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

Abstract

Objective: Ruta tuberculata forssk. (Rutaceae) is an aromatic plants widely used in Algerian traditionally 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, it’s major identified flavonoids namely 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 glycemia 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.

Phenolic Characterization Using cLC-DAD Analysis and Evaluation of In Vitro and In Vivo Pharmacological Activities of Ruta tuberculata Forssk

“…Moreover, quercetin and catechin were only determined by cLC-DAD in both concerning extracts, in which the higher amounts were quantified in RME. Indeed, the richness of this extract in flavonoids content has been confirmed by both analysis methods [ 3 ].…”

“…Several phytochemical studies reported on the richness of Ruta species in polyphenols and flavonoids [ 3 , 13 , 17 , 18 ], while a limited number of reports on phenolic screening of Ruta tuberculata (or Hapophyllum tuberculatum ) could be found in scientific literature. In this context, the actual lack of studies that focus on the phenolic characterization in different extracts of R. tuberculata from Algeria increased our interest and curiosity to study it in depth and motivated us to characterize the phenolic compounds of crude polar extracts of their aerial parts, using cLC-DAD quantitative analysis, but also to evaluate their pharmacological effects using both in vitro and in vivo approaches.…”

“…Nowadays, several pharmacological studies affirmed that free radicals generated during oxidation processes could be involved in protein alteration, lipid peroxidation, DNA oxidation and even cell apoptosis, which can significantly contribute to the development of many disorders, in particular, cardiovascular, rheumatoid diseases, gastric ulcers and Alzheimer disorders [ 1 , 2 , 3 ]. Indeed, the inflammatory response, as a complex and vital immune defense mechanism, displays a crucial role in the alleviation of tissue damage during injuries, such as pro-inflammatory mediators including prostaglandins, histamine, serotonin and some key cytokines, in the resolution step of the inflammatory process in order to repair and regenerate damaged tissues [ 4 , 5 ].…”

“…Among Ruta species, R. tuberculata is incorporated in Mediterranean traditional medicine and often used in Algeria to treat skin pathologies, gastric, intestinal diseases, rheumatism, diabetes and hypertension [ 11 , 12 ], but also to treat various neurological illness such as hysteria, vertigo and epilepsies, noting that their infused leaves are prescribed to prevent convulsion and other nervous disorders [ 11 ]. In addition, several studies have reported the antioxidant, anti-inflammatory, anti-ulcer, hepatoprotective and anti-Alzheimer effects of Ruta plants [ 1 , 2 , 3 , 13 ]. In fact, the pharmacological proprieties of Ruta species could be attributed to the presence of diverse chemical classes of secondary biocompounds, including coumarine, alkaloid derivatives [ 8 , 14 ], essential oils [ 11 , 15 ], lignanes [ 16 ], polyphenols and flavonoids [ 3 , 17 , 18 ].…”

“…In addition, several studies have reported the antioxidant, anti-inflammatory, anti-ulcer, hepatoprotective and anti-Alzheimer effects of Ruta plants [ 1 , 2 , 3 , 13 ]. In fact, the pharmacological proprieties of Ruta species could be attributed to the presence of diverse chemical classes of secondary biocompounds, including coumarine, alkaloid derivatives [ 8 , 14 ], essential oils [ 11 , 15 ], lignanes [ 16 ], polyphenols and flavonoids [ 3 , 17 , 18 ]. Based on the previous literature, there are no studies reported on phenolic characterization of the aerial parts of R. tuberculata growing in Algeria and their pharmacological activities.…”