| Summary: | We have investigated the in-vitro antioxidant activity and electrochemical redox properties of a number of natural compounds (carnosol, carnosic acid, 7-ethoxyrosmanol, ursolic acid, rosmanol and ladanein) isolated from the methanolic extract of <i>Salvia chamelaeagnea</i> collected from the Cape floristic region, South Africa. The results from trolox equivalent antioxidant capacity (TEAC), ferric-ion reducing antioxidant parameter (FRAP) oxygen radical absorbance capacity (ORAC), as well as the inhibition of Fe<sup>2+</sup>-induced lipid peroxidation showed strong antioxidant capacities for carnosol and rosmanol. A structural analysis of the compounds suggests that multiple OH substitution, conjugation and lactone ring in carnosol and rosmanol are important determinants of the free radical scavenging activity and electrochemical behavior. Pharmacophore generated demonstrates H-donor/acceptor capabilities of the most active compounds. Rosmanol, when compared to other compounds, exhibits the lowest oxidation potential value with an anodic peak potential (E<sub>pa</sub>) value of 0.11 V, indicating that rosmanol has the highest antioxidant power, which is in good agreement with ORAC and lipid peroxidation experiments. The lipophilic nature of carnosol, carnosic acid and rosmanol enhanced their absorption and activity against oxidative stress related to the treatment of age-related diseases. These results confirm the first report on the in-vitro antioxidant and electrochemical activities of <i>S. chamelaeagnea</i> constituents and underline the medicinal uses of this plant as natural preservatives for skin ageing or in pharmaceutical applications.
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