Rotarod Apparatus Research Articles

A Comparative Study of Skeletal Muscle Relaxant Effects of Thiocolchicoside, Diazepam and Their Combination in Wistar Rats Using the Rotarod Apparatus.

Introduction Thiocolchicoside (THC) is a semi-synthetic derivative of colchicoside and anaturally occurring compound in the seeds of the Gloriosa Superba L.plant. At present, it is used as a skeletal muscle relaxant. It is used to treat rheumatic arthritis, orthopaedic conditions, and trauma. Topically, it is used to relieve excruciating spasms in the muscles.It is also used to treat a wide range of conditions, which include surgical pain, cervicobrachial neuralgia, acute to chronic torticollis, Parkinson's disease, drug-induced Parkinsonism,spastic hemiplegia, tooth soreness,acute lower back pain, etc. THC is used in conjunction with non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and analgesics.By downregulating and inhibiting the synthesis of NF-κB-regulated gene products, it possesses anti-inflammatory properties. To prevent aneuploidy, the European Medical Agency has placed restrictions on the use of THC, stating that it should not be injected for five days or taken orally for longer than seven days. This is because its metabolism in the body may lead to the production of the metabolite M2. When used during pregnancy, the growing fetus is more negatively impacted. It has also been connected to infertility in men. Aim To study the skeletal muscle relaxant effects of THCin Wistar rats in comparison with standard drugs. Materials and methods The skeletal muscle relaxant activity level was measured using the rotarod apparatus. There were five groups of Wistar rats (n = 6). Group I received 0.9% normal saline (NS) as a control. Group II (test group) received THC 2 mg/kgintraperitoneally (ip).Group III (test group) received THC 4 mg/kg (ip). Group IV diazepam (DIZ) 3 mg/kg (ip) which is the standard treatment group.Group V received a combination of THC 2 mg/kg and DIZ 3 mg/kg. After treatment, retention time was noted at intervals of 30, 60, and 120 minutes. Results Group I (control), Group II (THC 2 mg/kg) and Group III (THC 4 mg/kg) did not demonstrate any skeletal muscle relaxant activity. Group IV (DIZ 3 mg/kg) and Group V (THC 2 mg/kg + DIZ 3 mg/kg) showed statistically significant skeletal muscle relaxant activity when compared to control. However, there was no statistically significant difference between the skeletal muscle relaxant activity of these two groups. This indicates that the addition of THC did not potentiate the skeletal muscle relaxant activity of DIZ. Conclusion THC didn't show skeletal muscle relaxant properties in both doses and did not potentiate the activity of DIZ.

Synthesis, In vivo, and In silico Evaluation of New Pyrazoline-Benzothiazole Conjugates as Antiepileptic Agents.

New 2-(4-benzothiazol-2-yl-phenoxy)-1-(3,5-diphenyl-4,5-dihydro-pyrazol-1-yl)-ethanones (9a-o) have been designed and synthesized. All the synthesized compounds were characterized by thin layer chromatography and spectral analysis. The antiepileptic potential of the synthesized compounds has been tested by following standard animal screening models, including maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The neurotoxic and antidepression effects of the synthesized compounds were checked by utilizing rotarod apparatus, and motor impairment test (by actophotometer) respectively. The study concluded that compounds 9c, 9d, 9f, 9i, 9n, and 9o possessed good antiepileptic potential compared to standard drugs like carbamazepine and phenytoin. The results of the rotarod performance test also established them without any neurotoxicity. The motor impairment test revealed that the synthesized compounds are also good antidepressants. In-silico studies have been performed for calculation of pharmacophore pattern, prediction of pharmacokinetic properties which determine the eligibility of synthesized compounds as orally administered molecules and interactions with the target proteins. The result of in-silico studies reinforced results obtained by in vivo study of the synthesized compounds and their possible mechanism of antiepileptic action i. e. via inhibiting voltage-gated sodium channels (VGSCs) and gamma-aminobutyric acid-A receptor.

Longitudinal quantitative assessment of TMEV-IDD-induced MS phenotypes in two inbred mouse strains using automated video tracking technology

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system affecting over 2.5 million people worldwide. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a murine model that reproduces the progressive form of MS and serves as a reference model for studying virus-induced demyelination.Certain mouse strains such as SJL are highly susceptible to this virus and serve as a prototype strain for studying TMEV infection. Other strains such as SWR are also susceptible, but their disease course following TMEV infection differs from SJL's.The quantification of motor and behavioral deficits following the induction of TMEV-IDD could help identify the differences between the two strains. Motor deficits have commonly been measured with the rotarod apparatus, but a multicomponent assessment tool has so far been lacking.For that purpose, we present a novel way of quantifying locomotor deficits, gait alterations and behavioral changes in this well-established mouse model of multiple sclerosis by employing automated video analysis technology (The PhenoTyper, Noldus Information Technology). We followed 12 SJL and 12 SWR female mice and their mock-infected counterparts over a period of 9 months following TMEV-IDD induction.We demonstrated that SJL and SWR mice both suffer significant gait alterations and reduced exploration following TMEV infection. However, SJL mice also display an earlier and more severe decline in spontaneous locomotion, especially in velocity, as well as in overall activity. Maintenance behaviors such as eating and grooming are not affected in either of the two strains. The system also showed differences in mock-infected mice from both strains, highlighting an age-related decline in spontaneous locomotion in the SJL strain, as opposed to hyperactivity in the SWR strain.Our study confirms that this automated video tracking system can reliably track the progression of TMEV-IDD for 9 months. We have also shown how this system can be utilized for longitudinal phenotyping in mice by describing useful parameters that quantify locomotion, gait and behavior.

Antinociceptive effects of fentanyl and nonopioid drugs in methocinnamox-treated rats

BackgroundA single administration of the opioid receptor antagonist methocinnamox (MCAM) antagonizes the antinociceptive effects of µ-opioid receptor agonists for 2 weeks or longer. Such a long duration of antagonism could necessitate the use of nonopioid drugs for treating pain in patients receiving MCAM for opioid use disorder (OUD). MethodsThe antinociceptive effects of fentanyl and nonopioid drugs were assessed in 24 male Sprague Dawley rats using a complete Freund’s adjuvant (CFA) model of inflammatory pain. Twelve rats received 10mg/kg MCAM and 12 received vehicle; half (n=6) of the animals from each treatment group were treated (intraplantar) with CFA or saline. Hypersensitivity to mechanical stimulation was measured using a von Frey anesthesiometer. Fentanyl (0.01–0.1mg/kg), ketamine (17.8–56mg/kg), gabapentin (32–100mg/kg), meloxicam (3.2–10mg/kg), and ∆9-tetrahydrocannabinol (THC, 1–10mg/kg) were administered intraperitoneally and tested every 3 days in a pseudorandom order. Next, the same drugs were studied for effects on motor performance using a rotarod apparatus. ResultsCFA-induced hypersensitivity was attenuated by fentanyl in vehicle- but not MCAM-treated rats. THC, ketamine, and gabapentin attenuated (up to 82, 66, and 46 %, respectively) CFA-evoked mechanical hypersensitivity in both MCAM- and vehicle-treated rats. Meloxicam failed to alter CFA-evoked mechanical hypersensitivity in either group. Fentanyl, THC, gabapentin, and meloxicam did not affect motor performance in either group whereas ketamine impaired motor performance in both groups (up to 71 % reduction in latency to fall). ConclusionsThese data suggest that ketamine, gabapentin, and THC could be effective for treating inflammatory pain under conditions of long term µ-opioid receptor antagonism.

Ethanolic Extract of <i>Alternanthera Sessilis</i>: A Potential Therapeutic Agent for Behavioral Improvements in Reserpine-Induced Parkinsonian Rats

The present study evaluated the potential of an ethanol extract from Alternanthera sessilis to alleviate reserpine-induced Parkinson's disease (PD) like behavioural manifestations in rats. The animals were grouped into five: a control group, a group receiving only reserpine, a group treated with levodopa and carbidopa, and two groups given different doses of the Alternanthera sessilis extract. Reserpine was used to mimic PD symptoms, while the extract was administered orally at two different concentrations. The behavioral tests were conducted to assess locomotor activity, grip strength, catalepsy, and rearing activity. Locomotor activity was measured using an actophotometer, where interruptions in light beams caused by the rates were recorded over a 10-minute period. Grip strength was evaluated using a rotarod apparatus, measuring the time taken for rats to fall off individual rods. Catalepsy was assessed through a bar test, measuring the time for rats to descend from a horizontal bar to the base. Rearing activity was observed in a round open field arena, with parameters including the occurrence rate of rearing, general movements score, and duration spent in the center of the arena. The results revealed administration of reserpine led to a decrease in body weight, locomotor activity, muscle coordination, catalepsy score, rearing activity, and grip strength compared to the control group. Conversely, treatment with levodopa and carbidopa resulted in increased values for these parameters. Importantly, administration of Alternanthera sessilis extract showed a dose-dependent reversal of the effects induced by reserpine, with significant increases observed in body weight, locomotor activity, muscle coordination, rearing activity, general movement, and grip strength, indicating its potential therapeutic effects. In conclusion, the present study results suggest that the extract from the Alternanthera sessilis plant might protect brain cells and improve symptoms of Parkinson's disease. However, more research is needed to understand how it works and if it can be used safely and effectively clinical trails.

Mitofusin 2 plays a critical role in maintaining the functional integrity of the neuromuscular-skeletal axis

PurposeMitofusin 2 (Mfn2) is one of two mitofusins involved in regulating mitochondrial size, shape and function, including mitophagy, an important cellular mechanism to limit oxidative stress. Reduced expression of Mfn2 has been associated with impaired osteoblast differentiation and function and a reduction in the number of viable osteocytes in bone. We hypothesized that the genetic absence of Mfn2 in these cells would increase their susceptibility to aging-associated metabolic stress, leading to a progressive impairment in skeletal homeostasis over time. MethodsMfn2 was selectively deleted in vivo at three different stages of osteoblast lineage commitment by crossing mice in which the Mfn2 gene was floxed with transgenic mice expressing Cre under the control of the promoter for Osterix (OSX), collagen1a1, or DMP1 (Dentin Matrix Acidic Phosphoprotein 1). ResultsMice in which Mfn2 was deleted using DMP1-cre demonstrated a progressive and dramatic decline in bone mineral density (BMD) beginning at 10 weeks of age (n = 5 for each sex and each genotype from age 10 to 20 weeks). By 15 weeks, there was evidence for a functional decline in muscle performance as assessed using a rotarod apparatus (n = 3; 2 males/ 1 female for each genotype), accompanied by a decline in lean body mass. A marked reduction in trabecular bone mass was evident on bone histomorphometry, and biomechanical testing at 25 weeks (k/o: 2 male/1 female, control 2 male/2 female) revealed severely impaired femur strength. Extensive regional myofiber atrophy and degeneration was observed on skeletal muscle histology. Electron microscopy showed progressive disruption of cellular architecture, with disorganized sarcomeres and a bloated mitochondrial reticulum. There was also evidence of neurodegeneration within the ventral horn and roots of the lumbar spinal cord, which was accompanied by myelin loss and myofiber atrophy. Deletion of Mfn2 using OSX-cre or Col1a1-cre did not result in a musculoskeletal phenotype. Where possible, male and female animals were analyzed separately, but small numbers of animals in each group limited statistical power. For other outcomes, where sex was not considered, small sample sizes might still limit the strength of the observation. ConclusionDespite known functional overlap of Mfn1 and Mfn2 in some tissues, and their co-expression in bone, muscle and spinal cord, deletion of Mfn2 using the 8 kB DMP1 promoter uncovered an important non-redundant role for Mfn2 in maintaining the neuromuscular/bone axis.

Pros and cons of narrow- versus wide-compartment rotarod apparatus: An experimental study in mice

The rotarod test, a sensorimotor assessment that allows for quantitative evaluation of motor coordination in rodents, has extensive application in many research fields. The test results exhibit extreme between-study variability, sometimes making it challenging to conclude the validity of certain disease models and related therapeutic effects. Although the variation in test paradigms may account for this disparity, some features of rotarod apparatus including rod diameter make differences. However, it is unknown whether the width of animal compartment has a role in rotarod performance. Here we comprehensively evaluated the active rotarod performance and adverse incidents in multiple strains of mice on an 11-cm- or a 5-cm-wide compartment apparatus. We found that mouse behaviors on these apparatuses were surprisingly different. It took a markedly longer time to train mice on the narrow- than wide-compartment rotarod. Further, non-transgenic B6129S and tau knockout mice aged 11 months and beyond showed different levels of improvement based on the compartment width. These mice had no overt improvements on accelerating rotarod over 4−5 training sessions on the narrow compartment, contrary to marked progress on the wide counterpart. The incidents of mice passively somersaulting round and fragmented running occurred significantly more on the wide than narrow compartment during accelerating rotarod sessions. Mice fell off rod more frequently on narrow than wide compartments upon attempt to turn around and when moving backward on rod. The pros and cons of narrow versus wide compartments are informative as to how to choose a rotarod apparatus that best fits the animal models used.

An aqueous Commiphora myrrha extract ameliorates paclitaxel-induced peripheral neuropathic pain in mice.

Background: Chemotherapy-induced neuropathic pain (CINP) is a debilitating side effect in individuals undergoing cancer treatment. Treatment of CINP with the current available classes of drugs is limited and often yields unsatisfactory results. Finding therapeutic alternatives of plant origin could provide a new way for the management of CINP. Commiphora myrrha (CM) resin extract has been reported to have anti-inflammatory and analgesic activities, but the effect of CM on neuropathic pain is yet to be investigated in CINP. Objectives: The aim of this study was to investigate the antinociceptive effect of CM extract in a mouse model of paclitaxel-induced neuropathic pain (PINP). Methods: The effects of CM on thermal hyperalgesia and mechanical allodynia were assessed in female BALB/c mice with PINP using a hot plate and a plantar aesthesiometer, respectively. Motor coordination was evaluated using a rotarod apparatus. The involvement of transient receptor potential vanilloid channel 1 (TRPV1) in CM actions was investigated using a capsaicin (a TRPV1 agonist)-induced nociception test. The genetic expression of Trpv1, Nrf2, Sod2, and Hmox1 was assessed using real-time PCR, while protein expression of TRPV1, Iba-1, and CD11b was assessed using Wes™. Results: Administration of CM to mice with established PINP produced a dose-dependent reduction in thermal hyperalgesia. Prophylactic treatment of mice with CM prevented the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia. CM did not change the motor coordination of mice, as the reaction latency and the rotational velocity of animals pretreated with CM extract were similar to those of animals pretreated with vehicle. CM significantly decreased the number and duration of the flick responses following capsaicin injection into the dorsal surface of the hind paw of mice. The protein expression of TRPV1 was upregulated in the spinal cord of paclitaxel-treated animals compared to vehicle-only-treated control animals, while CM-treated animals had values similar to vehicle-only-treated control animals. The mRNA expression of Nrf2, a major antioxidant transcription factor, was upregulated in the paw skin of mice treated with CM compared to those treated with paclitaxel alone. Conclusion: These results indicate that CM may both treat established and prevent the development of paclitaxel-induced thermal hyperalgesia and mechanical allodynia without any impairment in the motor activity of mice. CM may mediate its action through the peripheral inhibition of TRPV1 channel activity, restoration of normal TRPV1 protein expression in the spinal cord, and elevation of cellular antioxidant defenses. CM has the potential to be used as a therapeutic alternative to treat CINP.

NATURE'S SHIELD: UNVEILING THE PROTECTIVE POWER OF SHARKARA YUKTA GAU-DUGDHA AS PRATIVISHA AGAINST DATURA METEL INDUCED TOXICITY IN ALBINO WISTAR RATS - A RESEARCH ARTICLE

Datura (Datura metel) is recognized as a cerebrotoxic deliriant poison and is concurrently categorized as "Upavisha" within Ayurvedic principles. Ayurveda encompasses a spectrum of toxic substances along with their respective antidotes; however, the mechanisms underlying these antidotal effects remain unelaborated in the ancient texts. A segment in the "Rasa jal Nidhi" Part 3 (Chapter 8), titled "Dhusturbeejasya Shanti," delineates the potential antidote properties of Gau dugdha in a proportion of one prastha and sharkara (sugar) in a quantity of two pal, positing a potential counteraction against Datura toxicity. The objective of this study is to scientifically evaluate the efficacy of these antidotal agents in mitigating Datura seed-induced toxicity, so that it can be useful in emergencies. Methods: Albino Wistar rats are employed as the chosen animal model to investigate the antidotal effect of Sharkara Yuka Gau-dugdha against Datura beeja (seed) powder-induced toxicity. The assessment encompasses a comprehensive range of criteria encompassing alterations in weight, modifications in dietary and hydration habits, behavioral shifts, lethaginss, fluctuations in temperature, emergence of convulsive episodes, performance in the Radial Arm Test, Rotarod activity, locomotion, and mortality. Results: Following administration of Sharkara Yuka Gau-dugdha, discernible alleviation of the deleterious effects associated with Datura exposure is evident. Noteworthy observations encompass a reduction in responses during the Radial Arm Test, suggestive of a positive influence on cognitive faculties such as learning and memory. Additionally, an increase in time spent on the Rotarod apparatus signifies enhanced muscle strength and augmented motor function. Conclusion: The findings gleaned from this experimental study culminate in the conclusion that Sharkara Yuka Gau-dugdha holds moderate potential to ameliorate the extent of toxic manifestations elicited by Datura exposure.

Amelioration of Motor Performance and Nigrostriatal Dopamine Cell Volume Using a Novel Far-Infrared Ceramic Blanket in an A53T Alpha-Synuclein Transgenic Parkinson's Disease Mouse Model.

We had attended a Parkinson's Disease (PD) patient for a non-healing wound who reported a marked decrease in his hand tremor and freezing of gait when his wound was exposed to a ceramic far-field infrared (cFIR) blanket. PD is the most frequent motor disorder and the second most frequent neurodegenerative disease after Alzheimer's Disease (AD). The tremor, rigidity, and slowness of movement associated with Parkinson's disease (PD) affect up to 10 million people throughout the world, and the major contributing factor to the pathogenesis of PD is the accumulation and propagation of pathological α-synuclein (α-Syn) and the death of dopaminergic cells in the Nigrostriatal system. Efforts to slow or stop its spreading have resulted in the development and use of dopaminergic drug replacement therapy. Unfortunately, there is a loss of about 70-80% of substantia nigral dopaminergic neurons in patients by the time they are diagnosed with PD, and various dopaminergic drugs provide only temporary relief of their motor symptoms. There are limitations in treating PD with many conventional medications, necessitating a combination of pharmaceutical and non-pharmacological therapy as an essential adjunct to better address the health and welfare of PD patients. We used male adult A53T alpha-synuclein transgenic mice exposed to a ceramic far-infrared blanket. Motor activity was assessed using the rotarod apparatus, and mouse brains were examined to quantify the fluorescence intensities of the immunostained samples. A53T alpha-synuclein transgenic mice had a significantly shorter time stay on the rotating bar than the wild-type mice (B6C3H). The rotarod performance was significantly improved in A53T alpha-synuclein transgenic mice exposed to cFIR as well as B6C3H healthy wild mice exposed to cFIR. There was a significant statistical and substantive increase in the cellular composition of the Striatum and substantia nigra of cFIR-treated mice. Improvement in motor performance is seen in PD mice and wild mice and is associated with increases in cell volume in the substantia nigra and striatum after treatment.

Chemical characterization, antinociceptive and anti-inflammatory effect of Lippia lacunosa, a species used by the Bandeirantes

Ethnopharmacological relevanceLippia lacunosa Mart. & Schauer is an endemic plant from the Serra do Espinhaço mountain range located on the Atlantic plateau, Brazil. It is known as “chá de pedestre” and “rosmaninho” in folk medicine. This species has a characteristic mango aroma and is widely used by the population for flu, colds, sinus infections, coughing, relaxing baths, and foot baths after long walks. It is often confused with and, therefore, used interchangeably with L. rotundifolia and L. pseudothea. Aim of the studyThis study aimed to increase scientific knowledge on the ethnopharmacological use of Lippia lacunosa through the evaluation of the micromolecular composition and anti-inflammatory and antinociceptive activities of the hexane and ethanolic extracts, essential oil, and fractions in mice. Materials and methodsThe chemical profile of L. lacunosa extracts and fractions were obtained by chromatographic methods such as Ultra-Performance Liquid Chromatography (UPLC), Gas Chromatography (GC), Column Chromatography (CC), and Thin Layer Chromatography (TLC). Carrageenan-induced paw edema was used to investigate the anti-inflammatory activity in mice. Mechanical allodynia induced by carrageenan and hot plate tests were employed to evaluate the antinociceptive activity. ResultsThe main constituents found in the essential oil were the monoterpenes myrcene (13.81%), linalool (6.84%), ipsenone (21.2%), and myrcenone (25.44%); and sesquiterpenes elemol (7.30%) and spathulenol (3.15%). The chromatograph fractionation of essential oil yielded a fraction rich in the main compounds (F33), ipsenone and mircenone. In experimental models of paw edema and mechanical allodynia induced by carrageenan (600 μg, 30 μL, i.pl.), the administration of hexane extract, essential oil (50 or 100 mg/kg, p.o.) or majority fraction (10 mg/kg, p.o.) reduced paw edema. The ethanolic extract (100 mg/kg) reduced mechanical allodynia only in the 2 nd h of evaluation. On the other hand, the hexane extract (50 or 100 mg/kg) and essential oil (100 mg/kg), as well as the majority fraction (10 mg/kg), reduced mechanical allodynia throughout the evaluation period. The hexane extract, essential oil, and majority fraction F33 also reduced the heat-induced nociceptive response. Also, majority fraction F33 did not affect the time mice spent in the rota-rod apparatus. ConclusionsThe elucidation of the composition of the essential oil and the demonstration of the activity of L. lacunosa in experimental models of acute inflammation and also in models of nociceptive and inflammatory pain can help to increase knowledge on the ancient ethnopharmacological use by the Bandeirantes, aiming at the evaluation of the species as a candidate for herbal medicine or phytopharmaceutical in the treatment of patients with inflammatory and painful conditions.

Cucurbita maxima Seeds Reduce Anxiety and Depression and Improve Memory.

The current study was planned to assess the neuropharmacological benefits of the Cucurbita maxima seed. These seeds have been conventionally used for the nutritional as well as amelioration of various diseases. However, there was a need to provide a pharmacological basis for such use. Four central nervous system-related functions, that is, anxiety, depression, memory, and motor coordination, were evaluated, and the levels of brain biogenic amines were also assessed. Anxiety was evaluated through selected experimental models, such as light and dark apparatus, elevated plus maze, head dip, and open field test. The head dip test was mainly used to assess exploratory behavior. Depression was assessed by two animal models, that is, the forced swim test and tail suspension test. Memory and learning ability were assessed by the passive avoidance test, stationary rod apparatus, and Morris's water maze test. Motor skilled learning was assessed by stationary rod and rotarod apparatus. Reversed phase high-pressure liquid chromatography was used to determine biogenic amine levels. Results reveal that C. maxima exhibited anxiolytic and antidepressant effects with memory improvement. There was a reduction in the weight of the animal following chronic administration. Furthermore, no remarkable effects were observed on motor coordination. Norepinephrine was found elevated, which may be linked to its antidepressant effects. These biological effects of C. maxima may be due to the presence of secondary metabolites, such as cucurbitacin, beta-sitosterol, polyphenolic compounds, citrulline, kaempferol, arginine, β-carotene, quercetin, and other antioxidants. The outcomes of the present study authenticate that the chronic use of C. maxima seeds reduces the intensity of neurological problems like anxiety and depression.

Neuroprotective Property of Tecoma Stans Flower Extract in Scopolamine Induced Amnesia and Chlorpromazine Induced Rigidity in Laboratory Animals

Background and Aim Tecoma stans Linn is an important medicinal plant exhibiting anticancer antioxidant antimicrobial anti-proliferative properties. The present work was designed to investigate the neuroprotective efficacy of methanolic extract of Tecoma stans flowers METSF in laboratory animal models.Methodology The extract of Tecoma stans flowers was investigated against motor coordination test elevated plus maze and by morris water maze. The standard drugs various doses of METSF was administered to experimental animals to assess the motor coordination test using rotarod apparatus retention of memory in mice using elevated plus maze and learning amp memory study by morris water maze.Results The animals administered with drug and METSF showed a increase in muscle grip action on the 0 day 7th day 14th day and 21st day compared to positive control animals. Pretreatment with drug and test extract at different doses showed a reduction of LPO and nitrite levels in brain when compared to positive control animals. On administration of standard and test extract at changed doses showed a marked increase in levels of GSH and Total protein when matched to positive control animals. In elevated plus maze model the Donepezil and METSF of various doses significantly reversed decreased the TL scopolamine-induced memory impairment in mice as compared to scopolamine-treated groups. The scopolamine-administered mice showed a significant improvement in the ELT as compared to normal control group animals. However the administration of METSF at different doses and standard drug Donepezil was found to reduce the ELT significantly as compared to that of scopolamine-treated animals.Conclusion The protective property of METSF may be due to preventing the oxidative stress and potent anti-oxidant property.

Trans-cinnamaldehyde mitigates rotenone-induced neurotoxicity via inhibiting oxidative stress in rats

BackgroundThe second most prevalent age-related brain condition, Parkinson's disease (PD) is characterised by the loss of neurons in the substantia nigra pars compacta (SNpc). It is associated with symptoms like bradykinesia, stiffness, tremor, and impaired postural responses. Motor dysfunction, and neurochemical imbalance, are involved in the pathophysiology of PD. It has been hypothesised that trans cinnamaldehyde (TCA) a component of Traditional Chinese Medicine (TCM) can ameliorate Parkinson-like symptoms by altering the levels of different biochemical markers and reverse motor impairments. This research sought to determine the neuroprotective effect of TCA against the neurotoxicity caused by rotenone. Basic ProcedureRotenone (1.5 mg/kg/day; s.c. for 35 days) was given to rats to induce Parkinson-like symptoms. TCA (5, 10, and 20 mg/kg) and concomitant treatment of TCA (5 mg/kg) with L-NAME (10 mg/kg) were given one hour prior to rotenone administration. Every week until the 35th day, behavioral parameters (muscle coordination, spontaneous motor movement and gait abnormalities) were assessed using rotarod, actophotometer, and narrow beam apparatus respectfully. Rats were decapitated on the 35th day, the striatum and cortex were isolated for biochemical tests. Main findingsRotenone treatment reduced body weight, altered motor coordination and reduced the oxidative defense system. Treatment with TCA significantly improved the alterations in antioxidant levels as well as behavioral parameters. Furthermore, L-NAME (nitric oxide synthase inhibitor) in combination with TCA had a more significant effect as compared to TCA alone, signifying a possible drug interaction. Principal conclusionTCA could be employed as an adjuvant in PD management.

The peripheral dopamine 2 receptor antagonist domperidone attenuates ethanol enhancement of dopamine levels in the nucleus accumbens.

Dopamine neuron firing in the ventral tegmental area (VTA) and dopamine release in the nucleus accumbens have been implicated in reward learning. Ethanol is known to increase both dopamine neuron firing in the VTA and dopamine levels in the nucleus accumbens. Despite this, some discrepancies exist between the dose of ethanol required to enhance firing in vivo and ex vivo. In the present study we investigated the effects of peripheral dopamine 2 subtype receptor antagonism on ethanol's effects on dopamine neurotransmission. Plasma catecholamine levels were assessed following ethanol administration across four different doses of EtOH. Microdialysis and voltammetry were used to assess the effects of domperidone pretreatment on ethanol-mediated increases in dopamine release in the nucleus accumbens. A place conditioning paradigm was used to assess conditioned preference for ethanol and whether domperidone pretreatment altered this preference. Open-field and loss-of-righting reflex paradigms were used to assess the effects of domperidone on ethanol-induced sedation. A rotarod apparatus was used to assess the effects of domperidone on ethanol-induced motor impairment. Domperidone attenuated ethanol's enhancement of mesolimbic dopamine release under non-physiological conditions at intermediate (1.0 and 2.0g/kg) doses of ethanol. Domperidone also decreased EtOH-induced sedation at 2.0g/kg. Domperidone did not alter ethanol conditioned place preference nor did it affect ethanol-induced motor impairment. These results show that peripheral dopamine 2 receptors mediate some of the effects of ethanol on nonphysiological dopamine neurotransmission, although these effects are not related to the rewarding properties of ethanol.

Exercise improves the body function and protects the neuronal injury in Parkinson's disease rats by activating calpain 1 and kallikrein 6.

Parkinson's disease (PD) is a neurodegenerative disease, which alters body and cognitive functions. The present study evaluates the effect of exercise on body function and neuronal injury against a 6-hydroxydopamine hydrobromide (6-OHDA) induced PD rat model and postulates a possible molecular mechanism of its action. Parkinson's disease was induced by administration of (20 µg/5 µl at the rate of 1 µl/min) 6-OHDA and exercise training was given to mice by motorized rodent treadmill for a period of 14 days after the confirmation of PD. Behavioural changes were observed by apomorphine-induced rotation and motor function was assessed using the rotarod apparatus. The effect of exercise was observed on the levelof neurochemicals and the expression of calpain-1 (CAPN1) and kallikrein 6 (KLK6) was estimated in brain tissue of PD rats using western blot assay. A more significant improvement in the motor and cognitive function was observed in the PD + exercise group than in the PD group of rats. Exercise attenuates the altered level of g-aminobutyric acid (GABA), dopamine (DA) and glutamate in brain tissue of PD rats. Intracellular concentration of Ca+ ion was reduced significantly in brain tissue of the PD + exercise group compared to PD rats. Moreover, exercise activates the expression of KLK6 and CAPN1 protein in brain tissue of PD rats. In conclusion, data of the study reveal that exercise protects neuronal injury by reducing intracellular concentration Ca+ ion and activates KLK6 and CAPN1 in brain tissue of PD rats and thereby improves motor and cognitive functions.

Evaluation of Chenopodium Quinoa Extract on Diazepam Induced Memory Impairment in Animal Models

Aim: The present study explored the pharmacological and insilico studies of ethanolic seed extract of Chenopodium quinoa.
 Materials and Methods: The screening of in vivo anti- amnesic activity of the ethanolic seed extract of Chenopodium quinoa was carried out using Actophotometer and Rotarod apparatus. The extract exhibited active constituents like myristic acid, palmitic acid, eicosadienoic acid, pentadecanoic acid, tocopherols, stigmasterol, β-sitosterol, quercetin, benzoic acid, kaempferol, arachidonic acid, benzofuran and 2-bromodecanoic acid. In silico approaches like docking studies (Mcule software) and Ramchandran plot (procheck), online softwares were used in the study to establish mechanism of action of active constituents present in the extract.
 Results: The extract treated groups at doses (200 mg/kg and 400 mg/kg, bd.wt) showed significant anti-amnesic activity. The basal activity score in actophotometer is as an indicator for impairment of learning and memory. Fall of time by rotarod is used to evaluate learning and memory in rodent models of CNS disorders as in case of amnesia. The results revealed that quercetin, kaempferol, myristic acid, palmitic acid, stigmasterol, lenolenic acid, pentadecanoic acid, tocopherols, arachidonic acid and standard donepezil have got highest glide scores against selected Protein Data Bank (PDB ID): 1EVE, 2FY4, 7CUM and 3EJ8. According to Ramachandran plot a good quality model would be expected to have over 90% in the most favoured region. Proteins like PDB ID: 1EVE, 2FY4, 7CUM and 3EJ8 showed almost 80-90% favoured region which clearly indicates that the selected proteins in the present study are of good quality.
 Conclusion: Our research unveiled that ethanolic seed extract of Chenopodium quinoa possessed significant anti- amnesic activity.

Skeletal muscle relaxant activity of different formulation of span 60 niosomes

Introduction: Spasticity is a disease of motor neurons that manifests as accelerated muscle tone and stiffness. The niosomes can be formulated with the aid of proper adjustment of process parameters to enhance baclofen entrapment and sustaining the drug release.
 Method: The main purpose of this study is to compare different formulations of span 60 niosomes containing baclofen for skeletal muscle relaxant activity on mice (Swiss albino mice) by rota rod method.
 Results: The particle size of formulated niosomes was in the range of 3.62±0.54-4.08±0.64 µm and these were smooth, circular fit and generally small multilamellar. Entrapment efficiency of optimized formulation was 88.44±0.28 %. The most extreme % cumulative drug release was 87.88±8.66% after 10 h. The formulation stored at 4±2 °C temperature shows better stability (96.65±0.45) contrasted with raised temperature. Swiss albino mice were utilized for in vivo study and displayed improved muscle relaxant action as far as no. of tumbles from rota rod apparatus (p value =0.001) are concerned.
 Conclusions: Nonetheless, diazepam treated mice were observed to have higher muscle relaxation than any dose of formulation tested. The formulation F9 shows better skeletal muscle relaxant activity as compared to F6, F7, F8 and F10 on mice (Swiss albino mice) by the rota rod technique.

Study of Multifaceted Effect of Vitexnegundo Leaves Aqueous Extract and Decoction for Pain Relief in Experimental Models

Background: Pain is the warning signal of underlying pathology. Analgesic drugs are used as per the severity of pain. These drugs have their own adverse drug reactions, sometimes requiring the discontinuation of treatment. Perception and reaction to the pain are two important facets of pain. Reaction in the form of fear,restlessness, spasm of the muscles etc. are seen. Effectiveness of Vitexnegundoin pain have been studied, we planned to evaluate the associated components of it. Objectives: To evaluate, the Analgesic action, Anxiolytic action and Muscle relaxant action of Vitexnegundo leaves aqueous extract (VNLE) and Vitexnegundo dried leaves decoction (VNDLD). Material and methods: Fresh prepared VNLE and VNDLD are the two preparations of Vitexnegundo used to evaluate the analgesic, anxiolytic and skeletal muscle relaxant activity. Wistar rats and mice of either sex were divided into four groups, control, positive control, VNLE&VNDLD. Standard drug pentazocine& diazepam were used for analgesic & skeletal muscle relaxant property respectively. Rats were exposed to hot plate for Analgesic activity, elevated plus maze (EPM) for anxiolytic effect and mice to rotarod apparatus for checking skeletal muscle relaxation after the drug treatment.Analysis was done with graph pad prism 6. Results: Pain threshold was significantly increased at (p<0.001) Pentazocine and (p<0.01) in Vitexnigundo juice as observed from increase in reaction time. VNLE and VNDLD significantly showed positive effect on the parameters of the EPM. This observation was comparable with the standard drug diazepam. Time spent on the rota rod was significantly reduced in all drug treated mice. Conclusion:Analgesic and antianxiety activity of Vitexnegundo is confirmed.Fresh juice VNLE was more effective than the VNDLD. It also possesses skeletal muscle relaxant action, enhancing the pain relief.

Screening of aqueous extract of Myristica fragrans seed for sedative and sleep enhancing property in experimental animals

houtt or nutmeg, a commonly used spice is found to have several medicinal properties.The main aim of our study is to evaluate sedative and hypnotic activity of aqueous extract of houtt seeds in experimental animals.This is a preclinical study involving male and female Wistar albino rats and Swiss albino mice. Sedative and hypnotic properties were assessed using hole board test, open field apparatus, rota rod apparatus and thiopental induced sleeping time. aqueous extract( MFAE) was the test drug which was given at the dose of 200mg/kg body weight. Diazepam was used as the standard drug. Preliminary phytochemical analysis of MFAE was carried out.: Data was analyzed using one way ANOVA (Analysis of Variance) followed by Tukey Krammer Test. P value < 0.05 was considered as significant. Hole board test and open field test showed decrease in exploratory and locomotor activity and rota rod test showed decrease in time period of fall compared to normal and thiopental induced sleeping time showed that the test drug decreased the onset time of loss of righting reflex and prolonged the regaining time of righting reflex indicating hypnotic activity. Preliminary phytochemical screening showed the presence of alkaloids, glycosides, saponins, flavonoids, tannins and fixed oils.: Based on results we concluded that aqueous extract of seeds possess significant sedative hypnotic property.