Involvement of IGF-1 receptor signaling pathway in the neuroprotective effects of Icaritin against MPP + -induced toxicity in MES23.5 cells

Jiang, Mingchun; Chen, Xiaohan; Zhao, Xiuhe; Zhang, Xuejie; Chen, Wenfang

doi:10.1016/j.ejphar.2016.05.031

Cited by 22 publications

(8 citation statements)

References 33 publications

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“…Icariin, a well-known traditional Chinese drug, is extracted from Herba Epimedii . The pharmacological and biological effects of icariin, including anti-inflammatory ( 5 ), antitumor ( 6 ) and neuroprotective ( 7 ) effects, have been confirmed by previous studies. Its effects on keratinocytes, however, remain unclear.…”

Section: Introductionsupporting

confidence: 62%

Icariin promotes wound healing by enhancing the migration and proliferation of keratinocytes via the AKT and ERK signaling pathway

Liu

et al. 2018

Int J Mol Med

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Icariin is a traditional Chinese drug that has long been used to treat various diseases. In the present study, the effect of icariin was investigated on cutaneous wound healing. Using in vitro experiments, it was demonstrated that icariin significantly promoted the migration and proliferation of keratinocytes via the activation of AKT serine/threonine kinase 1 (AKT) and extracellular signal-regulated kinase (ERK). Inhibition of AKT or ERK reversed the effects of icariin on the proliferation and migration of keratinocytes. In addition, icariin inhibited the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and induced the production of IL-10. Finally, animal experiments demonstrated that icariin treatment accelerated the wound closure rate. The present findings revealed that icariin may be a promising drug to promote the migration and proliferation of keratinocytes, and to accelerate the healing of skin wounds, through its role in the upregulation of AKT and ERK signaling.

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Section: Introductionsupporting

confidence: 62%

Icariin promotes wound healing by enhancing the migration and proliferation of keratinocytes via the AKT and ERK signaling pathway

Liu

et al. 2018

Int J Mol Med

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“…This micromolecule steroid compound is extracted from herba epimedii and is mostly applied in the treatment of osteoporosis, especially in postmenopausal osteoporosis. What is more, icariin has also been reported to have protective effects against amyloid beta-induced apoptosis in PC-12 cells [ 9 ], attenuating LPS-induced acute inflammatory responses [ 10 ], and protecting against MPP(+)-induced toxicity in MES23.5 cells [ 11 ]. Additionally, several complex roles for icariin in a number of pathway activation instances have been proposed, such as the PI3K/AKT pathway [ 9 , 10 , 12 – 15 ], the ROS/JNK-dependent mitochondrial pathway [ 16 ], the Wnt/beta-catenin pathway [ 17 ], and NO/cGMP signaling [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Icariin Prevents IL‐1β‐Induced Apoptosis in Human Nucleus Pulposus via the PI3K/AKT Pathway

Deng

Liang

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Purpose To explore the effect and possible mechanism of icariin, a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum that was applied to IL-1β pretreated human nucleus pulposus (NP) cells. Methods Human NP cells were isolated from intervertebral discs of patients with scoliosis and lumbar spondylolisthesis. The cells were divided into five groups: A (blank control); B (20 ng/ml IL-1β); C (20 ng/ml IL-1β + 20 μM icariin); D (20 μM icariin + 20 ng/ml IL-1β + 25 μM LY294002); E (20 ng/ml IL-1β + 25 μM LY294002). For each of the five groups, the CCK8, apoptosis rates, ROS rates, and JC-1 rates were determined and an electron micrograph was performed. Different expression levels of apoptosis proteins and proteins in the PI3K/AKT pathway were detected via western blot. Results We found that the damage effects on human nucleus pulposus cells from 20 ng/ml of IL-1β exposure were attenuated by icariin. When the PI3K/AKT pathway was blocked by LY294002, a specific inhibitor of this pathway, the protective effect of icariin was impaired. In summary, icariin might be a protective traditional Chinese medicine, which prevents inflammation-induced degeneration of intervertebral discs partly through the PI3K/AKT pathway.

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“…Additionally, icaritin has neuroprotective effects against MPP + -induced toxicity in MES23.5 cells. IGF-I receptor mediated activation of PI3K/Akt and MEK/ERK1/2 pathways are involved in the neuroprotective effects of icaritin against MPP + -induced neuronal damage [11]. Recently, icaritin had been shown as a potential agent for the treatment of systemic lupus erythematosus [12].…”

Section: Introductionmentioning

confidence: 99%

Metabolite Profiling, Pharmacokinetics, and In Vitro Glucuronidation of Icaritin in Rats by Ultra-Performance Liquid Chromatography Coupled with Mass Spectrometry

Zhang

Chen

Zhang

et al. 2017

Journal of Analytical Methods in Chemistry

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Icaritin is a naturally bioactive flavonoid with several significant effects. This study aimed to clarify the metabolite profiling, pharmacokinetics, and glucuronidation of icaritin in rats. An ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) assay was developed and validated for qualitative and quantitative analysis of icaritin. Glucuronidation rates were determined by incubating icaritin with uridine diphosphate glucuronic acid- (UDPGA-) supplemented microsomes. Kinetic parameters were derived by appropriate model fitting. A total of 30 metabolites were identified or tentatively characterized in rat biosamples based on retention times and characteristic fragmentations, following proposed metabolic pathway which was summarized. Additionally, the pharmacokinetics parameters were investigated after oral administration of icaritin. Moreover, icaritin glucuronidation in rat liver microsomes was efficient with CLint (the intrinsic clearance) values of 1.12 and 1.56 mL/min/mg for icaritin-3-O-glucuronide and icaritin-7-O-glucuronide, respectively. Similarly, the CLint values of icaritin-3-O-glucuronide and icaritin-7-O-glucuronide in rat intestine microsomes (RIM) were 1.45 and 0.86 mL/min/mg, respectively. Taken altogether, dehydrogenation at isopentenyl group and glycosylation and glucuronidation at the aglycone were main biotransformation process in vivo. The general tendency was that icaritin was transformed to glucuronide conjugates to be excreted from rat organism. In conclusion, these results would improve our understanding of metabolic fate of icaritin in vivo.

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Involvement of IGF-1 receptor signaling pathway in the neuroprotective effects of Icaritin against MPP + -induced toxicity in MES23.5 cells

Cited by 22 publications

References 33 publications

Icariin promotes wound healing by enhancing the migration and proliferation of keratinocytes via the AKT and ERK signaling pathway

Icariin promotes wound healing by enhancing the migration and proliferation of keratinocytes via the AKT and ERK signaling pathway

Icariin Prevents IL‐1β‐Induced Apoptosis in Human Nucleus Pulposus via the PI3K/AKT Pathway

Metabolite Profiling, Pharmacokinetics, and In Vitro Glucuronidation of Icaritin in Rats by Ultra-Performance Liquid Chromatography Coupled with Mass Spectrometry

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