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Ginsenoside Rh2 inhibits vascular endothelial growth factor‐induced corneal neovascularization
Author(s) -
Zhang XiaoPei,
Li KeRan,
Yu Qing,
Yao MuDi,
Ge HuiMin,
Li XiuMiao,
Jiang Qin,
Yao Jin,
Cao Cong
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701074rr
Subject(s) - corneal neovascularization , neovascularization , vascular endothelial growth factor , angiogenesis , cornea , chemistry , microbiology and biotechnology , protein kinase b , vascular endothelial growth factor a , gene knockdown , cancer research , signal transduction , biology , biochemistry , vegf receptors , apoptosis , neuroscience
VEGF‐induced neovascularization plays a pivotal role in corneal neovascularization (CoNV). The current study investigated the potential effect of ginsenoside Rh2 (GRh2) on neovascularization. In HUVECs, pretreatment with GRh2 largely attenuated VEGF‐induced cell proliferation, migration, and vessel‐like tube formation in vitro. At the molecular level, GRh2 disrupted VEGF‐induced VEGF receptor 2(VEGFR2)‐Grb‐2‐associated binder 1 (Gab1) association in HUVECs, causing inactivation of downstream AKT and ERK signaling. Gab1 knockdown (by targeted short hairpin RN A ) similarly inhibited HUVEC proliferation and migration. Notably, GRh2 was ineffective against VEGF in Gab1‐silenced HUVECs. In a mouse cornea alkali burn model, GRh2 eyedrops inhibited alkali‐induced neovascularization and inflammatory cell infiltrations in the cornea. Furthermore, alkali‐induced corneal expression of mRNAs/long noncoding RNAs in cornea were largely attenuated by GRh2. Overall, GRh2 inhibits VEGF‐induced an‐giogenic effect via inhibiting VEGFR2‐Gab1 signaling in vitro. It also alleviates angiogenic and inflammatory responses in alkali burn‐treated mouse corneas.—Zhang, X.‐P., Li, K.‐R., Yu, Q., Yao, M.‐D., Ge, H.‐M., Li, X.‐M., Jiang, Q., Yao, J., Cao, C. Ginsenoside Rh2 inhibits vascular endothelial growth factor‐induced corneal neovascularization. FASEB J. 32, 3782–3791 (2018). www.fasebj.org