Antidepressant and Cardioprotective Effects of Self-Nanoemulsifying Self-Nanosuspension Loaded with Hypericum perforatum on Post-Myocardial Infarction Depression in Rats
Heba M. A. Khalil, Dina B. Mahmoud, Riham A. El‐Shiekh, Alaa F. Bakr, Amira A. Boseila, Sally Mehanna, Reham A. Naggar, Hesham A. Eliwa
Abstract
Hypericum perforatum (HP) is characterized by potent medicinal activity. However, the poor water solubility of many HP constituents limits their therapeutic effectiveness. Self-nanoemulsifying self-nanosuspension loaded with HP (HP.SNESNS) was formulated to improve the bioefficacy of HP. It was prepared using 10% triacetin, 57% Tween 20, and 33% PEG 400 and then incorporated with HP extract (100 mg/mL). HP.SNESNS demonstrated a bimodal size distribution (258.65 ± 29.35 and 9.08 ± 0.01 nm) corresponding to nanosuspension and nanoemulsion, respectively, a zeta potential of -8.03 mV, and an enhanced dissolution profile. Compared to the unformulated HP (100 mg/kg), HP.SNESNS significantly improved cardiac functions by decreasing the serum myocardial enzymes, nitric oxide (NO), and tumor necrosis factor- α (TNF-α) as well as restoring the heart tissue's normal architecture. Furthermore, it ameliorates anxiety, depressive-like behavior, and cognitive dysfunction by decreasing brain TNF-α, elevating neurotransmitters (norepinephrine and serotonin), and brain-derived neurotrophic factor (BDNF). In addition, HP.SNESNS augmented the immunohistochemical expression of cortical and hippocampal glial fibrillary acidic protein (GFAP) levels while downregulating the cortical Bcl-2-associated X protein (Bax) expression levels. Surprisingly, these protective activities were comparable to the HP (300 mg/kg). In conclusion, HP.SNESNS (100 mg/kg) exerted antidepressant and cardioprotective activities in the post-MI depression rat model.