Antiepileptic and Antipsychotic Effects of Ipomoea reniformis ( Convolvulaceae ) in Experimental Animals

Ipomoea reniformis Chaos is claimed in Indian traditional medical practice to be useful in the treatment of epilepsy and neurological disorders. In the present study, pretreatment effect of methanolic extract of Ipomoea reniformis on epilepsy and psychosis was evaluated in rodents using standard procedures. Besides evaluating epileptic and behavioral parameters, neurotransmitters such as Gamma-Amino Butyric Acid (GABA) in epilepsy and in psychosis dopamine, noradrenaline and serotonin contents in the rodent brain were estimated. The extract pretreatment reduced maximal electro shock; Isoniazid (INH) and Pentylenetetrazole (PTZ) induced seizures and also significantly inhibited the attenuation of brain GABA levels by INH and PTZ in mice. These results suggested that the observed beneficial effect in epilepsy may be by enhancing the GABAergic system. The test drug also inhibited the apomorphine induced climbing and stereotyped behavior and showed significantly reduced levels of brain dopamine, noradrenaline and serotonin which may be due to blocking of central dopaminergic, noradrenergic and serotonergic pathways or by enhancing the GABAergic system. The results obtained in present study suggest that the title plant possesses antiepileptic and antipsychotic activities in rodents.


Introduction
Ipomoea reniformis (IR) also called as merremia emarginata (Burm. f.) is a procumbent herb belonging to the family convolvulaceae. In India, it is commonly known as Undirkana and Mushakparni. The plant is widely distributed in India, Sri Lanka, Philippines, Malaysia, Tropical Africa and mainly grows in rainy and winter season. In India, it is found in Southern part mainly counting Chennai, and some places of Andhra Pradesh [1]. Traditionally, IR has been used to treat diverse clinical conditions ranging from pain; fever to neurological disorders [2]. IR has been claimed to be useful for inflammation, headache, fever, cough, neuralgia, rheumatism and also in liver and kidney diseases [3]. The powder of leaves is used as a snuff during epileptic seizures. Juice acts as purgative and the root is having diuretic, laxative actions and applied in the disease of the eyes and gums [4].
The plant contains various neuroprotective chemical constituents such as caffeic, p-coumaric, ferulic and sinapic acid esters. Petroleum ether extract contains fats and fixed oil while aqueous extract contains amino acids, tannins (condensed and pseudo tannins) and starch [5]. IR has been reported to possess various pharmacological actions, mainly antidiabetic [6], antiinflammatory [7], nephroprotective [8], antibacterial [9], antioxidant and antimicrobial activity [10]. Further, the principle constituents of IR such as sinapic and ferulic acids have exhibited behavioural and pharmacological

Introduction
Alzheimer's disease is a multifactorial neurodegenerative disorder affecting multiple clinical domains involving cognitive functioning, behavioral aspects, and functionalphysical skills, the causes and the progression are still not well-understood 1 . National estimates, one-third or 32% of people age 85 and older in the United States has Alzheimer's disease 2 . Charern boon and Phanasathit 3 evaluated the 62 patients who were diagnosed as having Alzheimer's disease, according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and received global Clinical Dementia Rating scale score of at least stage one. They used the Neuropsychiatric Inventory Questionnaire and the Thai Mental State Examination, the most common symptoms were apathetic, aberrant motor behavior, sleep and eating problems, agitation, aggression, euphoria and memory complaints. The pathological features that have been identified in the central nervous system in Alzheimer's disease are senile plaques and neurofibrillary tangles, oxidative and inflammatory processes, neurotransmitter disturbances, and cholinergic deficit. Thus, attempts to restore these features have been a rational target for drugs used to treat the symptoms of Alzheimer's disease. Approaches to enhance cholinergic function have included stimulation of cholinergic receptors or prolonging the availability of acetylcholine released into the neuronal synaptic cleft by inhibiting the acetylcholine hydrolysis by acetylcholinesterase 4 . Currently available treatment i.e., acetylcholinesterase inhibitors (rivastigmine, galantamine, and donepezil) and N-methyl-d-aspartate receptor antagonist (memantine) contribute minimal impact on the disease and target late aspects of the disease. These drugs decelerate the progression of the disease, provide symptomatic relief, but fail to achieve a definite cure 5 . Traditional practices of medicine, plants have been used to enhance cognitive function and to alleviate other symptoms associated with Alzheimer's disease 6-8 .

Morphological Characters
Clitoria ternatea ( growing wild and also in gardens, bearing conspicuous blue or white flowers resembling a conch-shell. The root system consists of a fairly stout taproot with few branches and many slender lateral roots. The thick horizontal root, which may grow to more than 2 m long, bears one to several purplish, glaucous, wiry stems. The leaves are pinnate, petioles 2-2.5 cm long; stipules 4 mm long, linear, acute. Leaflets 5-7, sub coriaceous, 2.5-5 by 2-3.2 cm, elliptic-oblong, obtuse or caute; stipules filiform. The flowers are solitary, deep blue to blue, mauve or sometimes white, with an orange center, very short pedicellate and 4-5 cm long. The pods are flat, linear, beaked, 6-12 cm long, 0.7-1.2 mm wide and slightly pubescent with up to 10 seeds. The seeds are yellowishbrown or blackish in color and sub-globose or oval in shape, 4.5-7.0 mm long and 3-4 mm wide 10,12 .
The major phytoconstituents found in C. ternatea are the pentacyclic triter penoids such as taraxerol and taraxerone 15 , ternatins 16,17 , alkaloids, flavonoids, saponins, tannins 18 , and anthocyanins 19,20 . In more detail, in 16  ternatea. In addition, the color of the anthocyanins is widely used as a natural food coloring, can range from deep blue to magenta depending on the pH of a surrounding 19 .

Neuropharmacological Effects
C. ternatea is reported to be a good "Medhya" (toning the brain) drug mainly used in the treatment of "Masasika roga" (mental illness). Author in 39 reported intraperitoneal administration of alcoholic extract of stem, flower, leave and fruit of C. ternatea to rats and mice, has been reported to produce sedation and diminished alertness. Taranalli  and root parts of C. ternatea at 300 and 500 mg/kg in rats in attenuating electroshock-induced amnesia, has been reported to improve memory retention, increase acetylcholine content and acetylcholinesterase activity in the different regions of the brain, viz., cerebral cortex, midbrain, medulla oblongata and cerebellum. Author in 41 studied the 50 and 100 mg/kg of C. ternatea aqueous root extract for 30 days in neonatal rat (7 days old) via behavioral tests as follows open field behavior test, passive avoidance test, and spatial learning test. The extract was significantly improved retention and spatial learning performance, indicating the memory enhancing. Author in 42 also reported the 100 mg/kg of C. ternatea aqueous root extract for 30 days in neonatal and young adult age groups of rat, significantly increased acetylcholine content in their hippocampus. It may be the neurochemical basis for their improved learning and memory. Author in 43 investigated the spectrum of activity of the methanolic extract of the aerial parts of C. ternatea on the central nervous system. They studied the effects on the cognitive behavior, anxiety, stress and convulsions induced by pentylenetetrazol and maximum electroshock in mice and rats. They also studied the effects on behavior mediated via dopamine (haloperidolinduced catalepsy), noradrenaline (clonidine-induced hypothermia), serotonin (lithium-induced head twitches) and acetylcholine (sodium nitrite-induced respiratory arrest). The results showed that the C. ternatea extract decreased time required to occupy the central platform or transfer latency in the elevated plus maze and increased discrimination index in the object recognition test, indicating nootropic activity. There was a reduction in the levels of super oxide dismutase, catalase, peroxidase and glutathione peroxidase in the liver and kidney of arthritic rats 9 . The commercial product, Perment ® , a polyherbal Ayurvedic formulation that contains equal parts of C. ternatea, Withania somnifera, A. racemosus, and B. monniera, is used clinically as mood elevators 47 . The 75 and 150 mg/kg of Perment ® predominantly exhibited antidepressant action than anxiolytic activity. Further Perment ® increased the plasma noradrenaline and serotonin levels in stressed rats but decreased adrenal corticosterone level 47 .
In conclusion, it was suggested that an increase in acetylcholine in the hippocampus may be the neurochemicals basis for improved learning and memory. The other mechanism is a neurogenic growth promoter that will increase in survival, growth and development of the newborn neurons, critical for the repair and restoration of the normal neural circuitry in various diseases. The present article reviews that C. ternatea may also be the memory booster or enhancer in any disorders related to loss of learning ability and disorders of memory as in Alzheimer's disease.

Conflict of Interests
The authors do not have any conflict of interest to declare.