Estrogen-like neuroprotection of isopsoralen against spinal cord injury through estrogen receptor ERα

Li, Xiaoming; Yang, Qi; Li, Xubo; Cheng, Qiang; Zhang, Kun; Han, Jing; Zhao, Jianning; Liu, Gang; Zhao, Ming

doi:10.1007/s11011-016-9913-z

Cited by 24 publications

(16 citation statements)

References 30 publications

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“…The treatment of MC3T3-E1 cells and primary rat osteoblast cells with angelicin increased the expression of ERa protein (Ge et al, 2018;Ge et al, 2019). A similar increase in ERa by angelicin in the grey matter of ventral and dorsal horns were also reported in adult male C57BL/6 mice that had suffered spinal cord injury (Li et al, 2017a). Other than that, to determine if angelicin were only upregulating ERa and not ERb, Xin et al (2010) incubated HeLa cells with angelicin and they confirmed that angelicin only increases ERa transcription activity.…”

Section: Angelicin As An Osteogenesis and Chondrogenesis Enhancersupporting

confidence: 56%

Angelicin—A Furocoumarin Compound With Vast Biological Potential

et al. 2020

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Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-kB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of proosteogenic and chondrogenic markers and activation of TGF-b/BMP, Wnt/b-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERa) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of

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Section: Angelicin As An Osteogenesis and Chondrogenesis Enhancersupporting

confidence: 56%

Angelicin—A Furocoumarin Compound With Vast Biological Potential

et al. 2020

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“…ERα potentiates bones response to mechanical strain, and regulates trabecular bone formation and thereby trabecular bone volume in female and male mice (35,36). A recent study demonstrated that angelicin exhibits estrogen-like activity and induces the upregulation of ERα in a spinal cord injury model (17). In the present study, angelicin was associated with an increase in ERα protein levels in rat primary osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis

Cui

Liu

et al. 2019

Mol Med Report

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Reports of the ameliorative effect of angelicin on sex hormone deficiency-induced osteoporosis have highlighted this compound as a candidate for the treatment of osteoporosis. However, the molecular mechanisms of action of angelicin on osteoblast differentiation have not been thoroughly researched. The aim of the present study was to evaluate the effect of angelicin on the proliferation, differentiation and mineralization of rat calvarial osteoblasts using a Cell Counting Kit-8, alkaline phosphatase activity and the expression of osteogenic genes and proteins. Treatment with angelicin promoted the proliferation, matrix mineralization and upregulation of osteogenic marker genes including collagen type I α 1 and bone γ-carboxyglutamate in fetal rat calvarial osteoblasts. Furthermore, angelicin promoted the expression of β-catenin and runt related transcription factor 2, which serve a vital role in the Wnt/β-catenin signaling pathway. Consistently, the osteogenic effect of angelicin was attenuated by the use of a Wnt inhibitor. Moreover, angelicin increased the expression of estrogen receptor α (ERα), which also serves a key role in osteoblast differentiation. Taken together, these results demonstrated that angelicin may promote osteoblast differentiation through activation of ERα and the Wnt/β-catenin signaling pathway.

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“…For studies of the effects of hippocampal estrogen depletion, mice were given systemic injections of formestane (2 mg/kg, s.c.; Tocris Bioscience) daily for 7 d with the last treatment 1 d before experimental use. For behavioral experiments, mice were given intraperitoneal injections of the following drugs (or vehicle): MPP or PHTPP (0.6 mg/kg, 60 min before behavior) dissolved in saline with 5% DMSO (Labouesse et al, 2015;Li et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus

et al. 2018

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Men are generally superior to women in remembering spatial relationships, whereas the reverse holds for semantic information, but the neurobiological bases for these differences are not understood. Here we describe striking sexual dimorphism in synaptic mechanisms of memory encoding in hippocampal field CA1, a region critical for spatial learning. Studies of acute hippocampal slices from adult rats and mice show that for excitatory Schaffer-commissural projections, the memory-related long-term potentiation (LTP) effect depends upon endogenous estrogen and membrane estrogen receptor α (ERα) in females but not in males; there was no evident involvement of nuclear ERα in females, or of ERβ or GPER1 (G-protein-coupled estrogen receptor 1) in either sex. Quantitative immunofluorescence showed that stimulation-induced activation of two LTP-related kinases (Src, ERK1/2), and of postsynaptic TrkB, required ERα in females only, and that postsynaptic ERα levels are higher in females than in males. Several downstream signaling events involved in LTP were comparable between the sexes. In contrast to endogenous estrogen effects, infused estradiol facilitated LTP and synaptic signaling in females via both ERα and ERβ. The estrogen dependence of LTP in females was associated with a higher threshold for both inducing potentiation and acquiring spatial information. These results indicate that the observed sexual dimorphism in hippocampal LTP reflects differences in synaptic kinase activation, including both a weaker association with NMDA receptors and a greater ERα-mediated kinase activation in response to locally produced estrogen in females. We propose that male/female differences in mechanisms and threshold for field CA1 LTP contribute to differences in encoding specific types of memories. There is good evidence for male/female differences in memory-related cognitive function, but the neurobiological basis for this sexual dimorphism is not understood. Here we describe sex differences in synaptic function in a brain area that is critical for learning spatial cues. Our results show that female rodents have higher synaptic levels of estrogen receptor α (ERα) and, in contrast to males, require membrane ERα for the activation of signaling kinases that support long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning. The additional requirement of estrogen signaling in females resulted in a higher threshold for both LTP and hippocampal field CA1-dependent spatial learning. These results describe a synaptic basis for sexual dimorphism in encoding spatial information.

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Estrogen-like neuroprotection of isopsoralen against spinal cord injury through estrogen receptor ERα

Cited by 24 publications

References 30 publications

Angelicin—A Furocoumarin Compound With Vast Biological Potential

Angelicin—A Furocoumarin Compound With Vast Biological Potential

ERα and Wnt/β‑catenin signaling pathways are involved in angelicin‑dependent promotion of osteogenesis

Memory-Related Synaptic Plasticity Is Sexually Dimorphic in Rodent Hippocampus

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