Aloe Polysaccharides against 3-Nitropropionic acid-induced Huntington’s disease-like symptoms: Role of BDNF/NF-κB/Nrf2 signaling pathways

Introduction:: Huntington’s Disease (HD) is a neurodegenerative ailment characterized by progressive motor, cognitive, and psychiatric decline, linked with mitochondrial dysfunction, oxidative stress, and neuroinflammation. Few effective treatments are available for Huntington's. Additionally, the therapeutic effects of natural polysaccharides against neurodegenerative disorders have not yet been fully explored. This study aimed to investigate the neuroprotective potential of Aloe Polysaccharides (APs) against 3-Nitropropionic Acid (3- NPA)-initiated HD-like symptoms in rats. materials and methods: The research utilized rotarod and open field strength behavioural tests in addition to assessments based on narrow beam walk tests. Researchers conducted examinations of inflammatory markers that included interleukin (IL) -1β, tumor necrosis factor (TNF) -α and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB). The research determined the quantities of brain-derived neurotrophic factor (BDNF) and succinate dehydrogenase (SDH) through extensive measurements. Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) along with superoxide dismutase (SOD) and catalase (CAT) and glutathione (GSH) and malondialdehyde (MDA) and nitric oxide (NO) formed part of the redox mediators studied. The research studied the levels of brain transmitters including dopamine (DA) and serotonin (5-HT) together with norepinephrine (NE) and acetylcholinesterase (AChE) and gamma-aminobutyric acid (GABA) and glutamate (Glu). The striatal brain region served as the main target area in neuropathological assessments. Methods:: Adult male rats were allocated to control, 3-NPA-treated, and APs-treated groups (100 and 200 mg/kg orally) following 3-NPA administration. Behavioral assessments (rotarod, open field, narrow beam walking) and biochemical analyses, including neurotransmitters Acetylcholinesterase (AChE), Acetylcholine (ACh), Dopamine (DA), Norepinephrine (NE), Serotonin (5-HT), Gamma-Aminobutyric Acid (GABA), Glutamate (Glu), oxidative/nitrative stress markers Malondialdehyde (MDA, Nitric Oxide (NO), antioxidant enzymes Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH), mitochondrial enzyme Succinate Dehydrogenase (SDH), inflammatory mediators Nuclear Factor Kappa B (NF-κB), Tumor Necrosis Factor Alpha (TNF-α), Interleukin- 1 Beta (IL-1β), Cyclooxygenase-2 (COX-2), neurotrophic factor Brain-Derived Neurotrophic Factor (BDNF), and apoptotic markers (caspase-3, caspase-9, B-Cell Lymphoma 2 (Bcl-2), Bcl-2-Associated X Protein (Bax)] were performed. Additionally, the impact of APs on regulators of mitochondrial biogenesis and antioxidant response Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Sirtuin 1 (Sirt1), Heme Oxygenase-1 (HO-1), NAD(P)H Quinone Dehydrogenase 1 (NQO1), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PGC-1α), Adenosine Monophosphate-Activated Protein Kinase (AMPK), Uncoupling Protein 1 (UCP1), Uncoupling Protein 2 (UCP2) was evaluated. Histopathological examination of the striatum was conducted. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. results: The study results showed that Applied Physiology Solution (APS) enhanced behavioural characteristics together with neurotransmission function while simultaneously reducing inflammatory response and cell stress and preserving striatal tissue structure. Results:: 3-NPA administration induced significant motor deficits, neurotransmitter imbalance, elevated oxidative stress, inflammation, mitochondrial impairment, BDNF depletion, apoptosis, and striatal degeneration (P < improved antioxidant enzymes (SOD, CAT, and GSH); mitigated MDA and NO effects; suppressed NF-κB, TNF-α, IL-1β, and COX-2; elevated BDNF and SDH activities; mitigated apoptosis (caspase-3 and 9, BAX, and BCl-2); and preserved striatal structure. APs showed neuroprotective potential in 3-NPA-induced HD rats by modulating the BDNF/NF-κB/Nrf2 pathway, controlling oxidative stress and neuroinflammation, restoring neurotransmitter function, and arresting striatal damage. Treatment with Aps markedly upregulated the levels of mitochondrial biogenesis-related proteins (Sirt1, PGC-1α, AMPK, UCP1, and UCP2) and antioxidant defense mediators (HO-1 and NQO1). In addition to behavioral and biochemical improvements, this study uniquely demonstrates that APs upregulate genes central to the mitochondrial biogenesis pathway, suggesting a new mechanistic basis for their neuroprotective effects in 3-NPA-induced HD. Discussion:: The study results showed that Applied Physiology Solution (APS) enhanced behavioural characteristics and neurotransmission function while simultaneously reducing the inflammatory response and cell stress and preserving striatal tissue structure. conclusion: The present study demonstrates the efficacy of APS in mitigating 3-NPA induced HD like symptoms in vivo. Conclusion:: These findings reveal that APs promote neuroprotection not only by modulating oxidative stress, neuroinflammation, neurotransmission, and apoptosis, but also by specifically upregulating genes in the mitochondrial biogenesis pathway, highlighting their potential as a natural therapeutic candidate for HD management.