Motherwort (Leonurus cardiaca) and Cardiovascular / heart health: evidence and sources

Leonurus cardiaca L. is known in Europe for its cardioactivity-also in interrelation with known risk factors of the metabolic syndrome-just as L. japonicus 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 L. cardiaca , 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 Leonurus 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.

Better understanding the mechanisms of Leonurus cardiaca L. extract (LCE) activity is necessary to prepare recommendations for the use of LCE-based herbal products for preventive/supportive purposes in case of infective endocarditis (IE) and other staphylococcal invasive infections. The aim of the study was to analyze molecular mechanisms of LCE effect on Staphylococcus aureus and blood platelets in the context of their interactions playing a pivotal role in such disorders. Using atomic force microscopy, we demonstrated that adhesion forces of S. aureus were markedly reduced after exposure to LCE at subinhibitory concentrations. The effect resulted from the impact of LCE on S. aureus cell morphology and the composition of phospholipids and fatty acids in bacterial membranes (assessed by HPLC), which modulated their stabilization, hydrophobicity, and charge. Moreover, using FACS we showed also that LCE significantly reduced GP IIb/IIIa expression on blood platelets, thus the disruption of platelet-fibrinogen interactions seems to explain antiplatelet effect of LCE. The obtained results prove the usefulness of LCE in the prevention of S. aureus adhesion, platelet activation, and vegetations development, however, also pointed out the necessity of excluding the cationic antibiotics from the treatment of S. aureus -associated IE and other invasive diseases, when motherwort herb is used simultaneously as an addition to the daily diet.

Leonurus cardiaca L. (motherwort) is a perennial herb, native to Asia and southeastern Europe, with widespread global occurrence in present days. The plant was historically used as cardiotonic and for treating gynaecological afflictions (such as amenorrhea, dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on Leonurus cardiaca L., herba (2010). The current study presents the progress made within the 2010-2018 timeframe regarding the potential applications and scientific evidences supporting the traditional use of motherwort, in the same time suggesting future research opportunities.

Leonurus cardiaca is a perennial plant indigenous to central Europe and Scandinavia, but it is also found in the area spanning temperate Russia to central Asia. It has been introduced to North America and has become established locally in the wild. Motherwort (Leonuri cardiacae herba) consists of aerial parts of Leonurus cardiaca gathered during the flowering period, dried at 35 °C and, according to European Pharmacopoeia 7th edition, should contain a minimum of 0.2% flavonoids, expressed as hyperoside. Compounds belonging to the group of monoterpenes, diterpenes, triterpenes, nitrogen- containing compounds, phenylpropanoids, flavonoids and phenolic acids, as well as volatile oils, sterols and tannins, have been identified in motherwort. Traditionally, extracts of the herb have been used internally, mainly for nervous heart conditions and digestive disorders. However, they have also been used for bronchial asthma, climacteric symptoms and amenorrhoea, as well as externally in wounds and skin inflammations. Mild negative chronotropic, hypotonic and sedative effects can be attributed to the herb and preparations thereof. Pharmacological studies have confirmed its antibacterial, antioxidant, anti-inflammatory and analgesic activity, as well as its effects on the heart and the circulatory system. Sedative and hypotensive activity has been demonstrated in clinical trials.