Effect of ursolic acid on olanzapine induced weight gain in Sprague Dawley rats

Parasuraman, Subramani ; Zhen, Khor Ming; Wen, Lim Ee; Hean, Chin Kean; Balamurugan, Subramani ; Christapher, Parayil Varghese; Banik, Urmila


Antipsychotics used in the treatment of schizophrenia are known to cause weight gain. Phytoconstituents are used to manage such drug-induced weight gain. Ursolic acid is a pentacyclic triterpenoid commonly present in many herbs and fruits which are used in daily life. The effect of ursolic acid on antipsychotic-induced weight gain is not clear. Here, we investigated the effect of ursolic acid on olanzapine-induced weight gain in rats. Sprague-Dawley (SD) rats were divided into six different groups viz., normal control, olanzapine control, betahistine (10 mg/kg), and ursolic acid 10, 20 and 40 mg/kg treated groups. All the drugs were administered once daily for 28 days orally. Except for the normal control group, all other animals were treated with olanzapine 4 mg/kg intraperitoneally to induce weight gain. During the experiment, animal’s behaviour variations were monitored at regular intervals. At the end of the experiment, blood sample was collected from all the experimental animals for biochemical analysis. Part of the brain, liver, heart, lung and kidney tissues were excised from the sacrificed animals and preserved in neutral formalin for histopathological studies. Ursolic acid showed a significant reduction in olanzapine-induced body weight gain on the rats. Increase in locomotor activity was also observed with the treatment of ursolic acid. Compared to ursolic acid, betahistine showed better tolerance against olanzapine-induced body weight gain.


Antipsychotics; Depression; Schizophrenia

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