Linalyl acetate restores endothelial dysfunction and hemodynamic alterations in diabetic rats exposed to chronic immobilization stress

Abstract

Although stress is one of the risk factors of diabetes, few studies have assessed the effects of stress on diabetic rats. This study, therefore, analyzed differences in cardiovascular-related factors among control, nonstressed diabetic, and stressed diabetic rats as well as assessed the effects of linalyl acetate (LA) on stressed diabetic rats. Male Sprague-Dawley rats were subjected to immobilization stress throughout the experimental period, and diabetes was induced on day 15 by a single injection of streptozotocin. After confirming the induction of diabetes, stressed diabetic rats were administered LA (10 or 100 mg/kg) or metformin (500 mg/kg) for the last 7 days. Compared with nonstressed diabetic rats, stressed diabetic rats had significantly lower body weight, body fat percentage, ACh-induced vasorelaxation, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and NF-κB expression as well as increased serum nitrite concentration. Although metformin increased serum insulin concentration significantly, 100 mg/kg LA showed only an increasing tendency. However, treatment with 100 mg/kg LA not only reduced serum glucose and NF-κB expression, but also restored ACh-induced vasorelaxation, SBP, DBP, HR, AMP-activated protein kinase expression, and serum nitrite almost to control levels. Importantly, 100 mg/kg LA was more effective than metformin in ameliorating serum glucose, endothelial nitric oxide synthase expression, HR, and serum nitrite. These findings suggest that chronic stress can aggravate endothelial dysfunction and hemodynamic alterations in diabetes and that LA may have potent therapeutic efficacy in diabetic patients with cardiovascular disease complications or chronic stress. NEW & NOTEWORTHY To our knowledge, this is the first study to assess the effects of linalyl acetate (LA) on cardiovascular-related factors in diabetic rats exposed to chronic stress. Treatment with LA restored acetylcholine-induced vasorelaxation, blood pressure, heart rate, and AMP-activated protein kinase and serum nitrite levels. The present results suggest that LA may have potent therapeutic efficacy in diabetic patients with complications of cardiovascular disease or chronic stress.

Influence of Xiaoyaosan on depressive-like behaviors in chronic stress-depressed rats through regulating tryptophan metabolism in hippocampus

“…The purpose of this study is to explore the pathogenesis of depression and the effect of Xiaoyaosan on the tryptophan metabolism, which was responsible for the increase in the synthesis and function of 5-HT. Immobilization stress, as a significant stress measure, has been widely applied in various animal experiments 26,27. The CIS-induced model, to a certain extent, simulates the state of depression in clinic 28,29.…”

Prophylactic Application of Lavandula Angustifolia Mill. Oil and Its Active Component Linalyl Acetate Alleviate Comorbidity and Exacerbation Risk in Rats With Collagen-Induced Arthritis Accompanied by Chronic Nicotine-Induced Hypertension.

“…In addition, treatments to prevent or reverse muscle atrophy have focused on IGF-1-associated muscle anabolic pathways [35]. Vasodilation following linalyl acetate associated maintenance of vascular endothelium supports results showing that linalyl acetate preserves normotensive levels of diastolic and systolic BP [20]. Linalyl acetate has also been shown to regulate intracellular Ca 2+ levels in vascular endothelial cells and smooth muscle cells, suggesting that the antihypertensive effects of linalyl acetate are associated with vasomotor enhancement [36].…”

“…In addition, lavender oil has possibility of preventing cardiovascular disease based on anti-diabetic [14] and antithrombotic activities [15]. Linalyl acetate, a volatile and low toxicity compound contained in citrus fruits, is the main component of lavender oil [16] Linalyl acetate has shown anti-in ammatory effects in vitro [17] and in vivo [18], as well as anti-hypertensive [19], anti-diabetic [20] and anti-stress [21] effects with the ability to prevent vascular endothelium dysfunction [18]. These pharmacological properties suggested that lavender and linalyl acetate could have preventive effects in our rat model of RA with chronic nicotine-induced HTN.…”

Effects of Terpenes and Terpenoids of Natural Occurrence in Essential Oils on Vascular Smooth Muscle and on Systemic Blood Pressure: Pharmacological Studies and Perspective of Therapeutic Use

“…It was reported that diabetic animals exposed to chronic stress showed a reduction in endothelial function, changes in SBP and HR. LA (100 mg/kg) was able to revert these parameters to close to control values [87].…”