Editing Mentha pulegium (section)

==Chemistry==

===Structure and reactivity===
[[File:Pulegon.svg|thumb|left|110px|Pulegone]]
The active chemical in pennyroyal is pulegone. Pulegone is a [[ketone]] and on the cellular level, ketones can act as [[enzyme inhibitor]]s. The carbonyl center of the pulegone structure acts as a strong electrophile, causing active sites on enzymes to bind with pulegone instead of the target protein.

The exocyclic [[double bond]] found in pulegone is vital to the activation and binding mechanism of the molecule and causes it to be an effective [[hepatotoxin]]. When ingested, pulegone targets the liver and kidney, among other organs. Studies conducted on rats show that one of the main effects is the inhibition of contractile activity in the [[myometrium]] and death by [[kidney failure]]. The studies also found that long-term exposure to pennyroyal increased incidences of urinary bladder tumors.<ref name="ReferenceA"/>

===Mechanism of action===
[[File:Menthofuran.svg|thumb|left|130px|Menthofuran]]
The exact [[mechanism of action]] by which pennyroyal induces [[menses]] and [[abortion]]s in humans is still unknown. Studies using animal models speculate the source of liver toxicity is due to one of the many constituents the plant contains: pulegone, a monoterpene. Pulegone is metabolized by [[cytochrome P450]] (CYP 1A2 and 2E1) and converted to several toxins.<ref>{{cite book|last1=Cassileth|first1=Barrie|last2=Yeung|first2=Simon|last3=Gubili|first3=Jyothirmai|title=Herb-drug Interactions in Oncology|date=2010|publisher=People's Medical Publishing House|location=Shelton, CT}}</ref> Both ''[[in vitro]]'' and ''[[in vivo]]'' studies have found the pulegone metabolite [[menthofuran]] to be an inhibitor of [[CYP2A6]], accounting for a significant degree of pennyroyal's [[hepatotoxicity]].<ref>{{cite journal|last1=Khojasteh-Bakh |first1=S.C.|last2=Koenigs |first2=L.L.|last3=Peter |first3=R.M.|last4=Trager |first4=W.F.|last5=Nelson |first5=S.D.|title=(R)-(+)-Menthofuran is a potent, mechanism-based inactivator of human liver cytochrome P450 2A6|journal=Drug Metabolism and Disposition|date=July 1998|volume=26|issue=7|pages=701–704|pmid=9660853}}</ref><ref name="Gordon">{{cite journal|last1=Gordon |first1=W.P.|last2=Huitric |first2=A.C.|last3=Seth |first3=C.L.|last4=McClanahan |first4=R.H.|last5=Nelson |first5=S.D.|title=The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran|journal=Drug Metabolism and Disposition|date=February 26, 1989|volume=15|issue=5|pages=589–594|pmid=2891472}}</ref><ref>{{cite journal|last1=Thomassen|first1=D.|last2=Pearson |first2=P.G.|last3=Slattery |first3=J.T.|last4=Nelson |first4=S.D.|title=Partial characterization of biliary metabolites of pulegone by tandem mass spectrometry. Detection of glucuronide, glutathione, and glutathionyl glucuronide conjugates.|journal=Drug Metabolism and Disposition|date=January 17, 1991|volume=19|issue=5|pages=997–104|pmid=1686249}}</ref>

The exact pathway pulegone undergoes to be converted to menthofuran is unknown, but one study strongly suggested it included allylic oxidation of a methyl group (from CYP450), intramolecular cyclization to form a hemiketal, and subsequent dehydration to form the furan.<ref name="Gordon"/> Additionally, pulegone and menthofuran may deplete glutathione levels, leaving hepatocytes vulnerable to free radical damage.<ref name="Gordon"/>