Canadian Medicinal Plant Research Articles

Antibiotic Mycotoxins from an Endophytic Fusarium acuminatum Isolated from the Medicinal Plant Geum macrophyllum

An extract of the endophytic fungus Fusarium acuminatum (TC2-084) isolated from the Canadian medicinal plant Geum macrophyllum exhibited significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra when fermented in both malt extract and potato dextrose broths. However, significant differences observed in the NMR spectra of the respective extracts led us to further investigate both. Bioassay guided fractionation revealed that lateropyrone was solely responsible for the bioactivity observed when TC2-084 was fermented in malt extract broth, while the antimycobacterial activity of the extract derived from the isolate fermented in potato dextrose broth was augmented by the presence of enniatins B, B1, and B4 in addition to lateropyrone.

Antimycobacterial 1,4-napthoquinone natural products from Moneses uniflora

A new 1,4-naphthoquinone derivative, 5,8-dihydro-3-hydroxychimaphilin (4) and five known compounds (1, 2 and 5–7) were isolated from an extract of the Canadian medicinal plant Moneses uniflora that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structure of 4 was established through analysis of NMR and MS data and the absolute configuration of the glycone of 5 was determined by chemical transformation and comparison with standards prepared from D- and L-glucose. All compounds isolated were screened against Mycobacterium tuberculosis (H37Ra) and the mammalian HEK 293 cell line and, with the exception of compounds 5 and 7, exhibited marked selectivity in their bioactivity: Compound 1 exhibited potent antimycobacterial activity (IC50 of 5.4 μM) and moderate cytotoxicity (IC50 of 30 μM); compounds 2, 4 and 6 showed moderate antimycobacterial activity (IC50 values from 28 to 47 μM) without affecting the viability of mammalian cells; compound 5 displayed moderate activity in both assays (IC50 values of 44 and 55 μM respectively); and compound 7 was not active in either assay. These data suggest that the Moneses napthaquinone derivatives elicit biological responses in mycobacterial and mammalian cells through disparate modes of action that warrant further investigation.

Antimycobacterial triterpenes from the Canadian medicinal plant Sarracenia purpurea

Ethnopharmacological relevanceThe purple pitcher plant, Sarracenia purpurea, is a medicinal plant used by the Canadian First Nations to treat a wide variety of illnesses. The Mi’kmaq and Wolastoqiyik (Maliseet) peoples of Eastern Canada have traditionally used infusions of S. purpurea for the treatment of tuberculosis-like symptoms. Previous investigations have shown methanolic extracts of S. purpurea to possess antimycobacterial activity. Aim of the studyTo isolate and identify antimycobacterial constituents from S. purpurea. Materials and MethodsMethanolic extracts of S. purpurea were 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. ResultsThe triterpenes betulinaldehyde, β-sitosterol, betulinic acid, and ursolic acid were isolated from S. purpurea. Betulinaldehyde, betulinic acid, and ursolic acid exhibited MICs of 450, 950, and 450μM and IC50s of 98, 169, and 93μM against M. tuberculosis H37Ra respectively whilst β-sitosterol was inactive (MIC and IC50 of >1000μM). ConclusionsBetulinaldehyde, betulinic acid, and ursolic acid were identified as the principal constituents responsible for the antimycobacterial activity of S. purpurea. This work is consistent with the ethnopharmacological use of S. purpurea by Canadian First Nations as a treatment against infectious diseases.

Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum.

Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 μM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 μM, respectively).

Isolation of Phomopsolide A and 6(E)-Phomopsolide A as Antimycobacterial Products from an Unidentified Endophyte of the Canadian Medicinal Plant Heracleum maximum

An extract of an unidentified endophyte from the Canadian medicinal plant Heracleum maximum exhibited a unique metabolomic profile and significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation of the extract led to the isolation of phomopsolide A (1) and 6(E)-phomopsolide A (2). This is the first report of antimycobacterial activity for 1 and 2.

Antimycobacterial Natural Products from Endophytes of the Medicinal Plant Aralia nudicaulis

Antimycobacterial extracts of a Penicillium sp. (isolate HL4-159-41B) and a Coniothyrium sp. (isolate HL6-097-027B) isolated from the rhizomes of the Canadian medicinal plant Aralia nudicaulis were found to contain palitantin (1) and botrallin (2), craterellin C (3), mycosporulone (4), spiromassaritone (5), and massarigenin D (6) respectively. Bioassays against Mycobacterium tuberculosis H37Ra revealed that 1 - 4 possess moderate antimycobacterial activity.

Anti-mycobacterial triterpenes from the Canadian medicinal plant Alnus incana

Ethnopharmacological relevanceAlnus incana, commonly known as the gray or speckled alder, is a medicinal plant used by some Canadian First Nations to treat symptoms associated with tuberculosis. The aim of this study was to assess the anti-mycobacterial activity of an Alnus incana bark extract and to identify the active constituents of the extract. Materials and MethodsMethanolic extracts of the bark of A. incana were subjected to bioassay guided fractionation using Mycobacterium tuberculosis (H37Ra). The active constituents were identified by NMR and MS. ResultsFour pentacyclic lupane triterpenes were isolated and were identified as betulin, betulinic acid, betulone and lupenone. Betulin displayed a MIC of 12.5μg/mL and an IC50 of 2.4μg/mL against M. tuberculosis (H37Ra). Betulinic acid and betulone showed lower anti-mycobacterial activities with IC50 values of 84 and 57μg/mL respectively. Lupenone was inactive against M. tuberculosis (H37Ra). ConclusionsBetulin, betulinic acid and betulone were identified as the major anti-mycobacterial constituents in the bark of A. incana and the functionality at carbons 3 and 28 of the lupane skeleton would seem to be important in determining the anti-mycobacterial activity of the triterpenes. This work supports the ethnopharmacological use of A. incana by Canadian First Nations communities as a treatment for tuberculosis.

Isolation of (–)–Avenaciolide as the Antifungal and Antimycobacterial Constituent of a Seimatosporium sp. Endophyte from the Medicinal Plant Hypericum perforatum

An extract of Seimatosporium sp., an endophyte from the Canadian medicinal plant Hypericum perforatum, exhibited significant antifungal and antimycobacterial activity against Candida albicans and Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation led to the isolation of (-)-avenaciolide as the only bioactive constituent of the extract. This is the first report of both the antimycobacterial activity of avenaciolide and its isolation from a Seimatosporium sp. fungus.

Isolation of the Plant Hormone (+)-Abscisic acid as an Antimycobacterial Constituent of the Medicinal Plant Endophyte Nigrospora sp

An extract of the endophytic fungus Nigropsora sp. (isolate TC2-054) from the Canadian medicinal plant Fragaria virginiana exhibited significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation revealed that linoleic acid derivatives and the plant hormone (+)-abscisic acid (ABA) were responsible for the observed antimycobacterial activity. This activity of ABA has not been previously reported.

The Canadian medicinal plant Heracleum maximum contains antimycobacterial diynes and furanocoumarins

Ethnopharmacological relevanceHeracleum 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. Materials and methodsA 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. ResultsThe 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. 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.

Anti-mycobacterial natural products from the Canadian medicinal plant Juniperus communis

Ethnopharmacological relevanceCommon juniper, Juniperus communis, is amongst the plants most frequently used by the indigenous peoples of North America for medicinal purposes. The First Nations of the Canadian Maritimes use infusions of juniper primarily as a tonic and for the treatment of tuberculosis. Previous investigations of extracts derived from the aerial parts of J. communis have shown it to possess anti-mycobacterial activity. The aim of the study is to isolate and identify anti-mycobacterial constituents from the aerial parts of J. communis. Materials and MethodsMethanolic extracts of J. communis needles and branches were subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The anti-mycobacterial constituents were identified by NMR, MS and polarimetry. ResultsThe diterpenes isocupressic acid and communic acid and the aryltetralin lignan deoxypodophyllotoxin were isolated from the J. communis extract. Isocupressic acid and communic acid (isolated as an inseparable 3:2 mixture of cis and trans isomers) displayed MICs of 78μM and 31μM and IC50s of 46μM and 15μM against M. tuberculosis H37Ra respectively. Deoxypodophyllotoxin was less active, with a MIC of 1004μM and an IC50 of 287μM. ConclusionsIsocupressic acid, communic acid and deoxypodophyllotoxin were identified as the principal constituents responsible for the anti-mycobacterial activity of the aerial parts of J. communis. Although further research will be required to evaluate the relative activities of the two communic acid isomers, this work validates an ethnopharmacological use of this plant by Canadian First Nations and Native American communities.

Anti-mycobacterial diynes from the Canadian medicinal plant Aralia nudicaulis

Ethnopharmacological relevanceAralia nudicaulis, or wild sarsaparilla, is used as a traditional medicinal plant for the treatment of various illnesses by many of the Canadian First Nations. Iroquois and Algonquin First Nations of Eastern Canada use a tea prepared from dried Aralia nudicaulis rhizome as a cough medicine and for the treatment of tuberculosis. Previous investigations of aqueous extracts of Aralia nudicaulis rhizomes have shown it to possess antimycobacterial activity. Aim of the studyTo isolate and identify antimycobacterial constituents from Aralia nudicaulis rhizomes. Materials and methodsMethanolic extracts of Aralia nudicaulis rhizomes were 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. ResultsTwo C17 polyacetylenes with significant antimycobacterial activity were isolated from the Aralia nudicaulis rhizome extract. The polyacetylenes were identified as (3R)-falcarinol and (3R, 9R, 10S)-panaxydol. Falcarinol and panaxydol displayed MICs of 25.6μM and 36.0μM and IC50s of 15.3μM and 23.5μM against Mycobacterium tuberculosis H37Ra. ConclusionsFalcarinol and panaxydol were identified as the principal constituents responsible for the antimycobacterial activity of Aralia nudicaulis rhizomes validating an ethnopharmacological use of this plant by the Canadian First Nations.