorch: Accelerating Hyperdimensional Computing with GP-GPUs for Design Space Exploration

HyperDimensional Computing (HDC) as a machine learning paradigm is highly interesting for applications involving continuous, semi-supervised learning for long-term monitoring. However, its accuracy is not yet on par with other Machine Learning (ML) approaches. Frameworks enabling fast design space exploration to find practical algorithms are necessary to make HD computing competitive with other ML techniques. To this end, we introduce HDTorch, an open-source, PyTorch-based HDC library with CUDA extensions for hypervector operations. We demonstrate HDTorch's utility by analyzing four HDC benchmark datasets in terms of accuracy, runtime, and memory consumption, utilizing both classical and online HD training methodologies. We demonstrate average (training)/inference speedups of (111x/68x)/87x for classical/online HD, respectively. Moreover, we analyze the effects of varying hyperparameters on runtime and accuracy. Finally, we demonstrate how HDTorch enables exploration of HDC strategies applied to large, real-world datasets. We perform the first-ever HD training and inference analysis of the entirety of the CHB-MIT EEG epilepsy database. Results show that the typical approach of training on a subset of the data does not necessarily generalize to the entire dataset, an important factor when developing future HD models for medical wearable devices.Comment: Submitted to the ICCAD 2022 conference (23.5.2022.

Antioxidant properties of Dichrocephala integrifolia (Asteraceae) in a mouse model of monosodium glutamate-induced neurotoxicity

Background: In Africa, neurodegenerative diseases in the elderly have become a major health concern due to the increase in live expectancy. Glutamate mediated neurotoxicity is involved in neurodegenerative diseases such as Ischemia, Epilepsy, Alzheimer’s and Parkinson diseases. Plants with antioxidant properties are reported to protect vital organs against glutamate toxicity. This study aims to assess the effect of Dichrocephala integrifolia against monosodium glutamatemediated neurotoxicity and oxidative stress.Methodology: The decoction prepared from the leaves of Dichrocephala integrifolia was evaluated against monosodium glutamate-induced neurotoxicity in mice. The animals were grouped in seven groups of 6 animals each. The animals received daily; distilled water (p.o) for the distilled water and the negative control groups, one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o) for the tests groups and memantine (20 mg/kg p.o) for the positive control group. Monosodium glutamate (2.5 g/kg ip) was injected daily to animals except those of the normal control group all the seven days of the experimentation. Animals were observed for aggressiveness, locomotor and forepaws muscle grip activities 30 min after monosodium injections. Brain reduced glutathione and malondialdehyde levels were also assessed following the behavioral tests on day 8.Results: The decoction of Dichrocephala integrifolia at the doses of 87.5 and 175 mg/kg significantly (p<0.01) inhibited the aggressiveness of monosodium treated mice, significantly (p<0.01) counteracted the reduction in locomotor and forepaws muscle grip capacity induced by monosodium glutamate. Furthermore, the decreases in reduced glutathione level and increases in lipid peroxidation level induced by monosodium glutamate were significantly (p<0.001) reversed by Dichrocephala integrifolia at the doses of 87.5 and 175 mg/kg.Conclusion: The results of this study reveal that Dichrocephala integrifolia is a medicinal plant that protects the brain against monosodium glutamate-mediated neurotoxicity. This can explain why this plant is intensively used in folk medicine in Cameroon to prevent and treat some central nervous system illnesses.Keywords: Neurotoxicity; Glutamate; Dichrocephala integrifolia; antioxidan

Nootropic and Neuroprotective Effects of Dichrocephala integrifolia on Scopolamine Mouse Model of Alzheimer’s Disease

Alzheimer’s disease the most common form of dementia in the elderly is a neurodegenerative disease that affects 44 millions of people worldwide. The first treatments against Alzheimer’s disease are acetylcholinesterase inhibitors; however, these medications are associated with many side effects. Dichrocephala integrifolia is a traditional herb widely used by indigenous population of Cameroon to treat and prevent Alzheimer’s disease and for memory improvement. In this study, we evaluated the effect of the decoction prepared from leaves of D. integrifolia, on scopolamine-induced memory impairment in mice. Seven groups of six animals were used. The first two groups received distilled water for the distilled water and scopolamine groups. The four test groups received one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o.) and the positive control group received tacrine (10 mg/kg), a cholinesterase inhibitor used in the treatment of Alzheimer’s disease, during 10 consecutive days. Scopolamine (1 mg/kg), a cholinergic receptor blocker, administered 30 min after treatments, was used to induce memory impairment to all groups except the distilled water group on day 10 of drug treatment. The behavioral paradigms used to evaluate the effects of the treatment were the elevated plus maze for learning and memory, Y maze for spatial short-term memory, the novel object recognition for recognition memory and Morris water maze for the evaluation of spatial long-term memory. After behavioral tests, animals were sacrificed and brains of a subset were used for the assessment of some biomarkers of oxidative stress (malondialdehyde and reduced glutathione levels) and for the evaluation of the acetylcholinesterase activity. From the remaining subset brains, histopathological analysis was performed. The results of this study showed that, D. integrifolia at the doses of 87.5 and 350 mg/kg significantly (p < 0.01) improved spatial short-term and long-term memory, by increasing the percentage of spontaneous alternation in the Y maze and reducing the escape latency in the Morris water maze. Furthermore, the results of histopathological evaluation showed that D. integrifolia attenuated the neuronal death in the hippocampus induced by scopolamine. The main finding of this work is that D. integrifolia improves learning capacities and counteracts the memory impairment induced by scopolamine. Thus, D. integrifolia can be a promising plant resource for the management of Alzheimer’s disease and memory loss