Prevention of sex-specific olanzapine-induced hyperphagia and weight gain in Drosophila melanogaster by treatment with Elecampane (Inula helenium L.)

Rationale . Despite the high clinical efficacy of the atypical antipsychotic drug olanzapine, its use is limited by serious metabolic side effects, including hyperphagia, weight gain, obesity, dyslipidemia, and insulin resistance. The aim . To study the effect of Inula helenium L. extract on the development of metabolic side effects induced by the atypical antipsychotic drug olanzapine using the Drosophila melanogaster model. Materials and methods . Male and female Drosophila melanogaster were maintained on standard medium supplemented with olanzapine (1 pg/ml) and/or Inula helenium L. extract (50 pg/ml) for 7 days. Food seeking/preference behavior was determined using the geotaxis behavioral test. The body weight of individual flies was determined using an analytical balance. Results . Olanzapine induced marked hyperphagia and weight gain, especially in males (~90 % increase in body weight). Addition of Inula helenium L. extract together with olanzapine completely prevented olanzapine-induced hyperphagia and weight gain in males; in females, the blocking effect was not observed. Administration of the extract alone had no effect on behavioral and morphometric parameters. Conclusion . Inula helenium L. extract exhibits protective properties against the metabolic side effects of olanzapine in a gender-specific manner, making it a promising candidate for the development of adjuvant agents in antipsychotic therapy. The obtained results demonstrate for the first time in an invertebrate model the potential of phytoextracts to modulate the metabolic side effects of drugs.