THE EFFECTS OF HESPERIDIN ON THE INFLAMMATORY MARKERS OF PSYCHOLOGICAL STRESS-INDUCED PTSD WISTAR RATS

Post-traumatic stress disorder (PTSD) is a psychiatric disorder characterized by depression and anxiety that arises due to an imbalance of neurotransmitters in response to excessive stress. Hesperidin (HSD) is a naturally occurring flavonoid shown to exert a variety of biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. We investigated the effects of hesperidin on the inflammatory markers of psychological stress-induced PTSD on Wistar rats. Thirty (30) adult male Wistar rats with an average of 180-220 g were randomized into 6 groups, each consisting of 5 rats. Group 1 (Normal control) received normal saline/distilled water of 1ml of 0.9% normal saline for 42days, Group 2 (negative control) received SPS only for 14 days, Group 3: receive SPS + Fluoxetine of 10mg/ (I.p injection once daily) for 14days treatment, Group 4: receive SPS + Hesperidin (Low dose) of 50mg/ (I.p injection once daily) for 14days treatment, Group 5: receive SPS + Hesperidin (Medium dose) of 100mg/ (injection once daily) for 14days treatment and Group 6: receive SPS + Hesperidin (High dose) of 200mg/ (I.p injection once daily) for 14days treatment. At the end of the experiments, the rats are fasted for 24 hours to prepare them for sacrifice on day 43. Rats for histological analysis are euthanized using 20mg/kg of ketamine (intraperitoneal). The blood serum collected via cardiac puncture, rat brain and adrenal were also investigated using enzyme-linked immunoassays (ELISAs). In this study, tumor necrotic factor (TNF) showed significantly high values in the stress only group (6.34±0.09) in comparison with the control group (7.81±0.07), the standard treatment group (fluoxetine group) showed reduced values (8.23±0.11), while the hesperidin treatment group showed fluctuating values, low dose (8.46±0.11), medium dose (8.16±0.06), high dose (8.35±0.09) with the medium dose group showing more favorable outcomes. This is in line with the findings of (Aggarwalet al 2020), who reported that TNF exert anti-inflammatory effect by activating immune cells and inducing cytokine production. The present studies showed that IL-6 showed significantly high values in stress only group (191.70±6.30) in comparison with the control group (197.24±6.17), the standard treatment group (fluoxetine group) showed values (234.45±8.27), while the hesperidin treatment group showed fluctuating values, low dose (229.40±4.84), medium dose (232.56±4.26), high dose (220.16±7.79) with medium dose group showing more favorable outcomes. This is consistent with the findings of (Hara et al. 2016), who reports that IL-6 promotes inflammation by activating immune cells and plays a crucial role in PTSD- related inflammation and immune dysfunction. Present study of interleukins-1 (IL-1) showed significantly high values in the stress only group (130.40±3.97) in comparison with the control group (134.59±3.97), the standard treatment group (fluoxetine group) showed reduced values (152.35±1.68), while the hesperidin treatment group showed fluctuating values, low dose (142.39±2.77), medium dose (148.70±0.57), high dose (148.41±091).in relation this, (Qinghuaet al, 2018) opined that IL-1 exerts its biological functions basically as a chief master regulator of inflammation via controlling a variety of innate immune processes. HSD was shown to exert antidepressant effects in rats exposed to PSTD suggesting that this natural flavonoid may be an effective medicine for PTSD.