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.
Ovarian cancer is one of the deadliest types of gynaecological cancers and more than half of the patients die within 5 years after diagnosis. Recurrence in advanced staged patients after chemotherapy is associated with increased chemoresistance, which results in poor prognosis. Regulator of G‐protein signalling 10 (RGS10) negatively regulates cell proliferation, migration and survival by attenuating G‐protein coupled‐receptors mediated signalling pathways. Recent studies have shown that loss of RGS10 expression is significantly associated with proliferation and cisplatin resistance in ovarian cancer cells.
Significance of the study
In this study, we analysed differential RGS10 expression levels using public microarray datasets from clinical and in vitro ovarian cancer samples. We validated that cancer progression and chemotherapy exposure change RGS10 expression. We enriched our study to evaluate the relationship between chemoresistance and differential RGS10 expression against ovarian cancer potential chemotherapeutic agent, palbociclib. Results showed that palbociclib treatment reduced cell viability, despite significantly decreased RGS10 expression in chemoresistant cells. Overall, the results confirmed that cancer progression and chemoresistance are significantly associated with the down‐regulation of RGS10 while some chemotherapeutics seem to be beneficial in decreasing chemoresistance in ovarian cancer.
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