Phenolic and Iridoid Glycosides from Leonurus cardiaca L. and Their Effects on the α, δ, and γ Subtypes of the PPAR System-Including the Discovery of the Novel Phenylethanoid Cardiaphenyloside A and the Most Active 7-Chloro-6-desoxy-harpagide
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View abstract on PubMed
Summary
This summary is machine-generated.Researchers identified active compounds in Leonurus species for metabolic syndrome. The iridoid 7-chloro-6-desoxy-harpagide showed significant PPARδ activity, indicating potential for anti-obesity therapies.
Area Of Science
- Pharmacology
- Natural Products Chemistry
- Metabolic Disease Research
Background
- Leonurus cardiaca and Leonurus japonicus possess known cardioactivity and relevance to metabolic syndrome risk factors.
- Peroxisome proliferator-activated receptors (PPARs) α, δ, and γ regulate lipid metabolism, with PPARδ being a key therapeutic target for metabolic syndrome, insulin resistance, and obesity.
- No clinically viable PPARδ agonists have been developed to date.
Purpose Of The Study
- To screen nineteen isolated constituents from L. cardiaca and L. japonicus for activity against metabolic syndrome-related PPAR subtypes (α, δ, γ).
- To identify novel active compounds and evaluate their potential as therapeutic agents for metabolic disorders.
Main Methods
- Bioassay-guided isolation and structural elucidation of constituents from L. cardiaca and L. japonicus.
- Utilized a newly developed luciferase reporter gene assay to screen compounds for PPAR α, δ, and γ activity.
- Tested nineteen isolated constituents and a positive control (GW0742) in transfected COS-1 cells for PPARδ agonism.
Main Results
- Eight phenylethanoid glycosides, including novel cardiaphenyloside A, and iridoids ajugol and harpagide were identified.
- The iridoid 7-chloro-6-desoxy-harpagide demonstrated significant PPARδ agonistic activity, exceeding the positive control at 100 μg/mL.
- Rutin, chicoric acid, and cardiaphenyloside A exhibited PPARα agonistic activity; no significant PPARγ activity was observed.
Conclusions
- The identified constituents, particularly 7-chloro-6-desoxy-harpagide, show potent PPARδ agonistic activity.
- Leonurus species extracts and their active compounds hold promise for developing novel anti-obesity therapies targeting the PPARδ pathway.
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