Kundu Payel, Yasuhara Kanon, Brandes Mikah S, Zweig Jonathan A, Neff Cody J, Holden Sarah, Kessler Kat, Matsumoto Steven, Offner Halina, Waslo Carin S, Vandenbark Arthur, Soumyanath Amala, Sherman Larry S, Raber Jacob, Gray Nora E, Spain Rebecca I
Department of Behavioral Neuroscience, Oregon Health & Science University (OHSU), Portland, OR 97239, USA.
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University (OHSU), Beaverton, OR 97006, USA.
Pharmaceuticals (Basel). 2024 Dec 13;17(12):1681. doi: 10.3390/ph17121681.
(L.) Urban (family Apiaceae) () is a traditional botanical medicine used in aging and dementia. Water extracts of (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology of oxidative stress and mitochondrial dysfunction with aging and dementia, neuropsychiatric symptoms in MS may also benefit from To determine whether CAW similarly benefits neuropsychiatric symptoms, ARE gene expression, and mitochondrial respiration in inflammatory models of MS, and to determine the effects of CAW on clinical disability and inflammation, we tested CAW using experimental autoimmune encephalomyelitis (EAE). C57BL/6J mice induced with EAE were treated with CAW or a placebo for 2 weeks. The outcomes were clinical disability, signs of anxiety (open field test), ARE gene expression, mitochondrial respiration, and inflammation and demyelination. At the dosing schedule and concentrations tested, CAW-treated mice with EAE demonstrated increased ARE gene expression and mitochondrial respiratory activity compared to those of placebo-treated mice with EAE. CAW was also associated with reduced inflammatory infiltrates in the spinal cord, but the differences between the populations of activated versus quiescent microglia were equivocal. CAW did not improve behavioral performance, EAE motor disability, or demyelination. In the inflammatory EAE model of MS, CAW demonstrates similar neuroprotective effects to those it exhibits in aging and dementia mouse models. These benefits, along with the anti-inflammatory effects of CAW, support further investigation of its neuropsychiatric effects in people with MS.
伞形科植物刺蒺藜（L.）Urban（）是一种用于治疗衰老和痴呆的传统植物药。刺蒺藜水提取物（CAW）已被用于治疗相关动物模型中的神经精神症状，并与抗氧化反应元件（ARE）基因增加、线粒体呼吸功能改善和神经元健康状况改善有关。由于多发性硬化症（MS）与衰老和痴呆症具有氧化应激和线粒体功能障碍的神经退行性病理特征，MS中的神经精神症状可能也会从CAW中受益。为了确定CAW是否同样有益于MS炎症模型中的神经精神症状、ARE基因表达和线粒体呼吸，并确定CAW对临床残疾和炎症的影响，我们使用实验性自身免疫性脑脊髓炎（EAE）对CAW进行了测试。用EAE诱导的C57BL/6J小鼠用CAW或安慰剂治疗2周。观察指标为临床残疾、焦虑症状（旷场试验）、ARE基因表达、线粒体呼吸、炎症和脱髓鞘。在所测试的给药方案和浓度下，与用安慰剂治疗的EAE小鼠相比，用CAW治疗的EAE小鼠的ARE基因表达和线粒体呼吸活性增加。CAW还与脊髓中炎症浸润减少有关，但活化小胶质细胞与静止小胶质细胞群体之间的差异不明确。CAW并未改善行为表现、EAE运动残疾或脱髓鞘。在MS的炎症性EAE模型中，CAW表现出与在衰老和痴呆小鼠模型中类似的神经保护作用。这些益处，连同CAW的抗炎作用，支持进一步研究其对MS患者神经精神方面的影响。
