Green Tea Catechins as Therapeutic Antioxidants for Glaucoma Treatment
Abstract
:1. Green Tea Catechins: Chemistry and Pharmacokinetics
1.1. Chemistry of Green Tea Constituents
1.2. Pharmacokinetics of Catechins in the Eye
2. Therapeutic Properties of Green Tea Catechins: Antioxidation and Anti-Inflammation in the Eye
3. Pathophysiological Conditions in Glaucoma: Oxidative Stress and Inflammation
4. Green Tea Catechins in Experimental Cellular Models of Glaucoma
5. Green Tea Catechins in Experimental Animal Models of Glaucoma
6. Clinical Applications of Green Tea Catechins for Glaucoma Treatments
7. Summary, Challenges, and Future Prospects
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Biological Properties | Mechanisms | References |
---|---|---|
| Electron resonance within the phenolic moiety following abstraction of proton by ROS. | [15,16] |
| High reduction potential of catechins compared to endogenous antioxidants; reducing and recycling the oxidized endogenous molecules. | [17] |
| Binding to 67LR to increase Tollip expression, which negatively regulates TLR signaling to suppress inflammatory mediators. | [18] |
| Binding to the active sites of p53 and changing the structural conformation to prevent ubiquitination by MDM2; retaining the biological level and activities of p53. Inhibiting the activation of the wild-type and some mutant EGF receptors in non-small cell lung cancer cell lines. | [19,21] |
| Binding to the EGF receptor to change the topology and block EGF to activate the receptor for subsequent inflammation activities. | [20] |
| Inhibiting anti-oxidative molecules, including the Trx/Trx receptor to increase ROS, which acts as a secondary messenger for various pathways Activating CaMKKβ to increase energy metabolism; elevating cytosolic calcium to increase nitric oxide production. Increasing cAMP to promote the phosphorylation of eNOS and vasodilator-stimulated phosphoprotein to cause vaso-relaxation. Activating AMPK to reduce endothelin-1 expression for vasodilation. | [22,24,25,26,27,28,29] |
Maximum Concentration | GTE | GC | EGC | C | EC | EGCG | GCG | ECG |
---|---|---|---|---|---|---|---|---|
Cmax (nM) | ||||||||
Plasma | Sunphenon DCF-1 | 91.5 ± 57.4 | 754.9 ± 235.8 | 139.0 ± 57.0 | 1258.4 ± 294.0 | 310.4 ± 59.9 | 50.8 ± 10.4 | 159.1 ± 33.9 |
Theaphenon® E | 530.8 ± 200.2 | 13718.0 ± 4948.0 | 2990.0 ± 1990.0 | 9143.0 ± 1912.0 | 6687.0 ± 4437.0 | 131.3 ± 91.7 | 443.8 ± 352.3 | |
Aqueous humor | Sunphenon DCF-1 | - | 602.9 ± 116.7 | 127.4 ± 62.8 | 138.9 ± 58.5 | 13.2 ± 5.1 | 33.5 ± 20.4 | 47.8 ± 8.1 |
Theaphenon® E | 246.9 ± 34.9 | 911.3 ± 250.5 | 98.3 ± 19.2 | 708.1 ± 127.8 | 284.4 ± 58.4 | 0.57 ± 0.98 | 26.5 ± 10.3 | |
Vitreous humor | Sunphenon DCF-1 | 110.6 ± 22.1 | 15.9 ± 7.0 | 96.5 ± 23.3 | 20.5 ± 10.6 | 15.4 ± 2.7 | 20.9 ± 9.9 | 14.0 ± 5.1 |
Theaphenon® E | 4492.0 ± 443.5 | 404.1 ± 102.5 | 321.7 ± 69.5 | 436.8 ± 102.5 | 2224.4 ± 805.4 | 33.9 ± 31.0 | 369.6 ± 74.0 | |
Cmax (ρmol/g) | ||||||||
Choroid–sclera | Sunphenon DCF-1 | 11461.8 ± 5168.7 | 1506.3 ± 941.1 | 477.6 ± 346.9 | 283.5 ± 66.5 | 184.4 ± 39.0 | 220.5 ± 69.7 | 10.7 ± 4.3 |
Theaphenon® E | 188.28 ± 111.3 | 542.2 ± 335.1 | 294.7 ± 32.8 | 1818.0 ± 563.0 | 1183.0 ± 611.0 | 59.0 ± 54.8 | 518.0 ± 292.0 | |
Retina | Sunphenon DCF-1 | 22729.4 ± 4229.4 | 8020.8 ± 1658.5 | 492.7 ± 235.2 | 608.0 ± 112.0 | 259.1 ± 67.2 | 3.2 ± 1.9 | - |
Theaphenon® E | 61.0 ± 43.5 | 118.2 ± 55.6 | 35.7 ± 15.0 | 174.5 ± 45.8 | 784.4 ± 195.9 | 59.0 ± 54.8 | 64.0 ± 16.0 | |
Lens | Sunphenon DCF-1 | 1558.1 ± 318.4 | 1172.3 ± 207.8 | 300.0 ± 151.5 | 72.3 ± 19.1 | 149.1 ± 26.5 | 18.0 ± 6.6 | 90.3 ± 45.8 |
Theaphenon® E | 1.9 ± 3.0 | 10.9 ± 8.9 | 4.1 ± 4.8 | 4.6 ± 6.9 | 43.9 ± 25.8 | 0.4 ± 0.6 | 1.0 ± 3.0 | |
Cornea | Sunphenon DCF-1 | - | 359.4 ± 66.8 | 58.5 ± 15.4 | 30.6 ± 5.7 | 25.2 ± 15.5 | 10.7 ± 3.9 | 91.1 ± 18.7 |
Theaphenon® E | 10.8 ± 16.7 | 59.5 ± 26.7 | 61.7 ± 17.5 | 536.4 ± 61.1 | 634.6 ± 122.9 | 18.8 ± 24.2 | 101.8 ± 43.1 | |
Elimination | GTE | GC | EGC | C | EC | EGCG | GCG | ECG |
λz (h−1) | ||||||||
Plasma | Sunphenon DCF-1 | 0.107 ± 0.010 | 0.213 ± 0.015 | 0.104 ± 0.038 | 0.371 ± 0.000 | 0.236 ± 0.007 | 0.171 ± 0.013 | 0.211 ± 0.010 |
Theaphenon® E | 0.270 ± 0.030 | 0.390 ± 0.040 | 0.370 ± 0.080 | 0.400 ± 0.050 | 0.230 ± 0.020 | 1.250 ± 0.380 | 0.210 ± 0.040 | |
Aqueous humor | Sunphenon DCF-1 | - | 0.045 ± 0.001 | 0.209 ± 0.012 | 0.093 ± 0.062 | 0.304 ± 0.012 | 0.111 ± 0.033 | 0.124 ± 0.043 |
Theaphenon® E | 0.110 ± 0.020 | 0.240 ± 0.020 | 0.130 ± 0.030 | 0.210 ± 0.040 | 0.090 ± 0.020 | - | 0.130 ± 0.120 | |
Vitreous humor | Sunphenon DCF-1 | 0.166 ± 0.010 | 0.041 ± 0.001 | 0.106 ± 0.030 | 0.067 ± 0.004 | 0.058 ± 0.012 | 0.042 ± 0.006 | 0.224 ± 0.035 |
Theaphenon® E | 0.020 ± 0.010 | 0.110 ± 0.090 | 0.110 ± 0.060 | 0.100 ± 0.030 | 0.080 ± 0.020 | - | - | |
Choroid–sclera | Sunphenon DCF-1 | 0.057 ± 0.001 | 0.461 ± 0.015 | 0.220 ± 0.014 | 0.488 ± 0.007 | 0.267 ± 0.019 | 0.929 ± 0.049 | - |
Theaphenon® E | - | 0.250 ± 0.090 | 0.220 ± 0.090 | 0.370 ± 0.060 | 0.080 ± 0.040 | - | 0.150 ± 0.070 | |
Retina | Sunphenon DCF-1 | 0.188 ± 0.045 | 0.203 ± 0.050 | 0.245 ± 0.010 | 2.432 ± 0.154 | 0.413 ± 0.040 | - | - |
Theaphenon® E | - | 0.040 ± 0.030 | 0.040 ± 0.010 | 0.060 ± 0.020 | 0.040 ± 0.020 | - | 0.090 ± 0.030 | |
Lens | Sunphenon DCF-1 | 0.302 ± 0.049 | 0.084 ± 0.020 | 0.234 ± 0.032 | 0.049 ± 0.004 | 0.269 ± 0.011 | 3.160 ± 0.130 | - |
Theaphenon® E | - | - | - | - | 0.130 ± 0.060 | - | - | |
Cornea | Sunphenon DCF-1 | - | 0.170 ± 0.031 | 0.116 ± 0.007 | 0.043 ± 0.012 | 0.125 ± 0.001 | 0.372 ± 0.006 | 0.477 ± 0.021 |
Theaphenon® E | - | - | 0.220 ± 0.100 | 0.220 ± 0.100 | 0.090 ± 0.020 | - | 0.100 ± 0.090 |
Identifier. | Country | Status | Phase | Enrollment | Targeted Eye Diseases or Conditions | Intervention | Dosage | Duration |
---|---|---|---|---|---|---|---|---|
NCT00476138 | Italy | Unknown | Phase I/II | 40 | Primary open angle glaucoma Ocular hypertension | Oral EGCG treatment | 200 mg/day | 3 months |
NCT00718653 | United States | Completed | Not Applicable | 40 | Eye health | Lutein plus green tea extract | Lutein (12 mg/day) Green tea extract (200 mg/day) | Unknown |
NCT01646047 | United States | Completed [118] | Not Applicable | 70 | Diabetes Mellitus—Type 1 Diabetes Mellitus—Type 2 Non-proliferative diabetic retinopathy | Multi-component nutritional supplement capsules (vitamin C, mixed tocopherols/tocotrienols, vitamin D, fish oil, lutein, zeaxanthin, pine bark extract, benfotiamine, curcumin, and green tea extract) | 2 capsules/day | 6 months |
NCT02984813 | United States | Terminated | Phase I | 21 | Open-angle glaucoma Diabetic retinopathy | Nutritional supplements capsules (alpha lipoic acid, citicoline, Co-enzyme Q10, Ginkgo biloba extract, grape seed extract, N-acetyl-cysteine, curcumin, and green tea extract) | 2 capsules/day | 3 months |
NCT03866005 | United States | Unknown | Not Applicable | 150 | Center-involved diabetic macular edema | Multi-component nutritional supplement capsules (macular carotenoids lutein, zeaxanthin, vitamins B1, B12, C, D, E, lipoic acid, coenzyme Q10, resveratrol, patented extract of French maritime pine bark grape seed, curcumin, and green tea extract) | 2 or 4 capsules/day | Study duration |
NCT04117022 | United States | Recruiting | Not Applicable | 45 | Diabetes Diabetic Retinopathy | Multi-component nutritional supplement capsules (vitamins C, D3 and E (d-α tocopherol), zinc oxide, eicosapentaenoic acid, docosahexaenoic acid, α-lipoic acid, coenzyme Q10, mixed tocotrienols/tocopherols, zeaxanthin, lutein, benfotiamine, N-acetyl cysteine, grape seed extract, resveratrol, turmeric root extract, Pycnogeno, and green tea leaf) | 2 capsules/day | 6 months |
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Ng, T.K.; Chu, K.O.; Wang, C.C.; Pang, C.P. Green Tea Catechins as Therapeutic Antioxidants for Glaucoma Treatment. Antioxidants 2023, 12, 1320. https://doi.org/10.3390/antiox12071320
Ng TK, Chu KO, Wang CC, Pang CP. Green Tea Catechins as Therapeutic Antioxidants for Glaucoma Treatment. Antioxidants. 2023; 12(7):1320. https://doi.org/10.3390/antiox12071320
Chicago/Turabian StyleNg, Tsz Kin, Kai On Chu, Chi Chiu Wang, and Chi Pui Pang. 2023. "Green Tea Catechins as Therapeutic Antioxidants for Glaucoma Treatment" Antioxidants 12, no. 7: 1320. https://doi.org/10.3390/antiox12071320