Abstract：
Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.
摘要：
氧化应激和炎症在糖尿病的发生发展中起重要作用。P-辛弗林,柑橘属植物的主要药理活性原生物碱，已被广泛用作减肥管理的膳食补充剂。然而,对-辛弗林对糖尿病的作用及其作用机制尚未明确阐明。在这项研究中,评价了P-辛弗林的体外抗氧化作用。数据显示，P-辛弗林治疗对DPPH具有明显的清除作用，ABTS和OH自由基显示出较高的还原能力。糖尿病小鼠是通过四氧嘧啶注射开发的，随后给予对-辛弗林以研究其体内降血糖作用。结果表明，P-辛弗林干预可明显防止四氧嘧啶引起的体重变化，器官指数,血清尿酸含量和血清肌酐含量。同时,P-synephrine的应用显着改善了血脂谱，糖尿病小鼠血清和肾脏中的超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以及谷胱甘肽（GSH）含量，降低了糖尿病小鼠血清中丙二醛（MDA）含量。进一步的分析表明，对-辛弗林治疗可改善四氧嘧啶诱导的葡萄糖耐量和胰岛素敏感性降低。此外，β-辛弗林补充改变了糖尿病小鼠肾脏和肩胛骨间棕色脂肪组织的组织病理学变化。此外,P-辛弗林通过抑制肿瘤坏死因子-α（TNF-α）抑制肾脏炎症，白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)基因表达水平,以及CD45表达水平。抗炎作用可能与核因子-κB（NF-κB）活化和丝裂原活化蛋白激酶（MAPK）磷酸化的调节有关。总之,P-synephrine的应用通过抑制NF-κB和MAPK途径来抑制氧化应激，从而显着改善了四氧嘧啶诱导的糖尿病。
