Obtusin

Obtusin is an orally active human monoamine oxidase A (hMAO-A) inhibitor discovered from the seeds of Cassia obtusifolia, with a K_i value of 6.15 μM. Obtusin inhibits high glucose-induced activation of the MAPKs/NF-κB/VEGF pathway and downregulates the expression of Poldip2, Nox4, VCAM-1, and HIF-1α, thereby alleviating oxidative stress, endothelial activation, and angiogenesis-related functions. Obtusin ameliorates diabetic retinopathy in vivo. Obtusin is used in research related to diabetes and neurodegenerative diseases (anxiety and depression)^[1][2]. IC50 & Target:IC50: 11.12 μM (hMAO-A)^[1]
Ki: 6.15 (hMAO-A)^[1] In Vitro:Obtusin (10-20 μM; 48 h) alleviates high glucose-induced HRMEC dysfunction, oxidative stress, and endothelial activation by inhibiting proliferation, migration, and tube formation, and downregulating the expression of Poldip2, Nox4, VCAM-1, and HIF-1α^[1].

Obtusin (10-20 μM; 2 h) inhibits the activation of high glucose-induced MAPKs/NF-κB/VEGF pathway in HRMECs and decreases the expression of phosphorylated p38 MAPK, phosphorylated NF-κB p65, and VEGFA^[1].

Obtusin selectively inhibits hMAO-A activity with an IC₅₀ of 11.12 μM^[2].
Obtusin competitively inhibits hMAO-A with a K_i value of 6.15 μM^[2].
Obtusin binds to the catalytic site of hMAO-A with a binding energy of -8.51 kcal/mol, forming key hydrogen bond interactions with Cys323 and Thr336^[2]. In Vivo:Obtusin (5-10 mg/kg/day; p.o.; daily; 12 weeks) ameliorates diabetic retinopathy in db/db mice by improving retinal histopathology, reducing oxidative stress, and inhibiting inflammation^[1].