Sesquiterpene Lactones from Cotula cinerea with Antibiotic Activity against Clinical Isolates of Enterococcus faecalis

Cotula cinerea, belonging to the tribe Anthemideae, is a plant widespread in the Southern hemisphere. It is frequently used in folk medicine in North African countries for several of its medical properties, shown by its extracts and essential oils. The dichloromethane extract obtained from its aerial parts demonstrated antibiotic activity against Enterococcus faecalis and was fractionated by bioguided purification procedures affording five main sesquiterpene lactones. They were identified by spectroscopic methods (NMR and ESIMS data) as guaiantrienolides, i.e., 6-acetoxy-1β-,6-acetoxy-1α-, and 6-acetoxy-10-β-hydroxyguaiantrienolide (1–3), and germacrenolides, i.e., haagenolide and 1,10-epoxyhaagenolide (4 and 5). The absolute configuration was assigned by applying the advanced Mosher’s method to haagenolide and by X-ray diffraction analysis to 1,10-epoxyhaagenolide. The specific antibiotic and antibiofilm activities were tested toward the clinical isolates of Enterococcus faecalis. The results showed that compounds 3–5 have antibacterial activity against all the strains of E. faecalis, while compound 2 exhibited activity only toward some strains. Compound 1 did not show this activity but had only antibiofilm properties. Thus, these metabolites have potential as new antibiotics and antibiofilm against drug resistant opportunistic pathogens.

Chemical Analysis of the Main Metabolites of Three Spontaneous Plants From the Saharan Area (Algeria)

Spontaneous plants metabolites are more widespread for their properties and biological functions. Also, natural products have reminded diverse scientists to take a delight in their medical and insecticidal applications linked to the environmental. A variety of metabolites have a defensive function for the plants. Thus, three spontaneous plants: Caroxylon imbricatum, Tetraena alba and Cotula cinerea collected from two ecotypes and analyzed by two known conventional methods:Gas Chromatography‐Mass Spectrometry GC QTOF(quadrupole time of flight )_MS and Liquid Chromatography-Mass spectrometry LCQTOF(quadrupole time of flight )_MS. The investigation conducted out on the identification and quantification of metabolites revealed the main metabolites which have biological activities as a part of an alternative to synthetic insecticides. The chemical study showed the presence of N-Butylbenzensulfonamide and Sulfoxycaprylicacid in the three plants. N-Carboxy-methionineresidue, Butanoicacid and Valine were found in those of Cotula cinerea and Caroxylon imbricatum (Forssk.). Artomunoxanthentrione, Glycoaldehyde, Indoline, ,Benzensulfonamide and Oxoproline were detected in extracts of Caroxylon imbricatum (Forssk.) and Tetraena alba (L.f.) In addition, Pyrroline is the only compound common in Cotula cinerea and Tetraena alba (L.f.).

Potentials of the Extracts of Algerian Saharan Plant Cotula cinerea for the Management of Two Insect Pests, Aphis fabae and Tribolium castaneum

The insecticidal potential of the Saharan plant Cotula cinerea, was evaluated on two insect species namely Aphis fabae and Tribolium castaneum by topical application (contact toxicity) and repellency test. A crude ethanolic extract of aerial part of the plant was prepared and tested in the laboratory on adults of both species. For contact toxicity, five doses were tested on each of the two species 1.56, 3.12, 6.25, 12.5 and 25 mg/ml for A. fabae and 25, 50, 250, 350 and 500 µg/insect for T. castaneum. The repellency of the extract was studied at the dose 500 μg/insect for T. castaneum and 25 µg/ml for A. fabae. Results showed that the repellency of the extract increased with exposure time and the highest rates were observed after 4 h of exposure (72.33 ± 22% for T. castaneum and 87 ± 3.6% for A. fabae). For insecticidal activity, at the highest doses (25 mg/ml and 500 µg/ml), 100% mortality is obtained 72 h after treatment for A. fabae and after 48 h for T. castaneum. The extract of this plant was found to be more toxic against T. castaneum adults. LD50 calculated 24 h after treatment for the two species is estimated at 1.7 mg/ml for A. fabae and at 30.3 µg/insect for T. castaneum. The extract of this plant inhibited the activity of acetylcholinesterase (AChE) in both insect species. This result suggests that this plant has a neurotoxic effect on A. fabae and T. castaneum. The results of phytochemical study showed that the plant is mainly rich in flavonoids, gallic tannins, alkaloids, saponosides and glucosides. The insecticidal effect obtained in this study could be due to the synergetic action of all constituents of the extract. Results suggest the possibility of using the extracts of this plant in integrated pest management to replace the chemical insecticides.

Antihyperglycemic, Antihyperlipidemic and Antioxidant Effects of Cotula cinerea (Del) in Normal and Streptozotocin-Induced Diabetic Rats

Aims: The current investigation aimed to assess the antioxidant, antidiabetic and antilipidemic effects of the aqueous extract of aerial part of Cotula cinerea (C. cinerea). Background: Cotula cinerea (Del). which belongs to the Asteraceae family is commonly used traditionally for the treatment of diabetes. Objective: The objective of the study was to study the effect of the aqueous C. cinerea extract on glucose and lipid metabolism in normal and streptozotocin-induced diabetic rats using a single and repeated oral administration. Methods: A preliminary phytochemical screening and the quantification of phenolic and flavonoid contents as well as the antioxidant activity using three methods (DPPH, FRAP and ABTS) were carried out. The effect of a single and repeated (15 days of treatment) oral administration of the aqueous extract of aerial part of Cotula cinerea (AEAPCC) at a dose of 20 mg/kg on glucose and lipid profile was examined in normal and streptozotocin-induced diabetic rats. Additionally, histopathological examination of the pancreas and liver was carried out according to the Hematoxylin-Eosin method. Results: AEAPCC (20 mg/kg) showed a significant blood glucose-lowering activity in both normal and diabetic rats after a single and repeated oral administration during 15 days. The aqueous extract was also able to decrease the plasma triglycerides levels in both normal and diabetic rats after 15 days of oral treatment at a dose of 20 mg/Kg while no effect was observed on plasma cholesterol levels. In addition, the results show that AEAPCC exhibits an in vitro antioxidant activity using different tests. Histopathological analysis of the pancreas and liver of AEAPCC-treated diabetic rats has revealed that AEAPCC had a beneficial effect on the architecture of these organs while no improvement of glucose tolerance was noticed using the glucose tolerance test. Furthermore, the results showed that the extract is rich in several phytochemical compounds and exhibited an important antioxidant activity. The phytochemical screening revealed that AEAPCC contains polyphenolic compounds, flavonoids, tannins, alkaloids, saponins, quinones, sterols, terpenoids, anthroquinones and reducing sugars. Whereas, it is free from glycosides. Conclusion: In conclusion, this study demonstrates that Cotula cinerea possesses a beneficial effect on diabetes. Further investigations are required to study the mechanism of action of the antidiabetic effect of this plant.

Phytochemical Investigation, Acute Toxicity, Central Analgesic and Antioxidant Activities of Extracts and Essential Oil of Cotula cinerea Del (Asteraceae)

Background: Cotula cinerea belongs to the Asteraceae family and grows in desert areas such as Moroccan Sahara. The use of this plant in Moroccan traditional medicine prompted us to investigate its chemical composition, its acute oral toxicity, its analgesic and antioxidative activities. Methods: Extraction was conducted by steam distillation for essential oil and by maceration using solvents (hexane, ethyl acetate, n-butanol) for other non-volatile compounds. Quantitative analysis of total polyphenols, procyanidins and flavonoids was conducted through spectrophotometric assays. Qualitative phytochemical composition of the essential oil was investigated by GC/MS analysis. Acute oral toxicity was tested at a dose of 2000 mg/kg in mice. Central analgesic effect was assessed in rat using tail flick and hot plate models and the obtained results were compared to morphine. Antioxidant activity of the essential oil and the obtained extracts was evaluated through 2,2-diphenyl-1- picrylhydrazyl (DPPH°) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and the obtained results were compared to TROLOX. Results: The obtained results showed that the studied extracts contained significant amounts of total polyphenols, flavonoids and condensed tannins. The phytochemical composition of the essential oil was predominated by thujone, eucalyptol and santolinatriene. The results of the acute oral toxicity showed that the tested essential oil and extracts were not toxic even at the highest dose of 2000 mg/kg. Experiments on analgesic activity showed that the administered extracts have a central analgesic effect. The highest effect was observed with the n-butanol and ethyl acetate extracts for both tail-flick and hot plate tests. The antioxidant activity of the explored extracts showed higher scavenging activities of the studied samples compared to TROLOX. Conclusion: Our results indicate thus that C. cinerea could be considered as a source of various secondary metabolites including terpenoids and polyphenols. Exploration of its biological activities showed that the plant essential oil and extracts possessed antioxidant and analgesic effects. Based on the results of this study, it is likely that extracts of C. cinerea could open perspectives for its use for pain relief.

Chemical Profile, in vitro Antibacterial and Antioxidant Activities ofJuniperus phoeniceaL. and Cotula cinerea (Del.) Essential Oils from Southwestern Algeria

This work aims to study the chemical composition, antimicrobial and antioxidant activities ofJuniperus phoeniceaL. andCotula cinerea(Del.) essential oils from southwestern Algeria. The hydrodistilled oils obtained were characterized by gas chromatography–mass spectrometry (GC– MS). A total of 45 and 25 compounds were identified representing 100% ofJuniperus phoeniceaL. andCotula cinerea(Del.) respectively. The dominant component was α-pinene (46.437%) forJuniperus phoeniceaL. and α-thujone (32.35%) forCotula cinerea(Del.). The in vitro antibacterial activity of the essential oils was evaluated against nine foodborne pathogenic bacteria and one yeast, Candida albicans, using the disk diffusion method; the minimum inhibitory concentration (MIC) values were examined (micro dilution). The results suggest that the essential oil ofJuniperus phoeniceahas a significant to moderate antibacterial activity on all strains of bacteria. The most sensitive strains were Bacillus cereus, Bacillus subtilis,Micrococcus luteus,Pseudomonas aeruginosa, andCandida albicanswith (MIC = 0.04 to 0.63 mg/ml).Cotula cinereaoil showed moderate to low sensitivity to the test strains. Its best activity was against Bacillus subtilis (MIC = 0.303 mg/ml). The DPPH test conducted to evaluate the antioxidant activity of both oils showed a good to moderate capacity forJuniperus phoeniceaL. (concentration of an inhibitor when the response is reduced by half, IC50 = 0.76 mg/ml) andCotula cinerea(Del.) [IC50 = 28. mg/ml] oils respectively. The promising bioactivities of these plants suggest that they may be a new source of preservative molecules.

Cytotoxicological Investigation of the Essential Oil and the Extracts of Cotula cinerea and Salvia verbenaca from Morocco

The objective of this work was to investigate the cytotoxicological effect of the extracts (hexane, ethyl acetate, and n-butanol) of Cotula cinerea and Salvia verbenaca in addition to the essential oil of Cotula cinerea. These plants are widely used in the Moroccan traditional folk medicine. The cytotoxic effect was explored against two cancer cell lines, Vero and RD, using the colorimetric MTT assay. The obtained results showed that the cytotoxicity differed according to the used extract with an efficient effect of Cotula cinerea extracts compared to Salvia verbenaca. A potent cytotoxicity was thus observed for the Cotula cinerea hexane extract which inhibited the growth of RD cell line at the lowest IC50 value (57.21±3.43 µg/mL). This was followed by the ethyl acetate extract and the essential oil with moderate effects against RD cell line and showed IC50 values of 187.52±6.27 µg/mL and 173.05±4.46 µg/mL, respectively. On the other hand, different results were obtained and Cotula cinerea essential oil was the most cytotoxic with the lowest IC50 value (72.72±2.18 µg/mL) against Vero cell line. In the same conditions, higher concentrations were needed in the case of Salvia verbenaca extracts. The results of this study showed thus that Cotula cinerea essential oil and hexane extract showed significant cytotoxic effects against RD and Vero cell lines, respectively, and could be considered as novel source of antitumor agents. This study is expected to be beneficial for clinical and traditional applications for Cotula cinerea as a remedy against cancer and opens new perspectives for further investigations on other types of cancer cell lines.