Salvia rosmarinus Callus as a Sustainable Source of Rosmarinic Acid and Its Anti-Inflammatory Potential and Toxicological Profile

In vitro plant culture is a biotechnological strategy that allows the conservation of biodiversity and the enhancement of pharmacological effects derived from secondary metabolite content in plants used traditionally in Mexican herbalism, such as Salvia rosmarinus. This study aimed to compare the phenolic profiles of two ethanolic extracts of S. rosmarinus from the leaves of plants and from the biomass of an in vitro callus culture, as well as their in vitro cytotoxicity, in vivo acute toxicity, and acute systemic and dermal anti-inflammatory effects. The results revealed that compared with the wild-type plant extract, the S. rosmarinus callus culture resulted in higher concentrations of three major metabolites, namely, rosmarinic acid, and in the in vitro cytotoxicity assay, only the callus line extract resulted in the same moderate activity (60% cell viability) against HeLa cells at all the tested concentrations (0.0039–0.250 mg/mL), whereas the activity of the wild-type plant extract was the same at higher concentrations (0.5–1 mg/mL); both extracts resulted in an LD50 > 2 g/kg BW after a single intragastric administration in male mice, but only for the wild-type plant extract was incipient kidney and spleen increased relative organ weight recorded at both intermediate and higher doses, which was not associated with lethality; in contrast, the liver weight of the callus extract was slightly altered at the low and intermediate doses tested. Finally, compared with the wild-type plant leaf extract, the extract of the callus biomass showed notable anti-inflammatory effects after single oral administration at the lower tested dose of 150 mg/kg, but with a weaker effect after single dermal application; however, it generated a moderate inhibition of the nitro-derived products in inflamed tissue concentration. The in vitro cell line of Salvia rosmarinus proved to be a viable, sustained and sustainable source of bioactive secondary metabolites such as rosmarinic acid, which are present at higher concentrations than those of wild-type plants.