# Stability and Bioaccessibility of \(\beta\)-Arbutin in Simulated Digestion Conditions
## 4 Discussion  
Considering the administration of phenolic substances in isolated forms (without the presence of a plant or food matrix), their bioaccessibility in a digestion environment can be regarded as a result of such phenomena as compound solubility, stability (i.e., resistance to degradation in digestion conditions), and occurrence in an uncomplexed and therefore potentially accessible form. It is reported that the low solubility of phenolic compounds in a digestion environment is one of the limiting factors influencing their bioaccessibility [9; 11; 21]. Furthermore, due to their specific chemical character, phenolic compounds are recognised as substances with generally low stability. The physicochemical environment of the digestion tract, including the water environment, the presence of residual oxygen (especially at the oral digestion stage), the action of temperature, changeable pH at the subsequent stages of digestion, and interactions with mineral components of digestion fluids, can promote their degradation or conversion to byproducts [11; 22; 23; 24]. On the other hand, in addition to their solubility and susceptibility to chemical degradation, phenolic compounds can associate with the biochemical components of digestion fluids like diges  
Figure 2: Chromatograms at 280 nm of the standard solution and in vitro bioaccessible fractions for the lowest dose of \(\beta\)-arbutin (1 mg). ST—standard solution of \(\beta\)-arbutin (12.5 ug/mL) and hydroquinone (12.5 ug/mL), GD—gastric digestion, ID—intestinal digestion. The other peaks that do not correspond with the standards represent digestion chyme components. tion enzymes and bile micelles, which results in a decrease in the amounts of their free and therefore bioaccessible form [25; 26; 27]. We found that, in the vast majority of cases, \(\beta\)-arbutin was generally unaffected by the digestion environment, especially when it was applied at the higher doses (7.5-100 mg). Even the application of the relatively high dose of \(\beta\)-arbutin (100 mg) allowed the full recovery of this compound from the electrolyte solution, which can only be obtained after its full solubilisation (which also implies its complete stability). As a polar substance, \(\beta\)-arbutin is well-soluble in the water environment, and its water solubility can reach 5 g/100 mL [28], which is a significantly higher concentration than those applied in the digestion experiment. Additionally, the high bioaccessibility of \(\beta\)-arbutin is a result of its high stability in digestion conditions. Despite the lack of statistically significant differences, the highest bioaccessibility among the samples (i.e., close to 100%), regardless of the applied dose, was observed after the electrolyte treatment at the gastric digestion stage (Figure 1). It is known that an important factor influencing the stability of phenolic compounds is the pH of the surrounding environment. In general, lower pH (e.g., pH 3 present at the gastric digestion stage) can contribute to higher resistance of phenolic substances to oxidative degradation than neutral pH values (i.e., pH 7 present at the intestinal digestion stage) and especially alkaline pH, which may induce the degradation of phenolic compounds [29; 30]. Considering the intestinal stage of digestion, a slightly negative impact of the physicochemical conditions on the stability of \(\beta\)-arbutin was noticed only at the lowest applied doses (1 and 2.5 mg), which suggests that this unfavourable phenomenon may be compensated for by the application of higher doses of the compound. We speculate that the higher \(\beta\)-arbutin concentration increases the antioxidant status of the bioaccessible fraction of digestion fluids, thus providing a more stable environment via the occurrence of the self-protection effects.