Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway

Abstract

β-amyloid (Aβ) is one of the inducing factors of astrocytes activation and neuroinflammation, and it is also a crucial factor for the development of Alzheimer’s disease (AD). Icariside II (ICS II) is an active component isolated from a traditional Chinese herb Epimedium , which has shown to attnuate lipopolysaccharide (LPS)-induced neuroinflammation through regulation of NF-κB signaling pathway. In this study we investigated the effects of ICS II on LPS-induced astrocytes activation and Aβ accumulation. Primary rat astrocytes were pretreated with ICS II (5, 10, and 20 μM) or dexamethasone (DXMS, 1 μM) for 1 h, thereafter, treated with LPS for another 24 h. We found that ICS II pretreatment dose dependently mitigated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in the astrocytes. Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ 1–40 , Aβ 1–42 , amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. Interestingly, molecular docking revealed that ICS II might directly bind to BACE1. It is concluded that ICS II has potential value as a new therapeutic agent to treat neuroinflammation-related diseases, such as AD.

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“…Accumulating evidence has suggested that ICAII may serve a beneficial impact in various types of disease, such as Alzheimer's disease, osteoporosis, stroke, breast cancer and leukemia, possibly due to its multiple bioactivities, including antioxidative, anti-inflammatory and anti-apoptotic properties (19). Recent studies have reported that ICAII may also be beneficial for cardiovascular disease; for example, Figure 5.…”

“…Accumulating evidence has suggested that ICAII may serve a beneficial impact in various types of disease, such as Alzheimer's disease, osteoporosis, stroke, breast cancer and leukemia, possibly due to its multiple bioactivities, including antioxidative, anti-inflammatory and anti-apoptotic properties ( 19 ). Recent studies have reported that ICAII may also be beneficial for cardiovascular disease; for example, in a rat model of spontaneous hypertension, Wu et al ( 13 ) demonstrated that the intra-gastric administration of ICAII (4, 8 or 16 mg/kg) significantly decreased the blood pressure, promoted heart functional recovery and improved ventricular remodeling.…”