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Review
. 2020 Nov 27;12(12):3651.
doi: 10.3390/nu12123651.

The Protective Effects of Flavonoids in Cataract Formation through the Activation of Nrf2 and the Inhibition of MMP-9

Aaron Hilliard  1 , Patricia Mendonca  1 , Tanya D Russell  2 , Karam F A Soliman  1
Affiliations
Review

The Protective Effects of Flavonoids in Cataract Formation through the Activation of Nrf2 and the Inhibition of MMP-9

Aaron Hilliard et al. Nutrients. .

Abstract

Cataracts account for over half of global blindness. Cataracts formations occur mainly due to aging and to the direct insults of oxidative stress and inflammation to the eye lens. The nuclear factor-erythroid-2-related factor 2 (Nrf2), a transcriptional factor for cell cytoprotection, is known as the master regulator of redox homeostasis. Nrf2 regulates nearly 600 genes involved in cellular protection against contributing factors of oxidative stress, including aging, disease, and inflammation. Nrf2 was reported to disrupt the oxidative stress that activates Nuclear factor-κB (NFκB) and proinflammatory cytokines. One of these cytokines is matrix metalloproteinase 9 (MMP-9), which participates in the decomposition of lens epithelial cells (LECs) extracellular matrix and has been correlated with cataract development. Thus, during inflammatory processes, MMP production may be attenuated by the Nrf2 pathway or by the Nrf2 inhibition of NFκB pathway activation. Moreover, plant-based polyphenols have garnered attention due to their presumed safety and efficacy, nutritional, and antioxidant effects. Polyphenol compounds can activate Nrf2 and inhibit MMP-9. Therefore, this review focuses on discussing Nrf2's role in oxidative stress and cataract formation, epigenetic effect in Nrf2 activity, and the association between Nrf2 and MMP-9 in cataract development. Moreover, we describe the protective role of flavonoids in cataract formation, targeting Nrf2 activation and MMP-9 synthesis inhibition as potential molecular targets in preventing cataracts.

Keywords: MMP-9; Nrf2; antioxidants; cataracts; flavonoids; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Keap1-Nrf2 system. The figure shows Nrf2 activation during stress conditions, which leads to the transcription of cytoprotective and antioxidant genes.
Figure 2
Figure 2
Flavonoid compounds and their chemical structure.
Figure 3
Figure 3
The protective effect of flavonoids in cataract formation. The diagram shows the effect of flavonoids on Nrf2 activation, leading to reduced inflammation, oxidative stress, and ROS, involved in cataract development. The figure also highlights Nrf2 modulation by epigenetic factors and the attenuation of MMP expression by flavonoids or by the inhibitory effect of the Nrf2 pathway in NFκB pathway activation.
See this image and copyright information in PMC

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