The Beneficial Effects of Chinese Herbal Monomers on Ameliorating Diabetic Cardiomyopathy via Nrf2 Signaling

Figure 3

The crosstalk between Nrf2 and other signaling pathways (created with BioRender.com). (a) AMPK could phosphorylate both Nrf2 (active) and GSK3β (deactivate) to prevent Nrf2 ubiquitinated by GSK3β to improve the nuclear accumulation of Nrf2. AMPK could promote autophagic degradation of Keap1. Besides, AMPK could activate SIRT1 to regulate Nrf2. (b) Akt could phosphorylate GSK3β to prompt nuclear accumulation of Nrf2. Furthermore, CK2 could not only activate Akt signaling pathway but also could directly phosphorylate Nrf2 to enhance its stability. (c) ERK, JNK, and p38 are always observed accompany by suppression of Nrf2. But the underlying mechanism is unclear. (d) Nrf2 could reduce MMP-9 to decrease the levels of TGF-β. Besides, Smad7 could form a complex type I receptor, and it recruits Smurf 1/2 to activate the type I receptor, thus negatively regulating TGF-β signaling pathway. And Nrf2 could enhance the level of Smad7. AMPK: adenosine monophosphate-activated protein kinase; GSK3β: glycogen synthase kinase 3β; SIRT: silent information regulator 1; Akt: phosphatidylinositol 3-kinase-protein kinase B; CK2: ceramide-protein kinase C ζ-casein kinase 2; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; MMP: matrix metalloproteinases; TGF-β: transforming growth factor-β; Smurf: Smad-mediated ubiquitination regulatory factor.