**3.1 Natural plant toxins (phytotoxin)**

Phytotoxins are toxic plant secondary metabolites employed for defense by the plant kingdom and are also similar to anthropogenic micropollutants in terms of persistence and toxicity [25]. The distribution of these natural products is diverse but present in most plant families used for medicinal purposes [19, 26]. They also differ in biological function and toxicities. Common classes of phytotoxins include the alkaloids, cynogenic glycosides, saponins, furocouramins, lectins, solanines, and chaconine [9]. Sources of some of these chemicals from plant species, such as *Atropa belladonna*, *Datura* spp., *Digitalis* spp., *Papaver somniferum,* and *Strophantus gratus,* are well documented [17, 27]. Apparently, no correlation exists between toxicity and chemical diversity [28], but these toxins might contribute to mixture toxicities and have the potential to overtake anthropogenic chemicals in their overall risk because of constant and ubiquitous production in plants. Since the presence and diversity of these compounds in plant materials are inducible by natural selection [13], medicinal plants with high local abundance often induced by human activity might be of great concern. Phytotoxins cause a variety of adverse effects and pose a serious health threat to man [25] ranging from acute poisoning to long-term health consequences. They mediate their biological activities through mechanisms such as covalent modification of proteins and DNA bases (e.g., furanocoumarins), nonlinam-covalent modification of proteins, and interaction with biomolecules [27]. The common adverse health effects of these phytotoxins in man had previously been reviewed [18, 29] (**Table 1**). Besides phytotoxins with intrinsic toxicity, the metabolic activation of certain inert classes of natural plant products can unmask potential toxicities. Most of these potential herbal toxins are mainly found in chemical classes, such as the pyrrolizidine alkaloids, furanoterpenoids, anthraquinones, bisbenzylisoquinolines, alkenylbenzenes, flavonoids, and alkaloids. Their activation is mainly mediated by hepatic cytochrome P450 and in few cases by intestinal bacteria leading to the generation of toxic and reactive metabolites capable of binding to cellular macromolecules/reduction systems with a consequent formation of intermediate complexes and resultant toxicities. A comprehensive review of the activation, mechanisms, and subsequent toxicity of these pretoxic compounds has recently been undertaken by Wang et al. [19] and summarized in **Table 2**.


#### **Table 1.**

*Some phytotoxins and common adverse effects.*

#### **3.2 Phytosteroids**

Another class of specialized secondary plant metabolites, which can affect human health, is the phytosteroids. These compounds can potentially bind to steroid receptors in animals/humans and, thus, trigger or repress downstream receptor-mediated signaling events [22]. Phytosteroids, usually diverse in structures from endogenous steroid, can act as agonists, antagonists, or agents with both agonist/antagonist activities for steroid receptors [30, 31]. Some of these phytosteroids are the culprit of receptor promiscuity and may also interfere with steroid metabolizing enzymes, gifting this class of compounds a complex modulatory ability on the endocrine and reproductive systems [22]. A prominent subclass of phytosteroids is termed phytoestrogen because of their similarity to the female hormone, estrogen. These estrogenlike substances are the basis for the use of some plants for medicinal purposes [32] and include such classes as isoflavones (e.g., genistein, diadzein, glycitein, and biochanin), lignans (e.g., sesamin, enterodiol, and enterolactone), coumestans (e.g., coumestrol, plicadin, and wedelolactone), and certain classes of phytoalexins (e.g., medicarpin) (**Figure 1**) [33]. Phytoestrogens have been isolated and identified in herbal medicines [34, 35] for the relief of menopausal symptoms and the prevention of osteoporosis and heart diseases [36]. Apparently, they also improve serum triglycerides, total cholesterol, low-density lipoprotein, apolipoproteins A-1

*Natural Does Not Mean Safe DOI: http://dx.doi.org/10.5772/intechopen.104732*


*Source: Wang et al. [19].*

#### **Table 2.**

*Potential toxic compounds activated by metabolic systems.*

and B, and cell adhesion molecules [37]. Despite these benefits, animal data had also revealed that phytoestrogens have a wide range of adverse molecular, cellular, behavioral, developmental, and reproductive effects at doses and plasma concentrations comparable to that in humans [20, 36, 38, 39]. Based on the estrogenic potential of phytoestrogen, exposure can disturb normal sexual differentiation in fetus and cause menstrual disturbances in females or low sperm counts in males. Owing to the potential interactions between phytoestrogens and the thyroid gland, it is possible that the thyroid function of hypothyroid individuals consuming high levels of phytoestrogen- or goitrogen-rich foodstuffs and supplements may be adversely affected [22]. Exposure to phytoestrogens may have a modest adverse effect on *carotid intima media* thickness (CIMT) progression particularly in postmenopausal women at an increased risk of developing atherosclerosis [37]. The harmful effects of phytoestrogens is a subject of scientific contestation; however, these effects depend on the exposure (type, amount consumed, and bioavailability), ethnicity, hormonal status (age and sex and physiological condition), and health status of the consumer [33]**.** Besides the phytoestrogens, ligands for receptors of hormones, such as progesterone, thyroid, and gluccocorticoids (**Figure 2**), have also been identified in botanicals [21, 22, 40]. Effects from phytoprogestins (e.g., apigenin), phytoandrogens (e.g., drupanol), and phytocorticoids (e.g., ginsenoside) in medicinal plants are also gaining attention. The promiscuity of these plant-sourced ligands for steroid receptors have been

**Figure 1.** *Structural classes of phytoestrogens. Source: Domínguez-López et al. [33].*

**Figure 2.** *Other examples of phytosteroids. Source: Dean et al. [22].*

reported [22, 41] and have the potential to precipitate side effects leading to cardiovascular disease, stroke, water retention, and weight gain.
