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1.
Neurochem Int ; 177: 105767, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38750962

ABSTRACT

AIM AND OBJECTIVE: The purpose of the study is to determine the neuroprotective effect of capric acid on sodium valproate-induced model of autism. METHODS: In this study, the effect of CA was observed in animals with single dose of valproic acid (600 mg/kg, i. p.) where the disease condition was confirmed by developmental impairment in pups. Behavioral tests that assess anxiety, depression, stereotypical and repetitive behavior, social interaction, learning and memory, and other confounding variables were performed. Subsequently, oxidative stress parameters, pro-inflammatory cytokine levels and mitochondrial complex activities in the selected brain regions were analyzed. RESULTS: Valproic acid successfully produced autism-like symptoms from post-natal day 7 and also demonstrated impairment in social behavior, learning and memory, and anxiety and depression. Valproic acid was found to produce oxidative stress and neuro-inflammation in the hippocampus, prefrontal cortex, and cerebellum. Treatment with capric acid produced a positive effect on the alterations with maximum effects evident at 400 mg/kg, p. o. through amelioration of behavioral as well as biochemical changes. CONCLUSION: The current study concluded that capric acid could act as a likely candidate for the treatment and management of autism via significant modulation of neurobehavioral parameters, oxidative stress, mitochondrial dysfunction and inflammatory markers.


Subject(s)
Autistic Disorder , Disease Models, Animal , Neuroprotective Agents , Oxidative Stress , Valproic Acid , Valproic Acid/pharmacology , Animals , Autistic Disorder/chemically induced , Autistic Disorder/drug therapy , Autistic Disorder/metabolism , Male , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Oxidative Stress/drug effects , Behavior, Animal/drug effects , Decanoic Acids/pharmacology , Female , Rats , Rats, Wistar , Brain/drug effects , Brain/metabolism
2.
Neurochem Res ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38814358

ABSTRACT

The study objectives are to investigate the ability of capsaicin to revert the toxic effects in glutamate and lipopolysaccharide (LPS)-induced neurotoxicity in Neuro2a (N2a) cells as well as thwarting cognitive impairments, mitochondrial deficits, and oxidative insults induced by 3-nitropropanoic acid (3-NP) in a rodent model of Huntington's disease. In-vitro study with N2a cells was performed through MTT and LDH assay and their biochemical examinations were also performed. 3-NP-administered mice (n = 6) were treated with capsaicin (5, 10, and 20 mg/kg) through the per-oral (p.o.) route for 7 consecutive days. Physiological and behavioral studies were performed in drug-treated mice. After behavioral studies, biochemical parameters were performed for cytokines levels, various oxidative stress parameters, and mitochondrial enzyme complex activities with mitochondrial permeability. N2a cells treated with capsaicin demonstrated neuroprotective effects and reduced neurotoxicity. Based on experimental observation, in an in-vitro study, the effective dose of CAP was 50 µM. Moreover, a 100 µM dose of capsaicin had toxic effects on neuronal cells (N2a cells). On the other hand, the effective dose of 3-NP was 20 mg/kg, (p.o.) in animals (in-vivo). All tested doses of capsaicin upturned the cognitive impairment and motor in-coordination effects induced by 3-NP. 3-NP-injected mice demonstrated substantially increased pro-inflammatory cytokine concentrations, defective mitochondrial complex activity, and augmented oxidative insult. However, capsaicin at different doses reduced oxidative damage and cytokines levels and improved mitochondrial complex activity along with mitochondrial permeability. Furthermore, capsaicin (10 and 20 mg/kg) improved the TNF-α concentration. These findings suggested because of the anti-inflammatory and antioxidant effect, capsaicin can be considered a novel treatment for the management of neurodegenerative disorders by reverting the antioxidant enzyme activity, pro-inflammatory cytokines concentration, and mitochondrial functions.

3.
Altern Ther Health Med ; 30(2): 68-75, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37883773

ABSTRACT

Huntington's disease (HD) is an autosomal neurodegenerative disease that involves movement disorders, cognitive impairments, and psychiatric symptoms. It is characterized by regionally selective cortical degeneration that proceeds from posterior to anterior cortical region which explains its heterogeneity. At present, the psychiatric symptoms of HD are mostly managed by antidepressant such as selective serotonin reuptake inhibitors or selective nor-epinephrine reuptake inhibitors, and atypical antipsychotics. Currently, there are no efficient pharmacological treatment available for HD. Thus, in order to avoid this void in effective pharmacotherapy, further supplemental and alternative approaches are being explored for the management of problems associated with HD. A literature review was performed using the databases PubMed and Google Scholar identifying clinical studies that were set to ameliorate the symptoms associated with HD. On critical analysis, it was found that alternative treatment modalities like music therapy, video games, Yoga, Physical therapy, and exercise-based programs have a potential and possible role in improving the symptoms of HD at varied degrees.


Subject(s)
Cognitive Dysfunction , Huntington Disease , Neurodegenerative Diseases , Humans , Huntington Disease/diagnosis , Huntington Disease/drug therapy , Exercise
4.
Neurochem Res ; 48(3): 697-712, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36342577

ABSTRACT

To solve the restrictions of a classical ketogenic diet, a modified medium-chain triglyceride diet was introduced which required only around 60% of dietary energy. Capric acid (CA), a small molecule, is one of the main components because its metabolic profile offers itself as an alternate source of energy to the brain in the form of ketone bodies. This is possible with the combined capability of CA to cross the blood-brain barrier and achieve a concentration of 50% concentration in the brain more than any other fatty acid in plasma. Natural sources of CA include vegetable oils such as palm oil and coconut oil, mammalian milk and some seeds. Several studies have shown that CA has varied action on targets that include AMPA receptors, PPAR-γ, inflammatory/oxidative stress pathways and gut dysbiosis. Based on these lines of evidence, CA has proved to be effective in the amelioration of neurological diseases such as epilepsy, affective disorders and Alzheimer's disease. But these studies still warrant more pre-clinical and clinical studies that would further prove its efficacy. Hence, to understand the potential of CA in brain disease and associated comorbid conditions, an advance and rigorous molecular mechanistic study, apart from the reported in-vitro/in-vivo studies, is urgently required for the development of this compound through clinical setups.


Subject(s)
Diet, Ketogenic , Epilepsy , Animals , Humans , Decanoic Acids/metabolism , Fatty Acids/metabolism , Mammals/metabolism
5.
Curr Alzheimer Res ; 20(9): 660-676, 2023.
Article in English | MEDLINE | ID: mdl-38213170

ABSTRACT

AIM: To evaluate the potential beneficial role of Capsaicin in cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice. BACKGROUND: Capsaicin is the chief phenolic component present in red chili and is responsible for its pungent and spicy flavor. It affects TRPV1 channels in nociceptive sensory neurons and is present in the hippocampus, and hypothalamus of the brains of rodents and humans. OBJECTIVE: The main objective is to investigate the effective role of capsaicin in attenuating cognitive dysfunction, mitochondrial impairment, and oxidative damage induced by scopolamine in mice and examine the feasible mechanisms. METHODS: Various doses of capsaicin (5, 10, and 20 mg/kg) were given orally to mice daily for 7 consecutive days after the administration of scopolamine. Various behavioral tests (motor coordination, locomotor counts, hole board test) and biochemical assay (Pro-inflammatory cytokines, catalase, lipid peroxidation, nitrite, reduced glutathione, and superoxide dismutase), mitochondrial complex (I, II, III, and IV) enzyme activities, and mitochondrial permeability transition were evaluated in the distinct regions of the brain. RESULTS: Scopolamine-treated mice showed a considerable reduction in the entries and duration in the light zone as well as in open arms of the elevated plus maze. Interestingly, capsaicin at different doses reversed the anxiety, depressive-like behaviors, and learning and memory impairment effects of scopolamine. Scopolamine-administered mice demonstrated substantially increased pro-inflammatory cytokines levels, impaired mitochondrial enzyme complex activities, and increased oxidative damage compared to the normal control group. Capsaicin treatment reinstated the reduced lipid peroxidation, nitric oxide, catalase, superoxide dismutase, reduced glutathione activity, decreasing pro-inflammatory cytokines and restoring mitochondrial complex enzyme activities (I, II, III, and IV) as well as mitochondrial permeability. Moreover, the IL-1ß level was restored at a dose of capsaicin (10 and 20 mg/kg) only. Capsaicin reduced the scopolamine-induced acetylcholinesterase activity, thereby raising the acetylcholine concentration in the hippocampal tissues of mice. Preservation of neuronal cell morphology was also confirmed by capsaicin in histological studies. From the above experimental results, capsaicin at a dose of 10 mg/kg, p.o. for seven consecutive days was found to be the most effective dose. CONCLUSION: The experiential neuroprotective effect of capsaicin through the restoration of mitochondrial functions, antioxidant effects, and modulation of pro-inflammatory cytokines makes it a promising candidate for further drug development through clinical setup.


Subject(s)
Mitochondrial Diseases , Scopolamine , Humans , Mice , Animals , Scopolamine/adverse effects , Catalase/metabolism , Catalase/pharmacology , Catalase/therapeutic use , Capsaicin/adverse effects , Acetylcholinesterase/metabolism , Antioxidants/pharmacology , Oxidative Stress , Memory Disorders/drug therapy , Glutathione/metabolism , Cytokines , Superoxide Dismutase/metabolism , Maze Learning
6.
Neurochem Res ; 47(6): 1513-1531, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35150419

ABSTRACT

Different pathological conditions that begin with slow and progressive deformations, cause irreversible affliction by producing loss of neurons and synapses. Commonly it is referred to as 'protein misfolding' diseases or proteinopathies and comprises the latest definition of neurological disorders (ND). Protein misfolding dynamics, proteasomal dysfunction, aggregation, defective degradation, oxidative stress, free radical formation, mitochondrial dysfunctions, impaired bioenergetics, DNA damage, neuronal Golgi apparatus fragmentation, axonal transport disruption, Neurotrophins (NTFs) dysfunction, neuroinflammatory or neuroimmune processes, and neurohumoral changes are the several mechanisms that embark the pathogenesis of ND. Capsaicin (8-Methyl-N-vanillyl-6-nonenamide) one of the major phenolic components in chili peppers (Capsicum) distinctively triggers the unmyelinated C-fiber and acts on Transient Receptor Potential Vanilloid-1, which is a Ca2+ permeable, non-selective cation channel. Several studies have shown the neuroprotective role of capsaicin against oxidative damage, behavioral impairment, with 6-hydroxydopamine (6-OHDA) induced Parkinson's disease, pentylenetetrazol-induced seizures, global cerebral ischemia, and streptozotocin-induced Alzheimer's disease. Based on these lines of evidence, capsaicin can be considered as a potential constituent to develop suitable neuro-pharmacotherapeutics for the management and treatment of ND. Furthermore, exploring newer horizons and carrying out proper clinical trials would help to bring out the promising effects of capsaicin to be recommended as a neuroprotectant.


Subject(s)
Neuroprotective Agents , Parkinson Disease , Capsaicin/pharmacology , Capsaicin/therapeutic use , Humans , Neurons , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Oxidative Stress , Parkinson Disease/drug therapy
7.
Ophthalmic Epidemiol ; 29(5): 566-572, 2022 10.
Article in English | MEDLINE | ID: mdl-34505552

ABSTRACT

PURPOSE: This study was undertaken to evaluate the complication rates and visual outcomes of outreach cataract surgeries done in makeshift operating rooms. METHOD: In this retrospective study, surgical outcomes of consecutive Manual Small Incision Cataract Surgeries (MSICS) done in 11 rural camps in Nepal were compared with the results of consecutive hospital surgeries (MSICS and phacoemulsification) done by the same surgeon. Surgeries were done from September 2018 to March 2020. RESULTS: Out of 1034 study population in each group, a significantly higher number (p < .001) of camp patients (27%, n = 279) were either blind or had severe visual impairment when compared to hospital patients (18.6%, n = 192). Around 88.9% (n = 919) of cases operated in camps and 85.7% (n = 886) in the hospital achieved uncorrected visual acuity (VA) of 6/18 or better on the first postoperative day. Poor outcome (VA<6/60) was seen in 3.7% (n = 38) of cases in camps and 3.9% (n = 40) in the hospital. The difference in visual outcomes was not significant (p = .162) when the results were controlled for other associated variables. There was no significant difference (p = .126) between complication rates in camps (1.9%, n = 20) and hospital surgeries (3.5%, n = 36) when preoperative conditions were statistically controlled. No cases of endophthalmitis were reported. CONCLUSIONS: Makeshift operating rooms can be used for cataract surgeries in rural areas where no standard operating rooms are available. If appropriate patient selection criteria and standard surgical protocols are followed, good surgical outcomes can be achieved in camps by an experienced surgical team.


Subject(s)
Cataract Extraction , Cataract , Cataract Extraction/methods , Hospitals , Humans , Lens Implantation, Intraocular/methods , Nepal/epidemiology , Operating Rooms , Retrospective Studies , Treatment Outcome
8.
Curr Drug Res Rev ; 13(3): 166-171, 2021.
Article in English | MEDLINE | ID: mdl-33719951

ABSTRACT

Evidence has emerged over the last 2 decades to ascertain the proof of concepts viz. mitochondrial dysfunction, inflammation-derived oxidative damage and cytokine-induced toxicity that play a significant role in Parkinson's disease (PD). The available pharmacotherapies for PD are mainly symptomatic and typically indicate L-DOPA to restrain dopamine deficiency and its consequences. In the 21st century, the role of antibiotics has emerged at the forefront of medicines in health and human illness. There are several experimental and pre-clinical evidences that support the potential use of antibiotics as a neuroprotective agent. The astonishing effects of antibiotics and their neuroprotective properties against neurodegeneration and neuro-inflammation would be phenomenal for the development of effective therapy against PD. Antibiotics are also testified as useful in not only preventing the formation of alpha-synuclein but also acting on mitochondrial dysfunction and neuro-inflammation. Thus, the possible therapy with antibiotics in PD would impact both pathways leading to neuronal cell death in substantia nigra and pars compacta in the midbrain. Moreover, the antibiotic-based pharmacotherapy will open a scientific research avenue to add more to the evidence-based and rational use of antibiotics for the treatment and management of PD and other neurodegenerative disorders.


Subject(s)
Parkinson Disease , Anti-Bacterial Agents/therapeutic use , Humans , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Pars Compacta , Substantia Nigra
9.
Neurol Sci ; 41(12): 3409-3418, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33052573

ABSTRACT

First in 2002, severe acute respiratory syndrome coronavirus (SARS-CoV), second in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV), and now the third in the December 2019, emergence of tremendously pathogenic and large-scale epidemic novel coronavirus (SARS-CoV-2) has brought the worst conditions into the human inhabitants of the twenty-first century. The SARS-CoV-2 uses the resembling receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly feasts through the respiratory tract. The ACE2 receptor appearances have been also detected upon glial cells and neurons, which makes them a potential target of SARS-CoV-2 disease (COVID-19). Consequently, cells expressing ACE2, apart from lung and cardiovascular tissue, neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 systemic infection as well as its central nervous system (CNS) comorbidities. Investigation of the neurological manifestations of COVID-19 is a step towards better understanding the SARS-CoV-2 infections, inhibiting the additional spread and treating patients affected by this pandemic. In this concern, more clinical examinations for CNS involvement of SARS-CoV-2 are warranted. In this article, we have reviewed the neurological characteristic features of COVID-19 patients, latent neurotropic mechanisms of SARS-CoV-2 involvement in the comorbidity associated with CNS disorders, and neurological manifestations associated with COVID-19. Therefore, in the perspective of COVID-19 pandemic, clinicians and healthcare workers should be aware of a wide spectrum of neurological manifestations associated with COVID-19 along with their signs and symptoms for initial diagnosis and isolation of the patients.


Subject(s)
Central Nervous System Diseases/epidemiology , Central Nervous System Diseases/virology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Comorbidity , Humans , Pandemics , SARS-CoV-2
10.
Mol Immunol ; 82: 104-113, 2017 02.
Article in English | MEDLINE | ID: mdl-28064069

ABSTRACT

In the present study, the efficacy of Leishmania donovani protein disulfide isomerase (LdPDI) as a DNA vaccine was evaluated in BALB/C mice. Mice immunized with the LdPDI-DNA construct were found to be the most immuno-reactive, as the construct induced higher T-cell proliferation. The increased T-cell proliferation was associated with a substantial rise in Th1 and Th17+ CD4 cell response and triggered a higher proportion of CD8+ T cells for the release of interferon-gamma along with a reduced splenic parasite load on Days20 and 60 post challenge (PC). Furthermore, the vaccine construct triggered increased interferon (IFN)-γ, interleukin(IL)-17A, and IL-22 release accompanied by decreased extracellular signal-regulated kinases (ERK) 1/2 signaling and increased mitogen-activated protein kinase (MAPK) signaling coinciding with an increase in the amount of nitrite and reactive oxygen species (ROS)in vaccinating the splenocyts. We summarize from our data that the PDI-DNA construct of Leishmania donovani has the potential to elicit protective immunity through the pro-inflammatory cytokines of CD8+ and CD4+(Th1 and Th17) following an intervention in the downstream signaling event of ERK1/2 (probably through p38MAPK signaling). Therefore, the study suggests a new control against visceral leishmaniasis in the future.


Subject(s)
Leishmaniasis Vaccines/immunology , Leishmaniasis, Visceral/immunology , Protein Disulfide-Isomerases/immunology , Protozoan Proteins/immunology , Animals , Blotting, Western , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Leishmania donovani , Male , Mice , Mice, Inbred BALB C , Signal Transduction/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Vaccines, DNA/immunology
11.
Indian J Med Res ; 146(6): 780-787, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29664038

ABSTRACT

BACKGROUND & OBJECTIVES: The existing antileishmanial drugs for complete cure of visceral leishmaniasis (kala-azar) are limited. The available drugs are either toxic or less effective leading to disease relapse or conversion to post-kala-azar dermal leishmaniasis. Several herbal extracts have been shown to have antileishmanial activity, but a herbal drug may not always be safe. In the present study, the extract of Cedrus deodara leaves has been standardized and tested for immunomodulatory antileishmanial activities. METHODS: The extracts of C. deodara leaves with different solvents such as benzene, chloroform, ethyl acetate and methanol were made by soxhlation process. Solvents were removed under reduced pressure and temperature using rotary evaporator. The antileishmanial bioassay test was performed with in vitro maintained parasites. Immunomodulatory activity of different extracts was tested by flow cytometry. Standardization of the effective fraction was performed with Linalool as a marker compound through reverse-phase high-performance liquid chromatography. RESULTS: The extract with the use of benzene solvent showed strong antileishmanial activities within a dose 25-200 µg/ml culture with non-significant haemolytic activities and significant immunomodulant activities against the host cells. Linalool was found to be 1.29 per cent in the effective extract of C. deodara. INTERPRETATION & CONCLUSIONS: The antileishmanial activity of C. deodara, as assessed by bioassay testing on. LEISHMANIA DONOVANI: parasites and immunomodulatory effect of benzene extract of leaves on host cells indicated that it might be a potential new safe therapeutic target to cure the visceral leishmaniasis.


Subject(s)
Antiprotozoal Agents/pharmacology , Cedrus/chemistry , Leishmaniasis, Visceral/drug therapy , Plant Extracts/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Antiprotozoal Agents/chemistry , Humans , Leishmania donovani/drug effects , Leishmania donovani/pathogenicity , Leishmaniasis, Visceral/epidemiology , Leishmaniasis, Visceral/parasitology , Plant Extracts/chemistry , Plant Leaves/chemistry
12.
Pharm Biol ; 54(9): 1528-38, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26810454

ABSTRACT

Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders. Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats. Materials and methods Streptozotocin-induced diabetic Charles Foster albino rats treated orally with a hydro-methanolic A. paniculata leaf extract (50, 100 and 200 mg/kg/day), or with pure andrographolide (15, 30 and 60 mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed. Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content. Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted.


Subject(s)
Andrographis , Behavior, Animal/drug effects , Brain/drug effects , Cholinesterase Inhibitors/pharmacology , Cognition Disorders/prevention & control , Cognition/drug effects , Diabetes Mellitus, Experimental/drug therapy , Diterpenes/pharmacology , Hypoglycemic Agents/pharmacology , Nootropic Agents/pharmacology , Plant Extracts/pharmacology , Acetylcholinesterase/metabolism , Andrographis/chemistry , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Blood Glucose/drug effects , Blood Glucose/metabolism , Brain/enzymology , Brain/physiopathology , Catalase/metabolism , Cholinesterase Inhibitors/isolation & purification , Cognition Disorders/chemically induced , Cognition Disorders/enzymology , Cognition Disorders/psychology , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , GPI-Linked Proteins/antagonists & inhibitors , GPI-Linked Proteins/metabolism , Hypoglycemic Agents/isolation & purification , Insulin/blood , Lipid Peroxidation/drug effects , Male , Maze Learning/drug effects , Methanol/chemistry , Nootropic Agents/isolation & purification , Oxidative Stress/drug effects , Phytotherapy , Plant Extracts/isolation & purification , Plant Leaves , Plants, Medicinal , Rats , Solvents/chemistry , Streptozocin , Superoxide Dismutase/metabolism , Time Factors
13.
J Tradit Complement Med ; 5(1): 42-50, 2015 Jan.
Article in English | MEDLINE | ID: mdl-26151008

ABSTRACT

Andrographolide is a major bioactive secondary plant metabolite isolated Andrographis paniculata (Burm. F.) Wall. Ex. Nees. ( chuan xin lián), a well-known traditionally used medicinal herb. The aim of the study was to pharmacologically evaluate the beneficial effect of andrographolide on stress-induced thermoregulatory and other physiological responses in mice. A stress-induced hyperthermia test was conducted in mice. The test agents were orally administered once daily for 11 consecutive days, and treatment effects on body weight changes, basal rectal temperature, and foot-shock-triggered hyperthermic responses were quantified on Day 1, Day 5, Day 7, and Day 10 of the experiments. Pentobarbital-induced hypnosis was quantified on the 11(th) day of treatment. Observations made during a pilot dose finding experiment revealed that, like A. paniculata extracts, pure andrographolide also possess adaptogenic properties. Observed dose-dependent efficacies of 3 mg/kg/d, 10 mg/kg/d, and 30 mg/kg/d andrographolide in the pilot experiment were reconfirmed by conducting two further analogous experiments using separate groups of either male or female mice. In these confirmatory experiments, efficacies of andrographolide were compared with that of 5 mg/kg/d oral doses of the standard anxiolytic diazepam. Significantly reduced body weights and elevated core temperatures of the three vehicle-treated control groups observed on the 5(th) day and subsequent observational days were completely absent even in the groups treated with the lowest andrographolide dose (3 mg/kg/d) or diazepam (5 mg/kg/d). Benzodiazepine-like potentiation of pentobarbital hypnosis was observed in andrographolide-treated animals. These observations reveal that andrographolide is functionally a diazepam-like desensitizer of biological mechanisms, and processes involved in stress trigger thermoregulatory and other physiological responses.

14.
Cell Mol Neurobiol ; 34(8): 1111-21, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25035059

ABSTRACT

This study was designed to experimentally verify the possibility that Andrographis paniculata could be another medicinal herb potentially useful for prevention of diverse spectrums of pathologies commonly associated with chronic unavoidable environmental stress, and whether andrographolide could as well be its quantitatively major bioactive secondary metabolite. Preventive effects of 21 daily oral 50, 100 and 200 mg/kg doses of a therapeutically used extract of the plant (AP) and 30 and 60 mg/kg/day of pure andrographolide were compared in rats subjected to 1-h daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, gastric ulcer, adrenal and spleen weights, and depressive state and sexual behavior in male rats were quantified. Other parameters quantified were plasma cortisol levels, and expressions of the cytokines TNF-α, IL-10 and IL-1ß in blood and brain. All observed stress-induced pathological changes were less pronounced or completely prevented by both AP and pure andrographolide. Even the lowest tested doses of AP (50 mg/kg/day) or of andrographolide (30 mg/kg/day) suppressed almost maximally the blood IL-1ß and IL-10 as well as brain TNF-α and IL-10 expressions induced by chronic stress. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both AP and andrographolide are pharmacologically polyvalent anti-stress agents, and that biological processes regulating corticosterone and cytokine homeostasis are involved in their modes of actions.


Subject(s)
Andrographis/chemistry , Diterpenes/therapeutic use , Plant Extracts/pharmacology , Protective Agents/pharmacology , Stress, Psychological/drug therapy , Adrenal Glands/drug effects , Adrenal Glands/pathology , Animals , Body Weight/drug effects , Chromatography, High Pressure Liquid , Chronic Disease , Corticosterone/blood , Cytokines/metabolism , Diterpenes/chemistry , Diterpenes/pharmacology , Learning/drug effects , Male , Organ Size/drug effects , Rats , Sexual Behavior, Animal/drug effects , Spleen/drug effects , Spleen/pathology , Stomach Ulcer/drug therapy , Stomach Ulcer/pathology , Withania/chemistry
15.
Indian J Exp Biol ; 52(6): 613-22, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24956892

ABSTRACT

The objective of the study was to evaluate for antidepressant like activity of a methanolic extract of B. juncea leaves (BJ 100, 200, and 400 mg/kg/day, po), and Imipramine (15 mg/kg/day, po) in alloxan monohydrate (120 mg/kg, ip) induced diabetic and nondiabetic rodents, using behavioural despair, learned helplessness, and tail suspension tests for antidepressants and locomotor activity test for quantifying the behavioural effects of treatments. In addition, effects of BJ treatments on brain levels of norepinephrine, serotonin and dopamine were also estimated. Enhanced depressive states, and motility were observed in diabetic animals. Antidepressant and motor function depressing effects of BJ were apparent in all behavioural tests in diabetic rats and mice only. Decreased contents of dopamine, norepinephrine and serotonin in brain of diabetic rats were also dose dependently compensated by repeated daily BJ treatments. However, brain dopamine level of BJ treated normal rats was higher than that in control nondiabetic. The results suggest that BJ could be a nutritional alternative for combating exaggerated depression commonly associated with diabetes.


Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder/drug therapy , Diabetes Mellitus, Experimental/complications , Mustard Plant , Plant Extracts/therapeutic use , Animals , Blood Glucose/drug effects , Depressive Disorder/etiology , Drug Evaluation, Preclinical , Female , Male , Mice , Mustard Plant/chemistry , Plant Leaves/chemistry , Rats
16.
Pharm Biol ; 51(10): 1304-10, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23848339

ABSTRACT

UNLABELLED: CONTEXT. Brassica juncea (BJ; Linnaeus) Czern & Coss (Brassicaceae), commonly known as Indian mustard, are enriched in redox-active polyphenols with antidiabetic activities. Diverse other health benefits of this edible plant have been described in classical Ayurvedic texts. OBJECTIVE: The reported experiments were designed to assess therapeutic potential of a methanol extract of BJ leaves for treatment of cognitive disorders associated with diabetes or caused by central cholinergic dysfunctions. MATERIALS AND METHODS: Elevated plus-maze and active- and passive-avoidance tests were used to assess anti-amnesic potentials of BJ (100, 200 and 400 mg/kg/day, p.o., for 10 days) in alloxan diabetic or scopolamine-challenged rats. Treatment effects on brain acetylcholinesterase (AChE), superoxide dismutase (SOD) and catalase (CAT) activities were quantified in behavioral tested animals. RESULTS: Anti-amnesic efficacy of all three tested BJ doses against scopolamine-induced amnesia was almost equal in all behavioral tests. Such efficacy of the extract in diabetic rats was increased always with its increasing doses. All treatments of BJ dose dependently decreased the elevated level of AChE, and significantly increased the SOD and CAT levels in brain homogenates of scopolamine-challenged and diabetic rats. Minimal effective oral daily doses of BJ in all tests were 100 mg/kg/day for 10 consecutive days. DISCUSSION AND CONCLUSION: Our observation indicates that BJ could be a therapeutic option for treatment of cognitive disorders associated with diabetes, or caused by cholinergic deficit and brain oxidative status. They also indicate that the bioactive constituents or mode of actions involved in observed effects of the extract in scopolamine-challenged or diabetic rats are most probably not the same.


Subject(s)
Amnesia/drug therapy , Behavior, Animal/drug effects , Brain/drug effects , Brassica napus , Cognition/drug effects , Diabetes Complications/drug therapy , Nootropic Agents/pharmacology , Plant Extracts/pharmacology , Acetylcholinesterase/metabolism , Amnesia/chemically induced , Amnesia/metabolism , Amnesia/physiopathology , Amnesia/psychology , Animals , Avoidance Learning/drug effects , Brain/metabolism , Brain/physiopathology , Brassica napus/chemistry , Catalase/metabolism , Diabetes Complications/chemically induced , Diabetes Complications/metabolism , Diabetes Complications/physiopathology , Diabetes Complications/psychology , Disease Models, Animal , Dose-Response Relationship, Drug , Female , GPI-Linked Proteins/metabolism , Male , Maze Learning/drug effects , Memory/drug effects , Methanol/chemistry , Nootropic Agents/chemistry , Nootropic Agents/isolation & purification , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves , Plants, Medicinal , Rats , Scopolamine , Solvents/chemistry , Superoxide Dismutase/metabolism , Time Factors
17.
Pathog Glob Health ; 106(7): 418-20, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23265614

ABSTRACT

The present study explains a novel method of Leishmania promastigotes culture decontamination. The method is based on motility of Leishmania promastigotes across agar barrier which facilitates decontamination from yeast and other non motile contamination. This is inexpensive, easy, rapid and reliable physical method and is able to save valuable isolates in culture.


Subject(s)
Fungi/isolation & purification , Leishmania/physiology , Parasitology/methods , Agar , Cell Culture Techniques/methods , Cell Separation , Humans , Leishmania/isolation & purification , Locomotion
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