Phenolic Profile, Acute Toxicity, and Hepatoprotective and Antiproliferative Activities of Algerian Ruta tuberculata Forssk

Objective: Ruta tuberculata forssk. (Rutaceae) is an aromatic plant widely used in traditional Algerian medicine due to its pharmaceutical virtues against various disorders. This study aims to determine the phenolic profile of aqueous (RAE) and methanol (RME) extracts of R. tuberculata aerial parts and to investigate their acute oral toxicity, as well as their possible antiproliferative and hepatoprotective effects. Methods: Polyphenols were identified by quantitative LC-MS/MS analysis. Oral acute toxicity was performed according to OCDE guidelines. The hepatoprotective activity was evaluated by paracetamol-induced hepatotoxicity and supported by biochemical and histological analysis of liver and kidneys. The antiproliferative activity against human colorectal HT-29 and ovarian OV2008 cancer cell lines was determined using SRB assay. Results: LC-MS/MS analysis revealed that RME has higher phenols and flavonoids content than RAE; however, its major identified flavonoids are Kaempferol, rutin, and naringenin. R. tuberculata seems mildly toxic at several doses, with oral LD50 greater than 5000 mg/kg. The significant increase in hepatic markers enzymes activities as well as cholesterol, triglycerides, and glycemic levels, caused by PCM-administration, was potentially reduced following the co-treatments with vitamin C and RME, respectively, compared to RAE. Moreover, RME-treatment markedly prevented all histological changes. Compared to RAE, RME (100 μg/mL) exhibited excellent antiproliferative activity against both tested cancer lines (% inhibition ≥ 80%). Conclusion: Both R. tuberculata extracts (200 mg/kg/daily) were non-toxic and exerted a potential hepatoprotective effect against PCM-induced hepatotoxicity. Accordingly, RME may be considered a good candidate for the development of new therapies against colorectal and ovarian cancers.