Ethnopharmacological communicationAnti-mycobacterial triterpenes from the Canadian medicinal plant Alnus incana
Graphical abstract
Introduction
Mycobacterium tuberculosis, the causative pathogen of tuberculosis (TB), is estimated to infect one third of the world׳s population (Koul et al., 2011). Globally, over 8 million people developed active TB and approximately one million died from the disease in 2012 (WHO, 2013). Given that the first line anti-TB drugs currently being used are over 40 years old combined with the alarming increase in the emergence of resistant strains of TB, there is an urgent need to develop new anti-TB drugs (Lienhardt et al., 2012, Phillips, 2013). The ethnopharmacological knowledge of the Canadian First Nations has provided a rich inventory of plants that may be a source of anti-TB compounds; unfortunately only a fraction of the plants have been investigated (Carpenter et al., 2012, Jovel et al., 2007, Li et al., 2012, Matsuura et al., 1995, Ming et al., 2002, O’Neill et al., 2013, Saxena et al., 1996, Yi et al., 2007).
Alnus incana (Betulaceae), commonly known as the gray or speckled alder, is distributed from coast to coast in North America (Furlow, 1979). Different parts of the tree have been used as medicines by various First Nations communities for many centuries (Johnsoton, 1987, Moerman, 1998). For example, the Blackfoot First Nations (Alberta) would use infusions of alder bark to treat scrofula caused by tuberculosis (Moerman, 1998); the Bella Coola First Nations (British Columbia) would make a poultice from the buds of A. incana to ease lung pains (Moerman, 1998); the Carrier peoples (British Columbia) would use a decoction of the bark as an anti-septic (RitchKrc et al., 1996); and the Cree (Ontario, Manitoba, Saskatchewan, Alberta and the Northwest Territories) would use infusions of the bark to treat diabetes (Leduc et al., 2006).
Although McCutcheon et al. reported that the closely related species Alnus rubra exhibited anti-mycobacterial, anti-viral and anti-fungal activities (McCutcheon et al., 1994, McCutcheon et al., 1995, McCutcheon et al., 1997), no investigations of the anti-mycobacterial activity of A. incana extracts have been reported. Since A. rubra and A. incana are congeneric and there is ethnopharmacological evidence that A. incana was used as treatment of TB-related symptoms, we speculated that A. incana may possess anti-mycobacterial activity. The present study was performed to assess the anti-mycobacterial activity of A. incana bark and to identify the active constituents of the extract.
Section snippets
General experimental procedures
All solvents for extraction and isolation were purchased from Fisher Scientific (Ottawa, ON, Canada). NMR solvents were purchased from Sigma-Aldrich (Oakville, ON, Canada). NMR spectra were recorded on an Agilent 400-MR DD2 NMR spectrometer and high-resolution mass spectrometry was performed on a Thermo LTQ Exactive instrument using either electrospray ionization (ESI) or atmosphere pressure chemical ionization (APCI). Optical rotations were determined on a Rudolph autopol III polarimeter and
Results and discussion
Alnus incana is a member of the genus Alnus Mill. that consists of 35 species of trees and shrubs distributed across the Northern hemisphere with a few species extending into the Andes in the Southern hemisphere (Chen and Li, 2004, Furlow, 1979). There are a total of nine Alnus species in North America, two of which are native to New Brunswick, Canada: A. incana and A. viridis (Furlow, 1979, Hinds et al., 2000). The traditional therapeutic uses of six of the nine North American Alnus species,
Conclusion
In conclusion, the isolation of anti-mycobacterial triterpenes from extracts of the bark of A. incana may support the traditional medicinal use of this plant by the First Nations peoples of Canada as a treatment of TB-related symptoms. Betulin (1), in particular, demonstrated significant activity in our anti-mycobacterial assays and it is interesting to note that birch bark (trees of the genus Betula), which also contains significant quantities of 1 (Krasutsky, 2006), has numerous documented
Acknowledgments
The authors would like to thank Stephen Clayden (New Brunswick Museum), Larry Calhoun (University of New Brunswick), Gilles Robichaud (Université de Moncton) and Fabrice Berrue and Patricia Boland (University of Prince Edward Island) for their assistance with plant identification, recording 2D NMR data, HEK293 cytotoxicity assays and obtaining HRMS data respectively; the Provincial Laboratory for Public Health in Edmonton, Alberta for provision of the M. tuberculosis H37Ra strain; and Emilie
References (43)
- et al.
Anti-mycobacterial natural products from the Canadian medicinal plant Juniperus communis
Journal of Ethnopharmacology
(2012) - et al.
Plants used by the Cree Nation of Eeyou Istchee (Quebec, Canada) for the treatment of diabetes: a novel approach in quantitative ethnobotany
Journal of Ethnopharmacology
(2006) - et al.
Anti-mycobacterial diynes from the Canadian medicinal plant Aralia nudicaulis
Journal of Ethnopharmacology
(2012) - et al.
C13 NMR-spectra of pentacyclic triterpenoids – a compilation and some salient features
Phytochemistry
(1994) - et al.
Antifungal screening of medicinal-plants of British–Columbian native peoples
Journal of Ethnopharmacology
(1994) - et al.
Antiviral screening of British Columbian medicinal plants
Journal of Ethnopharmacology
(1995) - et al.
Cytotoxic lupane-type triterpenoids from Acacia mellifera
Phytochemistry
(2004) - et al.
Cytotoxic constituents from Plumbago zeylanica
Fitoterapia
(2004) - et al.
The Canadian medicinal plant Heracleum maximum contains antimycobacterial diynes and furanocoumarins
Journal of Ethnopharmacology
(2013) - et al.
Carrier herbal medicine: an evaluation of the antimicrobial and anticancer activity in some frequently used remedies
Journal of Ethnopharmacology
(1996)
Analysis of fresh triterpenoid resins and aged triterpenoid varnishes by high-performance liquid chromatography atmospheric pressure chemical ionisation (tandem) mass spectrometry
Journal of Chromatography A
Antitubercular activity of pentacyclic triterpenoids from plants of Argentina and Chile
Phytomedicine
Lupenone isolated from Adenophora triphylla var. japonica extract inhibits adipogenic differentiation through the downregulation of PPAR in 3T3-L1 cells
Phytotherapy Research
Phylogenetics and biogeography of Alnus (Betulaceae) inferred from sequences of nuclear ribosomal DNA its region
International Journal of Plant Sciences
Cytotoxic terpenes and lignans from the roots of Ainsliaea acerifolia
Archives of Pharmacal Research
Microplate Alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium
Antimicrobial Agents and Chemotherapy
Pharmacological activities of natural triterpenoids and their therapeutic implications
Natural Product Reports
Systematics of the American Species of Alnus (Betulaceae)
Rhodora
Antitubercular constituents of Valeriana laxiflora
Planta Medica
Flora of New Brunswick: A Manual for the Identification of the Vascular Plants of New Brunswick
Plants and the Blackfoot
Cited by (32)
Two new compounds and the anti-mycobacterial activity of the constituents from Zanthoxylum leprieurii root bark
2023, Phytochemistry Letters3-Pentanol glycosides from root nodules of the actinorhizal plant Alnus cremastogyne
2023, PhytochemistryCitation Excerpt :In addition to diarylheptanoids (Ibrahim et al., 2016; Ilic-Tomic et al., 2017; Saxena et al., 2016; Sung and Lee, 2015), which are characteristic of the Alnus genus, triterpenoids (Novakovic et al., 2017), flavonoids (Ab Ghani et al., 2017), phenolic compounds (Kim et al., 2016), shikimic acid (Altinyay et al., 2016), sterols (Chen, C. K. et al., 2006; Knights et al., 1981), and xanthones (Khvorost et al., 1987) have been identified in Alnus species. Previous phytochemical analyses of Alnus species covered various organs, including leaves (Altinyay et al., 2016; Kim et al., 2016; Saxena et al., 2016), fruits (Sung and Lee, 2015), stems (Chen, C. K. et al., 2006), flowers (Ab Ghani et al., 2016, 2017), and bark (Ibrahim et al., 2016; Ilic-Tomic et al., 2017; Krasilnikova et al., 2018; Li, H. X. et al., 2015; Novakovic et al., 2017). Klika and colleagues isolated a compound, demethyl (C-11) cezomycin, from cultures of Frankia sp.
The discovery of novel immunomodulatory medicinal plants by combination of historical text reviews and immunological screening assays
2022, Journal of EthnopharmacologyAnti-mycobacterial natural products and mechanisms of action
2022, Natural Product ReportsAntimycobacterial activity of azepanobetulin and its derivative: In vitro, in vivo, ADMET and docking studies
2020, Bioorganic ChemistryCitation Excerpt :Nevertheless, compounds 1 and 2 are of high therapeutic interest for their antimycobacterial activity. Therefore, the structural derivatization of the lupane scaffold by the introduction of the azepane ring, led to an increase in the antimycobacterial activity recorded for the two derivatives compared to the same therapeutic effect reported for betulin [24]. MIC against resistant isolates