Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
University Institute of Pharma Sciences, Chandigarh University, Mohali, India.
Chem Biol Drug Des. 2024 Jan;103(1):e14353. doi: 10.1111/cbdd.14353. Epub 2023 Sep 18.
The increased prevalence of neurological illnesses is a burgeoning challenge to the public healthcare system and presents greater financial pressure. Formononetin, an O-methylated isoflavone, has gained a lot of attention due to its neuroprotective potential explored in several investigations. Formononetin is widely found in legumes and several types of clovers including Trifolium pratense L., Astragalus membranaceus, Sophora tomentosa, etc. Formononetin modulates various endogenous mediators to confer neuroprotection. It prevents RAGE activation that results in the inhibition of neuronal damage via downregulating the level of ROS and proinflammatory cytokines. Furthermore, formononetin also increases the expression of ADAM-10, which affects the pathology of neurodegenerative disease by lowering tau phosphorylation, maintaining synaptic plasticity, and boosting hippocampus neurogenesis. Besides these, formononetin also increases the expression of antioxidants, Nrf-2, PI3K, ApoJ, and LRP1. Whereas, reduces the expression of p65-NF-κB and proinflammatory cytokines. It also inhibits the deposition of Aβ and MAO-B activity. An inhibition of Aβ/RAGE-induced activation of MAPK and NOX governs the protection elicited by formononetin against inflammatory and oxidative stress-induced neuronal damage. Besides this, PI3K/Akt and ER-α-mediated activation of ADAM10, ApoJ/LRP1-mediated clearance of Aβ, and MAO-B inhibition-mediated preservation of dopaminergic neurons integrity are the major modulations produced by formononetin. This review covers the biosynthesis of formononetin and key molecular pathways modulated by formononetin to confer neuroprotection.
神经疾病的患病率不断上升，这对公共医疗体系构成了日益严峻的挑战，也带来了更大的财政压力。芒柄花素是一种 O-甲基化异黄酮，由于其在几种研究中表现出的神经保护潜力而备受关注。芒柄花素广泛存在于豆类和几种三叶草中，包括紫花苜蓿、膜荚黄芪、苦参等。芒柄花素通过调节各种内源性介质来发挥神经保护作用。它可以防止 RAGE 的激活，从而通过下调 ROS 和促炎细胞因子的水平来抑制神经元损伤。此外，芒柄花素还可以增加 ADAM-10 的表达，通过降低 tau 磷酸化、维持突触可塑性和促进海马神经发生来影响神经退行性疾病的病理。除此之外，芒柄花素还可以增加抗氧化剂、Nrf-2、PI3K、ApoJ 和 LRP1 的表达。而降低 p65-NF-κB 和促炎细胞因子的表达。它还可以抑制 Aβ 和 MAO-B 活性的沉积。抑制 Aβ/RAGE 诱导的 MAPK 和 NOX 的激活可以控制芒柄花素对炎症和氧化应激诱导的神经元损伤的保护作用。除此之外，PI3K/Akt 和 ER-α 介导的 ADAM10 的激活、ApoJ/LRP1 介导的 Aβ 的清除以及 MAO-B 抑制介导的多巴胺能神经元完整性的保存是芒柄花素产生的主要调节作用。本综述涵盖了芒柄花素的生物合成以及芒柄花素调节的关键分子途径，以发挥神经保护作用。
