title: The Canadian medicinal plant Heracleum maximum contains antimycobacterial diynes and furanocoumarins.
abstract: BACKGROUND
  Heracleum maximum is amongst the most commonly used plants by the indigenous peoples of North America. The First Nations of the eastern Canada use infusions of Heracleum maximum roots for the treatment of respiratory ailments including tuberculosis. Previous investigations of extracts derived from the roots of Heracleum maximum have shown it to possess antimycobacterial activity.
  
  
  OBJECTIVE
  To isolate and identify antimycobacterial constituents from the roots of Heracleum maximum.
  
  
  METHODS
  A methanolic extract of Heracleum maximum roots was subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The antimycobacterial constituents were identified by NMR, MS and polarimetry.
  
  
  RESULTS
  The polyacetylene (3R,8S)-falcarindiol and the furanocoumarins bergapten, isobergapten, angelicin, sphondin, pimpinellin, isopimpinellin and 6-isopentenyloxyisobergapten were isolated from the Heracleum maximum root extract. (3R,8S)-Falcarindiol and 6-isopentenyloxyisobergapten exhibited MICs of 24 μM and 167 μM and IC50s of 6 μM and 27 μM against Mycobacterium tuberculosis H37Ra respectively. The remaining furanocoumarins bergapten, isobergapten, angelicin, sphondin, pimpinellin, and isopimpinellin were less active, with MICs of 925, 1850, 2149, 1859, 812 and 1625 μM and IC50s of 125, 344, 350, 351, 389 and 406 μM.
  
  
  CONCLUSIONS
  (3R,8S)-Falcarindiol, bergapten, isobergapten, angelicin, sphondin, pimpinellin, isopimpinellin and 6-isopentenyloxyisobergapten were identified as the principal constituents responsible for the antimycobacterial activity of the roots of Heracleum maximum. This work supports the ethnopharmacological use of Heracleum maximum by Canadian First Nations and Native American communities as a treatment for infectious diseases, specifically tuberculosis.
authors.affiliation: Department of Biology, University of New Brunswick, Saint John, New Brunswick, Canada.
authors.forename: Taryn
authors.initials: T
authors.lastname: O'Neill
authors.forename: John A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Duncan
authors.initials: D
authors.lastname: Webster
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Gray
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001681:Biological Assay; D002170:Canada; D005591:Chemical Fractionation; D053280:Diynes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005470:Fluorometry; D011564:Furocoumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D030002:Heracleum / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D015591:Microspectrophotometry; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D010946:Plants, Medicinal; D012997:Solvents / Q000737:chemistry
chemical_list: D000995:Antitubercular Agents; D053280:Diynes; D011564:Furocoumarins; D010936:Plant Extracts; D012997:Solvents; D000432:Methanol