Anticonvulsant effect of Ficus religiosa: Role of serotonergic pathways

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Abstract

Ethnopharmacological relevance

Ficus religiosa (Moraceae) is reported to have numerous therapeutic utility in folk medicine. Among different biological activities on central nervous system, it has been reported to be used in ethnomedical treatment of epilepsy, which led us to further explore its anticonvulsant activity in various animal models of epilepsy.

Aim of the study

To investigate anticonvulsant activity of methanolic extract of figs of Ficus religiosa in animal models and to determine its possible anticonvulsant mechanism.

Materials and methods

Anticonvulsant activity of figs extract (25, 50 and 100 mg/kg, i.p.) was studied in seizures induced by maximum electroshock (MES), picrotoxin and pentylenetetrazol (PTZ). Cyproheptadine, a nonselective (5HT1/2) serotonin antagonist (4 mg/kg, i.p.) was used to study the reversal of protective effect of extract in the above mentioned models. Acute toxicity, neurotoxicity and potentiation of pentobarbitone induced sleep by extract was also studied.

Results

Extract showed no toxicity, potentiated pentobarbitone induced sleep and inhibited seizures induced by MES and picrotoxin in a dose dependent manner. Anticonvulsant effect of extract was comparable to clinically used antiepileptic drugs (phenytoin and diazepam). However, PTZ induced seizures were not inhibited. Animals pretreated with cyproheptadine showed inhibition of the anticonvulsant effect of extract.

Conclusions

These findings suggested that the methanolic extract of figs of Ficus religiosa had anticonvulsant activity against MES and picrotoxin induced convulsions, with no neurotoxic effect, in a dose dependent manner. Inhibition of the anticonvulsant effect of extract by cyproheptadine substantiates the involvement of serotonergic pathways for the anticonvulsant activity of extract.

Introduction

Ficus Linn being the largest genus of the family Moraceae comprises about 755 fig tree species worldwide (Van Noort et al., 2007). According to the reports of traditional healers, ficus species like Ficus schimperiana and Ficus sycomorus has been used for the treatment of epilepsy from ancient time (Mainen et al., 2005). Ficus sycomorus had shown anticonvulsant and sedative activity in animal models (Umar et al., 2003).

Ficus religiosa (Moraceae) commonly known as Bodhi tree is regarded as a sacred tree to both Hindus as well as Buddhists; it is used for medicinal as well as religious purposes in India (Kala et al., 2006). Ficus religiosa is reported to have numerous therapeutic uses in folk medicine viz.: leaf juice has been used for the treatment of asthma, cough, sexual disorders, diarrhea, haematuria, ear-ache and toothache, migraine, eye troubles, gastric problems and scabies; leaf decoction has been used as an analgesic for toothache; fruits for the treatment of asthma, other respiratory disorders and scabies; stem bark is used in gonorrhea, bleeding, paralysis, diabetes, diarrhea, bone fracture, antiseptic, astringent and antidote (Ripu and Rainer, 2006). In Ayurveda it is claimed that Ficus religiosa possesses anticonvulsant activity (Vyawahare et al., 2007). Many such reports had been validated pharmacologically for its actions on CNS viz.: different parts of Ficus religiosa showed acetyl cholinesterase inhibitory activity (Vinutha et al., 2007) and antianxiety activity (Ratnasooriya et al., 1998). Figs (fruits) of this plant contain numerous amino acids like asparagine and tyrosine in fruit edible part, alanine, threonine, tyrosine, and valine in seeds, alanine and valine in proteins (Ali and Qadry, 1987). Apart from amino acids figs of this plant has been reported to contain highest amount of serotonin (5-HT) as compare to figs of other Ficus species (Bliebtrau, 1968) and serotonergic neurotransmission is known to modulate a wide variety of experimentally induced seizures and is involved in seizure protection in various animal models of epilepsy by altering various GABAergic and glutamatergic functions (Bagdy et al., 2007). Reports, demonstrating the use of Ficus religiosa in ethnomedical treatment of epilepsy and presence of high serotonin content in its figs led us to hypothesize that figs of Ficus religiosa may possess anticonvulsant properties via modulating brain serotonin levels, which will be of clinical usefulness.

Hence, the present study was undertaken to investigate the anticonvulsant activity of methanolic extract of Ficus religiosa figs.

Section snippets

Plant material and preparation of extract

Ficus religiosa figs were collected from Botanical Garden of Guru Nanak Dev University, Amritsar, Punjab. The botanical identity of the plant material was verified and specimens were deposited at the Herbarium, Department of Botany, Punjabi University, Patiala, Punjab, for reference (vouchered no. 49371). Authenticated figs were washed with water, shade-dried, ground to a moderately coarse powder. The powdered figs were subjected to extraction by refluxing with 70% methanol (1:10, w/v) in a

Results

The optimal UV spectrum for serotonin detection was calibrated at 277 nm. The HPLC chromatogram of standard serotonin solution showed an absorption peak with a retention time of 12.563 min (Fig. 1). A similar peak was observed in the HPLC chromatogram of Ficus religiosa extract at same retention time indicating the presence of serotonin in the extract (Fig. 2).

In acute toxicity test no mortality was observed in animals treated with the extract at all doses (25, 50, 100, 250, 500 and 1000 mg/kg).

Discussion

Most of conventional antiepileptic drugs are associated with many side effects such as neurotoxic effects, cognitive deficits and teratogenic effects, which decrease their clinical utility (Trimble, 1987, Yerby, 1988, Meador et al., 1990). Recently, the search for novel pharmacotherapy from medicinal plants for neurological and psychiatric diseases has progressed significantly owing to their less side effects and better tolerability (Zhang, 2004). In the present study the anticonvulsant

Conclusions

Ficus religiosa extract increased the threshold of MES and picrotoxin induced convulsions with no neurotoxic effects, in a dose dependent manner. Inhibition of antiepileptic effect of extract with cyproheptadine pretreatment showed that the extract might be mediating its effect via modulating serotonin dependent GABAergic and/or glutamatergic neurotransmission. However, further research is warranted to determine the specific mode of its anticonvulsant activity.

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