Owona Brice Ayissi, Ngoungoure Viviane Ndam, Tchamba Jordas Tchana, Njayou Frederic Nico, Moundipa Paul Fewou
Laboratory of Pharmacology and Toxicology, Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon.
Metab Brain Dis. 2025 Jun 19;40(6):229. doi: 10.1007/s11011-025-01628-4.
Neuroinflammation has been described as one of the multiple clinical manifestations of Parkinson's and Alzheimer's diseases (PD and AD). Moreover, it was reported that amyloid-β deposition is associated with cognitive decline in PD. Here, Cola acuminata (CA) extract was used to inhibit NLRP3 inflammasome in THP-1 macrophages in vitro. CA showed significant anti-inflammatory effect by inhibiting nitric oxide (NO) release from cells after stimulation with LPS and Nigericin. Phagocytosis of amyloid-β by THP-1 cells showed that at 100 µg/ml, CA increases phagocytic activity of macrophages in vitro. Moreover, activation of NLRP3 inflammasome and subsequent treatment with CA showed a reduction of IL1-β and IL-18 cytokines release in ELISA assay. Furthermore, NLRP3, caspase-1, IL1-β and NF-kB expressions were significantly inhibited at the gene and protein levels as shown by RTqPCR and western blot assays respectively. Interestingly, colocalization analysis of activated inflammasome confirmed our results suggesting that CA disaggregates inflammasome assembly. Mass spectrometry analysis of CA has identified epicatechin, catechin, chlorogenic acid, quercetin and stigmasterol known as inflammasome inhibitors among the extract chemical constituents. Together, our results indicate that CA can inhibit inflammasome activation in macrophage, thereby opening future perspectives for PD treatment.
神经炎症被认为是帕金森病和阿尔茨海默病（PD和AD）的多种临床表现之一。此外，有报道称淀粉样β蛋白沉积与PD的认知衰退有关。在此，可乐果（CA）提取物被用于在体外抑制THP-1巨噬细胞中的NLRP3炎性小体。CA通过抑制脂多糖（LPS）和尼日利亚菌素刺激后细胞中一氧化氮（NO）的释放，显示出显著的抗炎作用。THP-1细胞对淀粉样β蛋白的吞噬作用表明，在100μg/ml时，CA可增加体外巨噬细胞的吞噬活性。此外，在ELISA检测中，NLRP3炎性小体的激活以及随后用CA处理显示白细胞介素1-β（IL1-β）和白细胞介素-18（IL-18）细胞因子的释放减少。此外，如RTqPCR和蛋白质印迹分析分别所示，NLRP3、半胱天冬酶-1、IL1-β和核因子κB（NF-κB）的表达在基因和蛋白质水平上均受到显著抑制。有趣的是，活化炎性小体的共定位分析证实了我们的结果，表明CA可分解炎性小体组装。对CA的质谱分析已在提取物化学成分中鉴定出表儿茶素、儿茶素、绿原酸、槲皮素和豆甾醇等已知的炎性小体抑制剂。总之，我们的结果表明CA可抑制巨噬细胞中炎性小体的激活，从而为PD治疗开辟了新的前景。
