Rosmarinic acid and its ester derivatives for enhancing antibacterial, α-glucosidase inhibitory, and lipid accumulation suppression activities

Abstract

Rosmarinic acid (RA), commonly found in Nepetoidae subfamily of Lamiaceae family, possesses various biological activities. To expand its application, RA was modified by esterification with methyl (me), propyl (pro), and hexyl (hex) alcohols and then tested antibacterial, α‐glucosidase inhibitory, and lipid accumulation suppression activities. Consequently, RA derivatives enhanced antibacterial activity, especially the RA‐pro and RA‐hex, which effectively inhibited the growth of Bacillus cereus rather than tannic acid, a natural antibacterial agent. RA‐hex also inhibited α‐glucosidase inhibitory activity greater than luteolin. By computational molecular docking, dihydroxyphenyl group and hexyl group were selected as essential groups for interaction with the active site of α‐glucosidase through hydrogen bonding and hydrophobic interaction, contributing to the great inhibitory activity. Furthermore, RA‐pro and RA‐hex effectively suppressed lipid accumulation of 3T3‐L1 cells, superior to EGCG, a well‐known anti‐obesity phytochemical. These biological effects of RA derivatives commonly attributed to hydrophobicity, hydrogen bonding, and steric bulkiness of the side chain. Practical applications Rosmarinic acid (RA), a fundamental compound in the family Lamiaceae, is one of powerful naturally occurring antioxidants as well as other biological activities. Furthermore, its abundance in nature was also high in amount in the plant kingdom. So, natural RA can be one of possible natural resources for creating potent natural drugs and biologically useful substances after chemical modification. Studies on various biological activities may intensively expand usage and application of RA. In this study, RA was derivatized to corresponding ester such as methyl, propyl, and hexyl alcohols with higher hydrophobicity, and found great antibacterial, α‐glucosidase inhibitory, and lipid accumulation suppression activities. RA‐pro and RA‐hex significantly suppressed lipid accumulation and cell differentiation. Therefore, RA derivatives with multiple biological activities have the potential to be applied in the food and pharmaceutical industries as food ingredients and supplements.

Effect of polyphenol, flavonoid, and saponin fractions from Thymus atlanticus on acute and chronic hyperlipidemia in mice

“…The activities of fractions were related to the presence of rosmarinic acid, which was the major compound in our fractions, and is known to have several pharmacological effects including hypolipidemic effect [51]. Rosmarinic acid has been also reported as a potential compound in hyperlipidemia and atherosclerosis, mainly by suppressing lipid accumulation in cells [52] and inhibiting lipid peroxidation [53]. Rosmarinic acid inhibits the formation of membrane cholesterol domains, which lead to the generation of extracellular crystals, a main non-cellular component of the atherosclerosis plaques [54].…”

Hydrolytic nondegradable bioactive rosmarinic acid particles

“…There are many studies in the literature about polyphenols that inhibit this enzyme 34 . RS is known to inhibit the α‐glucosidase enzyme 35 . The effects of RS, p(RS‐co‐STMP) particles and STMP on the enzyme activity of α‐glucosidase were determined by interacting them at pH 6.9 in phosphate buffer solution.…”

“…34 RS is known to inhibit the α-glucosidase enzyme. 35 The effects of RS, p(RS-co-STMP) particles and STMP on the enzyme activity of α-glucosidase were determined by interacting them at pH 6.9 in phosphate buffer solution. The inhibition % of α-glucosidase enzyme by RS, p(RS-co-STMP), and STMP are given in Figure 5B.…”

Bioactivity-Guided Separation of Potential α-glycosidase Inhibitor from Clerodendranthus Spicatus based on HSCCC with Molecular Docking

“…These hydrogen bonds overtly strengthened the interaction and anchored for binding the inhibitor in the active site. It is important to note that rosmarinc acid inhibited α-glucosidase activity in vitro (IC 50 , 2.52 mM) 37 . Therefore, C. spicatus may be a good source for isolating rosmarinc acid, and for α-glucosidase inhibitory activity.…”