👤 Ahmed M Atwa

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and behavioral impairments associated with striatal neuronal loss, for which effective symptom-attenuating therapies remain lacking. Artemisinin (ART), a natural sesquiterpene lactone with established antioxidant and anti-inflammatory actions, has recently gained attention as a potential neuroprotective agent. This study evaluated the therapeutic relevance of ART in a rat model of HD induced by 3-nitropropionic acid (3-NP). 3-NP administration caused severe behavioral deficits, including an 81.8% reduction in rearing and a 74.9% reduction in ambulation (p < 0.0001), a 63.7% decrease in novel object exploration, and a 53.5% decline in Morris water maze target quadrant time versus controls. Biochemically, 3-NP elevated HMGB1 (4.8-fold), TLR4 (6.8-fold), RIPK1 (6.4-fold), RIPK3 (5.2-fold), MLKL (5.5-fold), p38-MAPK (4.2-fold), NF-κB (2.1-fold), and TNF-α (4.5-fold), while reducing GSH (57.6%), Nrf2 (77.7%), Sig1R (86.2%), D2R (64%), XIAP (77.8%), BDNF (57.6%) and SDH (61.44%) (all p < 0.0001). Treatment with ART (100 mg/kg) markedly restored behavioral performance, increasing rearing and ambulation by 3.2- and 2.6-fold, novel object exploration by 2.4-fold, and target quadrant time by 1.7-fold compared to the 3-NP group. At the molecular level, ART reduced HMGB1 (69.2%), TLR4 (60.4%), RIPK1 (66.3%), RIPK3 (66.4%), MLKL (58%), and TNF-α (62.5%), while significantly restoring GSH (2.1-fold), Nrf2 (3.7-fold), Sig1R (5.2-fold), D2R (2.6-fold), XIAP (3.7-fold), BDNF (2.3-fold) and SDH (1.94-fold) relative to 3-NP-treated rats. Collectively, these results demonstrate that ART confers robust neuroprotection against 3-NP-induced HD-like pathology by attenuating oxidative stress, suppressing HMGB1/TLR4/NF-κB signaling, inhibiting necroptosis, and upregulating neuroprotective markers. These findings highlight ART not only as a neuroprotective agent but also as a promising symptom-attenuating therapeutic candidate for Huntington's disease and other neurodegenerative disorders driven by oxidative and inflammatory stress. Show less

Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and metabolic dysfunction, largely driven by mitochondrial impairment and defective energy metabolism. Altered signaling through hypoxia-inducible factor-1α (HIF-1α) and PI3K/AKT cascades contributes to neuronal vulnerability. Canagliflozin (Cana), a sodium-glucose cotransporter-2 inhibitor, has shown cognitive benefits in experimental studies. Here, we evaluated whether Cana mitigates 3-nitropropionic acid (3NP, 10 mg/kg, i.p., 14 days)-induced HD-like neurotoxicity in rats. Animals received Cana (5 or 10 mg/kg, p.o.) daily for 14 days, followed by behavioral assessments (open-field, Morris water maze, novel object recognition), histopathology, immunohistochemistry, and biochemical assays. Cana treatment significantly improved locomotor and memory performance, reduced striatal histopathological alterations, and attenuated GFAP immunoreactivity. Mechanistically, Cana upregulated HIF-1α and downstream GLUT1/GLUT3/HKII, restored PI3K/AKT/CREB/BDNF signaling, and enhanced SIRT1/PGC-1α/Nrf2 antioxidant responses, while suppressing inflammatory mediators and caspase-3 activation. These findings highlight Cana as a promising disease-modifying strategy for HD by targeting both energy metabolism and pro-survival pathways. Show less

Oxalis corniculata (O. corniculata) is a member of Oxalidaceae family, widely distributed in Asia, Europe, America, and Africa, used extensively as food and its traditional folkloric uses include management of epilepsy, gastric disorders, and neurodegenerative diseases, together with its use in enhancing health. Numerous pharmacological benefits of O. corniculata are linked to its anti-inflammatory and antioxidant abilities. One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD) in which neuroinflammation and oxidative stress are its main pathogenic processes. Our research aimed to study the neuroprotective effect of the methanolic extract of Oxalis corniculata Linn. (O. corniculata ME), compared to selenium (Se) against AlCl Forty male albino rats were allocated into four groups (Gps). Gp I a control group, the rest of the animals received AlCl The chemical profile of O. corniculata ME was studied using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry, allowing the tentative identification of sixty-six compounds, including organic acids, phenolics and others, cinnamic acid and its derivatives, fatty acids, and flavonoids. AlCl It was noted that O. corniculata ME showed a notable ameliorative effect compared to Se on Nrf2/HO-1, TLR4/NF-κβ/NLRP3, APOE4/LRP1, Wnt 3/β-catenin/GSK-3β and PERK axes. Show less