Capsaicin
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Basic Info
Common Name | Capsaicin(F04799) |
2D Structure | |
Description | Capsaicin is identified as the primary pungent principle in Capsicum fruits. Hot chili peppers that belong to the plant genus Capsicum (family Solanaceae) are among the most heavily consumed spices throughout the world. The capsaicin content of green and red peppers ranges from 0.1 to 1%. Capsaicin evokes numerous biological effects and thus has been the target of extensive., investigations since its initial identification in 1919. One of the most recognized physiological properties of capsaicin is its selective effects on the peripheral part of the sensory nervous system, particularly on the primary afferent neurons. The compound is known to deplete the neurotransmitter of painful impulses known as substance P from the sensory nerve terminals, which provides a rationale for its use as a versatile experimental tool for studying pain mechanisms and also for pharmacotherapy to treat some peripheral painful states, such as rheumatoid arthritis, post-herpetic neuralgia, post-mastectomy pain syndrome and diabetic neuropathy. Considering the frequent consumption of capsaicin as a food additive and its current therapeutic application, correct assessment of any harmful effects of this compound is important from the public health standpoint. Ingestion of large amounts of capsaicin has been reported to cause histopathological and biochemical changes, including erosion of gastric mucosa and hepatic necrosis. However, there are contradictory data on the mutagenicity of capsaicin. A recent epidemiological study conducted in Mexico revealed that consumers of chili pepper were at higher risk for gastric cancer than non-consumers. However, it remains unclear whether capsaicin present in hot chili pepper is a major causative factor in the aetiology of gastric cancer in humans. A growing number of recent studies have focused on anticarcinogenic or antimutagenic phytochemicals, particularly those included in human diet. In summary, capsaicin has dual effects on chemically induced carcinogenesis and mutagenesis. Although a minute amount of capsaicin displays few or no deleterious effects, heavy ingestion of the compound has been associated with necrosis, ulceration and even carcinogenesis. Capsaicin is considered to be metabolized by cytochrome P-450-dependent mixed-function oxidases to reactive species. (A7835). |
FRCD ID | F04799 |
CAS Number | 404-86-4 |
PubChem CID | 1548943 |
Formula | C18H27NO3 |
IUPAC Name | (E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methylnon-6-enamide |
InChI Key | YKPUWZUDDOIDPM-SOFGYWHQSA-N |
InChI | InChI=1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+ |
Canonical SMILES | CC(C)C=CCCCCC(=O)NCC1=CC(=C(C=C1)O)OC |
Isomeric SMILES | CC(C)/C=C/CCCCC(=O)NCC1=CC(=C(C=C1)O)OC |
Wikipedia | Capsaicin |
Synonyms | Isodecenoic acid vanillylamide Capsaicin 404-86-4 Zostrix CAPSAICINE (E)-Capsaicin Qutenza Styptysat Axsain E-CAPSAICIN |
Classifies | Plant Toxin |
Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
Kingdom | Organic compounds |
Superclass | Benzenoids |
Class | Phenols |
Subclass | Methoxyphenols |
Intermediate Tree Nodes | Not available |
Direct Parent | Methoxyphenols |
Alternative Parents | |
Molecular Framework | Aromatic homomonocyclic compounds |
Substituents | Methoxyphenol - Phenoxy compound - Anisole - Methoxybenzene - Phenol ether - Alkyl aryl ether - 1-hydroxy-2-unsubstituted benzenoid - Monocyclic benzene moiety - Fatty acyl - Fatty amide - N-acyl-amine - Carboxamide group - Secondary carboxylic acid amide - Carboxylic acid derivative - Ether - Organic nitrogen compound - Organonitrogen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Carbonyl group - Organopnictogen compound - Organic oxygen compound - Aromatic homomonocyclic compound |
Description | This compound belongs to the class of organic compounds known as methoxyphenols. These are compounds containing a methoxy group attached to the benzene ring of a phenol moiety. |
Properties
Property Name | Property Value |
---|---|
Molecular Weight | 305.418 |
Hydrogen Bond Donor Count | 2 |
Hydrogen Bond Acceptor Count | 3 |
Rotatable Bond Count | 9 |
Complexity | 341 |
Monoisotopic Mass | 305.199 |
Exact Mass | 305.199 |
XLogP | 3.6 |
Formal Charge | 0 |
Heavy Atom Count | 22 |
Defined Atom Stereocenter Count | 0 |
Undefined Atom Stereocenter Count | 0 |
Defined Bond Stereocenter Count | 1 |
Undefined Bond Stereocenter Count | 0 |
Isotope Atom Count | 0 |
Covalently-Bonded Unit Count | 1 |
ADMET
Model | Result | Probability |
---|---|---|
Absorption | ||
Blood-Brain Barrier | BBB+ | 0.6219 |
Human Intestinal Absorption | HIA+ | 0.9927 |
Caco-2 Permeability | Caco2+ | 0.5417 |
P-glycoprotein Substrate | Substrate | 0.6457 |
P-glycoprotein Inhibitor | Non-inhibitor | 0.7854 |
Inhibitor | 0.5479 | |
Renal Organic Cation Transporter | Non-inhibitor | 0.8013 |
Distribution | ||
Subcellular localization | Mitochondria | 0.9272 |
Metabolism | ||
CYP450 2C9 Substrate | Non-substrate | 0.7809 |
CYP450 2D6 Substrate | Non-substrate | 0.5809 |
CYP450 3A4 Substrate | Substrate | 0.7172 |
CYP450 1A2 Inhibitor | Inhibitor | 0.9107 |
CYP450 2C9 Inhibitor | Inhibitor | 0.8948 |
CYP450 2D6 Inhibitor | Inhibitor | 0.8932 |
CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
CYP450 3A4 Inhibitor | Inhibitor | 0.8287 |
CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.7551 |
Excretion | ||
Toxicity | ||
Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9638 |
Inhibitor | 0.6627 | |
AMES Toxicity | AMES toxic | 0.7678 |
Carcinogens | Non-carcinogens | 0.9153 |
Fish Toxicity | High FHMT | 0.6648 |
Tetrahymena Pyriformis Toxicity | High TPT | 0.9922 |
Honey Bee Toxicity | Low HBT | 0.5829 |
Biodegradation | Not ready biodegradable | 0.9069 |
Acute Oral Toxicity | III | 0.6676 |
Carcinogenicity (Three-class) | Non-required | 0.6924 |
Model | Value | Unit |
---|---|---|
Absorption | ||
Aqueous solubility | -2.9200 | LogS |
Caco-2 Permeability | 1.1643 | LogPapp, cm/s |
Distribution | ||
Metabolism | ||
Excretion | ||
Toxicity | ||
Rat Acute Toxicity | 2.2633 | LD50, mol/kg |
Fish Toxicity | 1.6986 | pLC50, mg/L |
Tetrahymena Pyriformis Toxicity | 0.5394 | pIGC50, ug/L |
References
Title | Journal | Date | Pubmed ID |
---|---|---|---|
Synthesis and characterization of manganese diselenide nanoparticles (MnSeNPs):Determination of capsaicin by using MnSeNP-modified glassy carbon electrode. | Mikrochim Acta | 2018 Jun 2 | 29860537 |
Influence of Fruit Ripening on Color, Organic Acid Contents, Capsaicinoids, AromaCompounds, and Antioxidant Capacity of Shimatogarashi (Capsicum frutescens). | J Oleo Sci | 2018 Jan 1 | 29238032 |
Capsaicin and nonivamide similarly modulate outcome measures of mitochondrialenergy metabolism in HepG2 and 3T3-L1 cells. | Food Funct | 2018 Feb 21 | 29362767 |
Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neuronsreduces food intake. | PLoS Biol | 2018 Apr 24 | 29689050 |
Pharyngeal stimulation with sugar triggers local searching behavior inDrosophila. | J Exp Biol | 2017 Sep 15 | 28684466 |
TRPV4 calcium-permeable channel is a novel regulator of oxidized LDL-inducedmacrophage foam cell formation. | Free Radic Biol Med | 2017 Sep | 28602913 |
Toxicity of emerging antifouling biocides to non-target freshwater organisms from three trophic levels. | Aquat Toxicol | 2017 Oct | 28843204 |
Nanoencapsulated capsaicin changes migration behavior and morphology of madindarby canine kidney cell monolayers. | PLoS One | 2017 Nov 6 | 29107993 |
Silica nanoparticles inhibit the cation channel TRPV4 in airway epithelial cells. | Part Fibre Toxicol | 2017 Nov 3 | 29100528 |
Antimicrobial Activity of Selected Polyphenols and Capsaicinoids Identified inPepper (Capsicum annuum L.) and Their Possible Mode of Interaction. | Curr Microbiol | 2017 Nov | 28721659 |
Capsaicin presynaptically inhibits glutamate release through the activation ofTRPV1 and calcineurin in the hippocampus of rats. | Food Funct | 2017 May 24 | 28418433 |
Desalted Duck Egg White Peptides Promote Calcium Uptake and Modulate BoneFormation in the Retinoic Acid-Induced Bone Loss Rat and Caco-2 Cell Model. | Nutrients | 2017 May 12 | 28498349 |
Desalted duck egg white peptides promote calcium uptake by counteracting theadverse effects of phytic acid. | Food Chem | 2017 Mar 15 | 27765248 |
Deconvoluting physical and chemical heat: Temperature and spiciness influenceflavor differently. | Physiol Behav | 2017 Mar 1 | 27988249 |
Cu Nanoparticles in Hydrogels of Chitosan-PVA Affects the Characteristics ofPost-Harvest and Bioactive Compounds of Jalapeño Pepper. | Molecules | 2017 Jun 2 | 28574445 |
Mechanism of capsaicin inhibition of aldose reductase activity. | J Biochem Mol Toxicol | 2017 Jul | 28217947 |
Nonivamide, a capsaicin analogue, exhibits anti-inflammatory properties in peripheral blood mononuclear cells and U-937 macrophages. | Mol Nutr Food Res | 2017 Feb | 27666931 |
Sensitive determination of capsaicin in pepper samples using a voltammetricplatform based on carbon nanotubes and ruthenium nanoparticles. | Food Chem | 2017 Aug 1 | 28317708 |
Fetal alcohol exposure reduces responsiveness of taste nerves and trigeminalchemosensory neurons to ethanol and its flavor components. | J Neurophysiol | 2017 Aug 1 | 28490641 |
Synthetic Fluororutaecarpine Inhibits Inflammatory Stimuli and Activates Endothelial Transient Receptor Potential Vanilloid-Type 1. | Molecules | 2017 Apr 19 | 28422079 |
Targets
- General Function:
- Cannabinoid receptor activity
- Specific Function:
- Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.
- Gene Name:
- CNR2
- Uniprot ID:
- P34972
- Molecular Weight:
- 39680.275 Da
References
- Appendino G, Ligresti A, Minassi A, Cascio MG, Allara M, Taglialatela-Scafati O, Pertwee RG, De Petrocellis L, Di Marzo V: Conformationally constrained fatty acid ethanolamides as cannabinoid and vanilloid receptor probes. J Med Chem. 2009 May 14;52(9):3001-9. doi: 10.1021/jm900130m. [19361197 ]
- General Function:
- Drug binding
- Specific Function:
- Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.
- Gene Name:
- CNR1
- Uniprot ID:
- P21554
- Molecular Weight:
- 52857.365 Da
References
- Appendino G, Ligresti A, Minassi A, Cascio MG, Allara M, Taglialatela-Scafati O, Pertwee RG, De Petrocellis L, Di Marzo V: Conformationally constrained fatty acid ethanolamides as cannabinoid and vanilloid receptor probes. J Med Chem. 2009 May 14;52(9):3001-9. doi: 10.1021/jm900130m. [19361197 ]
- General Function:
- Prostaglandin-endoperoxide synthase activity
- Specific Function:
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.
- Gene Name:
- PTGS1
- Uniprot ID:
- P23219
- Molecular Weight:
- 68685.82 Da
References
- Larsson J, Gottfries J, Bohlin L, Backlund A: Expanding the ChemGPS chemical space with natural products. J Nat Prod. 2005 Jul;68(7):985-91. [16038536 ]
- General Function:
- Temperature-gated cation channel activity
- Specific Function:
- Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
- Gene Name:
- TRPA1
- Uniprot ID:
- O75762
- Molecular Weight:
- 127499.88 Da
- Mechanism of Action:
- Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function. Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana. Not involved in menthol sensation. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity). Activation of cation channels in the membrane of sensory neurons, the so called TRP receptors (TRP = transient receptor potential)
References
- Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]
- General Function:
- Transmembrane signaling receptor activity
- Specific Function:
- Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli. Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis (By similarity). Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel.
- Gene Name:
- TRPV1
- Uniprot ID:
- Q8NER1
- Molecular Weight:
- 94955.33 Da
- Mechanism of Action:
- The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory neurons. Capsaicin, as a member of the vanilloid family, binds to the vanilloid receptor 1 (VR1). VR1 permits cations to pass through the cell membrane and into the cell when activated. The resulting depolarization of the neuron stimulates it to signal the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.
References
- Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V: Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001 Oct;134(4):845-52. [11606325 ]