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Stress is an emerging and inevitable entity. Stress causes anxiety, depression, imbalance of homeostasis, hormone imbalance, and sleep disturbances that are closely related to the onset of metabolic syndrome. The objective of this study was to investigate effects of Ocimum sanctum extract (TZ-OSE) on anti-anxiety, anti-stress, and control of physiological changes due to sleep disturbance in a rat model with restraint stress and sleep disorder induced. After inducing the rat model with restraint stress, three behavioral tests were performed and blood cortisol concentration was determined. In Elevated plus maze test, the test substance TZ-OSE at dose of 200 mg/kg showed the best effect in increasing time that stayed on the open arms. In tail suspension test (TST) and forced swimming test (FST), TZ-OSE significantly reduced immobility duration time (IMT). TZ-OSE also decreased plasma cortisol concentration. In the model after inducing sleep disturbance, ELISA, Western blotting, and Immuno-histochemistry (IHC) were conducted. TZ-OSE treatment decreased plasma cortisol, norepinephrine, glucose, and acylated ghrelin concentrations in the rat model with sleep disorders induced. Decreases of melatonin and leptin levels in the plasma of the rat model with sleep disorders induced were increased by TZ-OSE treatment. Finally, TZ-OSE treatment decreased metabolism-related markers (p-AMPK, Glut-4, p-ACC) in stomach and muscle tissues and decreased the expression of cortisol in adrenal gland tissues. Taken together, these results suggest that TZ-OSE can decrease anxiety, depression, and stress in vivo, regulate sleep-related factors, and control energy metabolism index factors. [ABSTRACT FROM AUTHOR]