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Oxidative profile in patients with colon cancer: Effects of Ruta chalepensis L.

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To verify the involvement of free radicals in tumor progression and to investigate the effects of an ethanolic extract of Ruta Chalepensis L. and of rutin in blood of patients with colon cancer. Leaves of Ruta Chalepensis L. were collected in the area around Catania (Italy). For the preparation of the ethanol extract of leaves, an exhaustive extraction of 100 g of the drug was carried out in Soxhlet with 800 ml of 95% ethanol. Fifty-six patients with colorectal cancer were randomly selected for this study; among these, 34 were affected by an early stage (T1 N0 M0 according to scale), while 22 were affected by an advanced stage (T4, N1-2, M0) of cancer. Data obtained from these patients were compared with those of a control group consisting of 20 healthy subjects. Plasma of each sample was used for determining non-proteic antioxidant capacity, thiol groups, lipid hydroperoxides and nitrite/nitrate levels, evaluated by spectrophotometric tests. In addition, percentage of haemolysis was evaluated incubating (for 2 hours at 37 degrees C) erythrocyte suspension with a free radical donor (50 mM 2,2'-azobis-amidino propane chloridrate), in the presence or absence of ethanolic extract of Ruta Chalepensis L. (250 microg/ml) or rutin (1 mM). Non-proteic antioxidant capacity was significantly lower in cancerous patients than in healthy subjects (p < 0.001). This decrease was stage-related. In fact, non-proteic antioxidant capacity resulted lower in advanced than in early colorectal cancer (p < 0.001). The same significant stage-related decrease was observed in plasma thiol groups (p < 0.001). Coherently with the decrease in non-proteic antioxidant capacity and thiol groups, higher levels of lipid hydroperoxides and nitrite/nitrate were observed in patients with colorectal cancer with respect to healthy subjects (p < 0.001) and the increase in these markers of oxidative stress was related to the cancer stadiation. Neoplastic patients also showed an increased percentage of oxidative hemolysis respect to controls and the haemolytic damage was correlated with the stage of colon cancer. Both the extract of Ruta Chalepensis L. and rutin were able to protect erythrocytes from oxidative stress induced by the free radical donor, but the extract of Ruta Chalepensis L. was more effective than rutin. This protective effect was significant only in erythrocytes from patients with early colorectal group, whereas no significant modification was induced by Ruta Chalepensis L. or rutin in red blood cells from advanced colorectal cancer patients exposed to the same experimental conditions. Oxidative stress correlates with colon cancer stadiation and both the extract of Ruta chalepensis and rutin are able to protect red blood cells from radical-induced damage. However, their effects are significant in early stages of cancer. So these natural antioxidants might be usefull to prevent carcinogenesis and/or tumor progression.
... In Lebanon is from March to May; in Algeria is at June; in Tunisia is at April Acquaviva et al. (2011); Bouabidi et al., (2015); Günaydin and Savci, 2005;; Iauk et al. (2004) ;Khoury et al. (2014); Pollio et al. (2008);De Sa et al., 2000;Soudani et al. (2018) R. graveolens ...
... In Algeria is at June; in Chine is from March to June Farzaei et al. (2017); Gentile et al. (2018); ; Table 3 Uses of Ruta species in folk medicine. R. chalepensis Dropsy, neuralgia, rheumatism and menstrual and other bleeding disorders India Acquaviva et al. (2011); Iauk et al. (2004); Laxative, analgesic, antispasmodic, abortifacient, antiepileptic, emmenagogue, for dermatopathy treatment, fever, anti-inflammatory, to treatment of gastric, diuretic, headache, rheumatism disorders, snake bites, and wounds Whole plant ND Many countries Bouajaj et al. (2014); Soudani et al. (2018); Alotaibi et al. (2018); Emam et al., 2009 Asthma, renal colic, arthritis, rheumatism, backache, skin bacterial and fungal diseases, eye inflammation and ear infection, as antitussive, antispasmodic, antiinflammatory, anti-lice, sedative, and bronchodilator and also for treatment of snake bites ...
... Whole plant ND Palestine Jaradat et al., 2017 Analgesic and antipyretic and for the treatment of rheumatism and mental disorders Aerial parts Decoction Saudi Arabia Acquaviva et al. (2011); Iauk et al. (2004); Khoury et al. (2014) Hysteria, epilepsy, vertigo, colic, intestinal worms, poisonings, anxiety and eye problems, antispasmodic, analgesic, antipyretic, anti-inflammatory, sedative, menstrual problems, rheumatism, mental disorders Whole plant/leaves Decoction ND Acquaviva et al. (2011); Iauk et al. (2004); Khadhri et al. (2017); Khoury et al. (2014) Treatment of convulsion and other nervous disorders in children sepsis. These results strongly suggest that most of the abortions happen in the context of herbal intoxication, most frequently following the ingestion of Ruta plants. ...
Article
Ethnopharmacological relevance Ruta genus is constituted by ten species, of which the most commonly described are R. chalepensis and R. graveolens. Ruta plants are perennial shrubs belonging to the family Rutaceae, which are traditionally used in folk medicine, since ancient times mostly for the treatment of various ailments of the womb. Aim of the study To provide a review of the different uses of Ruta species in traditional medicine, as well as, on their multifactorial biological and pharmacological properties. Material and methods A search of the literature on genus Ruta and Ruta species was performed using various scientific databases and search engines and the information of articles were reviewed and compiled. Results Different parts of the plants belonging to Ruta genus are used in folk medicine to treat a wide range of different diseases. The principal use of these is in gynaecological field, but the treatment of pain, fever, nausea, inflammation, infections, nervous disorders, among others, are also described. These plants have been used to fertility regulation, as anti-fertility agent, to control menstrual flux and bleedings, as abortifacient and as contraceptive. The phytochemical composition of these plants consists mainly in essential oil (EO), but phenolic compounds were also reported, like coumarins and flavonoids, as well as alkaloids. Ruta species products like extracts and EOs have shown broad pharmacological activities, such as antimicrobial and antifungal activities, as well as, antiviral and antiparasitic. Moreover, Ruta plants products present antioxidant, neuroprotective, anti-inflammatory, anti-cancer and anti-diabetic activities and demonstrated contraceptive and abortifacient effects. These plants were also tested to be used for non-therapeutic approaches, as bio-insecticides in the control of different insect pests showing to be able to reduce infestation. Conclusions Ruta species could be a potential source of natural products with biological activities. Ruta extracts, essential oils and isolated compounds have shown a diverse potential for use in the treatment of different diseases, as well as, for pests control, contributing to the valorisation of these plants. Nonetheless, this review indicates that more studies are needed to demonstrate the full potential of Ruta species, and to further explore the toxicology and safety of these plants.
... Histopathology of paw tissue showed decreased oedema formation and cellular infiltration on supplementation with MER. Thus, the results demonstrated the potential beneficiary effect of methanolic extract of Ruta graveolens on adjuvant induced arthritis in rats 9,10 . studied 56 patients with colorectal cancer )34 with early stage and 22 with advanced stage( where R. chalepensis was found to protect erythrocytes from oxidative stress caused by radicals. ...
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... Numerous studies have shown that the species of this family have anticancer properties against several cancerous lines. In particular, the two most abundant species of this family, such as R. chalepensis and R. graveolens, have shown positive effects in vitro, hence the results are promising for the treatment and prevention of cancer [28][29][30]. ...
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Ruta chalepensis L. (Rutaceae) is a tropical medicinal plant traditionally used in the Republic of Djibouti to treat several diseases, including tumors. In this study, the anticancer activities of this plant from Djibouti were investigated according to an in vitro evaluation method and statistical modeling. The results obtained will make it possible to complete the previous work already published on this genus of plant, in particular by using untested cancer cell lines, such as U87-MG, U2OS, RT4, PC3, NCI-N87, MRC-5, MIA-Paca2, K562, JIMT-T1, HEK293, HCT116, A549, and A2780. The main volatile compound turned out to be 2-undecanone (51.3%). Correlation modeling was performed from the principal component analysis (PCA) of IC50 of the essential oil and four active substances (vinblastine, doxorubicin, combrestatin A4, and monomethyl auristatin E) versus the cancer cell lines tested, which confirmed the effectiveness of the oil against 6 lines: U2OS, NCI-N87, MRC-5, MIA-Paca2, JIMT-T1, and HEK293. These data reveal promising prospects for good biomass management through the future exploitation of the R. chalepensis L. essential oil as a potential source of natural anticancer agents for targeted investigations. Keywords: R. chalepensis L.; essential oil; chemical composition; cytotoxic activity; cancer; modeling
... Nowadays, it is cultivated in many regions of the world, especially in temperate and equatorial countries [2], and usually growing on rocky slopes [3,4]. R. Chalepensis has various pharmacological properties, attributed to its high contents of phytochemicals such as alkaloids, flavonoids, cardiac glycosides, coumarins, tannins, saponins, anthraquinones, volatile oil, cynagenic glycosides, glucosinolates, triterpenes, sterols, amino acids, phenols, and furocoumarins [2,[4][5][6][7]. In many countries, including Saudi Arabia, Yemen, Algeria, China, and India, R. Chalepensis is used in traditional medicine because of its biological activities, which include antioxidant, anti-bacterial [8], anti-fungal [9], anti-inflammatory [1,10], and anthelmintic [11] properties. ...
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Ruta chalepensis L., an evergreen shrub in the citrus family, is well-known around the world for its essential oils and variety of bioactivities, indicating its potential medicinal applications. In this study, we investigated the effect of different culture conditions, including plant growth regulators, media types, pH of the medium, and carbon sources, on in vitro regeneration from nodal explants of R. chalepensis. Following 8 weeks of culture, the highest percentage of regeneration (96.3%) and maximum number of shoots (40.3 shoot/explant) with a length of 4.8 cm were obtained with Murashige and Skoog (MS) medium at pH 5.8, supplemented with 3.0% sucrose and 5.0 µM 6-Benzyladenine (BA) in combination with 1.0 µM 1-naphthaleneacetic acid (NAA). For rooting, individually harvested shootlets were transferred on ½ MS (half-strength) supplemented with IAA (indole-3-acetic acid), IBA (indole 3-butyric acid), or NAA, and the best response in terms of root induction (91.6%), number of roots (5.3), and root mean length (4.9 cm) was achieved with 0.5 µM IBA after 6 weeks. An average of 95.2 percent of healthy, in vitro regenerated plantlets survived after being transplanted into potting soil, indicating that they were effectively hardened. DNA assays (PCR-based markers) such as random amplification of polymorphic DNA (RAPD) and directed amplification of minisatellite-region (DAMD) were employed to assess in vitro cultivated R. chalepensis plantlets that produced a monomorphic banding pattern confirming the genetic stability. Additionally, no changes in the flow cytometric profile of ploidy between regenerated plantlets and donor plants were detected. Regeneration of this valuable medicinal plant in vitro will open up new avenues in pharmaceutical biotechnology by providing an unconventional steadfast system for mass multiplication and might be effectively used in genetic manipulation for enhanced bioactive constituents.
... Patients with colorectal cancer show an increase in oxidative hemolysis. Ruta chalepensis extracts and rutin, the main phytochemical observed in it, were proved by (Acquaviva et al. 2011) to inhibit oxidative hemolysis. Both, R. chalepensis extracts and rutin protected erythrocytes from hemolysis. ...
Chapter
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