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Neuroprotective mechanism of trans,trans-Farnesol in an ICV-STZ-induced rat model of Alzheimer's pathology.
Kadian, Monika; Saini, Neetu; Khera, Alka; Kumar, Anil.
Afiliación
  • Kadian M; Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, 160014, India.
  • Saini N; Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, 160014, India.
  • Khera A; Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
  • Kumar A; Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh, 160014, India. kumaruipspu@gmail.com.
Inflammopharmacology ; 32(2): 1545-1573, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38308793
ABSTRACT

BACKGROUND:

Alzheimer's disease (AD) is a prominent cause of dementia, resulting in neurodegeneration and memory impairment. This condition imposes a considerable public health burden on both patients and their families due to the patients' functional impairments as well as the psychological and financial constraints. It has been well demonstrated that its aetiology involves proteinopathy, mitochondriopathies, and enhanced reactive oxygen species (ROS) generation, which are some of the key features of AD brains that further result in oxidative stress, excitotoxicity, autophagy, and mitochondrial dysfunction.

OBJECTIVE:

The current investigation was created with the aim of elucidating the neurological defence mechanism of trans,trans-Farnesol (TF) against intracerebroventricular-streptozotocin (ICV-STZ)-induced Alzheimer-like symptoms and related pathologies in rodents. MATERIALS AND

METHODS:

The current investigation involved male SD rats receiving TF (25-100 mg/kg, per oral) consecutively for 21 days in ICV-STZ-treated animals. An in silico study was carried out to explore the possible interaction between TF and NADH dehydrogenase and succinate dehydrogenase. Further, various behavioural (Morris water maze and novel object recognition test), biochemical (oxidants and anti-oxidant markers), activities of mitochondrial enzyme complexes and acetylcholinesterase (AChE), pro-inflammatory (tumor necrosis factor-alpha; TNF-α) levels, and histopathological studies were evaluated in specific brain regions.

RESULTS:

Rats administered ICV-STZ followed by treatment with TF (25, 50, and 100 mg/kg) for 21 days had significantly better mental performance (reduced escape latency to access platform, extended time spent in target quadrant, and improved differential index) in the Morris water maze test and new object recognition test models when compared to control (ICV-STZ)-treated groups. Further, TF treatment significantly restored redox proportion, anti-oxidant levels, regained mitochondrial capacities, attenuated altered AChE action, levels of TNF-α, and histopathological alterations in certain brain regions in comparison with control. In in silico analysis, TF caused greater interaction with NADH dehydrogenase and succinate dehydrogenase.

CONCLUSION:

The current work demonstrates the neuroprotective ability of TF in an experimental model with AD-like pathologies. The study further suggests that the neuroprotective impacts of TF may be related to its effects on TNF-α levels, oxidative stress pathways, and mitochondrial complex capabilities.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Neuroprotectores / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Inflammopharmacology Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fármacos Neuroprotectores / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Inflammopharmacology Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Suiza