Novel Ocimum sanctum compounds modulate stress response: Role of CRF, POMC, GR and HSP-70 in the hypothalamus and pituitary of rats

The hypothalamic-pituitary-adrenal (HPA)-axis and the monoaminergic-sympathetic nervous systems play important roles in maintaining homeostasis. Therefore, therapies targeting central stress mechanisms at the molecular level are fundamental for the development of novel treatment strategies. Ocimum sanctum (OS) is an Indian medicinal plant traditionally used for the treatment of various stress-related conditions. The underlying molecular mechanism of these novel OS compounds (Ocimarin, Ocimumoside-A and Ocimumoside-B) particularly with reference to their modulatory role on the HPA axis in terms of the changes at the mRNA and protein level of stress regulating proteins have not yet been explored. The efficacy of these OS compounds was evaluated on the acute stress (AS)- induced alterations in the CRF, POMC, GR and HSP-70 expression level in the hypothalamus and pituitary of rat. AS induced a significant increase in the expression of CRF, POMC and HSP-70 with a significant decrease in GR levels. At the protein level also similar decrease in GR and increase in HSP-70 was observed, although these changes were differential showing brain region specific responses. Pretreatment with Ocimumoside-A and B (40 mg/kg per oral) normalized most of these changes. The restoration of altered level of CRF, POMC and GR expression is correlated to their attenuating effect on stress-induced activation of HPA-axis. The expression level of HSP-70 was decreased by the pretreatment of Ocimumoside-A and B could be attributed to their role in reducing the stress-induced oxidative loads. Thus, the possible anti-stress mechanism can be speculated in terms of their pharmacological effects on the secretory activity of HPA-axis and hence lesser induction of stress. The present finding provides an insight into the molecular mechanism of OS compounds and thus highlighting their significance for pharmacological interventions in the prevention of stress-induced neurological and related disorders.