Geraniol attenuates behavioral and neurochemical impairments by inhibitions of HPA-axis and oxido-inflammatory perturbations in mice exposed to post-traumatic stress disorder.

Geraniol is an acyclic isoprenoid monoterpenoid analogue that has been shown to elicit neuroprotective functions, primarily through its ability to stimulate antioxidant and anti-inflammatory systems. An increase in inflammatory cytokines and oxidative stress exacerbate activation hypothalamic-pituitary-adrenal axis (HPA), leading to neurochemical dysfunction, which has important roles in the pathogenesis of post-traumatic disorder (PTSD), a mental health disorder characterized of post-trauma-induced intense fear. The aim of this study was to evaluate the anti-PTSD-like effects and underlying mechanisms of geraniol against single-prolonged-stress (SPS)-induced PTSD in mice. Following concomitant exposure to SPS (triple-paradigm traumatic events) and isolation for 7 days, mice (n = 9) were treated with geraniol (50 and 100 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o.) from days 8-21. Mice were assessed for behavioral changes. Neurochemical changes, inflammatory, oxido-nitrergic markers, adrenal weight, serum glucose and corticosterone concentrations were assayed. Geraniol inhibits SPS-induced anxiety- and depressive-like features as well as behavioral despair in the depression paradigms. SPS-induced locomotor and memory impairments were also abated by geraniol treatment similarly to fluoxetine. SPS-induced adrenal hypertrophy and increased blood glucose and corticosterone concentrations, were attenuated by the geraniol treatment. Elevated levels of TNF-α and IL-6, and malondialdehyde, nitrite, acetylcholinesterase enzyme were reduced by geraniol. Geraniol also increased glutathione, superoxide-dismutase, and catalase levels as well as dopamine, serotonin concentrations and GABAergic glutamic acid decarboxylase enzyme activity in the striatum, prefrontal cortex and hippocampus in the PTSD-mice relative to SPS control. In conclusion, geraniol attenuates behavioral impairments and neurochemical dysregulations by inhibitions of HPA-axis and oxido-inflammatory perturbations in mice exposed to PTSD.

Co-administration of metformin and/or glibenclamide with losartan reverse NG-nitro-l-arginine-methyl ester-streptozotocin-induced hypertensive diabetes and haemodynamic sequelae in rats.

Over the years, there have been opinions on whether to reduced blood pressure (BP) to a different levels in patients with diabetes mellitus. Hence, this study investigated the efficacy of the co-administration of losartan (angiotensin receptor blocking antihypertensive agent) with metformin and/or glibenclamide (antidiabetic agents) on hypertensive-diabetic experimental rats induced by NG-nitro-l-arginine-methyl-ester hydrochloride (l-NAME), and streptozotocin (STZ). STZ (45 mg/kg, i.p.)-induced diabetic rats combined with l-NAME (40 mg/kg, p.o.)-induced hypertension were allotted into different groups. Group 1 received distilled water (10 mL/kg) and served as normal control, group 2 comprised hypertensive diabetic rats with distilled water, groups 3-5 were hypertensive-diabetic rats but received combination treatments of losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide daily for 8 weeks, respectively. Our finding revealed no changes in the body weights, but there was a significant increase in fasting blood sugar levels in l-NAME - STZ-induced hypertensive-diabetes, which were lowered by losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide treatments. Moreover, the increased systolic-BP, mean arterial pressure but not diastolic-BP and heart rate by l-NAME + STZ were attenuated more significantly by losartan + metformin + glibenclamide between weeks 2-8 relative to hypertensive-diabetic control. l-NAME + STZ-induced elevated levels of lactate dehydrogenase and creatinine kinase, were differentially reversed by losartan + metformin, losartan + glibenclamide, and losartan + metformin + glibenclamide. However, l-NAME + STZ-induced decreased nitrite level was significantly restored by all treatments, suggesting increased nitrergic transmission. Additionally, l-NAME + STZ-induced degeneration of pancreatic islet and myocardial cells were dramatically alleviated by losartan + metformin + glibenclamide treatments. Our findings suggest hyperglycemia with raised systolic-BP should be managed with losartan combined with both metformin and glibenclamide than single combination of losartan with antidiabetics.