Hotchkiss Brain Institute, Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada.
Department of Chemistry, University of Calgary, Calgary, AB T2N 4N1, Canada.
Cells. 2022 Jan 27;11(3):440. doi: 10.3390/cells11030440.
Iron deposition in the brain begins early in multiple sclerosis (MS) and continues unabated. Ferrous iron is toxic to neurons, yet the therapies used in MS do not counter iron neurotoxicity. Extracts of (HS) are used in many cultures for medicinal purposes. We collected a distinct HS extract and found that it abolished the killing of neurons by iron in culture; medications used in MS were ineffective when similarly tested. Neuroprotection by HS was not due to iron chelation or anthocyanin content. In free radical scavenging assays, HS was equipotent to alpha lipoic acid, an anti-oxidant being tested in MS. However, alpha lipoic acid was only modestly protective against iron-mediated killing. Moreover, a subfraction of HS without radical scavenging activity negated iron toxicity, whereas a commercial hibiscus preparation with anti-oxidant activity could not. The idea that HS might have altered properties within neurons to confer neuroprotection is supported by its amelioration of toxicity caused by other toxins: beta-amyloid, rotenone and staurosporine. Finally, in a mouse model of MS, HS reduced disability scores and ameliorated the loss of axons in the spinal cord. HS holds therapeutic potential to counter iron neurotoxicity, an unmet need that drives the progression of disability in MS.
铁在大脑中的沉积早在多发性硬化症（MS）中就开始了，并且仍在不断加剧。亚铁对神经元有毒性，但 MS 中使用的疗法并不能对抗铁神经毒性。（HS）的提取物在许多文化中被用于药用目的。我们收集了一种独特的 HS 提取物，发现它可以消除铁在培养物中杀死神经元的作用；同样测试 MS 中使用的药物时，它们无效。HS 的神经保护作用不是由于铁螯合或花青素含量。在自由基清除测定中，HS 与正在 MS 中测试的抗氧化剂α-硫辛酸具有同等功效。然而，α-硫辛酸仅对铁介导的杀伤具有适度的保护作用。此外，没有自由基清除活性的 HS 亚组分消除了铁毒性，而具有抗氧化活性的商业芙蓉制剂则不能。HS 可能改变了神经元内的特性以提供神经保护的观点得到了其减轻其他毒素（β-淀粉样蛋白、鱼藤酮和 staurosporine）引起的毒性的支持。最后，在 MS 的小鼠模型中，HS 降低了残疾评分并改善了脊髓中轴突的丢失。HS 具有对抗铁神经毒性的治疗潜力，这是一种未满足的需求，它推动了 MS 残疾的进展。
