Shikonin alleviates choroidal neovascularization by inhibiting proangiogenic factor production from infiltrating macrophages. (December 2021) - Wang, Ying
Abstract: Choroidal neovascularization (CNV), a feature of neovasular age-related macular degeneration (AMD), acts as a leading cause of vision loss in the elderly. Shikonin (SHI), a natural bioactive compound extracted from Chinese herb radix arnebiae, exerts anti-inflammatory and anti-angiogenic roles and also acts as a potential pyruvate kinase M2 (PKM2) inhibitor in macrophages. The major immune cells macrophages infiltrate the CNV lesions, where the production of pro-angiognic cytokines from macrophage facilitates the development of CNV. PKM2 contributes to the neovascular diseases. In this study, we found that SHI oral gavage alleviated the leakage, area and volume of mouse laser-induced CNV lesion and inhibited macrophage infiltration without ocular cytotoxicity. Moreover, SHI inhibited the secretion of pro-angiogenic cytokine, including basic fibroblast growth factor (FGF2), insulin-like growth factor-1 (IGF1), chemokine (C-C motif) ligand 2 (CCL2), placental growth factor and vascular endothelial growth factor (VEGF), from primary human macrophages by down-regulating PKM2/STAT3/CD163 pathway, indicating a novel potential therapy strategy for CNV. Highlights: SHI inhibited PKM2 expression in infiltrating macrophages, consequently decreasing the phosphorylation and nuclear translocation of STAT3. Transcription of the STAT3 target gene CD163 and the secretion of proangiogenic cytokines in macrophages decreased. SHI alleviated CNV formation and proangiogenic factor production by inhibiting the PKM2/STAT3/CD163 pathway in macrophages. SHI might be a promising candidate for the treatment of CNV.