Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of cell and animal models; however a comprehensive assessment has not been performed in a human model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons via multiple means by reducing the frequency of spontaneous Ca2+ signals and significantly reducing caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin against AD pathogenesis in a human disease model.

Apigenin induces ROS‐dependent apoptosis and ER stress in human endometriosis cells

“…Apigenin (4′,5,6‐trihydroxyflavone) extracted from various fruits and vegetables, including parsley, apples, and grapes, is a potential therapeutic agents against diverse diseases such as diabetes (Panda & Kar, ), cardiovascular diseases (Buwa, Mahajan, Patil, & Goyal, ), neuronal diseases (Balez et al, ), metabolic diseases (Feng et al, ), and cancers (Shukla & Gupta, ). To prevent or inhibit progression of those diseases, apigenin regulates a variety of intracellular signal transduction pathways.…”

Mechanisms of Neuroprotective Effects of Peptides Derived from Natural Materials and Their Production and Assessment

“…Neuronal cell death is closely associated with apoptosis, and many apoptosis factors can be observed in neurodegenerative disease. Previous studies have reported that inhibition of apoptosis can help protect damaged neuronal cells (Balez et al., ; Chuang et al., ; Wu et al., ). Neuroprotective effects related to apoptosis are commonly demonstrated using PI or Hoechst 33342 staining, Annexin V/PI staining, immunochemistry, calcium concentration, and western blot.…”

Autophagy Plays an Important Role in Anti-inflammatory Mechanisms Stimulated by Alpha7 Nicotinic Acetylcholine Receptor

“…However, the overactivation of microglia may lead to the pathogenesis and aggravation of CNS damage in inflammatory diseases including multiple sclerosis (MS) (3–5). MS is recognized as a chronic inflammatory autoimmune disorder featuring CNS demyelination and neurodegeneration (6, 7).…”