An Evaluation of Sanicula europaea L. for its Potential in the Treatment of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a damaging cardiovascular disease characterised by the narrowing of the small pulmonary blood vessels leading to right heart failure and pre-mature death. The treatment of PAH is limited and aimed to improve symptoms and hence there is an urgent need for new drugs. We hypothesised that the competing processes of bone morphogenetic protein (BMP) and TGF-β pathways are tightly regulated in PAH; agents that restore the balance between these two pathways may provide therapeutic intervention. Sanicula europaea L. is traditionally used for the treatment of wounds and respiratory disorders. Saponin glycosides and phenolic compounds, as major constituents, are responsible for antioxidant and antiproliferation activities that may have benefits in PAH.

S. europaea herb was extracted with 70% methanol and the concentrated extract partitioned with ethyl acetate and then with butanol. The dried butanol fraction was dissolved in methanol and dropped into diethyl ether to give crude glycosides. Biological evaluation of the ethyl acetate (E) and glycoside (G) fractions on BMP and TGFβ pathways was carried out using reporter assays, western blot and RT-PCR.

Both fractions, (E and G) inhibited TGF-β responsive reporter activity whilst eliciting no effect on the BMP- mediated reporter activation. Fraction G promoted SMAD 1/5 protein phosphorylation and Id1 gene transcription and inhibited the expression of Pai1 transcripts. Taken together, TGF-β signalling is inhibited by both fractions while fraction (G) promotes BMP signalling suggesting that further investigation of S. europaea in PAH would be worthwhile.

 

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Conflict of Interest

The authors declare no conflict of interest.

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023