scholarly journals Anti-inflammatory effects of paeoniflorin from Paeonia lactiflora Pall. on human corneal epithelial cells and a mouse model of dry eye disease

RSC Advances ◽  
2019 ◽  
Vol 9 (23) ◽  
pp. 12998-13006 ◽  
Author(s):  
Mincong Zhao ◽  
Li Liu ◽  
Yating Zheng ◽  
Guangrong Liu ◽  
Biao Che ◽  
...  

Dry eye disease (DED) is characterized by increased osmolality of tears due to a lack of production or increased evaporation of tears.

Author(s):  
Anita Kirti Ghosh ◽  
Rubina Thapa ◽  
Harsh Nilesh Hariani ◽  
Michael Volyanyuk ◽  
Karoline Anne Orloff ◽  
...  

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.


2017 ◽  
Vol 1 (Special Issue) ◽  
pp. 145-145
Author(s):  
Trailokyanath Panigrahi ◽  
Rohit Shetty ◽  
Shivakumar Shivapriya ◽  
E.J.R. Nelson ◽  
Nallathambi Jeyabalan ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1362
Author(s):  
Anita Kirti Ghosh ◽  
Rubina Thapa ◽  
Harsh Nilesh Hariani ◽  
Michael Volyanyuk ◽  
Sean David Ogle ◽  
...  

Oxidative stress is a known contributor to the progression of dry eye disease pathophysiology, and previous studies have shown that antioxidant intervention is a promising therapeutic approach to reduce the disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of the naturally occurring prenylated chalconoid, xanthohumol, in preclinical models for dry eye disease. Xanthohumol acts by promoting the transcription of phase II antioxidant enzymes. In this study, xanthohumol prevented tert-butyl hydroperoxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells in a dose-dependent manner and resulted in a significant increase in expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of phase II endogenous antioxidant enzymes. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced ocular surface damage and oxidative stress-associated DNA damage in corneal epithelial cells in the mouse desiccating stress/scopolamine model for dry eye disease in vivo. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1801
Author(s):  
Yi-Zhou Chen ◽  
Zhi-Yu Chen ◽  
Yu-Jun Tang ◽  
Cheng-Han Tsai ◽  
Yu-Lun Chuang ◽  
...  

Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of <5 μM lutein (L5) and <1% PVA (P1) maintained the cell viability at 80%. A real-time PCR showed that the inflamed human corneal epithelial cells (HCECs) cocultured with L5P1 had downregulated expression of inflammatory genes such as IL-1β, IL-6, and TNF-α. In a benzalkonium chloride- (BAC) induced DES mouse model, AT/L5P1 could repair damaged corneas, elevate tear secretion, increase the number of goblet cells, and inhibit the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in the cornea. In conclusion, we demonstrate that lutein/PVA as eye drops could prolong the drug ocular retention time and effectively to decrease inflammation in DES mice. Therefore, lutein, obtained from eye drops, has a potential therapeutic role for DES.


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