Sugimoto Masayuki, Arai Hidenori, Tamura Yukinori, Murayama Toshinori, Khaengkhan Parinda, Nishio Takuya, Ono Koh, Ariyasu Hiroyuki, Akamizu Takashi, Ueda Yukihiko, Kita Toru, Harada Shigeharu, Kamei Kaeko, Yokode Masayuki
Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Japan.
Atherosclerosis. 2009 Jun;204(2):388-94. doi: 10.1016/j.atherosclerosis.2008.10.021. Epub 2008 Oct 30.
Previous study showed that mulberry (Morus Alba L.) leaf (ML) ameliorates atherosclerosis in apoE(-/-) mice. Although the adipocytokine dysregulation is an important risk factor for atherosclerotic cardiovascular disease, the effect of ML on metabolic disorders related to adipocytokine dysregulation and inflammation has not been studied. Therefore, we studied the effects of ML in metabolic disorders and examined the mechanisms by which ML ameliorates metabolic disorders in db/db mice. We treated db/db mice with ML, pioglitazone, or both for 12 weeks and found that ML decreased blood glucose and plasma triglyceride. Co-treatment with ML and pioglitazone showed additive effects compared with pioglitazone. Moreover, their co-treatment attenuated the body weight increase observed under the pioglitazone treatment. ML treatment also increased the expression of adiponectin, and decreased the expression of TNF-alpha, MCP-1, and macrophage markers in white adipose tissue (WAT). Furthermore, ML decreased lipid peroxides and the expression of NADPH oxidase subunits in WAT and liver. Their co-treatment enhanced these effects. Thus, ML ameliorates adipocytokine dysregulation at least in part through inhibiting oxidative stress in WAT of db/db mice, and that ML may be a basis for a pharmaceutical for the treatment of the metabolic syndrome as well as reducing adverse effects of pioglitazone.
先前的研究表明,桑叶(Morus Alba L.)可改善载脂蛋白E基因敲除(apoE(-/-))小鼠的动脉粥样硬化。尽管脂肪细胞因子失调是动脉粥样硬化性心血管疾病的一个重要危险因素,但桑叶对与脂肪细胞因子失调和炎症相关的代谢紊乱的影响尚未得到研究。因此,我们研究了桑叶对代谢紊乱的影响,并探讨了桑叶改善db/db小鼠代谢紊乱的机制。我们用桑叶、吡格列酮或两者联合治疗db/db小鼠12周,发现桑叶可降低血糖和血浆甘油三酯。与吡格列酮相比,桑叶与吡格列酮联合治疗显示出相加效应。此外,它们的联合治疗减轻了吡格列酮治疗下观察到的体重增加。桑叶治疗还增加了脂联素的表达,并降低了白色脂肪组织(WAT)中肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)和巨噬细胞标志物的表达。此外,桑叶降低了WAT和肝脏中脂质过氧化物以及烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶亚基的表达。它们的联合治疗增强了这些效应。因此,桑叶至少部分通过抑制db/db小鼠WAT中的氧化应激来改善脂肪细胞因子失调,并且桑叶可能是治疗代谢综合征药物的基础,同时还可减轻吡格列酮的不良反应。