Plant-derived phenolic acids in the treatment of pulmonary hypertension: A review of the underlying mechanisms

Background Pulmonary arterial hypertension (PAH) is a progressive and debilitating disease, as the currently available medications such as endothelin receptor antagonists, nitric oxide, and prostacyclin agonists only provide symptomatic relief without offering a complete cure. Therefore, it is crucial to explore novel approaches that target the underlying cellular and molecular signaling pathways involved in PAH. Method Phenolic acids represent a class of phytochemical compounds that possess well-established antioxidant and anti-inflammatory properties, making them of significant interest in the treatment of PAH. In this review, we specifically focus on three bioactive components: salvianolic acids, magnesium lithospermate B extracted from Salvia miltiorrhiza, and osthole, which is a coumarin-type compound. Results By examining the therapeutic potential of these compounds, we aim to shed light on their role in mitigating the effects of PAH and contribute to the development of innovative treatment strategies. In the progression of PAH, various functional signaling molecules and pathways are inhibited by phenolic acids. These include p38MAPK, P38, ROS, ROCK, Ras, MEK 1/2, ERK 1/2, TGF β, BMPR-2, Smad 1/5/8, NOX2, NOX4, CDK 4/6. On the other hand, PI3K and AKT pathways are upregulated. Conclusion The lack of definitive treatment for PAH highlights the importance of further studies and evaluations to translate these therapies to the clinic, given the outstanding characteristics of phenolic acids.