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Background: Bromelain is a complex mixture of protease enzyme extract from the fruit or stem of the pineapple plant and it has a history of folk medicine use. It is known to have a wide range of biological actions and it is most commonly used as an anti-inflammatory agent, though scientists have also discovered its potential as an anticancer and antimicrobial agent, it has been reported to have positive effects on the respiratory, digestive, circulatory systems and potentially on the immune system. This study was designed to investigate the antidepressant potential of Bromelain in the chronic unpredictable stress (CUS) model of depression. Methods: We studied the antioxidant activity, and neuroprotective effect of Bromelain by analyzing the fear and anxiety behavior, antioxidants, and neurotransmitter levels, and also by analyzing the histopathological changes. Adult male Wistar albino rats were divided into 5 groups, Control; Bromelain; CUS; CUS + Bromelain, CUS + fluoxetine. Animals of the CUS group, CUS + Bromelain group, and CUS + Fluoxetine group were exposed to CUS for 30 days. Animals of the Bromelain group and CUS + Bromelain group were treated orally with 40mg/kg Bromelain throughout the period of CUS whereas, the positive control group was treated with fluoxetine. Results: Results showed a significant decrease in oxidative stress marker (lipid peroxidation), and the stress hormone cortisol, in Bromelain-treated CUS-induced depression. Bromelain treatment in CUS has also resulted in a significant increase in neurotransmitter levels, which indicates the efficacy of Bromelain to counteract the monamine neurotransmitter changes in depression by increasing their synthesis and reducing their metabolism. In addition, the antioxidant activity of Bromelain prevented oxidative stress in depressed rats. Also, hematoxylin and eosin staining of hippocampus sections has revealed that Bromelain treatment has protected the degeneration of nerve cells by chronic unpredictable stress exposure. Conclusion: This data provides evidence for the antidepressant-like action of Bromelain by preventing neurobehavioral, biochemical, and monoamine alterations.

Gut peptides are small peptides secreted by gut endocrine cells that can modulate the roles and functions of different organs through signaling. Gut peptides can also majorly impact the body’s energy homeostasis by regulating appetite and energy metabolism. The gut-brain axis (GBA) is bidirectional communication between the central nervous system (CNS) and the peripheral enteric nervous system. The regulation of appetite acts by hypothalamic neuronal activity. The complex interaction of hedonic and homeostatic factors implicates appetite regulation. In the CNS, the hypothalamus and brainstem have a dominating role in appetite regulation. The arcuate nucleus (ARC) of the hypothalamus plays a vital role in energy homeostasis, while other nuclei also play a role in appetite regulation. The gut conveys peripheral information about energy balance to the brain via gut peptides and receptors for the digestion of food. The varied gut peptides have different actions on appetite regulation.