Some like it pungent and vile. TRPA1 as a molecular target for the malodorous vinyl disulfides from asafoetida

Ferula assa-foetida L. is a major source of asafoetida, a foul-smelling gum-resin of dietary and medicinal relevance. Investigation of the roots and latex of F. assa-foetida yielded various mixed vinyl disulfides, including two novel asadisulfide-type esters. The reactivity of asadisulfide was investigated in the cysteamine NMR assay, where it behaved as disulfide shuffling agents due to the high mobility of the vinyl sulfide moiety. In accordance with their transthiolation capacity, these compounds potently activated TRPA1, the target of mustard oil and the pungent sulfur compounds from onion and garlic, qualifying S-alkyl-S-alkenyldisulfides, a rare class of natural products, as a novel class of dietary TRPA1 activators. These observations provide a mechanistic basis for rationalizing some of the sensory properties and potential beneficial health claims associated to the use of asafoetida as a spice and as a medicine.