AUTHOR=Xue Zhifeng , Li Yixuan , Zhou Mengen , Liu Zhidong , Fan Guanwei , Wang Xiaoying , Zhu Yan , Yang Jian TITLE=Traditional Herbal Medicine Discovery for the Treatment and Prevention of Pulmonary Arterial Hypertension JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.720873 DOI=10.3389/fphar.2021.720873 ISSN=1663-9812 ABSTRACT=

Pulmonary arterial hypertension (PAH) is characterized by pulmonary artery remodeling that may subsequently culminate in right heart failure and premature death. Although there are currently both non-pharmacological (lung transplantation, etc.) and pharmacological (Sildenafil, Bosentan, and new oral drugs on trial) therapies available, PAH remains a serious and fatal pulmonary disease. As a unique medical treatment, traditional herbal medicine (THM) treatment has gradually exerted its advantages in treating PAH worldwide through a multi-level and multi-target approach. Additionally, the potential mechanisms of THM were deciphered, including suppression of proliferation and apoptosis of pulmonary artery smooth muscle cells, controlling the processes of inflammation and oxidative stress, and regulating vasoconstriction and ion channels. In this review, the effects and mechanisms of the frequently studied compound THM, single herbal preparations, and multiple active components from THM are comprehensively summarized, as well as their related mechanisms on several classical preclinical PAH models. It is worth mentioning that sodium tanshinone IIA sulfonate sodium and tetramethylpyrazine are under clinical trials and are considered the most promoting medicines for PAH treatment. Last, reverse pharmacology, a strategy to discover THM or THM-derived components, has also been proposed here for PAH. This review discusses the current state of THM, their working mechanisms against PAH, and prospects of reverse pharmacology, which are expected to facilitate the natural anti-PAH medicine discovery and development and its bench-to-bedside transformation.