Nephroprotective mechanism of Kunkui Baoshen decoction in diabetic kidney disease: Targeting the HERC2/NCOA4-mediated autophagy-dependent ferroptosis pathway

Figure 12  Effects of Kunkui Baoshen decoction on the homologous to E6-AP C-terminus and RCC1-like domain-containing E3 ubiquitin protein ligase/nuclear receptor coactivator 4-mediated autophagy-dependent ferroptosis pathway in db/db mice. A-L: Western blot analysis of key proteins involved in the homologous to E6-AP C-terminus and RCC1-like domain-containing E3 ubiquitin protein ligase/nuclear receptor coactivator 4-mediated autophagy-dependent ferroptosis pathway in db/db mice; M: Immunohistochemical staining of renal tissues showing the expression of nuclear receptor coactivator 4, homologous to E6-AP C-terminus and RCC1-like domain-containing E3 ubiquitin protein ligase, and glutathione peroxidase 4. HERC2: Homologous to E6-AP C-terminus and RCC1-like domain-containing E3 ubiquitin protein ligase; NCOA4: Nuclear receptor coactivator 4; ATG7: Autophagy related 7; SQSTM1: Sequestosome 1; SLC7A11: Solute carrier family 7 member 11; GPX4: Glutathione peroxidase 4; FTH1: Ferritin heavy chain 1; LC3: Microtubule-associated protein light chain 3; GAPDH: Glyceraldehyde 3-phosphate dehydrogenase; L-KKBS: Low-dose Kunkui Baoshen decoction; H-KKBS: High-dose Kunkui Baoshen decoction. ^bP < 0.01 vs db/m group, ^cP < 0.001 vs db/m group, ^dP < 0.0001 vs db/m group; ^eP < 0.05 vs db/db group, ^fP < 0.01 vs db/db group, ^gP < 0.001 vs db/db group, and ^hP < 0.0001 vs db/db group.