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Authors: OLONODE, E. T.
Keywords: Morin hydrate
Anti-stress property
Antioxidant activity
Issue Date: Aug-2018
Abstract: Stress, is an integral component of life that distorts body homeostasis. The available anti-stress drugs are often ineffective in combating its multiple effects. Adaptogens with antioxidant and neuroprotective effects are known to relieve stress. Morin hydrate (MH), a flavonoid from Morus alba with known antioxidant and neuroprotective properties has not been investigated for its anti-stress potential. The study was designed to investigate the anti-stress property of MH and its mechanisms of action in mice. Eighty male Swiss mice (22.0 ± 2.5 g) were used for acute studies: Swimming Endurance Test (SET), Anoxic Tolerance Test (ATT) and Acute Restraint Stress (ARS). The SET and ATT consisted of 5 treatment groups each (n = 5): vehicle (normal saline, 10 mg/mL), MH (5, 10, 20 mg/kg) and adaptogen (ginseng, 25 mg/kg), administered intrapertioneally. Thirty minutes later immobility time was measured in SET and convulsion latency in ATT. In ARS, thirty male mice were allotted into treatment groups I-VI (n = 5): vehicle(10 mg/mL), vehicle-stress control (10 mg/mL), MH (5, 10, 20 mg/kg) and ginseng (25 mg/kg), and treated for 7 days prior to being restrained except group 1. Thereafter, mice were assessed for anxiety and depression in Elevated-Plus Maze (EPM) and Forced-Swim Test (FST), respectively. For chronic studies, ninety male mice were used in 3 models [Chronic- Restraint Stress (CRS), Paradoxical Sleep-deprivation (PSD) and Chronic-Unpredictable Stress (CUS) and grouped, respectively as in ARS. In CRS, mice were pre-treated and restrained for 14 days, and thereafter assessed for anxiety and depression in Mice were sleep-deprived for 48 hours in PSD, and exposed to stressors for 14 days in CUS before testing for memory and anxiety behaviours using Y-maze and EPM, respectively. Brain glutathione (GSH), malondialdehyde, nitric-oxide and blood glucose were determined spectrophotometrically in ARS, CRS, PSD and CUS. Serum corticosterone, brain tumor necrosis factor-alpha (TNF-α) and interleukin-l beta were measured in CUS using ELISA. Brain nuclear factor-kB (NF-kB) and inducible nitric-oxide synthase (iNOS) expressions in CUS were measured using immunohistochemistry. Data were analysed using ANOVA at α0.05. Morin hydrate (5, 10, 20 mg/kg) significantly reduced immobility (10.8 ± 0.20, 7.04 ± 0.77, 9.16± 0.59 s against 11.9 ± 0.25 s) in SET and prolonged convulsion latency ATT (33.1 ± 1.26, 34.1 ±2.40, 34.8 ± 1.06 s against 21.9 ± 1.15 s).The MH decreased anxiety, depression-like symptoms, malondialdehyde and nitric-oxide but increased GSH in ARS and CRS. The MH reversed memory impairment (65.87 ± 3.59, 69.17 ± 6.51, I 62.0± 5.12% against 50.87 ± 2.87%) and anxiety (64.75 ± 5.36, 57.75 ± 2.95, 61.00 ± 1.68 s against 45.0 ± 1.87 s) in PSD. Also, MH increased GSH (104.6 ± 8.50, 97.3 ±6.51, 91.5 ± 7.70 µmol/g tissue against 50.22 ±1.41 µmol/g tissue) but decreased malondialdehyde (7.57± 0.25, 4.50 ± 0.13, 3.16 ± 0.22 µmol/g tissue against 8.60 ± 0.14 µmol/g tissue) and nitric-oxide (163.0 ± 8.67, 121.3 ± 6.67, 124.7± 3.33 µmol/g tissue against 338.0 ± 16.77 µmol/g tissue). The MH increased GSH concentration in CUS and ameliorated CUS-induced increases in glucose, malondialdehyde and nitric oxide Ievels compared to controls. Morin hydrate reduced corticosterone (7.93 ± 0.19, 7.18 ±0.21, 7.46 ± 0.20 ng/mL. against 8.54 ±0.14 ng/mL), TNF-α (49.19 ± 0.55, 47.60± 2.48, 35.22 ± I .77 pg/mL against 92.37± 7.90 pg/mL), and interleukin-I beta (74.45 ± 2.18. 46.45 ± 2.71 43.12 ± 1.55 pg/mL, against 98.72 ± 4.03 pg/mL). Morin hydrate reduced iNOS and NF-kB protein levels in CUS. Morin hydrate exhibited anti-stress potential via mechanisms related to inhibition of hypothalamic-pitutary-adrenal axis hyperactivation, oxidative stress and neuroinflammation.
Description: A Thesis in the Department of Pharmacology and Therapeutics, submitted to the Faculty of Basic Medical Sciences in partial fulfillment of the requirement for the Degree of Doctor of Philosophy of the University of Ibadan, Ibadan
Appears in Collections:Theses in Pharmacology and Therapeutics

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