1. Metabolic Enzyme/Protease
  2. MMP Endogenous Metabolite
  3. Stigmasterol

Stigmasterol is an orally acitve, immunomodulatory agent with anti-inflammatory and neuroprotective effect, as well as able to cross the blood-brain barrier. Stigmasterol activates AMPK, which in turn inhibits NF-κB and NLRP3 signaling pathways, reduces microglia-mediated neuroinflammation, and alleviates cognitive impairment and Alzheimer's disease. Stigmasterol regulates M1/M2 polarization of microglia through the TLR4/ NF-κB pathway, thereby reducing neuropathic pain. Stigmasterol can be used for neurodegenerative diseases, inflammatory diseases, and pain management, among others.

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CAS No. : 83-48-7

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Customer Review

Based on 13 publication(s) in Google Scholar

Other Forms of Stigmasterol:

Top Publications Citing Use of Products

    Stigmasterol purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2024 Dec 23:15:1485915.  [Abstract]

    The cytotoxicity of Stigmasterol (Stigma) (25, 50, 100, 200 μM) is evaluated with CCK-8 assay.

    Stigmasterol purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2024 Dec 23:15:1485915.  [Abstract]

    Representative images of Hoechst 33,342 and PI staining in STC stimulated primary pancreatic acinar cells treated with or without Stigmasterol (Stigma) (50, 100 μM).

    Stigmasterol purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2024 Dec 23:15:1485915.  [Abstract]

    Representative images of Bax as well Bcl-2 proteins in STC-stimulated primary pancreatic acinar cells treated with or without Stigmasterol (Stigma) (50, 100 μM).

    Stigmasterol purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2024 Dec 23:15:1485915.  [Abstract]

    Representative immunohistochemistry images and quantitative analysis of p-ERK on the pancreas sections in sodium taurocholate (STC)-induced AP model mice treated with or without Stigmasterol (Stigma) (i.g, 50 or 100 mg/kg/d, 7d).

    Stigmasterol purchased from MedChemExpress. Usage Cited in: Front Pharmacol. 2024 Dec 23:15:1485915.  [Abstract]

    H&E staining revealed that Stigmasterol (Stigma) (50, 100 mg/kg, i.p.) mitigated STC-induced pancreatic tissue injury, including edema, inflammatory cell infiltration.
    • Biological Activity

    • Purity & Documentation

    • References

    • Customer Review

    Description

    Stigmasterol is an orally acitve, immunomodulatory agent with anti-inflammatory and neuroprotective effect, as well as able to cross the blood-brain barrier. Stigmasterol activates AMPK, which in turn inhibits NF-κB and NLRP3 signaling pathways, reduces microglia-mediated neuroinflammation, and alleviates cognitive impairment and Alzheimer's disease. Stigmasterol regulates M1/M2 polarization of microglia through the TLR4/ NF-κB pathway, thereby reducing neuropathic pain. Stigmasterol can be used for neurodegenerative diseases, inflammatory diseases, and pain management, among others[1][2][3][4][5].

    IC50 & Target

    Human Endogenous Metabolite

     

    Cellular Effect
    Cell Line Type Value Description References
    A549 IC50
    10.36 μM
    Compound: SS
    Cytotoxicity against human A549 cells assessed as decrease in cell viability after 24 hrs by MTT assay
    Cytotoxicity against human A549 cells assessed as decrease in cell viability after 24 hrs by MTT assay
    10.1039/C6MD00178E
    A549 IC50
    98.2 μM
    Compound: 4, stigmasterol
    Cytotoxicity against human A549 cells after 1 hr by MTT assay
    Cytotoxicity against human A549 cells after 1 hr by MTT assay
    [PMID: 18343122]
    Calu-1 IC50
    > 100 μM
    Compound: 7
    Inhibition of human Calu1 cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    Inhibition of human Calu1 cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    [PMID: 11374975]
    DU-145 IC50
    22.73 μM
    Compound: 3
    Cytotoxicity against human DU145 cells after 24 hrs by MTT assay
    Cytotoxicity against human DU145 cells after 24 hrs by MTT assay
    [PMID: 22687747]
    HEp-2 IC50
    37.5 μg/mL
    Compound: 6
    Antiviral activity against Parainfluenza virus type 3 infected in human Hep2 cells assessed as inhibition of virus-induced cytopathogenic effect
    Antiviral activity against Parainfluenza virus type 3 infected in human Hep2 cells assessed as inhibition of virus-induced cytopathogenic effect
    [PMID: 11678648]
    HeLa IC50
    12.21 μM
    Compound: SS
    Cytotoxicity against human HeLa cells assessed as decrease in cell viability after 24 hrs by MTT assay
    Cytotoxicity against human HeLa cells assessed as decrease in cell viability after 24 hrs by MTT assay
    10.1039/C6MD00178E
    HeLa IC50
    > 100 μM
    Compound: 7
    Inhibition of human HeLa cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    Inhibition of human HeLa cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    [PMID: 11374975]
    HeLa IC50
    > 50 μM
    Compound: 3
    Cytotoxicity against human HeLa cells by MTT assay
    Cytotoxicity against human HeLa cells by MTT assay
    [PMID: 19388709]
    J774 IC50
    > 242.3 μM
    Compound: 12
    Cytotoxicity against mouse J774 cells by alamar blue assay
    Cytotoxicity against mouse J774 cells by alamar blue assay
    [PMID: 17637068]
    K562 IC50
    11.14 μM
    Compound: 3
    Cytotoxicity against human K562 cells after 24 hrs by MTT assay
    Cytotoxicity against human K562 cells after 24 hrs by MTT assay
    [PMID: 22687747]
    K562 IC50
    > 100 μM
    Compound: 7
    Inhibition of human K562 cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    Inhibition of human K562 cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    [PMID: 11374975]
    KB ED50
    > 4 μg/mL
    Compound: stigmasterol
    Cytotoxicity against human KB cells after 72 hrs
    Cytotoxicity against human KB cells after 72 hrs
    [PMID: 9644061]
    KB IC50
    > 100 μM
    Compound: stigmasterol
    Cytotoxicity against human KB cells
    Cytotoxicity against human KB cells
    [PMID: 12398543]
    MCF7 IC50
    21.43 μM
    Compound: 3
    Cytotoxicity against human MCF7 cells after 24 hrs by MTT assay
    Cytotoxicity against human MCF7 cells after 24 hrs by MTT assay
    [PMID: 22687747]
    MDA-MB-231 IC50
    564 μM
    Compound: 8
    Cytotoxicity against human MDA-MB-231 cells after 3 days by Celltiter-Glo assay
    Cytotoxicity against human MDA-MB-231 cells after 3 days by Celltiter-Glo assay
    [PMID: 28945373]
    P388D1 IC50
    > 50 μM
    Compound: 3
    Cytotoxicity against mouse P388D1 cells by MTT assay
    Cytotoxicity against mouse P388D1 cells by MTT assay
    [PMID: 19388709]
    PC-3 IC50
    18.28 μM
    Compound: 3
    Cytotoxicity against human PC3 cells after 24 hrs by MTT assay
    Cytotoxicity against human PC3 cells after 24 hrs by MTT assay
    [PMID: 22687747]
    Raji IC50
    > 100 μM
    Compound: 7
    Inhibition of human Raji cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    Inhibition of human Raji cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    [PMID: 11374975]
    Vero IC50
    > 100 μM
    Compound: 7
    Inhibition of african green monkey Vero cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    Inhibition of african green monkey Vero cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    [PMID: 11374975]
    WISH IC50
    > 100 μM
    Compound: 7
    Inhibition of human WISH cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    Inhibition of human WISH cell proliferation assessed as [3H]thymidine incorporation after 3 days by scintillation counting
    [PMID: 11374975]
    In Vitro

    Preincubation of Stigmasterol to IL-1beta-treated cells shows signi cant reduction of MMP-3 mRNA in human and mouse, MMP-3 protein in mouse, MMP-13 mRNA in mouse and human, ADAMTS-4 mRNA in human, PGE2 protein in human and mouse. Stigmasterol is also capable of counteracting the IL-1beta-induced NF-κB pathway[1].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Viability Assay[2]

    Cell Line: GMI-R1 cells
    Concentration: 1 μM, 5 μM, 10 μM, 15 μM, 20 μM, 30 μM, 40 μM, 50 μM
    Incubation Time: 24 h
    Result: Showed that 1-50 μM stigmasterol did not affect the viability of GMI-R1 cells.

    Western Blot Analysis[1]

    Cell Line: BV2 cells
    Concentration: 10 μM, 20 μM
    Incubation Time: 4 h (after 24 h pretreatment with Aβ42 oligomers)
    Result: Rescued the reduction of p-AMPK(T 172) in Aβ42 oligomers treated BV2 cells.
    Suppressed the increase of p-IκBα and the decrease of IκBα induced by Aβ42 oligomers, reduced the nuclear translocation of NF-κB p65, and inhibited the increase of NLRP3 and Caspase-1 at 20 μM, which are components of the NLPR3 inflammasome.
    In Vivo

    Stigmasterol (50 mg/kg; gavage; once a day; one month) alleviates cognitive deficits in mice, reduced Aβ42 concentrations in the cerebral cortex and hippocampus, and inhibits neuroinflammation by reducing proinflammatory cytokine levels and microglial activation[1].
    Stigmasterol (40 mg/kg; gavage; twice a day; 21 days) reduces thermal and mechanical hyperalgesia, serum IL-1β and IL-8 levels, and increased serum IL-4 and TGF-β levels in rats with chronic constriction injury (CCI). Stigmasterol also reduces the expression of IL-1β, COX-2, and TLR4 in the right sciatic nerve and IL-1β in the spinal cord, and promoted the transformation of M1 microglia to M2 microglia in the spinal cord[2].
    Stigmasterol (50-100 mg/kg; intraperitoneal injection; injected before LPS treatment, single dose) can reduce the total febrile response induced by LPS in rats and mice, inhibit the proliferation of neutrophils in the blood and peritoneal fluid of mice, control lung and liver damage, and inhibit the lethal effect of LPS[3].
    Stigmasterol (20-80 mg/kg; intraperitoneal injection; injected 2 hours after ischemia, single dose) can effectively reduce neurological deficits and infarct damage, improve tissue pathological changes, restore the level of endogenous antioxidant defense system, reduce the expression level of beclin1 and the conversion of LC3 I to LC3 II, promote the phosphorylation of mTOR, and inhibit the phosphorylation of AMPK and JNK and the expression of JNK induced by 24 hours of reperfusion in the rat cerebral ischemia-reperfusion injury model[4].
    Stigmasterol (10 mg/kg; oral; single dose) significantly alleviates scopolamine-induced memory impairment in the passive avoidance and Morris water maze tasks, and increases the phosphorylation levels of ERK and CREB in the hippocampus in the scopolamine-induced memory impairment model in mice. This improvement can be blocked by dizocilpine (HY-15084B) and tamoxifen (HY-13757A)[5].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Model: Alzheimer's disease mouse model (APPswe/PS1dE9 male mice (male; 8-month-old))[1]
    Dosage: 50 mg/kg (dissolved in medium chain triglycerides (MCT))
    Administration: Gavage, once per day, one month
    Result: Significantly increased the stigmasterol concentration in the brain, liver and serum.
    In the Morris water maze test, it reduced the escape latency in the navigation trails and increased the time spent in the target quadrant and the number of crossovers in the probe test.
    ELISA results showed that it significantly reduced the Aβ42 concentration in the cortex and hippocampus, but had no significant effect on Aβ42 concentration.
    TMT-based quantitative proteomic analysis and subsequent experiments showed that it suppressed the elevation of pro-inflammatory cytokines TNFα and IL-1β in the cortex, hippocampus and serum, decreased the activation of microglia and astrocytes, and inhibited the activated NF-κB signaling and NLRP3 inflammasome in the brain.
    Animal Model: Chronic constriction injury (CCI) model (male Sprague-Dawley rats ;male; 180-220 g; 7-8 weeks old)[2]
    Dosage: 40 mg/kg
    Administration: Gavage, twice per day, 21 days
    Result: In behavioral evaluations, stigmasterol treatment relieved thermal and mechanical hyperalgesia from the 7th day to the 21st day.
    ELISA results showed that it decreased the levels of pro-inflammatory cytokines (IL-1β and IL-8) and increased the levels of anti-inflammatory cytokines (IL-4 and TGF-β in the serum.
    H&E staining and immunohistochemical analysis showed that it decreased the number of inflammatory cells in the injured sciatic nerve, partially restored the tissue structure, and improved neuroinflammation in the spinal cord by reducing the expression levels of IL-1β and COX-2 and increasing the expression level of IL-10.
    Immunofluorescence results showed that it reduced the expression of M1 markers (such as CD32) and increased the expression of M2 markers (such as CD206) in the spinal cord. Western blotting analysis showed that it decreased the expression of Iba-1, TLR4, MyD88, pNF-κB, pP38 MAPK, pJNK, and pERK in the spinal cord.
    Animal Model: LPS-induced pyrexia model (Wistar rats; 180-220 g)[3]
    Dosage: 10 mg/kg, 50 mg/kg, 100 mg/kg
    Administration: Intraperitoneal injection, once, 30 min before LPS challenge
    Result: Pretreatment with stigmasterol at 10, 50 and 100 mg/kg significantly reduced the peak increase in basal rectal temperature and the total pyrexia response (Thermal Index) compared to the control group. The inhibition rates of LPS-induced pyrexia were 39.93%, 53.05% and 77.27% respectively.
    Molecular Weight

    412.69

    Formula

    C29H48O

    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

    C[C@H](/C=C/[C@@H](CC)C(C)C)[C@H]1CC[C@@]2([H])[C@]3([H])CC=C4C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C

    Structure Classification
    Initial Source
    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMF : 5 mg/mL (12.12 mM; ultrasonic and warming and heat to 60°C)

    Acetone : 2 mg/mL (4.85 mM; ultrasonic and warming and heat to 60°C)

    Ethanol : < 1 mg/mL (insoluble)

    DMSO : < 1 mg/mL (insoluble or slightly soluble)

    H2O : < 0.1 mg/mL (insoluble)

    1M NaOH : < 1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4231 mL 12.1156 mL 24.2313 mL
    5 mM 0.4846 mL 2.4231 mL 4.8463 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    This equation is commonly abbreviated as: C1V1 = C2V2

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  10% DMF    40% PEG300    5% Tween-80    45% Saline

      Solubility: 0.5 mg/mL (1.21 mM); Suspended solution; Need ultrasonic

    For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  Corn Oil

      Solubility: 3.12 mg/mL (7.56 mM); Clear solution; Need ultrasonic and warming and heat to 50°C

    • Protocol 2

      Add each solvent one by one:  15% Cremophor EL    85% Saline

      Solubility: 10 mg/mL (24.23 mM); Suspended solution; Need ultrasonic

    In Vivo Dissolution Calculator
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    Calculation results:
    Working solution concentration: mg/mL
    Purity & Documentation

    Purity: 99.26%

    References

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    Acetone / DMF 1 mM 2.4231 mL 12.1156 mL 24.2313 mL 60.5782 mL
    DMF 5 mM 0.4846 mL 2.4231 mL 4.8463 mL 12.1156 mL
    10 mM 0.2423 mL 1.2116 mL 2.4231 mL 6.0578 mL
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      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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    Product Name:
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    Cat. No.:
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