**1.3 Biological activity**

Glycoalkaloids play an important role in plants, serving as defense compounds against a variety of pathogens and herbivores. They can inhibit fungal growth, interfere with viral infection, disrupt insect feeding and development, and deter mammalian predators by their bitter taste and toxicity [18]. Glycoalkaloids can also affect plant-plant and plant-microorganism interactions in the soil by exuding or leaking from plant organs [3]. For example, glycoalkaloids from potato tubers can inhibit the germination of weed seeds and suppress the growth of soil-borne pathogens [3]. Glycoalkaloids can also modulate the expression of genes involved in plant stress responses and biosynthesis of other secondary metabolites [1]. Studies have shown that glycoalkaloids are involved in the regulation of plant growth and development, including the formation of roots, shoots, and leaves. They have also been reported

*Perspective Chapter: Integrated Network Pharmacology and Multiomics Approach to Elucidate… DOI: http://dx.doi.org/10.5772/intechopen.112789*

#### **Figure 1.**

*Oligosaccharide can vary in length and composition. (A) α-solanine, 3 carbohydrate molecules, (B) β-solanine, 2 carbohydrate molecules and (C) γ-solanine, one carbohydrate molecules.*

to have antioxidant properties, which can help protect plants from oxidative stress caused by environmental factors, such as UV radiation [19, 20].

#### **1.4 Toxicity**

Regarding human toxicity, sporadic outbreaks of poisoning may occur due to elevated levels of glycoalkaloids, as indicated by research studies, as they are largely resistant to home processing conditions such as baking, boiling, frying, and microwaving [21]. In humans, acute toxicity of potato glycoalkaloids causes gastrointestinal symptoms such as nausea, vomiting, and diarrhea. As a reference for risk assessment, the European Food Safety Authority established a lowest-observed-adverse-effect level of 1 mg total potato glycoalkaloids per kilogram of body weight per day [14]. The toxic effects of glycoalkaloids are due to their ability to inhibit cholinesterase activity, which can lead to symptoms such as nausea, vomiting, diarrhea, and even death at high doses [22]. The mechanism of toxicity consists of two processes: disturbance of membranes phospholipids bilayer [23] and inhibition of acetylcholinesterase [24], the latter can lead to a decrease in the activity of the central nervous system and the manifestation of neurological symptoms observed during poisoning (hallucinations, convulsions, depression etc.).

### **1.5 SAR of glycoalkaloids**

The structure-activity relationship (SAR) of glycoalkaloids can be studied by analyzing the effects of modifications in the aglycone and the sugar moieties. The aglycone structure has a significant impact on the biological activity of glycoalkaloids. For example, solanine and solasonine differ only in their aglycone moieties; α-solanine has a solanidine aglycone, while solasonine has a solasodine aglycone. α-Solanine is more toxic than solasonine [25]. The teratogenic effect on hamsters when an alkaloid

is administered orally is more dependent on the presence or absence of unsaturation at C-5 and C-6 in the alkaloid rather than the specific molecular arrangement (stereochemistry) at C-22 or the position of the nitrogen atom in the ring [26, 27]. The biological activity of glycoalkaloids is influenced by the presence and type of sugar groups attached to them. Glycosylation can increase the solubility and stability of the aglycone, which may lead to better absorption by the body. Researchers examined the sensitivity of fungi to α-tomatine, its hydrolysis product β2-tomatine, and its aglycone tomatidine. The results showed that β2-tomatine was generally less toxic than α-tomatine, while the aglycone form was the least toxic, suggesting the role of the sugar in compound toxicity [28]. Enzymatic hydrolysis of one or more sugars from the tetrasaccharide moiety of α-tomatine has also been shown to restrict its binding to 3β-hydroxy sterols, thus reducing the toxicity of the compound [29].

In a cell model called RL95-2, it was discovered that α-chaconine has greater potential as an anticancer agent compared to α-solanine. Although both glycoalkaloids share the same aglycone component, they differ in their sugar groups, with α-chaconine containing chacotriose and α-solanine containing solatriose. This indicates that the higher toxicity of α-chaconine may be attributed to the presence of chacotriose in its sugar moiety [30]. Similarly, solamargine and solasonine are two glycoalkaloids that share the aglycone moiety while differ in the sugar moiety. Solamargine has chacotriose, while solasonine has solatriose. Solamargine exerted higher antiproliferative effect on all tested cancer and normal cell lines. Supporting that stronger toxicity is attributed to the chacotriose moiety [31]. More recently, a comparative study of solamargine and solasonine on Chinese hamster lung fibroblasts (V79) demonstrated that at a dose of 28.4 μg/ml of compounds the inhibition of proliferation for solamargine was more than 80%, while for solasonine did not exceed 40% [32].

When compared to α-solanine, α-chaconine, and solanidine, the glycoalkaloids extracted from potato sprouts demonstrated a higher level of inhibition of human serum cholinesterase, with inhibition level of 63%. The inhibition levels for α-solanine and α-chaconine were 52% and 41%, respectively, while solanidine showed no inhibition [33]. α-Solanine and α-chaconine show similar potential in their ability to inhibit the activity of bovine and human acetylcholinesterase (AChE). The aglycones solanidine, tomatidine, and solasodine do not have significant inhibitory effects. While the ability to disrupt cell membranes appears to be influenced by the sugar side chain, the structure of the steroid seems to play a more critical role in determining AChE inhibition. A sugar side chain is a necessary requirement for the inhibition of AChE to take place [23]. *In vitro* studies showed that solanidine demonstrated minimal estrogenic effects, while its parent glycoalkaloids α-chaconine and α-solanine did not exhibit such effects, suggesting the sugar moiety has a masking effect on the estrogenic activity of the aglycone [34]. Summary of SAR is presented in **Table 1**.

### **1.6 Potato glycoalkaloids**

α-Solanine and α-chaconine are important cholestane glycoalkaloids sharing the solanidine residue (**Figure 2A**). The structures of α-chaconine and α-solanine are nearly identical, with the exception of their side chains. α-Solanine contains glucose, galactose, and rhamnose molecules in its side chains (**Figure 2B**), and α-chaconine is constituted of glucose and two rhamnose molecules (**Figure 2C**) [35, 36]. α-Solanine and α-chaconine are glycoalkaloids found in potatoes that have been shown to be toxic


*Perspective Chapter: Integrated Network Pharmacology and Multiomics Approach to Elucidate… DOI: http://dx.doi.org/10.5772/intechopen.112789*

#### **Table 1.**

*Summary of structure activity relationship of glycoalkaloids.*

to humans and animals if consumed in high doses [37]. α-Solanine and α-chaconine are biosynthesized from spirosolane glycoalkaloids, and a DOX family enzyme is involved in this process [38]. The types and distribution of glycoalkaloids identified in potatoes, as well as the factors affecting their rates of formation and biosynthesis, have been extensively discussed [39].
