The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo

Lecanu, Laurent; Hashim, Areej I.; McCourty, Althea; Giscos-Douriez, Isabelle; Dinca, Ivona; Yao, Wenguo; Vicini, Stefano; Szabó, Gábor; Erdélyi, Ferenc; Greeson, Janet; Papadopoulos, Vassilios

doi:10.1016/j.neuroscience.2011.03.042

Cited by 34 publications

(14 citation statements)

References 49 publications

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“…TSPO levels are elevated in gliomas, neuroinflammation, and during axon elongation and neural stem cell differentiation (8). TSPO expression has also been shown in vivo to increase in ependymal cells upon stimulation with the neurogenic compound solasodine (73). In addition, TSPO ligands have been shown to exert neuroprotective properties (67).…”

Section: Early Steps In Neurosteroid Biosynthesismentioning

confidence: 99%

“…This ultimately led to the identification of the heterospirostenol, (22 R ,25 R )‐20α‐spirost‐5‐en‐3β‐yl hexanoate (diosgenin 3‐caproate; caprospinol), a naturally occurring compound in Gynura japonica , a plant from the Asteraceae family, that protects neuronal cells against Aβ 1–42 neurotoxicity (82). In parallel studies, we identified the naturally occurring compound, solasodine [(20α)‐25ξ‐methyl‐(22 R ,26)‐azacyclofurost‐5‐en‐3ξ‐ol], which is able to induce differentiation of neural stem cells and neurogenesis both in vitro and in vivo (73). Solasodine offers an interesting approach to stimulate in situ neurogenesis from resident neuronal progenitors as part of neuron replacement therapy and its pharmacological use remains to be explored further.…”

Section: Discovery Of Caprospinolmentioning

confidence: 99%

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Caprospinol: Discovery of a Steroid Drug Candidate to Treat Alzheimer’s Disease Based on 22R‐Hydroxycholesterol Structure and Properties

Papadopoulos

Lecanu

2011

J Neuroendocrinology

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The overall ability of the brain to synthesise neuroactive steroids led us to the identification of compounds that would reproduce aspects of neurosteroid pharmacology. The rate‐determining step in neurosteroid biosynthesis is the import of the substrate cholesterol into the mitochondria, where it is metabolised into pregnenolone via the intermediate 22R‐hydroxycholesterol. The levels of translocator protein 18‐kDa, mediating the import of cholesterol into mitochondria, correlated with increased pregnenolone formation and reduced levels of 22R‐hydroxycholesterol in biopsies from Alzheimer’s disease (AD), but not age‐matched control, brains. 22R‐hydroxycholesterol was shown to protect against β‐amyloid (Aβ42)‐induced neurotoxicity. In search of 22R‐hydroxycholesterol stable analogues, we identified the naturally occurring heterospirostenol, (22R,25R)‐20α‐spirost‐5‐en‐3β‐yl hexanoate (caprospinol) and derivatives that protect neuronal cells against Aβ1–42 neurotoxicity. The neuroprotective effect of caprospinol is the result of a combination of overlapping properties, including: (i) the ability to bind to Aβ42 and reduce plaque formation in the brain in vivo; (ii) interaction with components of the mitochondria respiratory chain resulting in an anti‐uncoupling effect; (iii) the capacity to scavenge Aβ42 monomers present in mitochondria; and (iv) the property of being a sigma‐1 receptor ligand. In vivo, caprospinol crosses the blood–brain barrier, accumulates in the brain, and restores cognitive impairment in a pharmacological rat model of AD. Caprospinol is stable, does not bind to known steroid receptors, is devoid of mutagenic and genotoxic properties, and is devoid of acute toxicity in rodents. The pharmacokinetics and pharmacodynamics of caprospinol were studied, and long‐term toxicity studies are under investigation, aiming to develop this compound as a disease‐modifying drug for the treatment of AD.

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Section: Early Steps In Neurosteroid Biosynthesismentioning

confidence: 99%

Section: Discovery Of Caprospinolmentioning

confidence: 99%

Caprospinol: Discovery of a Steroid Drug Candidate to Treat Alzheimer’s Disease Based on 22R‐Hydroxycholesterol Structure and Properties

Papadopoulos

Lecanu

2011

J Neuroendocrinology

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“…Natural products have been considered prominent sources for anticancer drug discovery with mild side‐effects . Solasodine, the aglycone of solamargine or solasonine after hydrolysis, displays a variety of pharmacological activities including anti‐oxidant, neurogenesis promotion, and inhibition of fungal infection . As a primary active ingredient of the traditional herb Solanum incanum L., recent studies have reported that solasodine has powerful anticancer properties by inducing apoptosis and cell cycle arrest in a wide variety of tumor cells including breast cancer, oral epidermoid carcinoma, chronic myelogenous leukemia, prostate cancer, and basal cell carcinoma, as well as stimulating persistent immunity against cancer such as sarcoma 180 .…”

mentioning

confidence: 99%

“…(11,12) Solasodine, the aglycone of solamargine or solasonine after hydrolysis, displays a variety of pharmacological activities including anti-oxidant, neurogenesis promotion, and inhibition of fungal infection. (13)(14)(15) As a primary active ingredient of the traditional herb Solanum incanum L., recent studies have…”

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confidence: 99%

Solasodine inhibits human colorectal cancer cells through suppression of the AKT/glycogen synthase kinase‐3β/β‐catenin pathway

Zhuang

Zhou

et al. 2017

Cancer Science

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Solasodine is a main active component isolated from Solanum incanum L. that performs a wide range of functions containing anti‐oxidant, anti‐infection, and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The results show that solasodine prohibited CRC cell proliferation dose‐ and time‐dependently and impeded CRC cell motility by downregulating MMPs. Solasodine was also found to fuel caspase‐cascade reaction and increase the ratio between Bax and Bcl‐2 so as to induce CRC cell apoptosis. When cells were pretreated with AKT activator (insulin‐like growth factor‐1) followed by solasodine, the solasodine‐induced apoptosis was partially abrogated by insulin‐like growth factor‐1. Moreover, solasodine hindered tumor development and stimulated similar mechanisms in vivo. In general, our study provides the first evidence that solasodine has a suppressive effect on CRC cells and that this agent may be a novel therapeutic drug for CRC treatment.

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“…which provide an alternative source of steroidal hormones (Sharma et al 1997;Weissenberg 2001;Jarald et al 2008;Patel et al 2013). Solasodine is the major alkaloid from this plant whose role in the promotion of neurogenesis, both under in vitro and in vivo conditions has recently been studied (Lecanu et al 2011), besides its commercial use as a precursor for the preparation of oral contraceptives equivalent to diosgenin (Sharma et al 1997). Berries of this shrub contains the highest concentration of solasodine (* 1.80 to 3.45%) (Sharma et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Physical state of the culture medium triggers shift in morphogenetic pattern from shoot bud formation to somatic embryo in Solanum khasianum

Pandey

Shukla

Misra

2018

Physiol Mol Biol Plants

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Solanum khasianum is a rich source of steroidal alkaloids that are important secondary metabolites with enormous pharmaceutical uses. Development of plantlets from somatic tissues, under in vitro conditions, takes place both through adventitious shoot bud differentiation or somatic embryogenesis (SE) pathway. We observed that the physical state of medium, solid or liquid, determined the regenerant differentiation patterns from root segment explants in S. khasianum. In the solidified medium, the root segments developed adventitious shoot buds whereas somatic embryos were regenerated in the liquid medium. Varying gradients from liquid to solid medium were further used to confirm the effect of solidified condition on regeneration pathway. Histological analysis of developing shoot buds and somatic embryos was also performed to confirm their development and differentiation patterns. In order to further confirm the developmental pathways, qRT-PCR analysis of the marker genes of SE and shoot regeneration was also performed. While SOMATIC EMBRYOGENESIS RECEPTOR KINASE1 (SkSERK1) expression was significantly up-regulated during the early embryogenic stage, the LATE EMBRYOGENESIS ABUNDANT (SkLEA) protein was found to be highly expressed in the mature embryos. Expression of the HISTONE DEACETYLASE (HDA6), a repressor of SE related genes, was highly decreased during embryogenesis in the liquid culture. Furthermore, expression of the ENHANCER OF SHOOT REGENERATION (ESR) gene was comparatively increased during shoot regeneration in the culture using solid medium. Our results point out that the physical state of the medium in S. khasianum plays a decisive role in differentiation pattern which was independent of hormonal supplements.

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The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo

Cited by 34 publications

References 49 publications

Caprospinol: Discovery of a Steroid Drug Candidate to Treat Alzheimer’s Disease Based on 22R‐Hydroxycholesterol Structure and Properties

Caprospinol: Discovery of a Steroid Drug Candidate to Treat Alzheimer’s Disease Based on 22R‐Hydroxycholesterol Structure and Properties

Solasodine inhibits human colorectal cancer cells through suppression of the AKT/glycogen synthase kinase‐3β/β‐catenin pathway

Physical state of the culture medium triggers shift in morphogenetic pattern from shoot bud formation to somatic embryo in Solanum khasianum

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