Abstract
Geraniol (GO) potent antitumor and chemopreventive effects are attributed to its antioxidant and anti-inflammatory properties. In the current study, the potential efficacy of GO (250 mg/kg) in ameliorating metabolic syndrome (MetS) induced by fructose in drinking water was elucidated. Moreover, the effect of pioglitazone (5 and 10 mg/kg; PIO) and the possible interaction of the co-treatment of GO with PIO5 were studied in the MetS model. After 4 weeks of treatment, GO and/or PIO reduced the fasting blood glucose and the glycemic excursion in the intraperitoneal glucose tolerance test. GO and PIO5/10 restrained visceral adiposity and partly the body weight gain. The decreased level of peroxisome proliferator activated receptor (PPAR)-γ transcriptional activity in the visceral adipose tissue of MetS rats was increased by single treatment regimens. Though GO did not affect MetS-induced hyperinsulinemia, PIO5/10 lowered it. Additionally, GO and PIO5/10 suppressed glycated hemoglobin and the receptor for advanced glycated end products (RAGE). These single regimens also ameliorated hyperuricemia, the disrupted lipid profile, and the elevated systolic blood pressure evoked by MetS. The rise in serum transaminases, interleukin-1β, and tumor necrosis factor-α, as well as hepatic lipid peroxides and nitric oxide (NO) was lowered by the single treatments to different extents. Moreover, hepatic non-protein thiols, as well as serum NO and adiponectin were enhanced by single regimens. Similar effects were reached by the combination of GO with PIO5; however, a potentiative interaction was noted on fasting serum insulin level, while synergistic effects were reflected as improved insulin sensitivity, as well as reduced RAGE and triglycerides. Therefore, GO via the transcriptional activation of PPAR-γ reduces inflammation and free radical injury produced by MetS. Thereby, these effects provide novel mechanistic insights on GO management of MetS associated critical risk factors. Moreover, the co-administration of GO to PIO5 exalted the antidiabetic drug anti-MetS efficacy.
Highlights
With the global adoption of the westernized diet and increased consumption of fructose, both metabolic syndrome (MetS) and type 2 diabetes mellitus reached epidemic proportions worldwide [1,2]
Rats in GO and/or PIO groups achieved appropriate glycemic control noted by the reduced glycemic excursion in intraperitoneal glucose tolerance test (IPGTT), area under the curve of glucose, and hyperglycemia (Tables 1 and 2)
In the MetS rat model induced by fructose, an increment in HOMAIR (800%) versus reductions in both QUICK (73%) and McAuley indices (53%) were observed, effects that were controlled to different extents by all treatment regimens (Table 2)
Summary
With the global adoption of the westernized diet and increased consumption of fructose, both metabolic syndrome (MetS) and type 2 diabetes mellitus reached epidemic proportions worldwide [1,2]. A strong correlation exists between MetS and cardiovascular disease metabolic risk factors [3] This cluster includes elevated plasma glucose and blood pressure, atherogenic dyslipidemia, as well as central obesity [4]. MetS is characterized by a pro-oxidant/proinflammatory status that predisposes patients to major cardiovascular events [5,6] Evidence exists that both hyperuricemia and atherogenic dyslipidemia are contributing factors in high blood pressure to augment insulin resistance [7,8,9]. GO possesses antioxidant activity and suppresses nitroactive stress [13,14] This acyclic monoterpene alcohol is a potent antiinflammatory compound that inhibits prostaglandin E2 and tumor necrosis factor (TNF)-α [14,15,16]. The latter action verifies GO antiatherogenic effect, noticed recently by Jayachandran et al [18] in hamsters
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