IN VITRO AND IN SILICO INHIBITORY ACTIVITY OF ANGIOTENSIN-CONVERTING ENZYME II AND ANTI-INFLAMMATORY EFFECTS OF NATURAL COMPOUNDS FROM RHEUM OFFICINALE ROOTS

Abstract

Rhubarb roots (Rheum officinale), a common medicinal plant in folk remedies, and their chemical compositions were investigated for their inhibitory activity of angiotensin-converting enzyme II and anti-inflammatory effects by inhibiting NO production and IL-6 expression. Four natural compounds, including two anthraquinones, chrysophanol (2) and emodin (3), and two stilbenes, rhapontigenin (1) and trans-piceatannol (4), were isolated from the roots of Rhubarb. The results showed that rhapontigenin (1) exhibited an inhibitory effect on the ACE-2 enzyme with an IC₅₀ value of 132 mM. In an in silico study, rhapotigenin (1) had a binding energy value of -9.32 kcal/mol, lower than MLN-4760, on ACE-2. Both rhapontigenin (1) and emodin (3) exhibited inhibitory activity on NO production in primary cultures of macrophages RAW264.7, with IC₅₀ values ranging from 5.65 to 32.3 µg/mL. This is the first study of the anti-ACE-2 and anti-inflammatory activity of Rhubarb root extract and its constituents.