Abstract:
:The therapy of type-2 diabetes mellitus is one of the major challenges of our age. A possible strategy to prevent the progression of this disease is the inhibition of protein tyrosine phosphatase 1B (PTP1B), a major negative regulator in the insulin and leptin signalling pathway. Phellodendri amurensis cortex is a well-known Asian herbal drug traditionally used as antiphlogistic, antibacterial, and anti-inflammatory agent, and its efficacy against diabetes-related symptoms is reported as well. However, information regarding active principle(s) or the molecular mode of action was scarce. By bioguided isolation using an IN VITRO enzyme assay with human recombinant PTP1B, (9 Z)-octadec-9-enoic acid (oleic acid) could be identified as a major PTP1B inhibitor in the bark of Phellodendron amurENSE Rupr. (Rutaceae); it showed an IC₅₀ value of 6.2 µM. Consistent with this inhibition of PTP1B, oleic acid was capable of enhancing insulin signalling in wild-type, but not PTP1B knockout fibroblasts. By testing a series of other fatty acids of different chain length and degree of saturation, their general PTP1B-inhibitory potential in the micromolar range was observed. More pronounced effects were associated with a longer carbon backbone and saturation of the double bonds. Therefore, our work provides first scientific evidences for the antidiabetic properties of P. amurense via a new target, effects which seem to be explainable by oleic acid. The discovery of a PTP1B inhibition by many fatty acids also adds a novel facet to the pharmacological properties of a class of compounds that is found in many food items in considerable amount and triggers speculation over their possible involvement in the feedback regulation of cellular fatty acid synthesis.
journal_name
Planta Medjournal_title
Planta medicaauthors
Steinmann D,Baumgartner RR,Heiss EH,Bartenstein S,Atanasov AG,Dirsch VM,Ganzera M,Stuppner Hdoi
10.1055/s-0031-1280377subject
Has Abstractpub_date
2012-02-01 00:00:00pages
219-24issue
3eissn
0032-0943issn
1439-0221journal_volume
78pub_type
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