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Planta Med 2011; 77(4): 346-353
DOI: 10.1055/s-0030-1250382
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Constituents from Cistus salvifolius (Cistaceae) Activate Peroxisome Proliferator-Activated Receptor-γ but Not -δ and Stimulate Glucose Uptake by Adipocytes

Claudia Kühn1 [*] , Niki Eliza Arapogianni2 [*] , Maria Halabalaki2 , Jana Hempel1 , Nicole Hunger1 , Jannette Wober1 , Alexios Leandros Skaltsounis2 , Günter Vollmer1
  • 1Molecular Cell Physiology & Endocrinology, Technische Universität Dresden, Dresden, Germany
  • 2Laboratory of Pharmacognosy & Natural Products Chemistry, School of Pharmacy, Athens, Greece
Weitere Informationen

Publikationsverlauf

received June 4, 2010 revised August 24, 2010

accepted August 27, 2010

Publikationsdatum:
04. Oktober 2010 (online)

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Abstract

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, PPARγ integrates the control of energy, lipid, and glucose homeostasis. In addition, PPARδ activity is involved in energy expenditure. Therefore the aim of this study was to investigate whether PPARγ and PPARδ 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 PPARγ and PPARδ 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 PPARγ 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 PPARδ. The same compounds, however, were also active in stimulating glucose uptake into 3T3-L1 adipocytes. In summary, the bioguided fractionation of Cistus salvifolius yields PPARγ stimulating metabolites with differing chemical natures. In conclusion, PPARγ represents a candidate molecule for the mediation of improvement of glucose metabolism by botanical/nutritional products.

Key words

Cistus salvifolius - Cistaceae - PPARγ transactivation - glucose uptake - adipocytes

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1 Both authors contributed equally.

Dr. Jannette Wober

Institute of Zoology
Molecular Cell Physiology & Endocrinology
Technische Universität Dresden

Zellescher Weg 20B

01217 Dresden

Germany

Telefon: +49 3 51 46 33 78 40

Fax: +49 3 51 46 33 19 23

eMail: Jannette.Wober@tu-dresden.de