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

Published on Mar 1, 2019in Biomedicine & Pharmacotherapy4.545
· DOI :10.1016/J.BIOPHA.2018.10.201
Jiayin Zhou2
Estimated H-index: 2
Yuanyuan Deng12
Estimated H-index: 12
(Zunyi Medical College)
+ 3 AuthorsQihai Gong1
Estimated H-index: 1
Abstract 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-1β (IL-1β), 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.
📖 Papers frequently viewed together
13 Citations
12 Authors (Jiayi Zhao, ..., Lihong Zhu)
89 Citations
#1Faizul Azam (Misurata University)H-Index: 13
#2Nada Hussin Alabdullah (Misurata University)H-Index: 1
Last. Sreedevi Upadhyayula (IITs: Indian Institutes of Technology)H-Index: 14
view all 6 authors...
Aggregation of amyloid beta (Aβ) protein considered as one of contributors in development of Alzheimer’s disease (AD). Several investigations have identified the importance of non-steroidal anti-inflammatory drugs (NSAIDs) as Aβ aggregation inhibitors. Here, we have examined the binding interactions of 24 NSAIDs belonging to eight different classes, with Aβ fibrils by exploiting docking and molecular dynamics studies. Minimum energy conformation of the docked NSAIDs were further optimized by den...
30 CitationsSource
#1Serena Venezia (Innsbruck Medical University)H-Index: 2
#2Violetta Refolo (Innsbruck Medical University)H-Index: 4
Last. Nadia Stefanova (Innsbruck Medical University)H-Index: 26
view all 6 authors...
Background Alpha-synuclein (α-syn) aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Toll-like receptors (TLRs) are a family of highly conserved molecules that recognize pathogen-associated molecular patterns and define the innate immunity response. It was previously shown that TLR4 plays a role in the clearance of α-syn, suggesting that TLR4 up-regulation in microglia may be ...
35 CitationsSource
#1Detlef Vullhorst (NIH: National Institutes of Health)H-Index: 18
#2Tanveer Ahmad (NIH: National Institutes of Health)H-Index: 1
Last. Andres Buonanno (NIH: National Institutes of Health)H-Index: 35
view all 5 authors...
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters, and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodom...
20 CitationsSource
#1Lingli YanH-Index: 2
#2Yuanyuan Deng (Zunyi Medical College)H-Index: 12
Last. Qi-Hai GongH-Index: 2
view all 7 authors...
Abstract: Icariside II (ICS II) is a broad-spectrum anti-cancer natural compound extracted from Herba Epimedii Maxim. Recently, the role of ICS II has been investigated in central nervous system, especially have a neuroprotective effect in Alzheimer's disease (AD). In this study, we attempted to investigate the effects of ICS II, on cognitive deficits and beta-amyloid (Aβ) production in APPswe/PS1dE9 (APP/PS1) double transgenic mice. It was found that chronic ICS II administrated not only effect...
21 CitationsSource
#1Jing Ma (CQMU: Chongqing Medical University)H-Index: 4
#2Yuan Gao (CQMU: Chongqing Medical University)H-Index: 10
Last. Yong TangH-Index: 17
view all 15 authors...
// Jing Ma 1,2 , Yuan Gao 3 , Lin Jiang 1,2 , Feng-lei Chao 1,2 , Wei Huang 1,2 , Chun-ni Zhou 1,2 , Wei Tang 1,2 , Lei Zhang 1,2 , Chun-xia Huang 4 , Yi Zhang 1,2 , Yan-min Luo 1,2 , Qian Xiao 1,2 , Hua-rong Yu 4 , Rong Jiang 1,2 and Yong Tang 1,2 1 Department of Histology and Embryology, Chongqing Medical University, Chongqing, P. R. China 2 Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China 3 Department of Geriatrics, The First Affiliated Hos...
21 CitationsSource
#1Yuanyuan DengH-Index: 1
#2Long LongH-Index: 1
Last. Qihai GongH-Index: 1
view all 7 authors...
Beta-amyloid (Aβ) 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 a...
23 CitationsSource
#1Jie Song (Nanjing University of Chinese Medicine)H-Index: 13
#2Feng LiangH-Index: 1
Last. Zhenhai ZhangH-Index: 3
view all 9 authors...
Abstract Inflammatory microenvironment created by immune cells is favorable for tumor metastasis. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in inflammatory microenvironment. In this study, we sought to investigate the effects of Icariside II, a flavonol glycoside isolated from Epimedium koreanum Nakai, on A549 and H1299 cells migration in inflammatory microenvironment. At non-cytotoxic concentrations, Icariside II could inhibit invas...
31 CitationsSource
#1Duraisamy Kempuraj (MU: University of Missouri)H-Index: 38
#2Ramasamy Thangavel (MU: University of Missouri)H-Index: 13
Last. Asgar Zaheer (MU: University of Missouri)H-Index: 33
view all 9 authors...
: Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple Sclerosis (MS) are characterized by neuronal degeneration and neuronal death in specific regions of the central nervous system (CNS). In AD, neurons of the hippocampus and entorhinal cortex are the first to degenerate, whereas in PD, dopaminergic neurons in the substantia nigra degenerate. MS patients show destruction of the myelin sheath. Once the CNS neurons are damaged, they are unable to reg...
130 Citations
#1Nan ZongH-Index: 1
#2Fei LiH-Index: 13
Last. Qihai GongH-Index: 7
view all 6 authors...
Abstract Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer’s disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitator...
13 CitationsSource
#1Caixia YinH-Index: 7
#2Yuanyuan Deng (Zunyi Medical College)H-Index: 12
Last. Qihai GongH-Index: 7
view all 6 authors...
Abstract Beta-amyloid (Aβ) deposition and neuroinflammation are involved in Alzheimer’s disease (AD)-type neurodegeneration with cognitive deficits. Phosphodiesterase-5 (PDE5) inhibitors have recently been studied as a potential target for cognitive enhancement by reducing inflammatory responses and Aβ levels. The present study was designed to investigate the effects of icariside II (ICS II), a novel PDE5 inhibitor derived from the traditional Chinese herb Epimedium brevicornum, on cognitive def...
28 CitationsSource
Cited By21
#1Wen LuoH-Index: 2
#1Wen Luo (Southern University of Science and Technology)
Last. Wei ZhangH-Index: 5
view all 6 authors...
#1Feng Gao (Qingdao Agricultural University)
#2Kaiqiang Fu (Qingdao Agricultural University)H-Index: 5
Last. Rongfeng Cao (Qingdao Agricultural University)H-Index: 8
view all 6 authors...
OBJECTIVES Clinical endometritis is a common reproductive disorder in mammals that seriously endangers animal health and causes economic losses worldwide. This study aims to use lipopolysaccharide and Trueperella pyogenes exotoxin as modelling reagents (LC) to perfuse the mouse uterus in order to establish a model of clinical endometritis and to investigate the anti-inflammatory and antioxidant effects of chlorogenic acid (CGA). METHODS In this study, five LC uterine perfusions were selected to ...
#1Ying Lu (Nantong University)H-Index: 6
#2De-Li Cao (Nantong University)H-Index: 16
Last. Yong-Jing Gao (Nantong University)H-Index: 37
view all 4 authors...
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be expressed in spinal astrocytes and is involved in neuropathic pain. In this study, we investigated the role and mechanism of TRAF6 in complete Freund's adjuvant (CFA)-evoked chronic inflammatory hypersensitivity and the effect of docosahexaenoic acid (DHA) on TRAF6 expression and inflammatory pain. We found that TRAF6 was dominantly increased in microglia at the spinal level after intraplantar injection of CFA. In...
#1Ayman E. El-Sahar (Cairo University)H-Index: 6
#2Nesma A Shiha (Cairo University)
Last. Lamiaa A. Ahmed (Cairo University)H-Index: 13
view all 4 authors...
1 CitationsSource
#1Fangfang Zhao (Henan University)H-Index: 1
#2Huijun TianH-Index: 1
Last. Hongan YangH-Index: 1
view all 5 authors...
Parkinson's disease (PD) is a complex neurodegenerative illness associated with the loss or damage to neurons of the dopaminergic system in the brain. Few therapeutic approaches and considerable side effects of conventional drugs necessitate a new therapeutic agent to treat patients with PD. Rhaponticin is a natural hydroxystilbene, found in herbal plants such as Rheum rhaponticum, and known to have desirable biological activity including anti-inflammatory properties. However, the neuroinflammat...
1 CitationsSource
#1Honghe Xiao (LNUTCM: Liaoning University of Traditional Chinese Medicine)H-Index: 3
#2Hongyan Li (LNUTCM: Liaoning University of Traditional Chinese Medicine)H-Index: 7
Last. Jingxian Yang (LNUTCM: Liaoning University of Traditional Chinese Medicine)H-Index: 14
view all 13 authors...
Abstract Ethnopharmacological relevance According to the theory of traditional Chinese medicine (TCM), Alzheimer's disease (AD) is identified as “forgetfulness” or “dementia”, and is mainly caused by “kidney essence deficiency” which ultimately induces “encephala reduction”. Therefore, herbal formulas possessing the efficacy of nourishing kidney essence or replenishing brain marrow are commonly served as effective strategies for AD treatment. Shenzao jiannao oral liquid (SZJN), a traditional Chi...
1 CitationsSource
Last. Fei Li (Zunyi Medical College)H-Index: 13
view all 5 authors...
#1Lingli Kong (Henan University)H-Index: 1
#2Laifang Wang (Henan University)H-Index: 3
Last. Huiqiang Wu (Henan University)H-Index: 1
view all 5 authors...
Rhodojaponin II (R-II) has been shown to possess anti-inflammatory activity. Herein, we aimed to explore the effect of R-II on tumor necrosis factor-α (TNF-α)-induced inflammation in MH7A rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs). We found that R-II treatment at high concentration suppressed the viability of MH7A cells. R-II suppressed the levels of nitric oxide and prostaglandin E2, and inhibited messenger RNA expression and concentrations of interleukin-1β (IL-1β), IL-6 and...
2 CitationsSource
#1Mu-Bo LiuH-Index: 1
#2Wei WangH-Index: 2
Last. Qi-Hai GongH-Index: 21
view all 6 authors...
Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood–brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which is derived from Herba Epimedii, attenuates cerebral I/R injury by inhibiting the GSK-3β-mediated activation of autophagy both in vitro and in vivo. However, the effect of ICS II on t...
4 CitationsSource
#1Hosein AhmadiH-Index: 1
#2Zahra NayeriH-Index: 1
Last. Mehdi MohammadiH-Index: 1
view all 5 authors...
Microglial activation can release free radicals and various pro-inflammatory cytokines, which implicates the progress of a neurodegenerative disease. Therefore suppression of microglial activation can be an appropriate strategy for combating neurodegenerative diseases. Betanin is a red food dye that acts as free radical scavenger and can be a promising candidate for this purpose. In this study, purification of betanin from red beetroots was carried out by normal phase colum chromatography, yield...
3 CitationsSource