Luteolin as potential treatment for Huntington's disease: Insights from a transgenic mouse model

• Published in: CNS neuroscience & therapeutics 2024-09, Vol.30 (9), p.e70025-n/a
• Main Authors: Mohammed, Abuelnor, Ramadan, Azza, Elnour, Asim Ahmed, Saeed, Ali Awadallah Ali Mohamed, Al Mazrouei, Nadia, Alsulami, Fahad T., Alqarni, Yousef Saeed, Menon, Vineetha, Amoodi, Abdulla Al, Abdalla, Sami Fatehi
• Format: Article
• Language: English
• Subjects: Age; Aggregates; Alzheimer's disease; Animals; Apoptosis; Atrophy; Brain; Brain - drug effects; Brain - metabolism; Disease Models, Animal; Flavonoids; Humans; Huntingtin; huntingtin aggregations; Huntingtin Protein - genetics; Huntington Disease - drug therapy; Huntington Disease - metabolism; Huntington's disease; Huntingtons disease; luteolin; Luteolin - pharmacology; Luteolin - therapeutic use; Male; Mice; Mice, Transgenic; Motor Activity - drug effects; motor behavior; Neostriatum; Neurodegeneration; Neurodegenerative diseases; Neurofilament Proteins - metabolism; neuroprotection; Original; Proteins; Software; Survival; Therapeutic applications; Transgenic animals; Transgenic mice; Western blotting
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.70025

Aims The study aimed to evaluate the potential benefits of luteolin treatment in Huntington's disease (HD), an inherited progressive neurodegenerative disorder. Methods HD N171‐82Q transgenic and WT mice received luteolin or vehicle for treatment at 6 weeks of age. The mice's body weight changes and survival rates were monitored throughout the study, and a series of motor functional tests were conducted. Serum level of the marker NfL was also determined. Immunohistochemical staining and western blotting were utilized to assess the expression of huntingtin aggregates. Results Luteolin treatment enhanced survival and prevented weight loss in HD mice compared to the vehicle‐treated HD group. Furthermore, the luteolin‐treated HD mice exhibited enhanced motor coordination and balance and significantly reduced motor dysfunction. Also, luteolin decreased serum NfL levels in HD mice. Notably, the accumulation of huntingtin aggregates was significantly reduced in the brain's cortex, hippocampus, and striatum of luteolin‐treated HD mice compared to the vehicle‐treated HD group. Conclusion Luteolin holds promise as a therapeutic agent for improving survival outcomes, managing motor dysfunction, and reducing huntingtin aggregates in HD. The findings are of significance as currently, there are no approved therapeutic interventions that reverse HD pathology or slow down its progression. Huntington's disease (HD) is an inherited progressive neurodegenerative disorder characterized by motor dysfunction and premature mortality. Luteolin, a natural flavonoid with known antioxidant and neuroprotective properties, has shown promise in various neurodegenerative diseases. This study aimed to evaluate the potential benefits of luteolin treatment in a mouse model of (HD). To assess the effects of luteolin treatment, HD N171 82Q transgenic mice received luteolin administration, while another group received a vehicle treatment for comparison. The mice's body weight changes and survival rates were monitored throughout the study. Additionally, they underwent a series of motor function tests, including the rotarod test, balance beam test, and limb clasping test. Immunohistochemical staining and western blotting were utilized to assess the localization and expression of huntingtin aggregates, respectively. Findings revealed a significant protective effect of luteolin treatment against premature mortality and prevented weight loss in HD mice compared to the non‐luteolin‐treated group. F