Icariside II attenuates lipopolysaccharide-induced neuroinflammation through inhibiting TLR4/MyD88/NF-κB pathway in rats.

Inflammation in central nervous system (CNS) plays a vital role in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (DLB), HIV-related dementia and traumatic brain injury. Icariside II (ICS II), an active flavonoid compound derived from a Chinese herbal medicine Epimedium brevicornum Maxim, has been shown to possess a neuroprotective effect on AD model. However, whether ICS II has a directly protective effect on acute neuroinflammation remains still unclear. Therefore, the current study was designed to investigate the possible protective effect of ICS II on acute neuroinflammation induced by intracerebroventricular (ICV) injection of lipopolysaccharide (LPS), and further to explore its possible mechanism. After ICS II was prophylactically administered for 7 days before LPS injection, the rats were randomly divided into five groups as follows: sham group (n = 9), sham + ICS II-H (10 mg/kg) (n = 9), LPS (n = 14), LPS + ICS II-L (3 mg/kg) (n = 14), LPS + ICS II-H (10 mg/kg) (n = 14) groups, respectively. As expected, LPS injection exhibited neuronal morphological damage, and ionized calcium binding adapter molecule 1 (IBA-1) of microglia and glial fibrillary acidic protein (GFAP) of astrocyte were activated. However, pre-treatment with ICS II not only inhibited the activation of microglia and astrocyte, but also significantly reversed the expressions of inflammatory factors such as interleukin-1ß (IL-1ß), tumor necrosis factor (TNF-α), cyclooxygenase-2 (COX-2), as well as the expressions of Toll-Like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and TNF receptor associated factor 6 (TRAF6). Furthermore, ICS II inhibited the degradation of IκB and the following activation of NF-κB. Hence it is concluded that ICS II attenuates LPS-induced neuroinflammation through inhibiting TLR4/MyD88/NF-κB pathway in rats, and it has potential value as a new therapeutic agent to treat neuroinflammation-related diseases, such as AD.

Icariside II, a Broad-Spectrum Anti-cancer Agent, Reverses Beta-Amyloid-Induced Cognitive Impairment through Reducing Inflammation and Apoptosis in Rats.

Beta-amyloid (Aß) deposition, associated neuronal apoptosis and neuroinflammation are considered as the important factors which lead to cognitive deficits in Alzheimer's disease (AD). Icariside II (ICS II), an active flavonoid compound derived from Epimedium brevicornum Maxim, has been extensively used to treat erectile dysfunction, osteoporosis and dementia in traditional Chinese medicine. Recently, ICS II attracts great interest due to its broad-spectrum anti-cancer property. ICS II shows an anti-inflammatory potential both in cancer treatment and cerebral ischemia-reperfusion. It is not yet clear whether the anti-inflammatory effect of ICS II could delay progression of AD. Therefore, the current study aimed to investigate the effects of ICS II on the behavioral deficits, Aß levels, neuroinflammatory responses and apoptosis in Aß25-35-treated rats. We found that bilateral hippocampal injection of Aß25-35 induced cognitive impairment, neuronal damage, along with increase of Aß, inflammation and apoptosis in hippocampus of rats. However, treatment with ICS II 20 mg/kg could improve the cognitive deficits, ameliorate neuronal death, and reduce the levels of Aß in the hippocampus. Furthermore, ICS II could suppress microglial and astrocytic activation, inhibit expression of IL-1ß, TNF-α, COX-2, and iNOS mRNA and protein, and attenuate the Aß induced Bax/Bcl-2 ratio elevation and caspase-3 activation. In conclusion, these results showed that ICS II could reverse Aß-induced cognitive deficits, possibly via the inhibition of neuroinflammation and apoptosis, which suggested a potential protective effect of ICS II on AD.