Ulmus davidiana 60% edible ethanolic extract for prevention of pericyte apoptosis in diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is a disease that causes visual deficiency owing to vascular leakage or abnormal angiogenesis. Pericyte apoptosis is considered one of the main causes of vascular leakage in diabetic retina, but there are few known therapeutic agents that prevent it. Ulmus davidiana is a safe natural product that has been used in traditional medicine and is attracting attention as a potential treatment for various diseases, but its effect on pericyte loss or vascular leakage in DR is not known at all. In the present study, we investigated on the effects of 60% edible ethanolic extract of U. davidiana (U60E) and catechin 7-O-β-D-apiofuranoside (C7A), a compound of U. davidiana, on pericyte survival and endothelial permeability. U60E and C7A prevented pericyte apoptosis by inhibiting the activation of p38 and JNK induced by increased glucose and tumor necrosis factor alpha (TNF-α) levels in diabetic retina. Moreover, U60E and C7A reduced endothelial permeability by preventing pericyte apoptosis in co-cultures of pericytes and endothelial cells. These results suggest that U60E and C7A could be a potential therapeutic agent for reducing vascular leakage by preventing pericyte apoptosis in DR.

Comparative analysis of co-culture and monoculture models in simulating diabetic neurovascular dysfunction: insights into diabetic retinopathy

“…Microglial cells act as modulators in the chronic inflammation process, in which microglia was activated at the transcriptional level, mediated through the nuclear factor kappa-light chain-enhancer of activated B cells and extracellular signal-regulated kinase signal pathways, resulting in the release of proinflammatory cytokine chemokines, caspases, and glutamate (23). Pericyte maintains the integrity of the blood-retinal barrier, increasing the expression of tight junction proteins by interactions with endothelial cells (24). Pericyte loss is the early pathological sign of DR (25).…”

Role of autophagy in angiogenic potential of vascular pericytes

“…Of note, the existence of sulfhydryl groups in the structure of ATG3, 7, and 10 makes them sensitive to ROS oxidation ( Filomeni et al, 2010 ). Because apoptosis is the dominant cell death mechanism in vascular cells, especially pericytes, in metabolic conditions and traumatic injury thus one can hypothesize that autophagy is inhibited under such conditions, or its overactivation provokes the apoptosis signaling pathway ( Kim et al, 2023 ).…”

Nutraceuticals for Diabetic Retinopathy: Recent Advances and Novel Delivery Systems

“…Pro-EGCG was reported to be anti-inflammatory and could mitigate cell proliferation and pro-angiogenic factor production through the ROS/Thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome axis [ 120 ]. Another catechin, catechin 7-O-β-D-apiofuranoside (C7A), the main bioactive component of Ulmus davidiana extract, was demonstrated to prevent pericyte apoptosis and reduce endothelial permeability, suggesting its potential as a protective agent for reducing vascular leakage in DR [ 121 ].…”