Molecular Cell Physiology & Endocrinology, Technische Universität Dresden, Dresden, Germany.
Planta Med. 2011 Mar;77(4):346-53. doi: 10.1055/s-0030-1250382. Epub 2010 Oct 4.
A number of medicinal/culinary herbs have been reported to improve glucose metabolism and to yield hypoglycemic effects in patients with diabetes. Since stimulation of insulin sensitivity appears to be a potential mechanism, peroxisome proliferator-activated receptor (PPAR) γ is a likely target molecule for small lipophilic compounds derived from endogenous metabolism and nutrition. Functionally, PPAR γ integrates the control of energy, lipid, and glucose homeostasis. In addition, PPAR δ activity is involved in energy expenditure. Therefore the aim of this study was to investigate whether PPAR γ and PPAR δ as well as the stimulation of glucose uptake is activated by botanical products. CISTUS SALVIFOLIUS (Cistaceae) has been identified as a candidate botanical in a preliminary screening of extracts from medicinal plants of Greek flora. In a bioguided approach, crude extracts, fractions and in the end purified compounds have been evaluated for PPAR γ and PPAR δ specific activities using cell-based transactivation assays. Glucose uptake was measured by nonradioactive 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) uptake. Concerning PPAR γ several extracts induced reporter gene activity, and clear dose-response patterns (0.1-100 µg/mL) could be established in the case of the cyclohexane and dichloromethane extracts. Isolation of individual compounds from the cyclohexane extract revealed that at least 6 out of 7 compounds isolated were active with TRANS-cinnamic acid showing a clear dose-response pattern. In contrast, they were found to be inactive on PPAR δ. The same compounds, however, were also active in stimulating glucose uptake into 3T3-L1 adipocytes. In summary, the bioguided fractionation of CISTUS SALVIFOLIUS yields PPAR γ stimulating metabolites with differing chemical natures. In conclusion, PPAR γ represents a candidate molecule for the mediation of improvement of glucose metabolism by botanical/nutritional products.
一些药用/食用草药已被报道能改善糖尿病患者的葡萄糖代谢并产生降血糖作用。由于刺激胰岛素敏感性似乎是一种潜在的机制，过氧化物酶体增殖物激活受体 (PPAR)γ 是内源性代谢和营养产生的小分子亲脂化合物的可能靶分子。从功能上讲，PPARγ 整合了能量、脂质和葡萄糖稳态的控制。此外，PPARδ 活性参与能量消耗。因此，本研究的目的是研究植物产品是否激活 PPARγ 和 PPARδ 以及葡萄糖摄取的刺激。在对希腊植物药用植物提取物的初步筛选中，CISTUS SALVIFOLIUS（Cistaceae）被确定为候选植物。在生物导向方法中，使用基于细胞的转激活测定法，对粗提取物、馏分和最终纯化化合物进行 PPARγ 和 PPARδ 特异性活性评估。通过非放射性 2-[N-(7-硝基苯并-2-氧杂-1,3-二唑-4-基)氨基]-2-脱氧葡萄糖 (2-NBDG)摄取来测量葡萄糖摄取。关于 PPARγ，几种提取物诱导报告基因活性，并且在环己烷和二氯甲烷提取物的情况下可以建立明确的剂量反应模式 (0.1-100μg/mL)。从环己烷提取物中分离出的个别化合物表明，至少 7 种化合物中的 6 种具有活性，反式肉桂酸表现出明显的剂量反应模式。相比之下，它们对 PPARδ 不起作用。然而，相同的化合物也能在刺激 3T3-L1 脂肪细胞摄取葡萄糖方面发挥作用。总之，CISTUS SALVIFOLIUS 的生物导向分离产生具有不同化学性质的刺激 PPARγ 的代谢物。总之，PPARγ 是植物/营养产品改善葡萄糖代谢的介导分子的候选分子。
