The perennial aromatic plant Ruta tuberculata Forssk (Rutaceae) has been traditionally used by Mediterranean peoples as folk medicine against several types of disease to treat diverse illness. The objective of this work is to evaluate the in vitro and in vivo pharmacological activities of the aqueous (RAE) and methanolic (MeOH) 80% (RME) extracts of Algerian R. tuberculata aerial parts. Antioxidant potential, neuro-protective and anti-arthritic activities were investigated in vitro using six antioxidant approaches and by determining acetyl-cholinesterase and bovine albumin denaturation inhibitory capacities, respectively. Furthermore, in vivo anti-ulcer and anti-inflammatory activities were evaluated on EtOH-induced gastric mucosal damage and carrageenan-induced paw edema models in mice. Moreover, bio-compounds’ contents were also quantified using spectrophotometric and cLC-DAD methods. Both in vivo and in vitro investigations showed remarkable antioxidant activity of Ruta tuberculata Forssk, while methanolic extract (RME) of Ruta tuberculata Forssk exhibited more significant neuro-protective and anti-inflammatory effects. However, the antiulcer activity was more pronounced with RAE of R. tuberculata, which suggests that this plant can be considered as a natural resource of potent bioactive compounds that may act as antioxidant and anti-inflammatory agents, which underlines the importance of incorporating them in therapies in order to treat various diseases linked to oxidative stress, and they may also provide crucial data for the development of new anticholinesterase drugs to improve neurodegenerative diseases, such as Alzheimer’s.

Among the Mediterranean aromatic plants, Ruta tuberculata Forssk. (Rutaceae) has been widely used as a traditional natural remedy against various disorders resulting from its divers’ pharmacological virtues. The aim of this study is to characterize for the first time the phenolic profile of its ethyl acetate (EtOAcE) and acetonic (AcE) extracts and to screen their in vitro antioxidant, antidiabetic, and neuroprotective activities. Phenolic content was determined using spectrophotometric and cLC-DAD analysis. Pharmacologically, in vitro antioxidant power was evaluated using six different antioxidant methods. Moreover, the antidiabetic and neuroprotective capacities were assessed in vitro by determining the α-amylase, α-glucosidase, and acetylcholinesterase inhibitory activities. Phytochemically, the highest flavonoid content was found in EtOAcE where the major identified compounds were myrecetin, rutin, sylimarin, naringenin, and quercetin. In presence of other phenolic acids, gallic acid was exclusively detected in AcE. Furthermore, both R. tuberculata extracts showed significantly remarkable antioxidant activities, especially the EtOAcE. Interestingly, AcE strongly inhibited the acetylcholinesterase and α-glucosidase, with the respective IC₅₀ values of 20.48 ± 0.2 and 104.5 ± 1.8 µg/mL. In this study, we also reported the nutritional quality associated with the identified phytocompounds. R. tuberculata organic extracts may offer exciting reserves to achieve new anti-diabetic and anti-Alzheimer drugs which have also antioxidant potential.