Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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
<i>Leonurus cardiaca</i> L. is known in Europe for its cardioactivity—also in interrelation with known risk factors of the metabolic syndrome—just as <i>L. japonicus</i> Houtt. in East Asia; however, up to now, no active constituents could be identified. The three sub-types o...
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2025-01-01
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| author | Kenny Kuchta Nobuyasu Matsuura Tung Huu Nguyen Christian Rusch Munekazu Iinuma Yukihiro Shoyama Hans Wilhelm Rauwald |
| author_facet | Kenny Kuchta Nobuyasu Matsuura Tung Huu Nguyen Christian Rusch Munekazu Iinuma Yukihiro Shoyama Hans Wilhelm Rauwald |
| author_sort | Kenny Kuchta |
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| description | <i>Leonurus cardiaca</i> L. is known in Europe for its cardioactivity—also in interrelation with known risk factors of the metabolic syndrome—just as <i>L. japonicus</i> Houtt. in East Asia; however, up to now, no active constituents could be identified. The three sub-types of PPARs (α, δ, and γ), are involved in controlling the lipid metabolism in the liver and skeletal muscles. Although PPARδ especially is a potential therapeutic target for the metabolic syndrome, insulin resistance, and obesity, no PPARδ agonists with clinical potential have presently been developed. Therefore, nineteen dominant isolated constituents of both species were screened for activity on the metabolic syndrome related PPAR α, δ, and γ in a newly developed luciferase reporter gene assay. Eight phenylethanoid glycosides not previously detected in <i>L. cardiaca</i>, including the novel cardiaphenyloside A, as well as the iridoids ajugol and harpagide were found via bioassay-guided isolation and structural elucidation of spectroscopic and chemical evidence. For the PPARδ experiment, all nineteen isolated constituents and GW0742 (positive control) were added to the medium of transfected COS-1 cells and further processed according to a standardized luciferase assay protocol. Only the major iridoid 7-chloro-6-desoxy-harpagide displayed significant activity in the PPARδ assay at 50 μg/mL, while the result for 100 μg/mL was higher than for the GW0742 positive control. Rutin, chicoric acid, and cardiaphenyloside A at 100 μg/mL showed PPARα agonistic activity. For PPARγ, no significant effects were observed. This activity of <i>Leonurus</i> extracts and especially of their active constituent 7-chloro-6-desoxy-harpagide on the δ subtype of the PPAR system strongly indicates their potential for anti-obesity therapy. |
| format | Article |
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| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Molecules |
| spelling | doaj-art-1bf921ba6821419b8f0d410c988e66352025-01-24T13:43:58ZengMDPI AGMolecules1420-30492025-01-0130241910.3390/molecules30020419Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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-harpagideKenny Kuchta0Nobuyasu Matsuura1Tung Huu Nguyen2Christian Rusch3Munekazu Iinuma4Yukihiro Shoyama5Hans Wilhelm Rauwald6Research Unit for Far Eastern Medicine, Department of Vegetation Analysis and Phytodiversity, Albrecht von Haller Institute of Plant Sciences, Georg August University, u. Karspüle 2, 37073 Göttingen, GermanyDepartment of Bioscience, Okayama University of Science, Okayama 700-0005, JapanDepartment of Pharmacognosy, Nagasaki International University, Sasebo 859-3243, JapanDepartment of Pharmaceutical Biology, Leipzig University, Johannisallee 21, 04103 Leipzig, GermanyDepartment of Pharmacognosy, Gifu Pharmaceutical University, Gifu 501-1113, JapanDepartment of Pharmacognosy, Nagasaki International University, Sasebo 859-3243, JapanDepartment of Pharmaceutical Biology, Leipzig University, Johannisallee 21, 04103 Leipzig, Germany<i>Leonurus cardiaca</i> L. is known in Europe for its cardioactivity—also in interrelation with known risk factors of the metabolic syndrome—just as <i>L. japonicus</i> Houtt. in East Asia; however, up to now, no active constituents could be identified. The three sub-types of PPARs (α, δ, and γ), are involved in controlling the lipid metabolism in the liver and skeletal muscles. Although PPARδ especially is a potential therapeutic target for the metabolic syndrome, insulin resistance, and obesity, no PPARδ agonists with clinical potential have presently been developed. Therefore, nineteen dominant isolated constituents of both species were screened for activity on the metabolic syndrome related PPAR α, δ, and γ in a newly developed luciferase reporter gene assay. Eight phenylethanoid glycosides not previously detected in <i>L. cardiaca</i>, including the novel cardiaphenyloside A, as well as the iridoids ajugol and harpagide were found via bioassay-guided isolation and structural elucidation of spectroscopic and chemical evidence. For the PPARδ experiment, all nineteen isolated constituents and GW0742 (positive control) were added to the medium of transfected COS-1 cells and further processed according to a standardized luciferase assay protocol. Only the major iridoid 7-chloro-6-desoxy-harpagide displayed significant activity in the PPARδ assay at 50 μg/mL, while the result for 100 μg/mL was higher than for the GW0742 positive control. Rutin, chicoric acid, and cardiaphenyloside A at 100 μg/mL showed PPARα agonistic activity. For PPARγ, no significant effects were observed. This activity of <i>Leonurus</i> extracts and especially of their active constituent 7-chloro-6-desoxy-harpagide on the δ subtype of the PPAR system strongly indicates their potential for anti-obesity therapy.https://www.mdpi.com/1420-3049/30/2/419<i>Leonurus cardiaca</i><i>L. japonicus</i>phenylethanoid glycosidesiridoid glucosidesPPARmetabolic syndrome |
| spellingShingle | Kenny Kuchta Nobuyasu Matsuura Tung Huu Nguyen Christian Rusch Munekazu Iinuma Yukihiro Shoyama Hans Wilhelm Rauwald Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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 Molecules <i>Leonurus cardiaca</i> <i>L. japonicus</i> phenylethanoid glycosides iridoid glucosides PPAR metabolic syndrome |
| title | Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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 |
| title_full | Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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 |
| title_fullStr | Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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 |
| title_full_unstemmed | Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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 |
| title_short | Phenolic and Iridoid Glycosides from <i>Leonurus cardiaca</i> 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 |
| title_sort | phenolic and iridoid glycosides from i leonurus cardiaca i 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 |
| topic | <i>Leonurus cardiaca</i> <i>L. japonicus</i> phenylethanoid glycosides iridoid glucosides PPAR metabolic syndrome |
| url | https://www.mdpi.com/1420-3049/30/2/419 |
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