Effects of medicinal plants of the genus Leonurus and seventeen of their isolated constituents on the activity of PPARα, β/δ, and γ in an in vitro luciferase reporter gene assay

K Kuchta; N Matsuura; HW Rauwald; C Rusch; Y Shoyama; M Iinuma

doi:10.1055/s-0035-1565632

Planta Medica, Inhaltsverzeichnis

Effects of medicinal plants of the genus Leonurus and seventeen of their isolated constituents on the activity of PPARα, β/δ, and γ in an in vitro luciferase reporter gene assay

K Kuchta ¹, N Matsuura ², HW Rauwald ³, C Rusch ³, Y Shoyama ⁴, M Iinuma ⁵

¹National Institute of Health Sciences, Division of Pharmacognosy, Phytochemistry and Narcotics, Setagaya-ku, Kamiyoga 1 – 18 – 1, 158 – 8501, Tokyo, Japan
²Department of Life Science, Okayama University of Science, 700 – 0005, Okayama, Japan
³Department of Pharmaceutical Biology, Leipzig University, Johannisallee 23, 04103, Leipzig, Germany
⁴Department of Pharmacognosy, Nagasaki International University, 2825 – 7 Huis Ten Bosch, Sasebo, Nagasaki, Japan
⁵Department of Pharmacognosy, Gifu Pharmaceutical University, 501 – 1196, Gifu, Japan

Abstract

Previously, we reported the effects of Leonurus japonicus Houtt. – used in TCM against the metabolic syndrome – and its N-containing constituents leonurine and stachydrine on the PPAR system [1]. However, no active constituents could be identified. Here we describe the isolation of 17 further dominant constituents of L. japonicus and the related European herb Leonurus cardiaca L. – namely 7R-chloro-6-desoxy-harpagide [2], ajugol, campneoside II, chicoric acid, ferulic acid, harpagide, isoacteoside, isocampneoside II, isoleosibirin, lavandulifolioside, leonoside A, rutin, and verbascoside, as well as four new phenylethanoids described here for the first time with the preliminary names LC139C, LC138C, LC141B, and LC140A1 – and their screening for activity on the metabolic syndrome related targets PPARα, β/δ, and γ in the above mentioned luciferase reporter gene assay [3]. All 17 isolated constituents (at 6.25, 25, 50, and 100 µg/mL each), and GW0742 (positive control, 0.1 nM) were dissolved in DMSO and added to the medium of the COS-1 cells, transfected as described at [1, 3]. For PPARα and γ, the positive controls WY14643 (50 µM) and troglitazone (10 µM), respectively, were used. In this assay, only 7R-chloro-6-desoxy-harpagide, which was recently isolated by our group for the first time [2], displayed significant activity in the PPARβ/δ assay at 50 µg/mL while the result for 100 µg/mL was even higher than for the GW0742 positive control. Furthermore, rutin at 100 µg/mL showed weak PPARα agonistic activity. For PPARγ no significant effects were observed. This activity of extracts of medicinal plants of the genus Leonurus and especially of their active constituent 7R-chloro-6-desoxy-harpagide on the PPARβ/δ subtype of the PPAR system strongly indicates their potential for anti-obesity therapy.

References:

[1] Kuchta K et al. Planta Med 2014; 80: P1L24.

[2] Rusch C et al. Planta Med 2010; 76: P235.

[3] Matsuura N et al. Biosci Biotechnol Biochem 2013; 77: 2430 – 2435.