Neuroprotective Effect of Swertiamarin in a Rotenone Model of Parkinson's Disease: Role of Neuroinflammation and Alpha-Synuclein Accumulation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079791" target="_blank" >RIV/00159816:_____/23:00079791 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acsptsci.2c00120" target="_blank" >https://pubs.acs.org/doi/10.1021/acsptsci.2c00120</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsptsci.2c00120" target="_blank" >10.1021/acsptsci.2c00120</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Neuroprotective Effect of Swertiamarin in a Rotenone Model of Parkinson's Disease: Role of Neuroinflammation and Alpha-Synuclein Accumulation

Popis výsledku v původním jazyce

Parkinson&apos;s disease (PD) is a progressive neurodegener-ative disease with no permanent cure affecting around 1% of the population over 65. There is an urgency to search for a disease-modifying agent with fewer untoward effects. PD pathology involves the accumulation of toxic alpha-synuclein (alpha-syn) and neuronal inflammation leading to the degeneration of dopaminergic (DAergic) neurons. Swertiamarin (SWE), a well-studied natural product, possesses a strong anti-inflammatory effect. It is a secoiridoid glycoside isolated from Enicostemma littorale Blume. SWE showed a reversal effect on the alpha-syn accumulation in the 6-hydroxydopamine (6-OHDA)-induced Caenorhab-ditis elegans model of PD. However, there are no reports in the literature citing the effect of SWE as a neuroprotective agent in rodents. The present study aimed to evaluate the anti-inflammatory activity of SWE against lipopolysaccharide (LPS)-induced C6 glial cell activation and its neuroprotective effect in the intrastriatal rotenone mouse PD model. SWE treatment showed a significant reduction in interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) levels in LPS-induced C6 glial cell activation. Further, our studies demonstrated the suppression of microglial and astroglial activation in substantia nigra (SN) after administration of SWE (100 mg/kg, intraperitoneally) in a rotenone mouse model. Moreover, SWE alleviated the rotenone-induced alpha-syn overexpression in the striatum and SN. SWE ameliorated the motor impairment against rotenone-induced neurotoxicity and mitigated the loss of DAergic neurons in the nigrostriatal pathway. Therefore, SWE has the potential to develop as an adjunct therapy for PD, but it warrants further mechanistic studies.

Název v anglickém jazyce

Neuroprotective Effect of Swertiamarin in a Rotenone Model of Parkinson's Disease: Role of Neuroinflammation and Alpha-Synuclein Accumulation

Popis výsledku anglicky

Parkinson&apos;s disease (PD) is a progressive neurodegener-ative disease with no permanent cure affecting around 1% of the population over 65. There is an urgency to search for a disease-modifying agent with fewer untoward effects. PD pathology involves the accumulation of toxic alpha-synuclein (alpha-syn) and neuronal inflammation leading to the degeneration of dopaminergic (DAergic) neurons. Swertiamarin (SWE), a well-studied natural product, possesses a strong anti-inflammatory effect. It is a secoiridoid glycoside isolated from Enicostemma littorale Blume. SWE showed a reversal effect on the alpha-syn accumulation in the 6-hydroxydopamine (6-OHDA)-induced Caenorhab-ditis elegans model of PD. However, there are no reports in the literature citing the effect of SWE as a neuroprotective agent in rodents. The present study aimed to evaluate the anti-inflammatory activity of SWE against lipopolysaccharide (LPS)-induced C6 glial cell activation and its neuroprotective effect in the intrastriatal rotenone mouse PD model. SWE treatment showed a significant reduction in interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) levels in LPS-induced C6 glial cell activation. Further, our studies demonstrated the suppression of microglial and astroglial activation in substantia nigra (SN) after administration of SWE (100 mg/kg, intraperitoneally) in a rotenone mouse model. Moreover, SWE alleviated the rotenone-induced alpha-syn overexpression in the striatum and SN. SWE ameliorated the motor impairment against rotenone-induced neurotoxicity and mitigated the loss of DAergic neurons in the nigrostriatal pathway. Therefore, SWE has the potential to develop as an adjunct therapy for PD, but it warrants further mechanistic studies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Pharmacology &amp; Translational Science

ISSN

2575-9108

e-ISSN

2575-9108

Svazek periodika

6

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

40-51

Kód UT WoS článku

000898917200001

EID výsledku v databázi Scopus

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