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on highly processed, nutritionally devoid staple foods have contributed to the conditions. Declining Native health status is the impetus behind the resurgence of interest in re‐examining wildcrafted subsistence foods, and re‐educating tribal youth on the health‐relevant attributes of traditional diets and plant‐based medicines (Burns Kraft et al. 2008; Kellogg et al. 2010; Schreckinger et al. 2010; Flint et al. 2011; Wapner 2012; Joseph et al. 2014; Kellogg et al. 2016).

3.3 How Wildcrafted Edible Plants Differ from Agricultural Commodities

Obviously, wildcrafted foods are more time consuming to source and to harvest as opposed to simply stopping by a grocery store. Fruits and vegetables foraged in the wild may, to some consumers, be less aesthetically appealing than typical commercial market produce (Soukand 2016; Pinela et al. 2017). For example, wild berryfruits may be smaller and less sweet, have larger, harder, and denser seeds, and provide lower yield per plant; root crops grown in unprepared soil will not be uniformly shaped or sized, fruit or vegetable produce that has not been sprayed routinely with pesticides may exhibit some insect or pathogen damage. However, it is the adversity of the harsh unprotected wild growing environment that specifically provokes accumulation of redundant, overlapping polyphenolic profiles, which effectively protect the plant from the ravages of nature (Wynn and Fougere 2007; Wapner 2012; Li et al. 2016; Pinela et al. 2017). The impetus behind a plant’s production of antioxidants is to counter the oxidative stressors in the natural habitat (Li et al. 2016). In addition, the unbuffered environmental pressures in the wild cause spatiotemporal variation in the chemical profiles of the plants (Dhami and Mishra 2015). Dar et al. (2017) hypothesized that in the wild, perhaps nature has preselected phytochemicals that influence health (primarily plant health) and then may have specific metabolic roles for all living things that consume or interface with those plants. Farm‐cultivated plants are bred to encourage higher yields of the edible plant part, but generally have less energy to expend on production of expansive root systems or generation of secondary compounds. Wild plants maintain a much higher level of genetic diversity than domesticated cultivars, which is in part responsible for the rich phytochemical multiplicity accumulated in the edible fruits and foliage, and is the impetus behind some current efforts to breed back key traits from wild relatives into farmed plants (Zhang et al. 2016).

      Wild plants demonstrate pharmacologically unique activities, and a plethora of phytochemical constituents with lesser pharmaceutical activity play roles in augmenting the activity of primary active constituents (Wynn and Fougere 2007; Dhami and Mishra 2015). Traditional medicine has rarely included identification of the specific bioactive components in the whole plant or whole wild fruit extract, in part because these recognized interactions (additive, concomitant, antagonistic, or synergistic) between the myriad phytochemical constituents potentiate their bioactivity once ingested by animals (Phan et al. 2018). The presence of multiple recognized biologically active constituents combined with a diversity of other phytochemicals with lesser (or moderating) bioactivities allows for a wide range of therapeutic coverage from wildcrafted botanical drugs; in herbal medicine, polypharmacy is de rigueur. The potency of wildcrafted medicines is linked to these interactive phytochemical effects, as a single isolated compound from the plant will not be as biologically active as a crude or semipurified extract that retains the potentiating interactions. Herbals have nutritional and pharmaceutical elements that interact with one another polyvalently; thus the clinical effects may have greater depth and breadth than those affected by synthetic drugs (Wynn and Fougere 2007; Joseph et al. 2014). Wild polyphenol‐enriched fruits have been noted for potent antiviral, antimicrobial, anti‐inflammatory, cognition enhancement, and cancer chemoprotective capacities, in addition to robust antioxidant activities, that generally exceed levels in cultivated fruits (Li et al. 2016).

Combination effects (additive or synergistic interactions, as well as antagonisms) that impact human health are widely cited for natural product compounds, although notoriously difficult to precisely characterize (Caesar and Cech 2019). Only recently, the crucial role of the gut microbiome in catabolizing polyphenolic compounds from plant foods, generating biologically active metabolites that return to circulation, has been documented, which has enriched our understanding of polyphenolic metabolite bioavailability (Lila et al. 2016). In terms of the potentiating interactions, pharmacokinetic synergy refers to the situation when one phytoactive component may enhance or alter intestinal absorption, metabolism, distribution, or elimination of another component (resulting in a change in concentration of the active component at the therapeutic target in the body). For example, herbal medicines with fibers, mucilage, or tannins can alter the absorption of other phytochemicals. Pharmacodynamic synergy refers to the case when two or more compounds interact with a single therapeutic target at a receptor site (Wynn and Fougere 2007).

      Three seismic changes in the food we eat have occurred over history: the discovery of cooking, the emergence of agriculture/cropping, and the invention of strategies for processing and preserving foods (Krebs 2013). The shift from hunter‐gatherer of wild foods to consumption of agricultural produce allowed the human population to increase and for greater socialization to occur (as foraging for food in hunter‐gatherer societies can take on average nearly seven hours of the waking day) (Soukand 2016), but the net effect on human health initially was negative. Early farmers suffered stunting (a form of malnutrition) and higher tooth decay than wild foragers, likely due to the less varied diet higher in farmed grains (carbohydrates), but as agriculture became better established and more efficient, it provided a more reliable and stable, easily stored food supply for humans (Krebs 2013). However, agriculture’s emergence has dramatically changed the nutritive and phytoactive content of plant foods.

      There are relatively few direct, side by side published compositional (or efficacy) comparisons of wild versus cultivated plants, in part because the genotypes of cultivated plants have for the most part been selected and bred for adaptation to a large‐scale cropping regime, and typically diverge widely from parent genotypes endemic in wild settings. A recent study analyzed the differences in mineral composition of wild, naturally growing and cultivated blueberries (V. myrtillus versus V. corymbosum, respectively) by inductively coupled plasma optical emission spectrometry, and reported that the wild species were higher in five minerals (Ca, Na, Mg, Mn, and Zn) while cultivated plants were higher in Fe and Cd, which was related to the composition of the soil at the farm site (Drozdz et al. 2018). However, it was necessary to examine two distinct species in order to compare wild to cultivated blueberries. Another recent study compared mineral composition of wild and cultivated blueberries and cranberries, but had to rely on comparisons of fruits and leaves of two different blueberry species (V. myrtillus and V. corymbosum) and two different cranberry species (V. oxycoccos and V. macrocarpon) to determine their statistically distinct micronutrient compositions in wild versus cultivated, respectively (Karlsons et al. 2018). Wild genotypes of Vaccinium species in general demonstrated higher health‐relevant bioactive potencies than cultivated selections in other studies (Braga et al. 2013). A wild banana species had higher phenolic and tannin content, and higher antioxidant capacities measured in three distinct assays than a commercial banana variety (Sasipriya et al. 2014), and wild strawberries recorded antioxidant capacity three times higher than cultivated strawberry genotypes (Ozgen et al. 2007). With few exceptions, studies have reported higher phytochemical content and bioactive potency for wild genotypes as compared to cultivated fruit selections, but in nearly all cases the species or genotypes collected in the wild were different than those produced under cultivation (Li et al. 2016).

3.4 Animal Mimickry/Zoopharmacognosy

      An evolutionary relationship between plants and mammals has conditioned the unique physiological/biomedical effects of wild plants (Wynn and Fougere 2007). Traditional ecological knowledge (as held in indigenous tribal communities) asserts that at least some animals instinctively know how to treat their own injuries or ills and self‐medicate using herbs growing in the wild. Consequently, traditional herbalists routinely use judicious observations of the behavior of sick or distressed wild animals to locate new potential human remedies derived from wild plants (Engel 2007; Wynn and Fougere 2007). Native Americans, as well as tribal groups

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