A Novel Integrated Active Herbal Formulation Ameliorates Dry Eye Syndrome by Inhibiting Inflammation and Oxidative Stress and Enhancing Glycosylated Phosphoproteins in Rats.

Omer Ersin Muz,Prafull Singh,Ibrahim Hanifi Ozercan,Cemal Orhan,Fusun Erten,Muralidhara Padigaru,Kazim Sahin,Abhijeet Morde,Deshanie Rai,Mehmet Tuzcu

doi:10.3390/ph13100295

Abstract

Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to the damaged ocular surface. Inflammation and oxidative stress play a significant role in the pathogenesis of the disease. In this study, the protective effect of different doses (100 or 200 mg/kg) of a novel multi-component oral formulation of lutein/zeaxanthin, curcumin, and vitamin D3 (LCD) was evaluated using a rat model with benzalkonium chloride (BAC)-induced dry eye syndrome. The formulation was administered orally to rats for 4 weeks. We observed a significant improvement in tear volume, tear breakup time, tear film integrity, and reduction in overall inflammation in rats fed with the LCD at dose 200 mg/kg performing better than 100 mg/kg. Furthermore, the formulation helped in lowering oxidative stress by increasing antioxidant levels and restored protective tear protein levels including MUC1, MUC4, and MUC5AC with 200 mg of LCD having the most significant effect. The results strongly suggest that the combination of lutein/zeaxanthin, curcumin, and vitamin-D3 is effective in alleviating the symptoms of dry eye condition with a multi-modal mechanism of action.

Highlights

Dry eye syndrome (DES) is a multifactorial disease of the tear film and ocular surface of the eye leading to reduced tear production, symptoms of discomfort, and visual disturbance with potential damage to the ocular surface
We measured the all the three active ingredients in the final formulation using high-performance liquid chromatography (HPLC) assay using in-house established reference samples to each of the actives to ensure that the total content of the each of the ingredient in the final formulation is not less than 33.26% of total curcuminoids, 3.47% of lutein, 0.7% of zeaxanthin, and 930 IU of vitamin D3
The HPLC chromatograms of curcuminoids, lutein/zeaxanthin, and vitamin D3 were shown in Supplementary Figures S1–S3

Summary

Introduction

Dry eye syndrome (DES) is a multifactorial disease of the tear film and ocular surface of the eye leading to reduced tear production, symptoms of discomfort, and visual disturbance with potential damage to the ocular surface. Inflammation mediated by pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-8 is high in tears of dry eye patients. These cytokines inhibit the release of neurotransmitters, and the activity of sensory nerves on the ocular surface weakens the secretion of lacrimal glands. Oxidative stress plays an important role in inducing damage to the ocular surface in DES with increased levels of malondialdehyde (MDA), lipid peroxidation markers, and decreased antioxidants such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) in the tear film and ocular surface of dry eye patients [12]

Methods

Results

Discussion

Conclusion