Indigenous Peoples of the boreal forest of Canada for symptoms associated with diabetes and the complications of diabetes. Thirty-five plant species were selected for analysis based on their use in the literature for three or more symptoms of diabetes and diabetes complications (see Table 22.1). The symptoms were selected following an MD-approved list of 21 symptoms (Carlson et al., 1997; Oubre et al., 1997). Using a similar list of 15 symptoms of diabetes, Elders of two communities of the Cree Nation of Eeyou Istchee were interviewed about plant treatments. The 22 plant species identified in the interviews included some of the same species as those of the literature study of Table 22.1. These included Abies balsamea or balsam fir, Juniperus communis common juniper, Kalmia angustifolia Sheep laurel, Lambkill kalmia, Lambkill, Picea glauca white spruce, Picea marianablack spruce, Populus balsamea balsam poplar, bam, bamtree, and Rhododendron (Ledum) groenlandicum Rhododendron. The similarity of these species lists corroborates the importance of these species to these symptoms and the continued use of these species for symptoms related to diabetes.
were interviewed about plant treatments (Fraser et al., 2007; Leduc et al., 2006). The 22 plant species identified in the interviews included some of the same species as those of the literature study of Table 22.1. These included Abies balsamea, Juniperus communis, Kalmia angustifolia, Picea glauca, Picea mariana, Populus balsamea, and Rhododendron (Ledum) groenlandicum. The similarity of these species lists corroborates the importance of these species to these symptoms and the continued use of these species for symptoms related to diabetes. 2.2 Selection by Symptom Use Analysis of symptom use and related antioxidant results revealed associations with the number of symptoms a plant species was used for and the plant extract’s antioxidant activity. Plant species used for more than five symptoms were statistically higher in activity than those used for three, four, or five symptoms (McCune and Johns, 2003). Cluster analysis also revealed groupings of symptoms associated with higher antioxidant activity. Plant species used for heart disease, diarrhea, urinary issues, circulation, blood disorders, or blood reviver/tonic tended to be higher in free radical scavenging activity. Most of these symptoms are known to be treatable with antioxidants. The proanthocyanin antioxidants in cranberry and blueberry have been shown to limit the binding of bacteria to bladder cell walls, thereby preventing urinary infections (Ofek et al., 1996). Diarrhea can be alleviated with the ingestion of tannins, known strong antioxidants, by binding proteins and providing a protective coat in the intestine (Haslam, 1996). Studies on the blockage of arteries, related to lipid peroxidation of low-density lipoprotein (LDL) and the lipids associated with the arterial wall membranes, indicate that antioxidants such as vitamin E and/or flavonoids can have an effect (Zern and Fernandez, 2005). This also relates to the fact that heart disease, circulation, and blood disorders are all influenced by arterial wall health. In addition, taking a reviver or tonic could be associated with the fatigue often associated with heart disease and poor blood flow. 2.3 Environmental Clues and Harvesting Selection An experienced herbalist with knowledge of the effectiveness of these traditional medicines in relation to the collection site could have learned to identify environmental clues related to the antioxidants available in plant species. Antioxidants in the form of carotenoids and anthocyanins give the red, yellow, and orange colors to flowers and fruits, as well as some barks and roots. Leaves that contain tannins can cause a circle devoid of growth around the trees where these leaves have dropped and leached their contents into the soil. Stresses to plants can increase the production of some antioxidants like those created in identifiable areas such as rocky, infertile soil, or drought conditions. As antioxidants are increased in plants to protect photosynthetic apparatus from damaging free radicals produced during bright and sunny high UV conditions, collections in open areas 226 L. would be beneficial. Repeated collection from an area could take advantage of the fact that when a plant is stressed from animal browsing, or harvesting by humans, secondary compounds are produced that include antioxidants (Polle and Rennenberg, 1993). The 35 plants listed inTable 22.1, and their antioxidant activities, have been analyzed in conjunction with plant part used, life-form of the plant species, and the associated growing condition/habitat (McCune and Johns, 2007). Those plant species typically located in areas of rocky/infertile conditions were found as a group to be statistically higher in antioxidant activity than those found in wet conditions. This coincides with the above theories of UV antioxidants in drought and stressed plants.When comparing trees versus shrub and herb, the trees as a group were higher in antioxidant activity than the shrubs, which in turn were higher than the herbs. As antioxidants are often protective in nature, the longer-lived life-form of trees would contain more of these compounds to protect the tree throughout the year. The bark would be the most accessible for collection year round and the most subject to the elements in the boreal forest. The potential for bacterial and microbial infections in the boundary between the sapwood and heartwood is potentially reduced due to the presence of tannin and flavonoid antioxidants (McKey, 1979). In fact, bark was the most often collected part of the selected trees. Further analysis of plant parts used revealed that the barks collected as a group were higher in activity than the leaves or roots (McCune and Johns, 2007). In McCune and Johns (2002, 2007), the differences between different parts of the same plant species were statistically significant, thereby highlighting the importance of correct collection methods and identification of the part of the plant used medicinally. Corroborating this, the studies of Fraser et al. (2007) indicated a difference in bioactivity from different collections of P. glauca and the environmental differences related to those discrepancies. In addition, the method of preparation (whether used fresh, dried, boiled, smoked, fermented, etc.) could affect the levels of antioxidants available. 3. ANTIOXIDANT ACTIVITY OF THE SELECTED PLANTS The results for free radical scavenging antioxidant activity (using 1,1-diphenyl-2-picrylhydroazyl or DPPH) of the selected 35 plant species are shown in Table 22.1, listed in alphabetical order by Latin binomial (McCune and Johns, 2002). The activity is inversely related to the value given – meaning, the lower the recorded value the greater the amount of scavenging. This is based on the concentration of extract that reduced the oxidant by half (IC50). Differences in types of antioxidant activity indicate different modes of action and potential abilities to influence the associated symptoms in different ways. The DPPH assay is used to illustrate the ability to donate hydrogen, thus potentially nullifying damaging freewheeling oxidants. The superoxide scavenging activity can indicate importance in ischemic tissue injury and endothelial dysfunction related to the balance of superoxide Antioxidant Activity of Traditional Medicinal Plants of Canada 227 and nitric oxide. Superoxide anions are known factors of inflammation that are greatly increased in diabetics. Peroxyl radical scavenging could be a benefit in lipid peroxidation and atherosclerosis (Halliwell, 1997). When these plant extracts were tested for the other levels of antioxidant activity, superoxide scavenging (using a hypoxanthine/xanthine oxidase and nitroblue tetrazolium assay), and peroxyl radical scavenging (using an azo initiator and 2,7-dichlorofluorescein-diacetate), the rankings among these species changed significantly (McCune and Johns, 2002). This was particularly true for Gaultheria procumbens and Solidago canadensis in the peroxide scavenging assay. Solidago canadensis was also considerably higher in rank in the peroxyl radical scavenging than in the other assays. The top five plant species in each of the three antioxidant assays are listed in Table 22.2. Fourteen percent of these species showed similar free radical scavenging activity to vitamin C, a well-known antioxidant. Eight of the plant species had activity similar to green tea as well as an analogue of vitamin E (TroloxW). This indicates that these plant species are significant sources of antioxidants and could be a benefit to those following the traditional lifestyle. Sixty-three percent of the species had activity similar in superoxide scavenging as ascorbic acid/vitamin C, while in peroxyl radical scavenging, 60% of the plant species extracts had activity similar to TroloxW. Solidago canadensis and Rhus hirta both had mean activities in peroxyl radical scavenging higher than those produced with green tea, ascorbic acid, or TroloxW. Of the 35 plant species selected for testing, 89% of them showed higher antioxidant activity than the market produce of potatoes, carrots, lettuce, and garlic (McCune and Johns, 2002). Of the 35 identified plant species used for symptoms associated with diabetes, the literature associated 63% of them with food use and 60% as used for tonic or beverage. This additional usage increases their respective antioxidant effect as a result of increased consumption. With the knowledge that 37% were already reported to have vitamin A and C, adding medicinal plant’s vitamin content to diet analysis would increase the vitamins (and antioxidants) associated with a particular traditional lifestyle. Table 22.2 Top 5 Selected Boreal Forest Plants in Each Antioxidant Assay Free radical scavenging Superoxide scavenging Peroxyl radical scavenging Rhus hirta Rhus hirta Rhus hirta Cornus stolonifera Quercus alba Solidago canadensis Nuphar variegatum Juniperus communis Quercus alba Quercus alba Quercus rubra Juniperus communis Corylus cornuta Nuphar variegatum Picea glauca Reproduced from McCune, L.M., Johns, T., 2002. Antioxidant activity in medicinal plants associated with the symptoms of diabetes mellitus as used by the Indigenous Peoples of the North American boreal forest. Journal of Ethnopharmacology 82, 197–205. 228 L.M. McCune 4. FOUR SELECTED HIGH ANTIOXIDANT SPECIES As plants are a mix of compounds, some of which are antioxidants, it is possible in addition to antioxidant action that these plant species have other types of antidiabetic activity. Listed below is more information on four of the species identified above as high in antioxidant activity and having further potential in antidiabetic action. 4.1 Rhus hirta Rhus hirta, also known as Rhus typhina, is commonly referred to as staghorn sumac and lemonade tree. It grows throughout eastern North America as a shrub with bright red terminal conic fruit clusters covered in red tart hairs (Figure 22.1). Rhus hirta fruit had the highest activity in all the assays tested for different types of antioxidant activity (McCune and Johns, 2002). The extract had a mean free radical scavenging and peroxyl radical scavenging activity higher than ascorbic acid and green tea. It is listed as used by multiple Native Americans for numerous medicinal purposes (Moerman, 1998). The leaves and bark are known to be high in tannins and used for tanning purposes. Close relatives in the Rhus genus have shown antimicrobial, antioxidant, anticlotting, antimalarial, and antimutagenicity activity (Rayne and Mazza, 2007). In the 1940s, Banting, a co-discoverer of insulin, tested the leaves for antidiabetic properties and Fortier determined that fruit extract could produce hypoglycemia in dogs. It was also determined that Rhus coriaria can lower glucose in diabetic rabbits (Fortier, 1949). Its ability to inhibit tumor necrosis-a production in a human U-937 macrophage system suggests a possible action on insulin resistance (McCune, 1999). 4.2 Solidago canadensis Solidago canadensis, commonly known as Canada goldenrod, is an herbaceous perennial in the Asteraceae family that grows throughout most of North America. The root extract had mean peroxyl radical scavenging activity higher than green tea, ascorbic acid, and TroloxW (an analogue of Vitamin E). In a human U-937 macrophage system, the extract produced a highly significant inhibition of tumor necrosis-a production with inhibition throughout the concentration range tested (McCune, 1999). Two anti-inflammatory quinoline alkaloid mannopyranosides have been identified from S. Canadensis (Li et al., 2009). Rutin has been reported as the major flavonoid, with the presence of phenolic glycosides, labdane diterpenes, and lupinechinensis, with reports of anti obese properties in rats as well as the ability to affect blood glucose, total cholesterol, and triglycerides (Kim et al., 2008). Extracts of Juniperus oxycedrus berries and leaves have the ability to decrease blood glucose and levels of lipid peroxidation in diabetic rats (Orhan et al., 2010). 4.4 Picea glauca Picea glauca, commonly known as white spruce, is a member of the Pinaceae family and grows throughout the northern areas of North America. The bark extract had a high rate of peroxyl radical scavenging activity (McCune and Johns, 2002), and the needle extract had a high rate of free radical scavenging (Harbilas et al., 2009). The total phenolic content of P. glauca needle, bark, and cones was assessed with the identification of flavonoids, stilbenes, and phenolic acids (Harris et al., 2008). In conjunction with the different traditional uses for the different parts of the plant, the activities were different for leaves, cones, and root. The needle extracts had a cytoprotective effect in a cell culture Figure 22.1 Rhus hirta. 230 L.M. McCune study representative of peripheral neuropathies when stressed with glucose toxicity and glucose deprivation (Harbilas et al., 2009). The close relative P. mariana had fairly high free radical scavenging activity in its leaf extract (Table 22.1) and the ability to affect triglyceride metabolism and protect cells from glucose toxicity and deprivation (Spoor et al., 2006). 5. CONCLUDING STATEMENT This chapter has highlighted only some species of the boreal forest of Canada; certainly, in other areas of the world, with the aid of the Indigenous Peoples familiar with the local plant species’ medicinal capabilities, other plant species could be identified as used for symptoms of diabetes. Further studies could then identify antioxidant and other antidiabetic components of the species and their part in preventing diabetes in those populations. The traditional lifestyle of Indigenous Peoples, an important component of health considering the diabetes epidemics following a move away from traditional ways of life, includes not only medicinal plants but also local traditional food and beverage plants that contribute to the overall health that prevents diabetes
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