Phytochemicals: Target-Based Therapeutic Strategies for Diabetic Retinopathy

Abstract

Background: A variety of causative factors are involved in the initiation of diabetic retinopathy (DR). Current antidiabetic therapies are expensive and not easily accessible by the public. Furthermore, the use of multiple synthetic drugs leads to severe side effects, which worsen the diabetic patient’s condition. Medicinal plants and their derived phytochemicals are considered safe and effective treatment and their consumption can reduce the DR risk. In this article, we discuss a variety of medicinal plants, and their noteworthy bio-active constituents, that will be utilized as target based therapeutic strategies for DR. Methods: A broad-spectrum study was conducted using published English works in various electronic databases including Science Direct, PubMed, Scopus, and Google Scholar. Results: Targeting the multiple pathological factors including ROS, AGEs formation, hexosamine flux, PARP, PKC, and MAPK activation through variety of bioactive constituents in medicinal plants, diabetes progression can be delayed with improved loss of vision. Conclusions: Data reveals that traditional herbs and their prominent bioactive components control and normalize pathological cellular factors involved in DR progression. Therefore, studies should be carried out to explore the protective retinopathy effects of medicinal plants using experimental animal and humans models.

Keywords: advanced glycation end-products; aldose reductase; diabetic retinopathy; metalloproteinase-9; mitogen-activated protein kinases; oxidative stress; phytochemicals; poly (ADP-ribose) polymerase; protein kinase C; reactive oxygen species; vascular endothelial growth factor.

Figure 1

Signaling pathways involved in DR. eNOS, Endothelial nitric oxide synthase; ET-1, Endothelin-1; VEGF, Vascular endothelial growth factor; TGF-β1, Transforming growth factor beta; PAI-1, Plasminogen activator inhibitor-1; IL- Interleukin; TNF-α, Tumor necrosis factor alpha; VACM-1, Vascular cell adhesion molecules-1; DAG, Diacylglycerol; PKC, Protein kinase C; NF-κB, Nuclear factor kappa; ROS, Reactive oxygen species; MAPK, Mitogen-activated protein kinase; RAGE; Receptor for AGE; CDC42, Cell division control protein 42; UDP-GlcNAC, Uridine diphosphate N-acetylglucosamine; AR, Aldose reductase; TCA, Tricarboxylic acid; STAT1, Signal transducer and activator of transcription 1; IRF-1; Interferon regulated factor 1; PARP; Poly (ADP-ribose) polymerase; GLUT, Glucose transporter; RAS, Renin-angiotensin system.

Figure 2

1. Acetoside—Abeliophyllum distichum; 2. benzo[b]-1,4-diazabicyclo[2.2.2]octane—Aegle marmelos; 3. Cinnamic acid—Aegle marmelos; 4. Agrimoniin—Agrimonia pilosa; 5. Ellagic acid—Carpobrotus edulis; 6. Chlorogenic acid—Aster Koraiensis; 7. 3,5-dicaffeoylquinic acid—Aster koraiensis; 8. Isorhamnetin—Cochlospermum religiosum; 9. Gigantol—Dendrobium chrysotoxum; 10. Syringic acid—Dendrobium chrysotoxum; 11. Specnuezhenide—Ligustrum lucidum; 12. Rosmarinic acid—Melissa officinalis; 13. Astragalin—Moringa oleifera; 14. 5′-methoxybiphenyl-3,4,3′-triol—Osteomeles schwerinae.

Figure 3

15. Luteolin—Platycodon grandiflorum; 16. Resveratrol—Polygonum cuspidatum; 17. Puerarin—Puerariae lobate; 18. luteolin-7-glucoside—Vitex negundo; 19. Coumaric acid—Zea mays; 20. Labdadiene—Alpinia zerumbet; 21. Andrographolide—Andrographis paniculata; 22. Astragaloside IV—Astragalus membranaceous; 23. Ursolic acid—Origanum majorana L.; 24. Oleanolic acid—Origanum majorana L.; 25. Ginsenoside-Rb1—Panax quinquefolius; 26. Zerumbone—Zingiber zerumbet; 27. Aminoguanidine—Paenonia lactiflora.

Figure 4

1. Abeliophyllum distichum; 2. Aegle marmelos; 3. Agrimonia pilosa ledeb; 4. Aster Koraiensis; 5. Camellia nitidissima Chi; 6. Carpobrotus edulis; 7. Cochlospermum religiosum; 8. Dendrobium chrysotoxum; 9. Ginkgo biloba; 10. Glycyrrhiza uralensi; 11. Juglans regia L.; 12. Litchi chinenesis; 13. Ligustrum lucidum Ait; 14. Lonicerae japonicae Flos; 15. Melissa officinalis; 16. Morniga oleifera Lam; 17. Morus alba; 18. Osteomeles schwerinae C.K. Schneid; 19. Perilla frutescens; 20. Platycodon grandiflorum; 21. Polygonatum odoratum; 22. Polygonum cuspidatum; 23. Polygonum multiflorum; 24. Prunella vulgaris; 25. Pueraria lobata; 26. Salvia miltiorrhiza Bge; 27. Stauntonia hexaphylla; 28. Tephrosia purpurea; 29. Terminalia catappa; 30. Vitex negundo; 31. Zea mays L.; 32. Alpinia zerumbet; 33. Andrographis paniculata Nees; 34. Astragalus membranaceous; 35. Origanum majorana L.; 36. Panax quinquefolius; 37. Zingiber zerumbet; 38. Cnidium Officinale; 39. Lycium barbarum; 40. Paenonia lactiflora.