Enhanced Water Dispersibility of Curcumin Encapsulated in Alginate-Polysorbate 80 Nano Particles and Bioavailability in Healthy Human Volunteers.

BACKGROUND: The turmeric (Curcuma longa) plant, a perennial herb of the ginger family, is an agronomic crop in the south and southeast tropical Asia. Turmeric an Indian yellow gold and universal spice is described in Ayurveda, an ancient treatise on longevity and quality life for the treatment of various inflammatory disorders. The oral bioavailability of curcumin is low due to poor aqueous solubility, alkaline instability and speedy elimination. OBJECTIVE: The present study is designed to prepare alginate polysorbate 80 nanoparticles to enhance aqueous solubility/dispersibility, hence bioavailability. METHOD: Curcumin-loaded alginate - polysorbate 80 nanoparticles were prepared by ionotropic gelation technique. RESULTS: The optimized nano particles exhibited higher encapsulation efficiency (95%), particle size of 383 nm and Zeta potential of +200 mV. Formulations exhibited very low dissolution in Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), but the major portion released in SCF which is attributed to the digestibility of alginate in Simulated Colonic Fluid (SCF) under the influence of colonic micro flora. FTIR and DSC observations revealed the successful entrapment of curcumin in alginate polysorbate-80 nanoparticles. The nanoparticles were more spherical, discrete and homogeneous. In healthy human volunteers, the oral bioavailability (AUC) of curcumin increased 5-fold after the consumption of curcumin nanosuspension compared to curcumin suspension. Maximum plasma concentration Cmax- 636 ± 122 ng/ml was observed at tmax- 2h for nanosuspension, whereas Cmax-87.7 ± 17.9ng/ml at tmax- 4h for suspension. CONCLUSION: Curcumin-loaded alginate - polysorbate 80 nanoparticles prepared by ionotropic gelation method, successfully entrapped curcumin. Both curcumin suspension and curcumin nanosuspension were safe and well tolerated and may thus be useful in the prevention or treatment of various inflammatory diseases of mankind.

Cerebroprotective effect of isolated harmine alkaloids extracts of seeds of Peganum harmala L. on sodium nitrite-induced hypoxia and ethanol-induced neurodegeneration in young mice.

The aim of the study was to isolate the harmine alkaloids from the seeds of Peganum harmala (TAPH) and its cerebroprotective effect on cognitive deficit mice. The tested doses of TAPH were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models. The TAPH was found to be non-neurotoxic and Psychoactive by preventing the motor impairment and increasing the locomotion activity of animals in Rota rod and Actophotometer respectively. TAPH (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. In Elevated Plus Maze (EPM) and Passive Shock Avoidance paradigm (PSA) the TAPH shown improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transverse Latency Time (TLT) and increasing the Step Down Latency (SDL), respectively in dose dependent manner. The results were well supported by biochemical parameters, by inhibiting the Acetylcholinestrase (p < 0.01) activity, increasing the GSH (p < 0.001) level and decreasing the TBARS (p < 0.001) level of whole brain. Moreover TAPH has shown the significant Monoamine oxidase-A (MAO-A) inhibition action (p < 0.001), hence it reduces the metabolism of epinephrine, 5-HT and other monoamines and enhances the action of these neurotransmitters indirectly; this adrenergic system plays an important role in learning and memory. Further, TAPH (5 mg kg(-1)) protect the DNA fragmentation of frontotemporal cortex of the brain from hypoxic effect induced by Sodium nitrite in Gel Electrophoresis studies. The results were comparable to their respective standards. Hence, harmine alkaloids are potential enough to utilize in the management of Neurodegenerative disorders of the type Alzheimer's diseases.

Neuropharmacological effect of Mangiferin on brain cholinesterase and brain biogenic amines in the management of Alzheimer's disease.

The present study was conducted to evaluate the neuropharmacological effect of Mangiferin on brain cholinesterase and brain biogenic amines along with its antioxidant status. Scopolamine and natural aging were employed as an experimental amnesia inducing agents. The tested dose of Mangiferin (40, 20 and 10 mg/kg) significantly improved the learning ability and retention of learned memory in Elevated plus Maze and Passive Shock Avoidance exteroceptive behavioural models. Pre-treatment with Mangiferin restored increased whole brain acetylcholinestrease, lipid peroxidation and reduced glutathione due to scopolamine and natural aging. Whole brain increased dopamine and nor-adrenaline content in brain in the inducing groups were reversed by tested doses of Mangiferin insignificantly. Moreover the cerebroprotective effect of Mangiferin was well supported by photomicrographs of Hippocampus of brain, where as severity of cell damage, number of pyknotic black neurons, formation of karyorrhexis, karyolysis and number of neuronal cell death were less comparative to scopolamine group. The observed effects of Mangiferin claim that it would be worthwhile to utilize in the treatment of Alzheimer's disease.

Protective effect of menthol on ß-amyloid peptide induced cognitive deficits in mice.

Cognitive impairment is a multidimensional concept that subsumes the attention and concentration, learning and memory, problem-solving ability, visuospatial abilities, mental flexibility, psychomotor efficiency and manual dexterity. The intrinsic mechanisms of the behavioural effects may involve neuronal damage in the brain structure. A lower concentration of glutamate receptor co-agonists in the striatum indicates the general malfunction of the brain glutamatergic system. It is suggested that a selective decrease in hippocampal glutamate concentration may account for deterioration in learning and memory process, considering the important role of this neurotransmitter in the cognitive functions. Nootropic agents like piracetam and anticholinesterase inhibitors are commonly used for improving memory, mood and behaviours. The present study was undertaken to assess the nootropic potential of menthol on learning and memory employing exteroceptive and interoceptive behavioral model in young and aged mice. To delineate the mechanism by which menthol decreases cognitive impairment and protect the brain, various biochemical parameters such as brain glutamate, glycine, glutathione and thiobarbituric acid reactive substances were determined. Menthol produced significant improvement in learning and memory. Menthol exhibited excellent antioxidant effect and maintain glutamate concentration in various region of the mouse brain for management of preliminary symptoms of memory impairment.

Antiamnesic evaluation of C. phlomidis Linn. bark extract in mice / Avaliação da atividade antiamnésica da casca de C. phlomidis Linn. em camundongos

Clerodendron phlomidis Linn. (Verbenaceae) is known as Agnimantha in sanskrit. Bark of the plant is used in treating various nervous disorders. In the present study C. phlomidis was investigated for its potential as a nootropic agent in mice. The aqueous extract of the C. phlomidis (100 and 200 mg/kg, p.o.) was administered for 6 successive days to both young and aged mice. Exteroceptive behavioral models such as elevated plus maze and passive avoidance paradigm were employed to evaluate short term and long term memory respectively. Scopolamine (0.4 mg/kg, i.p.), diazepam (1 mg/kg, i.p.) were employed to induce amnesia in mice. To delineate the mechanism by which C. phlomidis exerts nootropic action, its effect on brain acetyl cholinesterase levels were determined. Piracetam (200 mg/kg, i.p.) was used as a standard nootropic agent. Pretreatment with C. phlomidis (100 and 200 mg/kg, p.o.) for 6 successive days significantly improved learning and memory in mice. It reversed the amnesia induced by scopolamine, diazepam and natural ageing. It also decreased the acetyl cholinesterase levels in the whole brain. The bark of C. phlomidis can be of enormous use in the management of treatment of cognitive disorders such as amnesia and Alzheimer's disease.

Clerodendron phlomidis Linn. (Verbenaceae) é conhecida como Agnimantha em sânscrito. A casca da planta é utilizada no tratamento de várias disfunções neurológicas. No presente estudo, C. phlomidis foi investigada pelo seu potencial como agente nootrópico em camundongos. O extrato aquoso de C. phlomidis (100 e 200 mg/kg, p.o.) foi administrado por seis dias consecutivos tanto para camundongos jovens quanto para idosos. Modelos comportamentais exteroceptivos, tais como labirinto em cruz elevada e paradigma de esquiva passiva foram empregados para avaliar memória recente e tardia, respectivamente. Escopolamina (0,4 mg/kg i.p.), diazepam (1 mg/kg i.p.) foram empregados para induzir amnésia em camundongos. A fim de delinear o mecanismo pelo qual C. phlomidis exerce ação nootrópica, determinaram-se seus efeitos nos níveis cerebrais de acetilcolinesterase. Utilizau-se piracetam (200 mg/kg i.p.) como nootrópico padrão. O pré-tratamento com C. phlomidis (100 e 200 mg/kg, p.o.) por seis dias sucessivos melhorou, significativamente, o aprendizado e a memória em camundongos. Ela reverteu a amnésia induzida por escopolamina, diazepam e pelo envelhecimento normal. Também, diminuíram-se os níveis de acetilcolinesteraseem todo o cérebro. A casca de C. phlomidis pode ser de grande uso no tratamento de disfunções cognitivas, como amnésia e doença de Alzheimer.

Hepatoprotective and antioxidant effects of Argyreia speciosa in rats.

The present study has been designed to evaluate the liver protective and in-vivo antioxidant role of Ethanolic extract (EtAS) and Ethyl acetate extract (EAAS) of roots of Argyreia speciosa, an important 'rasayana' herb in Indian System of medicine, in CCl(4)-induced hepatotoxicity and oxidative stress in rats. Animals were treated with EtAS and EAAS at doses of 200 mg and 400 mg/kg body weight p.o. along with CCl(4) (0.7 ml/kg in olive oil, 1:1 v/v i.p. on every alternate days) for seven days. Serum biochemical parameters such as SGOT, SGPT, ALP, cholesterol, total and direct bilirubin were determined. Antioxidant status in liver was determined by measuring the activities of Super oxide dismutase (SOD), catalase and peroxidase. Histopathological study of isolated liver specimens was also carried out to know the protection offered by the extracts. There was a significant rise in the levels of serum GOT, GPT, and ALP and other biochemical parameters, decrease in the levels of SOD, catalase and peroxidase after administration of CCl(4). Suspensions of EtAS and EAAS (200 and 400 mg/kg) successfully prevented the alterations of these effects in rats (p< 0.001). Histopathological examination demonstrated that CCl(4) treated group induces ballooning degeneration and centrilobular necrosis. Groups treated with EtAS and EAAS showed recovery on ballooning degeneration and centrolobular bridging necrosis was occasionally present. Data also showed that these extracts possessed strong antioxidant activity, and were comparable to Silymarin, a well known liver protecting herbal formulation.

Evaluation of the antiamnesic effects of Phyllanthus amarus in mice / Evaluación de los efectos antiamnésicos de Phyllanthus amarus en ratones

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by a gradual decline in memory. Phyllanhus amarus is commonly known as bhumi amla in India and is traditionally used since centuries in ayurveda medicine. The present study was undertaken to investigate the effects of Phyllanhus amarus (PA) on cognitive functions and brain cholinesterase activity in mice. Elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (50, 100 and 200 mg/kg, p.o.) of aqueous extract of PA were administered for 8 successive days to both young and aged mice. PA (50, 100 and 200 mg/kg) produced a dose-dependent improvement in memory scores of young and older mice. PA also reversed successfully the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, brain acetyl cholinesterase activity was also reduced. The underlying mechanism of action for the observed nootropic effect may be attributed to pro-cholinergic activity exhibited by PA in the present study. Therefore, it would be worthwhile to explore the therapeutic potential of PA in the management of patients with cognitive disorders.

La enfermedad de Alzheimer es un desorden neuro-degenerativo progresivo que se caracteriza por una disminución gradual de la memoria. El Phyllanhus amarus (PA), se conoce comúnmente como bhumi amla en la India, y tradicionalmente se ha usado durante siglos en la medicina ayurvédica con diversas indicaciones. Este estudio se hizo para investigar los efectos del PA en las funciones cognitivas y en la actividad de la colinesterasa cerebral. Se emplearon las pruebas de laberinto complejo y el paradigma de evitación pasiva a fin de evaluar los parámetros de memoria y aprendizaje. Se administraron tres dosis (50, 100 y 200 mg/kg vía oral) de extracto acuoso de PA durante 8 días sucesivos, tanto a ratones jóvenes como adultos. El PA (50, 100 y 200 mg/kg) produjo una mejoría que depende de la dosis en los puntajes de memoria en los ratones jóvenes y en los adultos. EL PA también revirtió con éxito la amnesia inducida por escopolamina (0.4 mg/kg, i.p.) y diazepam (1 mg/kg, i.p.). Es de interés anotar que asimismo disminuyó la actividad de la acetil colinesterasa cerebral. El mecanismo de acción subyacente para el efecto nootrópico observado se puede atribuir a la actividad pro-colinesterasa demostrada en el presente estudio. Por tanto, se justificaría explorar el potencial terapéutico del PA en el manejo de pacientes con desórdenes cognitivos.

Antiamnesic effects of Desmodium gangeticum in mice.

Dementia is a mental disorder characterized by loss of intellectual ability sufficiently severe enough to interfere with one's occupational or social activities. Desmodium gangeticum commonly known as Salparni, is widely used in ayurveda for the treatment of neurological disorders. The present work was designed to assess the potential of aqueous extract of D. gangeticum (DG) as a nootropic agent in mice. DG (50, 100 and 200 mg/kg, p.o.) was administered for 7 successive days to both young and older mice. Exteroceptive behavioral models such as elevated plus maze and passive avoidance paradigm were employed to evaluate learning and memory. Scopolamine (0.4 mg/kg, i.p.) induced amnesia and ageing induced amnesia were the interoceptive behavioral models. To delineate the mechanism by which DG exerts nootropic activity, the effect of DG on whole brain AChE activity was also assessed. Piracetam (200 mg/kg, i.p.) was used as a standard nootropic agent. Pretreatment with DG (50, 100 and 200 mg/kg p.o.) for seven successive days significantly improved learning and memory in mice and reversed the amnesia induced by both, scopolamine (0.4 mg/kg, i.p.) and natural ageing. DG also decreased whole brain acetyl cholinesterase activity. Hence, D. gangeticum appears to be a promising candidate for improving memory and it would be worthwhile to explore the potential of this plant in the management of dementia and Alzheimer disease.

Cholinergic basis of memory-strengthening effect of Foeniculum vulgare Linn.

Alzheimer's disease is a neurodegenerative disorder associated with a decline in cognitive abilities. Dementia is one of the age-related mental problems and a characteristic symptom of Alzheimer's disease. Nootropic agents are used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of Foeniculum vulgare Linn. extract as a nootropic and anticholinesterase agent in mice. Methanolic extract of the whole plant of F. vulgare Linn. administered for eight successive days ameliorated the amnesic effect of scopolamine (0.4 mg/kg) and aging- induced memory deficits in mice. The passive avoidance paradigm served as the exteroceptive behavioral model for assessing memory. F. vulgare extract increased step-down latency and acetylcholinesterase inhibition in mice significantly. Hence, F. vulgare can be employed in treatment of cognitive disorders such as dementia and Alzheimer's disease.

Nardostachys jatamansi improves learning and memory in mice.

Cure of cognitive disorders such as amnesia, attention deficit, and Alzheimer's disease is still far from being realized in the field of medicine. Nootropic agents such as piracetam, aniracetam, and choline esterase inhibitors like donepezil are being used for improving memory, mood, and behavior, but the resulting side effects associated with these agents have made their applicability limited. In Ayurveda, the roots of Nardostachys jatamansi have been clinically employed for their anti-ischemic, antioxidant, anticonvulsant, and neuroprotective activities. The present study was undertaken to assess the potential of N. jatmansi as a memory enhancer. The elevated plus maze and the passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (50, 100, and 200 mg/kg, p.o.) of an ethanolic extract of N. jatamansi were administered for 8 successive days to both young and aged mice. The 200 mg/kg dose of N. jatmansi ethanolic extract significantly improved learning and memory in young mice and also reversed the amnesia induced by diazepam (1 mg/kg, i.p.) and scopolamine (0.4 mg/kg, i.p.). Furthermore, it also reversed aging-induced amnesia due to natural aging of mice. As scopolamine-induced amnesia was reversed, it is possible that the memory improvement may be because of facilitation of cholinergic transmission in the brain. Hence, N. jatmansi might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly persons. The underlying mechanism of action can be attributed to its antioxidant property.

Brahmi rasayana improves learning and memory in mice.

Cure of cognitive disorders such as amnesia, attention deficit and Alzheimer's disease is still a nightmare in the field of medicine. Nootropic agents such as piracetam, aniracetam and choline esterase inhibitors like Donepezil are being used to improve memory, mood and behavior, but the resulting side effects associated with these agents have made their use limited. The present study was undertaken to assess the potential of Brahmi rasayana (BR) as a memory enhancer. BR (100 and 200 mg kg(-1) p.o.) was administered for eight successive days to both young and aged mice. Elevated plus maze and passive-avoidance paradigm were employed to evaluate learning and memory parameters. Scopolamine (0.4 mg kg(-1) i.p.) was used to induce amnesia in mice. The effect of BR on whole brain AChE activity was also assessed. Piracetam (200 mg kg(-1) i.p.) was used as a standard nootropic agent. BR significantly improved learning and memory in young mice and reversed the amnesia induced by both scopolamine (0.4 mg kg(-1) i.p.) and natural aging. BR significantly decreased whole brain acetyl cholinesterase activity. BR might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly.

Evaluation of nootropic potential of Ocimum sanctum Linn. in mice.

Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.