Table 1.
Catechin use in neurodegenerative disorders.
| Author (Year) | Objective | Type of Study and Sample Size | Inclusion and Exclusion Criteria | Interventions | Methodology | Main Outcomes | Conclusions | Quality of Evidence |
|---|---|---|---|---|---|---|---|---|
| Huntington disease | ||||||||
| Beasley et al., 2019 [51] | To investigate the ability of EGCG to inhibit aggregation in the presence of lipid vesicles (POPC or TBLE) | In-vitro model | Glutathione S-transferase (GST)-htt-exon1(46Q) fusion protein purified from E. coli | EGCG co-incubation with -exon1(46Q) | POPC or TBLE lipid vesicles preparation. ThT aggregation assays Image acquisition by atomic force microscopy Vesicle-binding assay |
↓ exon 1(46Q) aggregation (p < 0.01) ↓ exon 1(46Q) fibril formation and aggregation in the presence of lipid vesicles (POPC or TBLE) (p < 0.01) |
EGCG inhibitory effect on htt aggregation process persists in the presence of lipid vesicles | ++ |
| Ehrnhoefer et al., 2006 [52] | To analyze the dose-dependent effect of EGCG on mutant htt exon 1 protein aggregation | In-vitro model | Yeast cultures and transgenic HD flies overexpressing a pathogenic htt exon 1 protein | Mutant GST-tagged htt exon 1 fusion protein with 51 glutamines (GST-HDQ51) was incubated with green tea polyphenols (GCG, GC, EGC, and EGCG) | Dot blot assays Atomic force microscopy studies |
↓ mutant htt exon 1 protein aggregation, polyQ-mediated htt protein aggregation and cytotoxicity ↓ photoreceptor degeneration ↑ motor function |
EGCG acts as modulator of htt exon 1 misfolding and oligomerization reducing polyQ-mediated toxicity in vivo | ++ |
|
Varga et al., 2018 [53] |
To study the effects of green tea on HD pathogenesis | Experimental transgenic Drosophila model of HD n = 356 (HttQ93on CM), n = 345 (HttQ93 on GTM), n = 122 (HttQ20on CM), n = 118 (HttQ20 on GTM) |
Inclusion: Neuron-specific GAL4 driver strain w P{GawB}elavC155 males and w; UAS-Httex1p-Q93 or control w; UAS-Httex1p-Q20 females | Drosophila strain exposure to green tea medium | Eclosion, survival, climbing assay and pseudopupil tests Polyphenol content determination by Folin-Ciocalteau method Huntingtin protein level measurement by Immunoblot |
Mutant huntingtin expressing Drosophila exposed to green tea presented: =Viability (p < 0.001) ↓ Neurodegeneration (p < 0.001) ↑ Longevity (p < 0.001) |
Green tea consumption might modulate symptoms of HD. | ++ |
| Multiple sclerosis | ||||||||
| Bellmann-Strobl et al., 2021 [54] | To evaluate the safety and efficacy of EGCG + GA in RRMS patients | Prospective, double blind, Ph II, randomized controlled trial. n = 122 |
Inclusion: age: 18–60, EDSS score 0–6.5, stable with GA. Exclusion: other forms of MS, major diseases, laboratory abnormalities, other medication | 800 mg oral EGCG/day or placebo for 18 months | Neurologic assessments, safety monitoring, laboratory exams and MRI at baseline and every three months | No differences with EGCG + GA treatment on brain MRI and on SAE and AE in comparison to placebo + GA. |
No superiority of EGCG + GA compared to placebo + GA in MRI changes or clinical disease activity. EGCG at 800 mg/day was safe | ++++ |
| Rust et al., 2021 [55] | To evaluate if treatment with EGCG affects progression of brain atrophy and its safety on primary and SPMS | Prospective, double blind, phase II, randomized controlled trial. n = 61 | Inclusion: age: 18–65, EDSS score: 3–8, relapse-free period of minimum 30 days. No MS modifying therapy. Exclusion: RRMS, major diseases, laboratory abnormalities, hepatotoxic medications. |
Increasing doses of EGCG until reaching 1200 mg or placebo, for 36 months | Neurologic assessments at baseline and every six months. Safety monitoring and laboratory exams every 2–3 months. MRI at baseline and every year evaluating PBF | No differences on PBF decrease, SAE and AE between groups. | No differences on EGCG group didn’t on brain atrophy compared with placebo. EGCG 1200 mg/day was safe | ++++ |
| Mossakowski et al., 2015 [56] | To investigate the role of oxidative stress on neuronal degeneration and on antioxidant therapy | Murine and human: n = 6. Groups: RRMS GA, RRMS GA + EGCG, RRMS untreated, CIS, controls, SPMS) | Patients with RRMS, SPMS, or CIS | EGCG 600 mg or placebo in groups of RRMS + GA. EAE murine model of MS |
Examine the oxidation of NADH and NADPH in mononuclear cells with a two-photon laser-scanning microscopy to see activation of NOX enzymes | EGCG + GA ↓ NOX in CD11b + monocytes in MS and EAE. | EGCG counteracted NOX overactivation in MS patients | ++ |
| Mähler et al., 2015 [57] | To investigate if EGCG improves energy metabolism and substrate utilization in MS | Randomized, double blind, placebo-controlled, crossover trial n = 18 (eight men) |
Inclusion: RRMS, treated with GA for six months. EDSS score: 4.5. Age: 20–60. BMI: 18.5–30.0. Exclusion: other MS forms. Relapses three months before or during the study. Other diseases. Regular caffeine or green tea intake, social drugs |
EGCG (600 mg/day) and placebo 12 weeks (four weeks of washout). | Measurements from blood samples, microdialysates from adipose tissue and skeletal muscle, fasting and postprandial EE, FAOx and CHOx rates, at rest or during 40-min of exercise | Working efficiency: placebo: 20 +/− 3 EGCG: 25 +/− 6 (p = 0.004) Postprandial FAOx: Placebo: 8.3 +/− 4.3 EGCG: 8.6 +/− 5.0 (sex differences) |
EGCG given to MS patients over 12 weeks improves muscle metabolism during moderate exercise, predominantly in men | ++ |
| Lovera et al., 2015 [58] | To evaluate the safety and futility of Polyphenon E treatment | PhI: single group. PhII: randomized double blind placebo-controlled study. n = 10 on phI n = 13 on phII |
Inclusion: MS with RRMS or SPMS. six-month stability. Treatment with GA or no treatment in PhI, GA or Interferon β in PhII. Exclusion: Bone marrow ablation or alemtuzumab use. Mitoxantrone, cyclophosphamide, natalizumab or fingolimod use during the past nine months. Other diseases |
PhI: Polyphenon E capsules (400 mg of EGCG) twice daily for six months. PhII: Polyphenon E or placebo, same dose for one year | Measure plasma levels. Evaluate adverse events monthly. Evaluate NAA levels at 0, 6, and 12 months using MRI |
Polyphenon E: ↑ NAA adjusted creatinine. 5/7 participants had elevated liver enzymes in Ph 2 | 400 mg of EGCG/12 h olyphenon E increased NAA brain levels. Polyphenon E may increase the risk of hepatotoxicity | +++ |
| Wang et al., 2012 [59] | Determine the effect and mechanisms of EGCG on EAE development. | Experimental animal model. Four groups, n = 12/group |
Specific pathogen-free C57BL/6 female mice. | Diet supplement with 0%, 0.15%, 0.3%, or 0.6% EGCG 30 days, after produce EAE. | Signs were daily scored from day 0 to 30 after EAE induction. Euthanasia and histology and molecular evaluation. | EGCG ↓ symptoms and pathological features in the central nervous system. | EGCG may attenuate EAE autoimmune response. | + |
| Sun et al., 2013 [60] | Investigate the mechanism of EGCG on amelioration of EAE | Experimental animal model n = 10/group. |
Male C57BL/6 mice, 7 weeks old | EAE induction. When clinical signs start: 300 μg EGCG in 100 μL PBS daily or PBS alone. | Clinical signs evaluation. After death histopathology and molecular evaluation. |
EGCG ↓ disease severity in EAE, ↓ brain inflammation and ↓ demyelination damage. | EGCG may be useful for the MS treatment. | + |
| Herges et al., 2011 [61] | Evaluate the effect of GA and EGCG in vitro and in a EAE model. | Experimental animal model and in vitro. n = 8/group |
6–8 week old female SJL/L mice | Prevention and treatment with EGCG 300 μg/12 h or vehicle and 50–150 μg GA/24 h from day 9 before EAE production. | Valuation of clinical signs and histological examination. | EGCG + GA ↓ disease onset, ↓ clinical severity and ↓ inflammatory infiltrates. | GA + EGCG may be useful and safe approach for MS. | + |
| Semnani et al., 2016 [62]; Semnani et al., 2017 [63] | Study EGCG effects on the PLP and Olig1 expression. | Experimental animal model. n = 60 (6 groups, n = 10) | C57BL/6 male mice, 8 weeks old. | Induction demyielinization with cuprizone. Injection of EGCG 50 mg/Kg/day, PBS, or nothing. | After 2 or 4 weeks, euthanasia and cerebral exam Western Blot or Real-time PCR | EGCG: ↑ PLP and Olig1 expression | EGCG increases PLP and Olig1 expression in the cerebral cortex of this mouse model of MS. | + |
Abbreviations. ↓: Decrement ↑: Increment EGCG: epigallocatechin-3-gallate; POPC: 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine; TBLE: total brain lipid extract; GST: glutathione S-transferase; PoliQ: polyglutamine; HD: Hungtinton disease; GCG: gallocatechin 3-gallate; GC: gallocatechin; EGC: epigallocatechin; GA: Glatiramer acetate; RRMS: relapsing-remitting multiple sclerosis; EDSS: Expanded Disability Status Scale; MS: multiple sclerosis; MRI: magnetic resonance imaging; AE: adverse event; SAE: several adverse event; PBF: parenchymal brain function; CIS: clinically isolated syndrome; SPMS: secondary progressive multiple sclerosis; EAE: experimental autoimmune encephalomyelitis; NADPH: nicotinamide adenine dinucleotide phosphate; NADH: nicotinamide adenine dinucleotide; NOX: nitrogen oxides; BMI: body mass index; EE: energy expenditure; FAOx: fat oxidation; CHOx: carbohydrate oxidation; PhI: Phase I; PhII: Phase II; NAA: N-acetyl aspartate; IHC: immunohistochemistry; CNS: central nervous system; PCR: polymerase chain reaction; PBS: phosphate-buffered saline; LDH: Lactate dehydrogenase; MOG: myelin oligodendrocyte glycoprotein; PLP: proteolipid protein; Olig 1: oligodendrocyte transcription factor 1; Th 17: T helper 17; Th1: T helper 1;ThT: thioflavin T. GTM: Green tea containing medium. CM: control medium. ↑: increment; ↓: reduction. Quality of evidence grades: high (++++), moderate (+++), low (++), very low (+).