ROCK Kinase Inhibitory Activity of Some Isoflavonoids and Their Pharmacological Significance in Glaucoma

Glaucoma is a chronic inflammatory disorder characterized by the loss of optic nerve fibers and the formation of retinopathy. The redox homeostasis pathway plays an important role in the pathogenesis of this disease. In this study, the Rho-associated protein kinase inhibitory activity of various isoflavonoids, such as genistin, genistein, daidzein, glycitein, and daidzin, was investigated in vitro in PC12 neuronal cells which are utilized to create a pressure model of ocular hypertension. The results showed that these isoflavonoids showed a diverse range of inhibitory activities against Rho-associated protein kinase II, displaying genistin as the most potent inhibitor, which showed a significant reduction in the myeloperoxidase activity, and levels of cathepsins B and D with an increase in glutathione level in PC12 neuronal cells. It also showed a significant reduction in the levels of cyclooxygenases, lipoxygenases, phospholipase A2, and leukotriene B4 12-hydroxydehydrogenase in glaucoma-modelled PC12 cells in a dose-dependent manner. A docking study showed that genistin interacted with the amino acids MET167, MET169, GLU170, MET172, ASP176, and ASP218 found in the active site of ROCK II. These findings suggested that genistin has strong antioxidant and anti-inflammatory effects on glaucoma-modelled PC12 cells.