# Therapeutic Potential of Pistachio Green Hull Extract in Treating Parkinson's Disease: A Comprehensive In Vivo and In Vitro Investigation

**Authors:** Maedeh Tavakoli, Negin Mohammadi, Mohsen Barzegar, Neda Valian, Narges Hosseinmardi, Mohammad Ali Sahari, Sabereh Saremi

PMC · DOI: 10.1002/fsn3.70204 · Food Science & Nutrition · 2025-05-16

## TL;DR

Pistachio green hull extract shows promise in treating Parkinson's disease by improving motor function and reducing harmful protein buildup.

## Contribution

PGHE is introduced as a novel dietary supplement with neuroprotective effects in Parkinson's disease models.

## Key findings

- PGHE improved motor impairments in a rat model of Parkinson's disease.
- PGHE reduced α-synuclein aggregation in vitro at 250 μg/mL.
- PGHE was found to be non-toxic with an LD50 greater than 5000 mg/kg.

## Abstract

Pistachio green hull extract (PGHE), an agro‐industrial by‐product, is rich in phenolic compounds with significant inherent antioxidant and anti‐inflammatory activities. In this study, the neuroprotective effects of PGHE against Parkinson's disease (PD), a progressive neurodegenerative disorder, were evaluated both in vivo and in vitro. The lethal dose (LD50) of PGHE was greater than 5000 mg/kg, indicating its safety and nontoxicity. Rats were orally treated with PGHE (800 mg/kg/day) 24 h after injection of 6‐OHDA (20 μg/rat in right MFB) for 14 days. Motor function was evaluated on Days 7 and 15 after 6‐OHDA administration using the cylinder, narrow beam, pole, rotarod, and apomorphine‐induced rotations tests. PGHE significantly improved motor impairments induced by 6‐OHDA. An in vitro study indicated that increasing concentrations of PGHE up to 250 μg/mL resulted in a reduction in the aggregation of α‐synuclein characterized by thioflavin T fluorescence and Congo red assays. Transmission electron microscopy images further confirmed a decrease in α‐synuclein aggregation in the presence of PGHE. In conclusion, these findings indicated that PGHE improved motor deficits in a rat model of PD and decreased α‐synuclein aggregation in vitro, suggesting that it can be considered a novel dietary supplement for PD therapy. However, more studies are needed to clarify the underlying mechanisms of PGHE's effect on PD pathogenesis and its potential applications in developing functional foods or nutraceuticals.

A new natural extract (PGH) was introduced for the treatment of Parkinson disease (PD). PGHE treatment of PD in a rat model led to better behavioral results. PGHE has a neuroprotective effect in the 6‐OHDA‐induced model of PD, and at 250 μg/ml had the highest inhibitory effect on α‐synuclein fibrillation.

## Linked entities

- **Chemicals:** 6-OHDA (PubChem CID 4624), thioflavin T (PubChem CID 16953), Congo red (PubChem CID 11313)
- **Diseases:** Parkinson's disease (MONDO:0005180)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, Snca (synuclein alpha) [NCBI Gene 29219]
- **Diseases:** hypertension (MESH:D006973), dyskinesias (MESH:D004409), inflammatory (MESH:D007249), neuroinflammation (MESH:D000090862), IPTG (MESH:D014808), movement disorders (MESH:D009069), MFB (MESH:C566067), brain injuries (MESH:D001930), anti-diabetic (MESH:D003920), amyloid fibrillation (MESH:D014693), Lewy (MESH:D018827), Alzheimer's (MESH:D000544), postural instability (MESH:D054972), neurodegeneration (MESH:D019636), mitochondrial dysfunction (MESH:D028361), contralateral rotation (MESH:D009759), motor deficits (MESH:D009461), decline in motor coordination (MESH:D001259), Bradykinesia (MESH:D018476), Oral Toxicity (MESH:D064420), behavioral dysfunctions (MESH:D001523), rigidity (MESH:D009127), balance problems (MESH:D019973), PGH (OMIM:614156), Motor impairment (MESH:D000068079), degeneration (MESH:D009410), akinesia (MESH:C537921), PD (MESH:D010300), tremors (MESH:D014202)
- **Chemicals:** ThT (MESH:C121030), acetonitrile (MESH:C032159), phosphate (MESH:D010710), uranyl acetate (MESH:C005460), Baicalein (MESH:C006680), levodopa carbidopa (MESH:C009265), xylazine (MESH:D014991), ascorbate (MESH:D001205), formic acid (MESH:C030544), ROS (MESH:D017382), imidazole (MESH:C029899), Ni (MESH:D009532), phloroglucinol (MESH:D010696), gallic acid (MESH:D005707), iron (MESH:D007501), vanillic acid (MESH:D014641), ellagic acid (MESH:D004610), naringin (MESH:C005274), carbon (MESH:D002244), polyunsaturated fatty acids (MESH:D005231), Polyphenols (MESH:D059808), L-dopa (MESH:D007980), Apomorphine (MESH:D001058), myricetin (MESH:C040015), tyrosol (MESH:C011867), SDS (MESH:D012967), quercetin (MESH:D011794), potassium phosphate (MESH:C013216), Congo Red (MESH:D003224), 6-OHDA (MESH:D016627), naringenin (MESH:C005273), agarose (MESH:D012685), quercetin-3-O-galactoside (MESH:C021304), H2O (MESH:D014867), Desipramine (MESH:D003891), kanamycin (MESH:D007612), flavonoids (MESH:D005419), Dopamine (MESH:D004298), quercetin-3-O-rutinoside (MESH:C404204), rotenone (MESH:D012402), curcumin (MESH:D003474), 6-Hydroxydopamine hydrochloride (-), NaCl (MESH:D012965), DA (MESH:C025953), Thioflavin (MESH:C009462)
- **Species:** Pistacia vera (pistachio, species) [taxon 55513], Rattus norvegicus (brown rat, species) [taxon 10116], Escherichia coli (E. coli, species) [taxon 562], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** SHSY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), BL21 — Homo sapiens (Human), EBV-related Burkitt lymphoma, Cancer cell line (CVCL_M639)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12082081/full.md

## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC12082081/full.md

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Source: https://tomesphere.com/paper/PMC12082081