Smilagenin
目录号 : GC37652
Smilagenin (SMI) 是一种脂溶性小分子甾体皂苷元，来自知母 Rhizoma anemarrhenae 和天竺葵 Radix asparagi，广泛用于治疗慢性神经退行性疾病的中药。Smilagenin (SMI) 通过增加毒蕈碱受体亚型 1 (M1)-受体的的密度来改善老年大鼠的记忆。Smilagenin (SMI) 通过刺激脑源性神经营养因子的基因表达减弱 Aβ(25-35) 诱导的神经变性，可能代表 AD 的新型治疗策略。
Cas No.:126-18-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Smilagenin (SMI) is a lipid-soluble small-molecule steroidal sapogenin from Rhizoma anemarrhenae and Radix asparagi widely used in traditional Chinese medicine for treating chronic neurodegeneration diseases[1]. Smilagenin (SMI) improves memory of aged rats by increasing the muscarinic receptor subtype 1 (M1)-receptor density[2].Smilagenin (SMI) attenuates Aβ(25-35)-induced neurodegenerationvia stimulating the gene expression of brain-derived neurotrophic factor, may represents a novel therapeutic strategy for AD[3].
Smilagenin (10 μM; 24 hours) increases SH-SY5Y cell survival compared with Aβ(25-35) intoxicated cells[3]. Smilagenin (10 μM; 24 hours) increases neurotrophic factor (GDNF) and neurotrophic factor (BDNF) mRNA level by promoting CREB phosphorylation in 1-methyl-4-phenylpyridimium (MPP+) treated SH-SY5Y cells[2]. Cell Viability Assay[3] Cell Line: SH-SY5Y cells
Smilagenin (intragastric administration; 10 or 26 mg/kg, once daily; 60 days) prevents the impairment of dopaminergic neurons in chronic MPTP/probenecid-induced mouse model[2]. Animal Model: MPTP/probenecid-induced mouse model[2]
[1]. He X, et al. Smilagenin Protects Dopaminergic Neurons in Chronic MPTP/Probenecid-Lesioned Parkinson's Disease Models. Front Cell Neurosci. 2019 Feb 5;13:18. [2]. Hu Y, et al. Regulation of M1-receptor mRNA stability by smilagenin and its significance in improving memory of aged rats. Neurobiol Aging. 2010 Jun;31(6):1010-9. [3]. Zhang R, et al. Smilagenin attenuates beta amyloid (25-35)-induced degeneration of neuronal cells via stimulating the gene expression of brain-derived neurotrophic factor. Neuroscience. 2012 May 17;210:275-85
| Cas No. | 126-18-1 | SDF | |
| Canonical SMILES | C[C@@H]1[C@@]2(CC[C@@H](C)CO2)O[C@]3([H])[C@@]1([H])[C@@]4([C@@]([C@@]5([H])[C@]([C@@]6([C@](C[C@@H](O)CC6)([H])CC5)C)([H])CC4)([H])C3)C | ||
| 分子式 | C27H44O3 | 分子量 | 416.64 |
| 溶解度 | Ethanol: ≥ 10 mg/mL (24.00 mM); DMSO: < 1 mg/mL (insoluble or slightly soluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4002 mL | 12.0008 mL | 24.0015 mL |
| 5 mM | 0.48 mL | 2.4002 mL | 4.8003 mL |
| 10 mM | 0.24 mL | 1.2001 mL | 2.4002 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
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2.
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Smilagenin Protects Dopaminergic Neurons in Chronic MPTP/Probenecid-Lesioned Parkinson's Disease Models
Front Cell Neurosci 2019 Feb 5;13:18.PMID:30804756DOI:10.3389/fncel.2019.00018.
Current therapies for Parkinson's disease (PD) only offer limited symptomatic alleviation but fail to hamper the progress of the disease. Thus, it is imperative to establish new approaches aiming at protecting or reversing neurodegeneration in PD. Recent work elucidates whether Smilagenin (abbreviated SMI), a steroidal sapogenin from traditional Chinese medicinal herbs, can take neuroprotective effect on dopaminergic neurons in a chronic model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) conjuncted with probenecid mice. We reported for the first time that SMI significantly improved the locomotor ability of chronic MPTP/probenecid-lesioned mice. SMI increased the tyrosine hydroxylase (TH) positive and Nissl positive neuron number in the substantia nigra pars compacta (SNpc), augmented striatal DA and its metabolites concentration and elevated striatal dopamine transporter density (DAT). In addition, dopamine receptor D2R not D1R was down-regulated by MPTP/probenecid and slightly raised by SMI prevention. What's more, we discovered that SMI markedly elevated striatal glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) protein levels in SMI prevented mice. And we found that SMI increased GDNF and BDNF mRNA level by promoting CREB phosphorylation in 1-methyl-4-phenylpyridimium (MPP+) treated SH-SY5Y cells. The results illustrated that SMI could prevent the impairment of dopaminergic neurons in chronic MPTP/probenecid-induced mouse model.
Synthesis and biological evaluation of 3-carbamate Smilagenin derivatives as potential neuroprotective agents
Bioorg Med Chem Lett 2019 Oct 1;29(19):126622.PMID:31444084DOI:10.1016/j.bmcl.2019.08.026.
Studies indicated that Smilagenin, isolated from Anemarrhena asphodeloides Bunge, could improve cognitive impairment and exhibit neuroprotective activity. On the basis of the structure of Smilagenin, a series of derivatives were synthesized and evaluated for their neuroprotective effects of H2O2-induced, oxygen glucose deprivation-induced neurotoxicity in SH-SY5Y cells and LPS-induced NO production in RAW264.7 cells. Structure activity relationship of derivatives revealed that benzyl-substituted piperazine formate derivatives showed the potent neuroprotective activity such as A12. These findings may provide new insights for the development of neuroprotective agents against Alzheimer's disease.
Smilagenin attenuates beta amyloid (25-35)-induced degeneration of neuronal cells via stimulating the gene expression of brain-derived neurotrophic factor
Neuroscience 2012 May 17;210:275-85.PMID:22441042DOI:10.1016/j.neuroscience.2012.03.017.
The development of drugs that attenuate neurodegeneration is important for the treatment of Alzheimer's disease (AD). We previously found that Smilagenin (SMI), a steroidal sapogenin from traditional Chinese medicinal herbs improves memory in animal models, is neither a cholinesterase inhibitor nor a glutamate receptor antagonist, but can significantly elevate the declined muscarinic receptor (M receptor) density. In this article, to clarify whether SMI represents a new approach for treating neurodegeneration disease, we first demonstrate that SMI pretreatment significantly attenuates the neurodegenerative changes induced by beta amyloid 25-35 (Aβ(25-35)) in cultured rat cortical neurons, including decreased cholinergic neuron number, shortened neurite outgrowth length, and declined M receptor density. Brain-derived neurotrophic factor (BDNF) protein levels in the culture medium were also decreased by Aβ(25-35) and significantly elevated by SMI. Parallel experiments revealed that when the trk receptors were inhibited by K252a or the action of BDNF was inhibited by a neutralizing anti-BDNF antibody, the effects of SMI on the Aβ(25-35)-induced neurodegeneration in rat cortical neurons were almost completely abolished. In the all-trans retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cells, the BDNF transcription rate measured by a nuclear run-on assay was significantly suppressed by Aβ(25-35) and elevated by SMI, but the BDNF degradation rate measured by half-life determination was unchanged by Aβ(25-35) and SMI. Transcript analysis of the SH-SY5Y cells using quantitative RT-PCR (qRT-PCR) showed that the IV and VI transcripts of BDNF mRNA were significantly decreased by Aβ(25-35) and elevated by SMI. Taken together, we conclude that SMI attenuates Aβ(25-35)-induced neurodegeneration in cultured rat cortical neurons and SH-SY5Y cells mainly through stimulating BDNF mRNA transcription implicating that SMI may represent a novel therapeutic strategy for AD.
Regulation of M1-receptor mRNA stability by Smilagenin and its significance in improving memory of aged rats
Neurobiol Aging 2010 Jun;31(6):1010-9.PMID:18676061DOI:10.1016/j.neurobiolaging.2008.06.008.
The purpose of this work is to study the effect of Smilagenin on the mRNA stability of muscarinic receptor subtype 1 (M(1); m1 mRNA) in aged rat brains and its significance in improving memory. The Y-maze avoidance task showed that oral administration of Smilagenin significantly improved spatial memory performance in aged rats. Mechanistic studies showed that Smilagenin was neither a ligand of the M receptors nor a cholinesterase inhibitor, while radioligand binding assays revealed that Smilagenin significantly increased the M(1)-receptor density. The increase of M(1)-receptor density correlated with memory improvement. Real-time polymerase chain reaction (RT-PCR) revealed that the m1 mRNA in m1 gene-transfected CHO cells increased significantly, and the average half-life of m1 mRNA was approximately doubled by Smilagenin treatment. These results suggest that Smilagenin improves memory of aged rats at least partially by increasing the stability of m1 mRNA. However since the ChAT activity in the cortex of aged rats was also elevated by Smilagenin, it cannot be excluded that the increase of intrinsic acetylcholine excretion also plays a role in the memory-improvement effect of Smilagenin.
Outlining In Vitro and In Silico Cholinesterase Inhibitory Activity of Twenty-Four Natural Products of Various Chemical Classes: Smilagenin, Kokusaginine, and Methyl Rosmarinate as Emboldening Inhibitors
Molecules 2021 Apr 1;26(7):2024.PMID:33916300DOI:10.3390/molecules26072024.
Cholinesterase (ChE) inhibition is an important treatment strategy for Alzheimer's disease (AD) as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are involved in the pathology of AD. In the current work, ChE inhibitory potential of twenty-four natural products from different chemical classes (i.e., diosgenin, hecogenin, rockogenin, Smilagenin, tigogenin, astrasieversianins II and X, astragalosides I, IV, and VI, cyclocanthosides E and G, macrophyllosaponins A-D, kokusaginin, lamiide, forsythoside B, verbascoside, alyssonoside, ipolamide, methyl rosmarinate, and luteolin-7-O-glucuronide) was examined using ELISA microtiter assay. Among them, only Smilagenin and kokusaginine displayed inhibitory action against AChE (IC50 = 43.29 ± 1.38 and 70.24 ± 2.87 µg/mL, respectively). BChE was inhibited by only methyl rosmarinate and kokusaginine (IC50 = 41.46 ± 2.83 and 61.40 ± 3.67 µg/mL, respectively). IC50 values for galantamine as the reference drug were 1.33 ± 0.11 µg/mL for AChE and 52.31 ± 3.04 µg/mL for BChE. Molecular docking experiments showed that the orientation of Smilagenin and kokusaginine was mainly driven by the interactions with the peripheral anionic site (PAS) comprising residues of hAChE, while kokusaginine and methyl rosmarinate were able to access deeper into the active gorge in hBChE. Our data indicate that similagenin, kokusaginine, and methyl rosmarinate could be hit compounds for designing novel anti-Alzheimer agents.