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Sabinene

Alias: SABINENE; 3387-41-5; Sabinen; 4(10)-Thujene; 4-methylidene-1-(propan-2-yl)bicyclo[3.1.0]hexane; 1-Isopropyl-4-methylenebicyclo[3.1.0]hexane; Bicyclo[3.1.0]hexane, 4-methylene-1-(1-methylethyl)-; CHEBI:50027;
Cat No.:V8739 Purity: ≥75%
Sabinene is a natural bicyclic monoterpene compound used as a fragrance, flavor additive, fine chemical and advanced biofuel.
Sabinene
Sabinene Chemical Structure CAS No.: 3387-41-5
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
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Product Description
Sabinene is a natural bicyclic monoterpene compound used as a fragrance, flavor additive, fine chemical and advanced biofuel. Sabinene is also an orally biologically active compound that reduces skeletal muscle atrophy and modulates the ROS-mediated MAPK/MuRF-1 pathway.
Biological Activity I Assay Protocols (From Reference)
Targets
Flavoring, perfume additives
ln Vitro
Under starvation conditions, sabinene (10-300 μM; 18 hours) induces a significant restoration of myotube diameter reduction [2]. In starved myotubes, sabinene (300 μM; 18 hr) sever extracellular ligases, reduces elevated E3 ubiquitin ligase ring finger protein-1 (MuRF-1) expression, and phosphorylates Signal regulatory switch 1/2 (ERK1/2) [2]. Sabinene (180 hours at 300 μM)
ln Vivo
By modifying ROS-mediated activation of MAPK/MuRF-1 starvation in starved myotubes, sabinene (6.4 mg/kg; oral; once daily; during a two-day fasting) reduces the likelihood of eventual muscle atrophy and may even reverse reduced amputation.
Chrysanthemum boreale Makino essential oil (CBMEO) has diverse biological activities including a skin regenerating effect. However, its role in muscle atrophy remains unknown. This study explored the effects of CBMEO and its active ingredients on skeletal muscle atrophy using in vitro and in vivo models of muscle atrophy. CBMEO reversed the size decrease of L6 myoblasts under starvation. Among the eight monoterpene compounds of CBMEO without cytotoxicity for L6 cells, sabinene induced predominant recovery of reductions of myotube diameters under starvation. Sabinene diminished the elevated E3 ubiquitin ligase muscle ring-finger protein-1 (MuRF-1) expression and p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylations in starved myotubes. Moreover, sabinene decreased the increased level of reactive oxygen species (ROS) in myotubes under starvation. The ROS inhibitor antagonized expression of MuRF-1 and phosphorylation of MAPKs, which were elevated in starved myotubes. In addition, levels of muscle fiber atrophy and MuRF-1 expression in gastrocnemius from fasted rats were reduced after administration of sabinene. These findings demonstrate that sabinene, a bioactive component from CBMEO, may attenuate skeletal muscle atrophy by regulating the activation mechanism of ROS-mediated MAPK/MuRF-1 pathways in starved myotubes, probably leading to the reverse of reduced muscle fiber size in fasted rats.[2]
Cell Assay
cytotoxicity assay [2]
Cell Types: IL-6 Myoblast
Tested Concentrations: 300 μM
Incubation Duration: 18 and 48 hrs (hours)
Experimental Results: Failed to affect reactive oxygen species (ROS) in myotubes under starvation conditions levels increase[2]. IL-6 myoblast viability after 48 hrs (hours) of culture restored more than 50% of starvation-induced myoblast atrophy after 18 hrs (hours).

Western Blot Analysis[2]
Cell Types: IL-6 Myoblasts
Tested Concentrations: 300 μM
Incubation Duration: 18 hrs (hours)
Experimental Results: Phosphorylation of muscle atrophy-related signaling proteins is diminished in starved myotubes.
Animal Protocol
Animal/Disease Models: Rat fasted animal model [2]
Doses: 6.4 mg/kg
Route of Administration: po (oral gavage); fasted fiber size [2]. one time/day; fasted for 2 days.
Experimental Results: diminished gastrocnemius muscle fiber atrophy levels and MuRF-1 expression in fasted rats.
References

[1]. Biosynthesis and production of sabinene: current state and perspectives. Appl Microbiol Biotechnol. 2018 Feb;102(4):1535-1544.

[2]. Sabinene Prevents Skeletal Muscle Atrophy by Inhibiting the MAPK-MuRF-1 Pathway in Rats. Int J Mol Sci. 2019 Oct 8;20(19):4955.

Additional Infomation
Sabinene is a thujene that is a bicyclic monoterpene isolated from the essential oils of various plant species. It has a role as a plant metabolite.
Sabinene has been reported in Humulus lupulus, Pimpinella serbica, and other organisms with data available.
See also: Black Pepper (annotation moved to); Carrot Seed Oil (annotation moved to); Nutmeg (annotation moved to) ...
Sabinene is an important naturally occurring bicyclic monoterpene which can be used as flavorings, perfume additives, fine chemicals, and advanced biofuels. Up to now, this valuable terpene is commercially unavailable since there is no applicable manufacturing process. Microbial synthesis can be a promising route for sabinene production. In this review, we summarize knowledge about the metabolic pathway and key enzymes for sabinene biosynthesis. Recent advances that have been made in production of sabinene by microbial fermentation are highlighted. In these studies, researchers have identified the general synthetic pathway of sabinene from simple intermediate metabolites. Sabinene synthases of different origins were also cloned and characterized. Additionally, heterologous systems of the model microbes Escherichia coli and Saccharomyces cerevisiae were constructed to produce sabinene. This review also suggests new directions and attempts to gain some insights for achieving an industrial level production of sabinene. The combination of traditional molecular biology with new genome and proteome analysis tools will provide a better view of sabinene biosynthesis and a greater potential of microbial production.[1]
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C10H16
Molecular Weight
136.23
Exact Mass
136.125
Elemental Analysis
C, 88.16; H, 11.84
CAS #
3387-41-5
PubChem CID
18818
Appearance
Colorless to light yellow liquid
Density
0.9±0.1 g/cm3
Boiling Point
164.0±0.0 °C at 760 mmHg
Flash Point
36.7±0.0 °C
Vapour Pressure
2.6±0.1 mmHg at 25°C
Index of Refraction
1.484
LogP
4.13
Hydrogen Bond Donor Count
0
Hydrogen Bond Acceptor Count
0
Rotatable Bond Count
1
Heavy Atom Count
10
Complexity
179
Defined Atom Stereocenter Count
0
SMILES
CC(C12CCC(C1C2)=C)C
InChi Key
NDVASEGYNIMXJL-UHFFFAOYSA-N
InChi Code
InChI=1S/C10H16/c1-7(2)10-5-4-8(3)9(10)6-10/h7,9H,3-6H2,1-2H3
Chemical Name
4-methylidene-1-propan-2-ylbicyclo[3.1.0]hexane
Synonyms
SABINENE; 3387-41-5; Sabinen; 4(10)-Thujene; 4-methylidene-1-(propan-2-yl)bicyclo[3.1.0]hexane; 1-Isopropyl-4-methylenebicyclo[3.1.0]hexane; Bicyclo[3.1.0]hexane, 4-methylene-1-(1-methylethyl)-; CHEBI:50027;
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : ~33.33 mg/mL (~244.66 mM)
Solubility (In Vivo)
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

Injection Formulations
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO 400 μLPEG300 50 μL Tween 80 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).
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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL Saline)


Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 7.3405 mL 36.7026 mL 73.4053 mL
5 mM 1.4681 mL 7.3405 mL 14.6811 mL
10 mM 0.7341 mL 3.6703 mL 7.3405 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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g/mol

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01836393 COMPLETED Drug: Plavina cream Knee Osteoarthritis Khon Kaen University 2013-01 Phase 3
NCT05803031 COMPLETED Drug: Melaleuca Alternifolia Oil
Procedure: Non-surgical periodontal debridement
Periodontal Pocket Ain Shams University 2022-11-01 Not Applicable
Biological Data
  • Effect of sabinene on atrophy of starved myotubes. (A) Effect of sabinene on myotube viability. L6 myotubes were incubated in the presence or absence of sabinene (10–2000 μM) for 48 h, and cell viability was measured using an XTT assay. Cell response in the quiescent state was considered as 100% (n = 16). * p < 0.05 vs. untreated cells. (B,C) Effect of sabinene on starvation-induced atrophy of L6 myotubes. L6 myotubes were incubated with serum-free DMEM in the absence or presence of sabinene (10–300 μM) for 18 h and immunostained with anti-myosin heavy-chain (MYH)-2 and anti-DAPI antibodies. Diameters of myotubes were measured as described in Materials and Methods. Green and blue indicate MYH-2-positive myotubes and DAPI-positive nucleus, respectively. Scale bar: 100 μm. (B) Representative images. (C) Statistical graph obtained from panel (B). Myotube size in the quiescent state was considered as 100% (n = 12). * p < 0.05 vs. starved myotubes without sabinene treatment. # p < 0.05 vs. the quiescent state.[2]. Ryu Y, et al. Sabinene Prevents Skeletal Muscle Atrophy by Inhibiting the MAPK-MuRF-1 Pathway in Rats. Int J Mol Sci. 2019 Oct 8;20(19):4955.
  • Effects of sabinene on muscle atrophy-related signaling proteins in starved myotubes. (A) Effects of sabinene on muscle atrophy-related signaling proteins. L6 myotubes were incubated with serum-free DMEM in the absence or presence of sabinene (300 μM) for 18 h. Myotube lysates were immunoblotted with indicated antibodies. (B–D) Statistical graphs obtained from panel (A). Expression of each protein in the quiescent state was considered as 100% (n = 10 for each protein). * p < 0.05 vs. starved myotubes in the absence of sabinene. # p < 0.05 vs. the quiescent state. p-ERK1/2, phosphorylated ERK1/2; p-p38 MAPK, phosphorylated p38 MAPK.[2]. Ryu Y, et al. Sabinene Prevents Skeletal Muscle Atrophy by Inhibiting the MAPK-MuRF-1 Pathway in Rats. Int J Mol Sci. 2019 Oct 8;20(19):4955.
  • Effect of sabinene on the expression of reactive oxygen species in starved myotubes. (A,B) Effect of sabinene on the level of reactive oxygen species (ROS) in starved myotubes. L6 myotubes were incubated with serum-free DMEM in the absence or presence of sabinene (300 μM) for 18 h. Myotubes were loaded with fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA). The level of intercellular ROS was determined using a fluorescence microscope (A) and a microplate reader (B). (A) Representative images obtained by a fluorescence microscope. Green color indicates ROS positive response. N = 3, Scale bar: 100 μm. (B) Statistical graph of results measured by a microplate reader. The cell response in the quiescent state is expressed as 100% (n = 16). * p < 0.05 vs. starved myotubes in the absence of sabinene. # p < 0.05 vs. the quiescent state. (C–F) Effects of ROS inhibition on expression levels of MuRF-1 and MAPKs in starved myotubes. L6 myotubes were incubated in serum-free DMEM in the absence or presence of NAC (1 mM) for 18 h. These myotubes were immunoblotted with indicated antibodies. Panel (C) consists of representative images showing the altered expression of MuRF-1 and phosphorylation of MAPKs after treatment with N-acetyl-l-cysteine (NAC). The other panels (D–F) are statistical graphs obtained from panel (C). Expression of each protein in a NAC-untreated state is expressed as 100% (n = 4). * p < 0.05 vs. starved myotubes in the absence of NAC.[2]. Ryu Y, et al. Sabinene Prevents Skeletal Muscle Atrophy by Inhibiting the MAPK-MuRF-1 Pathway in Rats. Int J Mol Sci. 2019 Oct 8;20(19):4955.
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