_applied sciences_  
_Article_  
**Interactions of Oleanolic Acid, Apigenin, Rutin, Resveratrol and Ferulic Acid with Phosphatidylcholine Lipid Membranes--A Spectroscopic and Machine Learning Study**  
[PERSON] 1,*\({}^{\copyright}\), [PERSON] 2\({}^{\copyright}\), [PERSON] 1, [PERSON] 1 and [PERSON] 3\({}^{\copyright}\)  
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and unsolic acid, which show a moderate fluidity-modulating effect in liquid-crystalline liposomes made from dipalmitoyl phosphatidylcholine (DPPC), and a distinct condensing effect in liquid-crystalline and crystalline membranes. These effects were comparable to those observed in the presence of cholesterol [5]. Other secondary metabolites that are widespread in the plant kingdom are polyphenols. Also in this case, some manifestations of biological activity and pro-health effects are related to interaction with lipid cell membranes, as reported for green tea catechins [6; 7]. Hydrophobic interactions between polyphenols and lipid membranes are also observed [8]. Planar aromatic moieties of phenolic compounds enable van der Waals forces, promoting a hydrophobic model of interactions. Flavonoids containing hydroxyl, galloyl and gallate groups affect the mainly hydrophilic domain of bilayers, forming hydrogen bonds. These compounds cause lipid aggregation, resulting in a reduction of membrane surface area and an increase of membrane rigidity. Trans-stilbenes, characterized by an open benzyl ring, penetrate more deeply into hydrophobic parts of the membrane, thereby increasing membrane area. Consequently, the membrane becomes more fluid and undergoes fluctuations [9]. Ferulic acid interacts electrostatically with phospholipids, zwitterionic polar groups within liposomal membranes. The affinity of ferulic acid to liposomes depends on their lipid composition. In simplified models composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), there is an increase in membrane rigidity. Conversely, no alterations in fluidity were observed in rigid membranes containing cholesterol and sphingomyelin [10]. Food ingredients, as well as secondary plant metabolites, can interact with biological membranes, which can have significant consequences for various biological functions of organisms. Understanding these interactions could lead to the discovery of new mechanisms of action of nutrients and plant metabolites, affecting cell signaling pathways and metabolism in organisms. The rigid planar multicyclic structure and hydrophilic 3\(\beta\)-hydroxyl group of oleanolic acid confers a structural feature close to cholesterol. As cholesterol is an essential component of lipid membranes in animal cells, we can assume that oleanolic acid will also exert a significant impact on the structure and biophysical properties of lipid membranes. Although this effect has been determined in liposome models, to date there has been no study of how the simultaneous presence of OA and phenolic compounds affect the properties of lipid membranes. The combination of OA and phenolic compounds is a characteristic feature of the Mediterranean diet.