7‐Methoxy‐(9H‐β‐Carbolin‐1‐il)‐(E)‐1‐Propenoic Acid, a β‐Carboline Alkaloid From Eurycoma longifolia, Exhibits Anti‐Inflammatory Effects by Activating the Nrf2/Heme Oxygenase‐1 Pathway

ABSTRACT Eurycoma longifolia is an herbal medicinal plant popularly used in Southeast Asian countries. In the present study, we show that 7‐methoxy‐(9H‐β‐carbolin‐1‐il)‐(E)‐1‐propenoic acid (7‐MCPA), a β‐carboline alkaloid isolated from E. longifolia, exerted anti‐inflammatory effects by activating the nuclear factor‐E2‐related factor 2 (Nrf2)/heme oxygenase‐1 (HO‐1) pathway. 7‐MCPA inhibited lipopolysaccharide (LPS)‐induced production of nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin‐6 (IL‐6) in RAW264.7 cells and rescued C57BL/6 mice from LPS‐induced lethality in vivo. LPS‐induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), and IL‐6 was also significantly suppressed by treatment of 7‐MCPA in RAW264.7 cells. 7‐MCPA induced nuclear translocation of Nrf2 and increased transcription of its target genes, such as HO‐1. Treating RAW264.7 cells with 7‐MCPA increased the intracellular level of reactive oxygen species (ROS) and the phosphorylation level of p38 mitogen‐activated protein kinase (MAPK); however, co‐treatment with the antioxidant N‐acetyl‐cysteine (NAC) blocked 7‐MCPA‐induced p38 MAPK phosphorylation. Moreover, NAC or SB203580 (p38 MAPK inhibitor) blocked 7‐MCPA‐induced nuclear translocation of Nrf2, suggesting that 7‐MCPA activated Nrf2 via a ROS‐dependent p38 pathway. 7‐MCPA induced HO‐1 protein and mRNA expression and knockdown of Nrf2 w...
Source: Journal of Cellular Biochemistry - Category: Biochemistry Authors: Tags: Article Source Type: research