Nrf2 signaling: an important approach for the botanical drug and metabolites to ameliorate pulmonary hypertension via regulating pulmonary artery endothelial cells

Abstract

Pulmonary hypertension (PH) is a life-threatening condition characterized by pulmonary vascular remodeling and elevated pulmonary artery pressure. Its pathophysiology is marked by a remarkable rise in pulmonary artery pressure and an escalating vascular resistance, ultimately leading to right-sided heart failure and an elevated mortality rate. The cellular death machinery is pivotal in both development and tissue homeostasis, maintaining the equilibrium between cell proliferation and differentiation. Various modes of cell death are intricately associated with the pathogenesis of PH. Emerging evidence suggests that nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a crucial transcription factor regulating endogenous antioxidant defenses. Nrf2 and its downstream transcriptional targets modulate cell death and contribute to pulmonary vascular remodeling. Nevertheless, the therapeutic potential and underlying mechanisms of targeting Nrf2 to safeguard endothelial cells remain elusive. This review summarizes current insights into the botanical drugs and metabolites that modulate Nrf2 to protect endothelial cells in PH treatment and explains the molecular mechanisms of PH. Exploring cell death pathways could lead to new preventive and therapeutic strategies for PH.