Geraniol, alone and in combination with pioglitazone, ameliorates fructose-induced metabolic syndrome in rats via the modulation of both inflammatory and oxidative stress status.
Geraniol, alone and in combination with pioglitazone, ameliorates fructose-induced metabolic syndrome in rats via the modulation of both inflammatory and oxidative stress status.
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DOI：
10.1371/journal.pone.0117516
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Abdallah DM
中科院分区：
文献类型：
--
作者：
Ibrahim SM;El-Denshary ES;Abdallah DM
香叶醇（GO）具有抗氧化和抗炎作用，具有抗肿瘤和化学预防作用。在本研究中，阐明了GO（250 mg/kg）在改善饮用水中果糖诱导的代谢综合征（MetS）中的潜在功效。此外，在MetS模型中研究了吡格列酮（5和10 mg/kg; PIO）的作用以及GO与PIO 5联合给药的可能相互作用。治疗4周后，GO和/或PIO降低空腹血糖和腹腔葡萄糖耐量试验中的血糖波动。GO和PIO 5/10抑制内脏脂肪形成，部分抑制体重增加。MetS大鼠内脏脂肪组织中过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）-γ转录活性的降低水平通过单一治疗方案而增加。尽管GO对MetS诱导的高胰岛素血症没有影响，但PIO 5/10可降低其水平，此外，GO和PIO 5/10抑制糖化血红蛋白和晚期糖化终末产物受体（AGEs）。这些单一的方案也改善了高尿酸血症，破坏血脂谱，并升高收缩压引起的MetS。单药治疗可不同程度地降低血清转氨酶、白细胞介素1β、肿瘤坏死因子α及肝组织脂质过氧化物和一氧化氮（NO）的升高。此外，肝脏非蛋白巯基，以及血清NO和脂联素增强由单一方案。GO与PIO 5的组合达到了类似的效果;然而，在空腹血清胰岛素水平上注意到了潜在的相互作用，而协同效应反映为改善的胰岛素敏感性以及降低的甘油三酯和甘油三酯。因此，GO通过PPAR-γ的转录激活减少MetS产生的炎症和自由基损伤。因此，这些影响提供了新的机制的见解GO管理MetS相关的关键风险因素。此外，GO与PIO 5的共同施用提高了抗糖尿病药物抗MetS的功效。
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.