College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Republic of Korea.
Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, #26, Kyungheedaero, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Food Funct. 2022 Jul 18;13(14):7638-7649. doi: 10.1039/d2fo01150f.
Neuroinflammation, which occurs due to microglia, is related to the pathogenesis of neurodegenerative disorders. Recently, the development of functional foods that down-regulate over-activated microglial cells to prevent the progression of neurodegenerative disorders has been proposed, since over-activated microglia induce a chronic source of neurotoxic factors and reduce neuronal survival. Thus, the anti-neuroinflammatory effects of a functional food mixture (CCL01) including seeds and NK112 on lipopolysaccharide (LPS)-induced experimental models were investigated. In LPS-induced models, the expression levels of inflammatory mediators (, inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2) and pro-inflammatory cytokines (, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) were decreased upon CCL01 treatment. CCL01 showed an anti-neuroinflammatory effect in LPS-induced microglial cells the inhibition of the mitogen-activated protein kinase (MAPK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway and the activation of the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In the LPS-treated mouse models, the increased expression of ionized calcium binding adaptor molecule 1 (Iba-1), which indicates microglial activity, was markedly decreased upon treatment with CCL01 (50 and 200 mg kg) in the hippocampus and cortex areas of the mouse brains in comparison with the LPS-injected group. In addition, the groups to which CCL01 was administered had significantly decreased plasma levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in the LPS-injected mouse models. Our data suggest that CCL01 may be a potential anti-neuroinflammatory agent that can prevent microglia overactivation, and it could be useful for developing functional foods.
神经炎症是由小胶质细胞引起的，与神经退行性疾病的发病机制有关。最近，人们提出了开发具有下调过度激活小胶质细胞作用的功能性食品，以预防神经退行性疾病进展的设想，因为过度激活的小胶质细胞会产生慢性神经毒性因子来源，并减少神经元的存活。因此，研究了一种包含种子和 NK112 的功能性食品混合物（CCL01）对脂多糖（LPS）诱导的实验模型的抗神经炎症作用。在 LPS 诱导的模型中，CCL01 处理可降低炎症介质（、诱导型一氧化氮合酶、环氧化酶-2、一氧化氮和前列腺素 E2）和促炎细胞因子（、肿瘤坏死因子-α、白细胞介素（IL）-1β和 IL-6）的表达水平。CCL01 对 LPS 诱导的小胶质细胞具有抗神经炎症作用，其机制与抑制丝裂原活化蛋白激酶（MAPK）/核因子κ轻链增强子的激活 B 细胞（NF-κB）途径和激活核因子红细胞 2 相关因子 2（Nrf2）/血红素加氧酶-1（HO-1）途径有关。在 LPS 处理的小鼠模型中，LPS 注射组的小鼠海马和皮质区域中，离子钙结合接头分子 1（Iba-1）的表达增加，这表明小胶质细胞活性增加，而用 CCL01（50 和 200 mg/kg）处理后，其表达明显降低。此外，与 LPS 注射组相比，给予 CCL01 的组的小鼠模型中，肿瘤坏死因子-α、白细胞介素（IL）-1β和 IL-6 的血浆水平显著降低。我们的数据表明，CCL01 可能是一种潜在的抗神经炎症剂，可预防小胶质细胞过度激活，并可用于开发功能性食品。
