Fig. 5

Andrographolide’s effects on Nrf2 and HO-1 in astrocytes. Summary schematic of findings of the current study. Black solid arrows indicate positive regulation, while activation effects of andrographolide are denoted by green arrows, and inhibitory effects are denoted by red arrows. a Andrographolide activates Nrf2 transcription between 8 and 24 h, leading to b increased Nrf2 proteins, which may also accumulate rapidly (within 1 h) through a process of altered ubiquitination which c does not alter Keap1 levels and d does not disrupt Nrf2-Keap1 binding through Ser40 phosphorylation within the Nrf2 Neh2 domain. Instead, andrographolide treatment leads to e reduced Nrf2 ubiquitination efficiency and subsequent 26S proteasomal turnover via p38 MAPK- and ERK-dependent pathways, although it is unclear whether the kinases directly act on Nrf2, or through regulation of other signaling molecules, for, e.g., GSK-3β. Further studies are required