drug candidates (Andrae‐Marobela et al. 2012). The ethnomedical approaches (workshops) were conducted in hot spots of biodiversity as well as ethnic diversity. The bioassays revealed “first hits” of bioactivity to medicinal plants that had previously never been examined using these tools, and provided a way to conserve traditional knowledge in qualitative and semiquantitative data formats. One of the most appreciated features of this approach was that the indigenous healers were true research partners given all rights to transparency and benefits, and were never undermined as informant sources only.
3.5.4 Antidiabetic Mechanisms of Wild Tundra Berries
Wild berries have traditionally been integral dietary components for Native Americans and Alaska Natives, are used ceremonially and medicinally, and remain a treasured resource today (Burns Kraft et al. 2008; Kellogg et al. 2010). In Alaska and northern Canadian territories, lands with a high proportion of indigenous people, wild berry species often are the only edible terrestrial plants endemic to the environments. Site‐specific variation in anthocyanin and proanthocyanidin levels in these wild berries, and more concentrated phytoactive constituents in the more spartan, high‐stress environments of the arctic have been documented. Initial on‐site mobile bioassays conducted with Alaska Natives identified a wealth of primary bioactivities relevant to human health, including higher antioxidant potentials (relative to commercially harvested domestic berries), more concentrated and diverse phytochemical profiles, and significant effects of climatic fluctuations on berry abundance and quality. The strong partnerships forged in workshops that put scientific inquiry in the context of traditional knowledge (Flint et al. 2011) were followed by more extensive laboratory bioassays of wild berry species.
The incredibly diverse phenolic profiles of wild tundra berries (Figure 3.4), in particular, were found to include abundant A‐type proanthocyanidins, and were linked to the berries’ efficacy against diabetes and metabolic syndrome biomarkers, including expression of preadipocyte factor 1. Berry‐derived flavonoids and, more specifically, their gut‐derived phenolic microbial metabolites have demonstrated efficacy in modulation of serum glucose levels (Grace et al. 2009; Kellogg et al. 2010), in neuroprotective properties (Gustafson et al. 2012; Lila et al. 2014), and in wound healing and other anti‐inflammatory bioactivities (Grace et al. 2014; Nieman et al. 2018; Esposito et al. 2019; Nieman et al. 2019).
Figure 3.4 (a) Wild Vaccinium uliginosum (bog blueberry) growing on the Alaskan tundra. (b) Representative anthocyanins from Alaskan berries. (c) Proanthocyanidin A‐type structure characteristic of many Alaskan berry genotypes.
Source: (a) Mary Ann Lila.
3.6 Commercialization Prospects for Wildcrafted Polyphenol‐rich Plants
The exceptionally high polyphenol content and diverse profiles found in wild plants have led to their incorporation in new functional food and cosmeceutical formulations. There is a global trend favoring clean labels on food and cosmetic products, which has been the impetus behind industrial interest in using wild‐harvested plants as natural sources for antioxidants, flavorings, and antimicrobials in unique yogurt and cheese products and topical moisturizers (Pinela et al. 2017; Jacobsen et al. 2019).
For example, as a consequence of the current consumer trend towards natural, healthy foods from clean environments, edible macroalgae or seaweeds are increasingly consumed as trendsetting foods and condiments. Seaweeds, which were until recently harvested only by native groups, feature a range of antioxidant compounds (phlorotannins, pigments, tocopherols, and polysaccharides) which can now be efficiently, economically extracted from wild species, and/or wild seaweeds have been brought into industrial cultivation (Jacobsen et al. 2019). These advances have increased the impetus for the pharmaceutical industry to develop novel antidiabetic, anticarcinogenic, and anti‐inflammatory drugs from extracted phytoactives from seaweeds, particularly in Asia (Abirami et al. 2018). The polyphenolic (phlorotannin) content of seaweeds has been the impetus for the launch of new cosmeceutical and pharmacological products based on radiation protective, prebiotic, antibiotic, and antidiabetic attributes. The resiliency of native plants thriving under harsh environmental extremes has provided a novel marketing angle for these derived products. Biorefineries worldwide are currently using seaweeds in bulk as feedstock based on functional (prebiotic and anti‐inflammatory) bioactive properties (Holdt and Kraan 2011). Similarly, arctic berries which flourish in the extended 23 h photoperiod of the tundra regions and survive harsh conditions have become niche ingredients for novel edible products as well as cosmeceutical formulations (Kellogg et al. 2011).
Despite escalating investments in pharmaceutical research, the innovation capacity of industrial R and D models has appeared to stagnate. Safety issues are generally addressed rather late in the typical drug development pipeline, and can easily be responsible for failure of drug approval. In contrast, the alternative and time‐tested “reverse pharmacology” approach, based on the leads from traditional ecological medicines and a long history of human use, allows safety issues to be addressed early in the discovery process, and can significantly reduce time and costs while introducing novel new treatment approaches to modern consumers (Andrae‐Marobela et al. 2012).
3.7 Acknowledgements
We are grateful to the Southeast Alaska Regional Health Consortium (SEARHC) for their help in identifying selected natural resources. We gratefully acknowledge support from USDA NIFA HEC Grant 10790074, entitled In‐Field Biodiscovery Framework—a Catalyst for Science Education and Validation of Traditional Knowledge, from the Global Institute for BioExploration (GIBEX), and from USDA NIFA ANNH grant 561939‐02689, entitled Back to the River: the Science Behind Alaska’s Traditional Subsistence Lifestyle.
References
1 Abirami, A., Uthra, S., and Arumugam, M. (2018). Nutritional value of seaweeds and their potential pharmacological role of polyphenolic substances. Journal of Emerging Technologies and Innovative Research (JETIR) 5: 930–939.
2 Alarcomicronn, R., Pardo‐de‐Santayana, M., Priestley, C., et al. (2015). Medicinal and local food plants in the south of Alava (Basque country, Spain). Journal of Ethnopharmacology 176: 207–224.
3 Al‐Gubory, K., and Laher, I. (eds.). (2018). Nutritional Antioxidant Therapies: Treatments and Perspectives. NY: Springer.
4 Ali‐Shtayeh, M., Jamous, R., and Abu Zaitoun, S. (2015). A comprehensive science‐based field assessment of bioactive properties of the native plants of Palestine. Journal of Biodiversity, Bioprospecting and Development 2: 151.
5 Allkin, B. (2017). Useful plants—medicines: At least 28,187 plant species are currently recorded as being of medicinal use. In: State of the World’s Plants 2017 (ed. K.J. Willis). London (UK).
6 American Diabetes Association (2018). http.www.diabetes.org.
7 Andrae‐Marobela, K., Ntumy, A., Makobela, M., et al. (2012). “Now I heal with pride”—the application of screens‐to‐nature technology to indigenous knowledge systems research in Botswana: Implications for drug discovery. In: Drug Discovery in Africa. Impacts of Genomics, Natural Products, Traditional Medicines, Insights into Medicinal Chemistry, and Technology Platforms in Pursuit of New Drugs (eds. K. Chibale, M. Davies‐Coleman
