# Neuroprotective Effects of the Combination of Green Tea, Saffron, Docosahexaenoic Acid, and α-Lipoic Acid in an In Vitro Model of Parkinson's Disease

**Authors:** Rebecca Galla, Simone Mulè, Stefania Battaglia, Valeria Curti, Francesca Romana Ranieri, Francesca Parini, Francesca Uberti

PMC · DOI: 10.1007/s12035-026-05800-4 · Molecular Neurobiology · 2026-03-15

## TL;DR

This study shows that a mix of green tea, saffron, DHA, and ALA protects brain cells in a lab model of Parkinson's disease.

## Contribution

The study introduces a novel combination of four bioactive compounds with synergistic neuroprotective effects in Parkinson's disease.

## Key findings

- The combination significantly restored cell viability after 6-OHDA exposure.
- The mix reduced oxidative stress, lipid peroxidation, and pro-inflammatory cytokines.
- The treatment downregulated PINK1 and Parkin, key markers of PD-related neurodegeneration.

## Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterised by dopamine deficiency and the accumulation of α-synuclein (α-syn), which aggregates into pathological inclusions known as Lewy bodies and Lewy neurites, distributed across multiple brain regions, with a particular prevalence in dopaminergic neurons. Alongside hallmark motor symptoms, PD is often accompanied by non-motor manifestations that severely affect patients’ quality of life. Levodopa remains the most effective therapy; however, it is associated with a wide range of side effects and shows little to no efficacy against non-motor symptoms. This study investigates the neuroprotective effects of a combination of four bioactive compounds—green tea, saffron, docosahexaenoic acid (DHA) and α-lipoic acid (ALA)—against the PD-related neurodegeneration. Their ability to cross the blood–brain barrier (BBB) while maintaining its integrity was evaluated using a validated in vitro model. Individual and combined effects of these compounds were assessed on mesencephalic dopaminergic cells exposed to 6-hydroxydopamine (6-OHDA), a widely used in vitro model of PD-like neurotoxicity. The results demonstrated that the combined treatment (Mix) significantly restored cell viability after 6-OHDA exposure and more effectively reduced oxidative and nitrosative stress, as well as lipid peroxidation, compared to single compounds. Furthermore, the Mix markedly decreased the production of pro-inflammatory cytokines (including tumour necrosis factor-alpha (TNF-α) and interleukins) and downregulated the expression of PTEN-induced kinase 1 (PINK1) and Parkin, two key markers of PD-related neurodegeneration. In conclusion, these results indicate that the Mix has a suggest a synergistic-like impact on various disease-causing pathways in PD, highlighting its promise as a multi-faceted neuroprotective approach.

## Linked entities

- **Genes:** PINK1 (PTEN induced kinase 1) [NCBI Gene 65018], park (parkin) [NCBI Gene 40336]
- **Chemicals:** 6-hydroxydopamine (PubChem CID 4624), docosahexaenoic acid (PubChem CID 445580), α-lipoic acid (PubChem CID 864)
- **Diseases:** Parkinson's disease (MONDO:0005180)

## Full-text entities

- **Genes:** CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}, Keap1 (Kelch-like ECH-associated protein 1) [NCBI Gene 117519] {aka Inrf2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, MAOB (monoamine oxidase B) [NCBI Gene 4129], Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, SLC6A3 (solute carrier family 6 member 3) [NCBI Gene 6531] {aka DAT, DAT1, PKDYS, PKDYS1}, DDC (dopa decarboxylase) [NCBI Gene 1644] {aka AADC}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, COMT (catechol-O-methyltransferase) [NCBI Gene 1312] {aka HEL-S-98n}, MIXL1 (Mix paired-like homeobox) [NCBI Gene 83881] {aka MILD1, MIX, MIXL}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}
- **Diseases:** gait abnormalities (MESH:D020233), shaking palsy (MESH:D010243), dopamine deficiency (MESH:C567730), hyposmia (MESH:D000086582), inflammation (MESH:D007249), bradykinesia (MESH:D018476), tremor (MESH:D014202), anxiety (MESH:D001007), degeneration of dopaminergic neurons (MESH:D009410), motor disorders (MESH:D000068079), fatigue (MESH:D005221), urinary disturbances (MESH:D014548), balance problems (MESH:D019973), motor deficits (MESH:D009461), NMS (MESH:D020879), depression (MESH:D003866), constipation (MESH:D003248), neuropathic pain (MESH:D009437), paresthesia (MESH:D010292), excessive daytime sleepiness (MESH:D006970), neurodegeneration (MESH:D019636), inflammatory cytokine (MESH:D000080424), rigidity (MESH:D009127), Rapid Eye Movement Sleep Behaviour Disorder (MESH:D020187), dopaminergic (MESH:D009422), mitochondrial (MESH:D028361), gastrointestinal dysfunction (MESH:D005767), dysautonomia (MESH:D054969), neuroinflammation (MESH:D000090862), neurotoxic (MESH:D020258), cognitive decline (MESH:D003072), PD (MESH:D010300), sleep disorders (MESH:D012893), mood disorders (MESH:D019964), neuropsychiatric manifestations (MESH:D012877), cytotoxic (MESH:D064420), pain (MESH:D010146)
- **Chemicals:** PBS (MESH:D007854), ethyl acetate (MESH:C007650), penicillin (MESH:D010406), omega-3 fatty acids (MESH:D015525), PUFAs (MESH:D005231), phosphate (MESH:D010710), DHA (MESH:D004281), ROS (MESH:D017382), methylmalonic acid (MESH:D008764), vitamin E (MESH:D014810), 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), serotonin (MESH:D012701), homocysteine (MESH:D006710), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MESH:D015632), safranal (MESH:C087963), EGCG (MESH:C045651), L-DOPA (MESH:D007980), MTT (MESH:C070243), dopamine (MESH:D004298), P/S (MESH:D010758), water (MESH:D014867), ascorbic acid (MESH:D001205), CO2 (MESH:D002245), crocin (MESH:C029036), polyphenol (MESH:D059808), O2- (MESH:D013481), L-Glutamine (MESH:D005973), NO (MESH:D009569), DMEM (-), picrocrocins (MESH:C087962), nitrate (MESH:D009566), hydrocortisone (MESH:D006854), streptomycin (MESH:D013307), rotenone (MESH:D012402), Hepes (MESH:D006531), Lipid (MESH:D008055), norepinephrine (MESH:D009638), catechin (MESH:D002392), 6-OHDA (MESH:D016627), polyester (MESH:D011091), thiobarbituric acid (MESH:C029684), heparin (MESH:D006493), SDS (MESH:D012967), ALA (MESH:D008063), iron (MESH:D007501), phenol red (MESH:D010637)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Camellia sinensis (black tea, species) [taxon 4442], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), mesencephalic dopaminergic — Homo sapiens (Human), Conditionally immortalized cell line (CVCL_B056), HUVEC — Homo sapiens (Human), Finite cell line (CVCL_2959), SK-N-AS — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0528), N27 — Rattus norvegicus (Rat), Transformed cell line (CVCL_D584), CCF-STTG1 — Homo sapiens (Human), Astrocytoma, Cancer cell line (CVCL_1118)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12989466/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12989466/full.md

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Source: https://tomesphere.com/paper/PMC12989466