Spilanthol (affinin) is a

fatty acid amide Fatty acid amides (FAAs) are amides formed from a fatty acid and an amine. In nature, many FAAs have ethanolamine as the amine component. Also known as ''N''-acylethanolamines, they contain the functionality RC(O)N(H)CH2CH2OH. A well known examp ...

isolated from ''

Acmella oleracea ''Acmella oleracea'' is a species of flowering herb in the family Asteraceae. Common names include toothache plant, Szechuan buttons, paracress, jambu, buzz buttons, tingflowers and electric daisy. Its native distribution is unclear, but it is li ...

''. It is believed to be responsible for the

local anesthetic A local anesthetic (LA) is a medication that causes absence of all sensation (including pain) in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensati ...

properties of the plant. Spilanthol permeates the human skin and the inside lining of the cheeks in the mouth (

buccal mucosa The oral mucosa is the mucous membrane lining the inside of the mouth. It comprises stratified squamous epithelium, termed "oral epithelium", and an underlying connective tissue termed ''lamina propria''. The oral cavity has sometimes been describ ...

), resulting in local as well as systemic pharmacological concentrations. In the skin and in the pancreas, spilanthol has also been shown to exert anti-inflammatory effects. The underlying mechanism involves inhibition of

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

production due to reduced expression of inducible

nitric oxide synthase Nitric oxide synthases (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristal ...

enzyme (iNOS) in

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

s. Transcription factor array experiments revealed that spilanthol inhibits the activation of several transcription factors ( NFκB,

ATF4 Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein that in humans is encoded by the ''ATF4'' gene. Function This gene encodes a transcription factor that was originally identified as a w ...

FOXO1 Forkhead box protein O1 (FOXO1), also known as forkhead in rhabdomyosarcoma (FKHR), is a protein that in humans is encoded by the ''FOXO1'' gene. FOXO1 is a transcription factor that plays important roles in regulation of gluconeogenesis and glyco ...

IRF1 Interferon regulatory factor 1 is a protein that in humans is encoded by the ''IRF1'' gene. Function Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially desc ...

ETS1 Protein C-ets-1 is a protein that in humans is encoded by the ''ETS1'' gene. The protein encoded by this gene belongs to the ETS family of transcription factors. Function There are 28 ETS genes in humans and 27 in mice. They bind the DNA via ...

, and AP-1) which may explain the effect of spilanthol on gene expression. The antihypertensive effect of spilanthol was blocked by CB1 antagonist

rimonabant Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) is an anorectic antiobesity drug approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in the United State ...

and TRPV1 antagonist capsazepine, suggesting spilanthol mediates some activity by interaction with the cannabinoid receptors and TRPV1 channels.

References

{{reflist Fatty acid amides Local anesthetics

See also

References