# The Neuroameliorative Effects of Enzymatically Modified Isoquercitrin and Sodium R-lipoate on the Rotenone rat Model of Parkinson’s Disease

**Authors:** Imam Hassouna, Omar H. Hassanein, Ibrahim A. El-Elaimy, Hany M. Ibrahim

PMC · DOI: 10.1007/s11064-026-04715-9 · Neurochemical Research · 2026-03-25

## TL;DR

This study shows that EMIQ and NaRLA reduce neuroinflammation and improve motor function in a rat model of Parkinson's disease.

## Contribution

The study demonstrates the neuroameliorative effects of EMIQ and NaRLA in a rotenone-induced PD model.

## Key findings

- EMIQ and NaRLA reduced neuroinflammation by lowering TLR4, IL-1β, and IL-6 levels.
- The compounds improved motor impairments by increasing dopamine and TH immunoreactivity.
- They decreased IBA1+ microglial cells, indicating reduced neuroinflammation.

## Abstract

Parkinson’s disease (PD) is a neurodegenerative condition distinguished by both motor and non-motor signs. Currently, therapeutic interventions effectively mitigate motor symptoms; however, they fail to impede the progression of neurodegeneration. Enzymatically modified isoquercitrin (EMIQ) is a variant of isoquercitrin with enhanced bioavailability and potentially greater health benefits. Sodium R-Lipoate (NaRLA) is a modified form of lipoic acid with improved stability and efficacy. The current work assessed EMIQ and NaRLA neuroameliorative properties in a rotenone (ROT) model of PD in rats. The study employed open field and hanging tests to evaluate motor effects, and used dopamine (DA) estimation and tyrosine hydroxylase (TH) immunoreactivity to confirm motor abnormalities and neurodegeneration. Furthermore, neuroinflammation was evaluated through ELISA of proinflammatory cytokines (IL-1β, IL-6), expression of Toll-like receptor 4 (TLR4) via qRT-PCR, and immunoreactivity of ionized calcium-binding adaptor molecule 1 (IBA1). The findings indicated that the use of EMIQ and NaRLA with ROT reduced the neuroinflammation via decreasing: the expression level of TLR4, IL-1β and IL-6 levels, and the number of IBA1+ microglial cells. Moreover, EMIQ and NaRLA ameliorated motor impairments induced with ROT through the enhancement of rats’ behavior, increasing DA concentration and TH immunoreactivity in the striatum. In the light of the findings of the current investigation, EMIQ and NaRLA exerted neuroameliorative effects against the ROT‐induced PD model. These results provide support for the potential impact of EMIQ and NaRLA in the treatment of PD and other diseases related to mitochondrial dysfunction and neuroinflammation.

The online version contains supplementary material available at 10.1007/s11064-026-04715-9.

## Linked entities

- **Chemicals:** Sodium R-lipoate (PubChem CID 56653697), rotenone (PubChem CID 6758), dopamine (PubChem CID 681), IL-6 (PubChem CID 165368475)
- **Diseases:** Parkinson’s disease (MONDO:0005180)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], Aif1 (allograft inflammatory factor 1) [NCBI Gene 29427] {aka BART-1, Bart1, iba1, mrf-1}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 24383] {aka BARS-38, Gapd}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 24770] {aka MCP-1, MCP1, Scya2, Sigje}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Th (tyrosine hydroxylase) [NCBI Gene 25085] {aka The}, Tlr4 (toll-like receptor 4) [NCBI Gene 29260], Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Prkaca (protein kinase cAMP-activated catalytic subunit alpha) [NCBI Gene 25636] {aka Cs-PKA, PKCA1}
- **Diseases:** movement slowness (MESH:D020754), sensory impairment (MESH:D012678), dopamine (DA) deficiency (MESH:C567730), cognitive and mental abnormalities (MESH:D060825), catalepsy (MESH:D002375), nervous system injury (MESH:D020196), brain injury (MESH:D001930), damage (MESH:D020263), Motor deficits (MESH:D009461), Alzheimer's disease (MESH:D000544), behavioral (MESH:D001523), brain damage (MESH:D001925), Neuroinflammation (MESH:D000090862), sleep disturbances (MESH:D012893), PD (MESH:D010300), autonomic dysfunction (MESH:D001342), neurotoxic (MESH:D020258), postural instability (MESH:D054972), Dopaminergic (MESH:D009422), neurological disease (MESH:D020271), motor impairments (MESH:D000068079), degeneration (MESH:D009410), mitochondrial dysfunction (MESH:D028361), bradykinesia (MESH:D018476), rigidity (MESH:D009127), Huntington's disease (MESH:D006816), inflammation (MESH:D007249), degenerative neuropathies (MESH:D019636), gait imbalance (MESH:D020234), Proinflammatory Cytokines (MESH:D000080424), motor abnormalities (MESH:D000014), resting tremor (MESH:D014202)
- **Chemicals:** citrate (MESH:D019343), Formalin (MESH:D005557), rutin (MESH:D012431), isoflurane (MESH:D007530), Isoquercitrin (MESH:C016527), EMIQ (-), Paraffin (MESH:D010232), ethanol (MESH:D000431), Triton-X (MESH:D017830), DMSO (MESH:D004121), SYBR Green (MESH:C098022), glutathione (MESH:D005978), PBS (MESH:D007854), polypropylene (MESH:D011126), DAPI (MESH:C007293), ALA (MESH:D008063), iron (MESH:D007501), malto-oligosaccharides (MESH:C021705), LPS (MESH:D008070), 6-hydroxydopamine (MESH:D016627), water (MESH:D014867), Alexa Fluor555 (MESH:C000608607), DA (MESH:D004298), Quercetin (MESH:D011794), ROT (MESH:D012402), saline (MESH:D012965), lipid (MESH:D008055), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MESH:D015632), xylene (MESH:D014992)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Gallus gallus (bantam, species) [taxon 9031], Homo sapiens (human, species) [taxon 9606]

## Full text

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Source: https://tomesphere.com/paper/PMC13018002