Jo, Hyo-Sung Lee, Youn-Woo Son, So-Ri Jang, Dae Sik Kwon, Tae Woo Ha, Yujeong Moon, Sang-Kwan Kim, Min Soo Cho, Ik-Hyun 2025-01-20T01:00:27Z 2025-01-20T01:00:27Z 2025-01-17 2024-12 1663-9812 https://pubs.kist.re.kr/handle/201004/151586 Background Huntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. Schisandra chinensis has various pharmacologic effects such as antioxidant and anti-inflammatory activities. However, the neuroprotective value of seed oil of S. chinensis (SOSC) has not been elucidated yet. The purpose of this study was to determine neuroprotective effects of SOSC by supercritical fluid extraction against 3-nitropropionic acid (3-NPA)-induced HD-like symptoms and neuropathology in an experimental mouse model.Methods SOSC (75, 150, and 300 mg/kg/day) was orally pre-administration once daily at 1 hour before 3-NPA intoxication.Results SOSC ameliorated movement dysfunction and lethality following 3-NPA intoxication in connection with reduction of lesion area, neurodegeneration/apoptosis, microglial migration/activation, and mRNA expression of pro-inflammatory cytokines/enzymes in the striatum. SOSC inhibited the activation of nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPKs) pathways but stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the striatum after 3-NPA intoxication. Schizandrin, a main component of SOSC, reduced protein expression levels of Iba-1 and p-NF-kappa B in 3-NPA-induced BV2 cells (murine microglia cell line). BV2 cell's conditioned medium inhibited cleaved caspase-3 in 3-NPA-induced SH-SY5Y cells (a neuroblastoma cell line).Conclusion SOSC might ameliorate movement dysfunction by inhibiting neuropathology through its anti-inflammatory and antioxidant activities in the striata of 3-NPA-intoxicated mice. These findings suggest that SOSC could serve as a promising therapeutic candidate for HD-like symptoms, providing a foundation for future treatment strategies targeting neuroinflammation and oxidative stress. English Frontiers Media S.A. A supercritical oil extract of Schisandra chinensis seeds ameliorates Huntington’s disease-like symptoms and neuropathology: the potential role of anti-oxidant and anti-inflammatory effects Article 10.3389/fphar.2024.1471024 1 Frontiers in Pharmacology, v.15 Frontiers in Pharmacology 15 Y scie scopus 001389822300001 2-s2.0-85214113574 Pharmacology & Pharmacy Pharmacology & Pharmacy Article INDUCED STRIATAL TOXICITY 3-NITROPROPIONIC ACID MICROGLIAL ACTIVATION GLIAL-CELLS MECHANISMS TETRABENAZINE MICE seed oil of Schisandra chinensis Huntington&apos s disease-like symptoms anti-inflammation antioxidant neuroprotection