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Background <p>Parkinson’s disease (PD) is second most common neurodegenerative disorder characterized by gradual loss of dopaminergic neurons in the substantia nigra. Its pathophysiology reflects interlinked processes of oxidative stress, inflammation, and altered gene expressions of ubiquitin-proteasome pathway. The current therapy, L-DOPA (Sinemet) provides only symptomatic relief without modifying disease progression. This study aimed to evaluate stigmasterol, a bioactive phytocompound having antioxidant and anti-inflammatory properties and blood brain barrier permeability, as a potential candidate for modifying disease progression in PD.</p> Methods <p>PD was induced in mice using neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals were randomly assigned to five groups: healthy control (HC), MPTP only (PC), MPTP + Sinemet (SC), MPTP + stigmasterol therapeutic (StigTx), and stigmasterol preventive (StigPre). Oxidative stress markers, inflammatory mediators (IL-1β, IL-6, TNF-α, CRP), hepatic and renal markers were evaluated. Dopaminergic neuronal survival was examined by tyrosine hydroxylase immunostaining, and PD-related gene expression (PRKN, PINK1, UCHL1, LRRK2) was analysed.</p> Results <p>MPTP exposure caused marked motor decline, strong oxidative stress and inflammation. Sinemet partially improved motor functions and antioxidant status but showed limited effects on lipid peroxidation and induced mild hepatic stress. In contrast, stigmasterol reduced inflammation, enhanced antioxidant defences, and improved motor ability without inducing organ toxicity. Preventive use showed more promising results by preserving dopaminergic neurons and modulated PD related gene expression.</p> Conclusion <p>Stigmasterol improves motor dysfunction and provides significant neuroprotection, highlighting its potential as a multitarget therapeutic candidate capable of modifying disease related molecular pathways.</p>

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Neuroprotective role of stigmasterol through restoration of ubiquitin-proteasome gene expression in an MPTP-induced rodent model of Parkinson’s disease

  • 期刊论文

  • 发表日期：

    2026年4月28日

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  • Shazia Sukhera,
  • Imtiaz Mustafa,
  • Sadia Zafar,
  • Qurat ul Ain Javaid,
  • Imran Mukhtar,
  • Jaweria Nisar,
  • Ahsaan Ali

摘要

Background

Parkinson’s disease (PD) is second most common neurodegenerative disorder characterized by gradual loss of dopaminergic neurons in the substantia nigra. Its pathophysiology reflects interlinked processes of oxidative stress, inflammation, and altered gene expressions of ubiquitin-proteasome pathway. The current therapy, L-DOPA (Sinemet) provides only symptomatic relief without modifying disease progression. This study aimed to evaluate stigmasterol, a bioactive phytocompound having antioxidant and anti-inflammatory properties and blood brain barrier permeability, as a potential candidate for modifying disease progression in PD.

Methods

PD was induced in mice using neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animals were randomly assigned to five groups: healthy control (HC), MPTP only (PC), MPTP + Sinemet (SC), MPTP + stigmasterol therapeutic (StigTx), and stigmasterol preventive (StigPre). Oxidative stress markers, inflammatory mediators (IL-1β, IL-6, TNF-α, CRP), hepatic and renal markers were evaluated. Dopaminergic neuronal survival was examined by tyrosine hydroxylase immunostaining, and PD-related gene expression (PRKN, PINK1, UCHL1, LRRK2) was analysed.

Results

MPTP exposure caused marked motor decline, strong oxidative stress and inflammation. Sinemet partially improved motor functions and antioxidant status but showed limited effects on lipid peroxidation and induced mild hepatic stress. In contrast, stigmasterol reduced inflammation, enhanced antioxidant defences, and improved motor ability without inducing organ toxicity. Preventive use showed more promising results by preserving dopaminergic neurons and modulated PD related gene expression.

Conclusion

Stigmasterol improves motor dysfunction and provides significant neuroprotection, highlighting its potential as a multitarget therapeutic candidate capable of modifying disease related molecular pathways.