Suppressive Effect of Arctium Lappa L. Leaves on Retinal Damage Against A2E-Induced ARPE-19 Cells and Mice

Abstract

Age-related macular degeneration (AMD) is a major cause of irreversible loss of vision with 80–90% of patients demonstrating dry type AMD. Dry AMD could possibly be prevented by polyphenol-rich medicinal foods by the inhibition of N-retinylidene-N-retinylethanolamine (A2E)-induced oxidative stress and cell damage. Arctium lappa L. (AL) leaves are medicinal and have antioxidant activity. The purpose of this study was to elucidate the protective effects of the extract of AL leaves (ALE) on dry AMD models, including in vitro A2E-induced damage in ARPE-19 cells, a human retinal pigment epithelial cell line, and in vivo light-induced retinal damage in BALB/c mice. According to the total phenolic contents (TPCs), total flavonoid contents (TFCs) and antioxidant activities, ALE was rich in polyphenols and had antioxidant efficacies on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2′,7′-dichlorofluorescin diacetate (DCFDA) assays. The effects of ALE on A2E accumulation and A2E-induced cell death were also monitored. Despite continued exposure to A2E (10 μM), ALE attenuated A2E accumulation in APRE-19 cells with levels similar to lutein. A2E-induced cell death at high concentration (25 μM) was also suppressed by ALE by inhibiting the apoptotic signaling pathway. Furthermore, ALE could protect the outer nuclear layer (ONL) in the retina from light-induced AMD in BALB/c mice. In conclusion, ALE could be considered a potentially valuable medicinal food for dry AMD.

Medication Trends for Age-Related Macular Degeneration

“…Based on the apoptotic pathway, the candidates can be grouped into (1) anti-oxidative stress, (2) anti-inflammation, and (3) anti-carbonyl stress candidates. One hundred percent EtOH extract of Arctium lappa L. leaves has been found to have plentiful amounts of phenolics and flavonoids, and it effectively suppressed both oxidative stress by scavenging effects of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) and apoptosis by modulating bcl-2 family and caspase cascade [ 104 ]. Genipin is a glycosidic ligand that has been found to suppress H 2 O 2 -induced oxidative stress and apoptosis via nuclear factor-erythroid 2-related factor-2 (Nrf2), which regulates the expression of heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQOA) [ 105 ].…”

“…From this reason, many natural products that can possibly constrain AMD severity have been used and investigated. Based on their modes of action, they can be divided into those that are preventers of RPE death/cell cycle arrest (anti-apoptosis inducers and cell cycle arrest modulators) [ 104 , 105 , 107 , 108 , 109 , 110 , 111 , 112 ] and those that are inhibitors of VEGF activation (VEGF inactivators) [ 38 ]. Natural products are safer than synthetic chemicals, as they have been used for a long time, they have an easy route of administration, with most able to be orally applied, and they can be used as combined therapies, such as with device-based therapy, anti-inflammatory drugs, and anti-VEGF molecules.…”

Exploring the Mechanism ofArctium LappaL. Leaves in the Treatment of Alzheimer's Disease Based on Chemical Profile, Network Pharmacology and Molecular Docking

“…[7] Modern research implied that burdock leaves can have anti-microbial, anti-cancer, anti-inflammatory, anti-oxidant effects, and retinal protective effects. [7,12,13] The theory of "toxin damaging brain collaterals" is a major pathogenesis of AD in TCM. [14] Heat-clearing and toxicityremoving therapy, such as Huang-Lian-Jie-Du Decoction, was widely used to ameliorate AD.…”

“…[ 7 ] Modern research implied that burdock leaves can have anti‐microbial, anti‐cancer, anti‐inflammatory, anti‐oxidant effects, and retinal protective effects. [ 7,12,13 ]…”

Identification of a Sesquiterpene Lactone from Arctium lappa Leaves with Antioxidant Activity in Primary Human Muscle Cells

“…Moreover, they suggested that compounds such as chlorogenic acid, o-hydroxybenzoic acid, caffeic acid, p -coumaric acid and rutin present in A. lappa leaves extracts could be involved in antioxidant activity. More recently, Kim et al [ 28 ] showed that an A. lappa leaves extract has a protective effect on an age-related macular degeneration model and they suggested that this effect could be due to antioxidant properties of phenolic and flavonoid content present in the leaves extract. Thus, all these studies have reported a potential antioxidant ability of A. lappa leaves but no specific compound has been isolated from the extracts.…”