The Canadian medicinal plant Heracleum maximum contains antimycobacterial diynes and furanocoumarins

• Published in: Journal of ethnopharmacology Vol. 147; no. 1; pp. 232 - 237
• Main Authors: O׳Neill, Taryn, Johnson, John A., Webster, Duncan, Gray, Christopher A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 02.05.2013
• Subjects: (3R8S)-falcarindiol; antibacterial properties; Antimycobacterial activity; Antitubercular Agents - chemistry; Antitubercular Agents - isolation & purification; Antitubercular Agents - pharmacology; bergapten; bioassays; Biological Assay; C-17 diynes; Canada; Chemical Fractionation; Diynes - chemistry; Diynes - isolation & purification; Diynes - pharmacology; First Nations; Fluorometry; Furanocoumarins; Furocoumarins - chemistry; Furocoumarins - isolation & purification; Furocoumarins - pharmacology; Heracleum; Heracleum - chemistry; Heracleum maximum; Magnetic Resonance Spectroscopy; medicinal plants; Methanol - chemistry; Microbial Sensitivity Tests; Microspectrophotometry; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - growth & development; nuclear magnetic resonance spectroscopy; Phytotherapy; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Roots; Plants, Medicinal; psoralens; roots; Solvents - chemistry; tuberculosis; North America; Canada; DMSO; (3R8S)-falcarindiol; [α]D; TLC; bs; SD; C-17 diynes; 2D; HRESIMS; IC50; nBuOH; Furanocoumarins; HPLC; CH2Cl2; EtOAc; c; d; MIC; MS; LC–MS; IR; m; ACS; q; NMR; 1D; s; t; Heracleum maximum; Mycobacterium tuberculosis; MeOH; NaCl; MRA; Antimycobacterial activity
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2013.03.009

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. Aim of the study: To isolate and identify antimycobacterial constituents from the roots of Heracleum maximum. 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. 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 24μM and 167μM and IC50s of 6μM and 27μM 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 1625μM and IC50s of 125, 344, 350, 351, 389 and 406μM. (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. [Display omitted]