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ORIGINAL ARTICLE
Year : 2018  |  Volume : 10  |  Issue : 2  |  Page : 119-123  

Antilymphoma potential of the ethanol extract and rutin obtained of the leaves from schinus molle linn.


1 Medical Research Unit in Pharmacology, UMAE Speciality Hospital-2° Floor CORCE, National Medical Center Siglo XXI, IMSS, Av. Cuauhtemoc 330, Col. Doctores, CP 06725, México City, México
2 Medical Research Unit in Human Genetics UMAE Pediatric Hospital, National Medical Center Siglo XXI, IMSS, Av. Cuauhtemoc 330, Col. Doctores, CP 06725, México City, México
3 Academic Area of Pharmacy, Institute of Health Sciences, Autonomous University of the State of Hidalgo, Circuito Ex Hacienda la Concepción S/N Carretera Pachuca-Actopan, San Agustın Tlaxiaca. C. P. 42160 Pachuca, Hidalgo, México
4 Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politecnico Nacional, CP 11340, Ciudad de México, México

Date of Web Publication20-Apr-2018

Correspondence Address:
Dr. Fernando Calzada
Medical Research Unit in Pharmacology, UMAE Speciality Hospital-2° Floor CORCE, National Medical Center Siglo XXI, IMSS, Av. Cuauhtemoc 330, Col. Doctores, CP 06725, Mexico City
México
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pr.pr_90_17

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   Abstract 


Background: Schinus molle Linn. (Anacardiaceae) is a medicinal plant used by traditional healers in Mexican traditional medicine as antitumoral. Objective: This study was undertaken to obtain information that support the traditional use of the leaves from S. molle as antitumoral. Material and Methods: Antilymphoma properties of the ethanol extract of the leaves from S. molle (EELSm) and rutin were made on athymic CD-1 nu/nu and CD-1 mice inoculated with U-937 cell line (human leukemic monocyte lymphoma [HLML]), and for their antiproliferative effects on U-937 cell line by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Furthermore, the extract and rutin were tested for brine shrimp (BS) toxicity test. In addition, HPLC analysis was realized to known the content of rutin in the leaves from S. molle. Results: An EELSm and rutin exhibited important cytotoxic effects on U-937 cells line (IC50from 172.0 μg/mL and 9.6 μg/mL, respectively) and showed in vivo antitumoral properties on HLML in two murine models (EC50from 52.2 and 9.5 mg/kg to CD-1 nu/nu mice; EC50from 99.4 mg/kg and 6.8 mg/kg to CD-1 mice, respectively). In addition, both showed strong lethality on BS larvae (LC50≤ 22.2 μg/mL). The result of HPLC showed that rutin was the major constituent of EELSm. Conclusions: These test results support traditional medicinal use of S. molle as antitumoral and also suggest that both rutin and EELSm possess antitumor effect on HLML in murine models. Finally, rutin may play an important role in anticancer properties of S. molle.
Abbreviations used: EELSm: Ethanol extract of the leaves from S. molle, HLML: Human leukemic monocyte lymphoma, HPLC: High pressure liquid chromatography, BS: Brine shrimp, BSLT: BS lethality test, DMSO: Dimethyl sulfoxide, MTT: 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide.

Keywords: Anacardiaceae, antilymphoma properties, rutin, Schinus molle


How to cite this article:
Calzada F, Solares-Pascasio JI, Valdes M, Garcia-Hernandez N, Velázquez C, Ordoñez-Razo RM, Barbosa E. Antilymphoma potential of the ethanol extract and rutin obtained of the leaves from schinus molle linn. Phcog Res 2018;10:119-23

How to cite this URL:
Calzada F, Solares-Pascasio JI, Valdes M, Garcia-Hernandez N, Velázquez C, Ordoñez-Razo RM, Barbosa E. Antilymphoma potential of the ethanol extract and rutin obtained of the leaves from schinus molle linn. Phcog Res [serial online] 2018 [cited 2018 Oct 16];10:119-23. Available from: http://www.phcogres.com/text.asp?2018/10/2/119/230758

Summary

  • Antilymphoma properties of the ethanol extract of the leaves from S. molle (EELSm) and rutin were made on athymic CD-1 nu/nu and CD-1 mice inoculated with U-937 cell line (human leukemic monocyte lymphoma/HLML), and for their antiproliferative effects on U-937 cell line by MTT assay. Also, the extract and rutin were tested for brine shrimp toxicity test. In addition, HPLC analysis was realized to known the content of rutin in the leaves from S. molle. The results suggest that both rutin and EELSm possess antitumor effect on HLML in murine models.




   Introduction Top


Schinus molle Linn.(Anacardiaceae) is an evergreen tree with leaves imparipinnate and a winged rachis and 20–40 leaflets; leaflets linear-lanceolate, margins entire or dentate, 2–5 cm × 4–8 mm and found in many parts worldwide and it has different uses.[1] In Mexico, the plant grows in Guerrero, Morelos, Oaxaca, Puebla, and Cd de México. It has different vernacular names in different places such as “pirú, pirul, preconcuahuitl, copalquahuitl, yag lachi (zapoteco), and ntaka (popoloca).” In Mexico, the leaves are used by traditional healers to treat stomach ache, colic, heartburn, diarrhea, and inflammatory disorders such as rheumatism and asthma and also are used to treat urogenital infections, endometritis, and leukorrhea. In addition, the leaves are used to treat malaria and as antitumoral.[2]S. molle possess terpenoids, flavonoids, and other phenolic compounds.[2],[3],[4],[5],[6],[7] Biological studies carried out with alcoholic extracts of the leaves of S. molle show that this plant exerts several pharmacological effects such as antioxidant, trypanocidal, insecticidal, repellent, antidepressant, and cytotoxic.[6],[8],[9],[10],[11],[12] Furthermore, the acute and subchronic exposure caused an increase in locomotor activity in rodents.[9],[13],[14] In addition, it is important to point out that histopathological studies in mice showed that extract is safe.[14]

Flavonoids occur in a variety of medicinal plants and display a broad variety of biochemical and pharmacological activities.[15] In fact, flavonoids have been reported to have antimicrobial, antiallergenic, antithrombotic, anti-inflammatory, antiproliferative, antiprotozoal, and antihyperglycemic activities.[15],[16],[17],[18],[19] In the case of rutin is extensively found in many plants, including S. molle, Azadirachta indica, Tribulus terrestris, Olea europaea, Annona cherimola, Nelumbo nucifera, Croton lechleri, and Phoradendron serotinum.[5],[20],[21],[22],[23],[24] This flavonoid glycoside has a wide range of pharmacological activities such as anti-inflammatory, neuroprotective, antiulcerogenic, antimicrobial, antiviral, antiparasitic, antiurolithiatic, antihyperglycemic, antitumoral, and antioxidant.[5],[18],[20],[21],[22],[23],[24],[25],[26] Although rutin has shown antitumor properties in many murine models, its anticancer properties on human leukemic monocyte lymphoma remain to be researched. Therefore, the present work aimed to evaluate the antilymphoma potential of the ethanol extracts and rutin obtained from the leaves of S. molle using two induced lymphoma mice model systems; their cytotoxic activity on U-937 cells and lethality on brine shrimp (BS) larvae. Furthermore, HPLC analysis was realized to known the content of rutin in the leaves from S. molle.


   Material and Methods Top


Plant material

S. molle leaves were collected by Dr. Fernando Calzada in May 2010 in the garden at National Medical Center Siglo XXI, IMSS, Cd Mexico, Mexico. Plant material was identified by M. en C. Abigail Aguilar Contreras of the Herbarium IMSSM of the Instituto Mexicano del Seguro Social (IMSS) where the voucher specimen is conserved under reference number No: 15670. The fresh plant material (600 g) was ground and extracted with EtOH (4 L) by maceration for 1 week (twice) at room temperature. Then, the macerate was filtered and evaporated to dryness under reduced pressure at 40°C. The EtOH extract (67 g; 11.1% w/w yield) was stored at −20°C for further analysis.

Chemicals

Rutin, isoquercitrin, quercitrin, quercetin, methotrexate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), dimethyl sulfoxide (DMSO), L-glutamine, penicillin/streptomycin, RMPI 1640 medium, acetonitrile HPLC grade, acetic acid HPLC grade were purchased from Sigma-Aldrich, USA. EtOH and MeOH AR grade were purchased from JT Baker, Mexico. Fetal bovine serum was purchased from Gibco, Mexico.

Animals

Male CD-1 nu/nu nude and CD-1 mice (25–30 g) were obtained from the animal house of the IMSS. These studies were conducted with the approval of the Speciality Hospital Bio-Ethical Committee of the National Medical Center “Siglo XXI” from IMSS (Approval No: R-2014-3601-217, R-2012-3601-207, R-2014-785-015, and R 2014 3601 217). Investigation using experimental animals was conducted in accordance with the official Mexican norm NOM 0062-ZOO-1999 entitled technical specifications for the production, care, and use of laboratory animals.[27] To CD-1 mice, the animals were maintained with a 12 h light-dark cycle at 22°C ± 2°C at the controlled condition. They were fasted overnight, but tap water was available ad libitum until the start of the experiments. In the case of CD-1 nu/nu mice were housed under pathogen-free conditions with a 12 h light/12 h dark schedule and fed with an autoclaved diet and water ad libitum.

Cell culture

The human leukemic monocyte lymphoma U-937 cell line (ATCC: CRL 1593.2, Middlesex, UK) was used. Cell culture was tested for mycoplasma contamination using the MycoAlert mycoplasma detection kit (Lonza Walkersville, Inc.).

Culture conditions

Two million cells per milliliter were seeded in T75 cm2 flasks (Invitrogen, Paisley, UK) in RPMI 1640 medium (Invitrogen, Paisley, UK) supplemented with 10% (v/v) fetal bovine serum, 1.5 mM L-Glutamine, and 100 μg/ml penicillin/streptomycin (complete RPMI) and incubated at 37°C with 5% CO2.[28]

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

This assay was used to determine the effect of the extract of the leaves from S. molle (EELSm) and rutin on cellular viability of U-937 cells. The EELSm and rutin were dissolved in DMSO, and the final concentration of DMSO used was 0.1% (v/v) for each treatment. Cells were seeded into white 96-well plates (Fisher Scientific, Loughborough, UK) at a density of 5.0 × 103 cells per well in 100 μL and treated with rutin or EELSm at five serial concentrations between 2 and 500 μg/mL for 24 h in 5% CO2 at 37°C. Control cells treated with 0.1% DMSO served as the vehicle group. All treatments were performed in triplicate, in three independent experiments. After incubation for specified times, MTT reagent (10 μl, 5 mg dissolved in 1 mL of PBS) was added to each well and incubated for 4 h. The plates were centrifuged (10 min at 350 × g) and the purple formazan crystals of metabolized yellow tetrazolium salt by viable cells were dissolved in 150 μl of DMSO. Absorbance was quantified at 570 nm using the ELISA plate reader. Results were expressed as a percentage of viability, with 100% representing control cells treated with 0.1% DMSO alone. Then, the IC50 was determined. This was defined as the treatment concentration at which 50% reduction in cellular proliferation was observed. This was calculated from a linear regression equation; the regression coefficient, its level of significance, and correlation coefficient were calculated.[28]

Determination of the effect of ethanol extract of the leaves from Schinus molle and rutin on induced lymphoma mice model systems

Eleven groups (6 animals per group) of CD-1 nu/nu male nude mice or CD-1 mice (G1, G2, G3 [G3a, G3b, and G3c], G4 [G4a, G4b, and G4c], and G5 [G5a, G5b, and G5c]). For comparison, G1 was neither inoculated with cancer cells nor treated with EELSm or rutin. Groups G2 to G5 were injected intraperitoneally with 1 × 106 U-937 cells. As the group G2 was reserved as cancer control, it was not treated with EELSm or rutin but only with saline. Twenty-four hours after, the animals of G3, G4, and G5 were treated with EELSm (150, 100, and 50 mg/kg), rutin (15, 10, and 5 mg/kg), and methotrexate (1.5, 1.25, and 0.5 mg/kg) orally, respectively. The treatment was continued for 9 days. Animals were maintained under observation for 30 days recording the daily survival.[29] After completion of the experiment, all animals were sacrificed, and axillary and inguinal lymph nodes were removed and weighted. Antilymphoma activity of the samples was measured as the total of weight of lymph nodes and expressed in percent of inhibition. After the plot of percentage of inhibition against concentration was made, the best straight line was determined by regression analysis and the 50% effective inhibitory concentration (EC50) values were calculated. The regression equation and the coefficient of correlation were then derived from the curve.

Brine shrimp lethality test

The extract and pure compounds were routinely tested for BS lethality test (BSLT) using procedures and analysis described previously.[30],[31] Samples of the EELSm (20 mg) and rutin (2 mg) for BSLT were dissolved in 2 mL of EtOH from this solution transfer 500, 50, and 5 μL to vials of 10 mL to obtain the final concentrations of 1000, 100, and 10 μg/mL (or 10, 1, and 0.1 in the case of rutin and methotrexate), respectively. Then, the EtOH was evaporated and was obtained six replicates in each concentration. Methotrexate (2 mg) was used a standard anticancer test drug and a control test (vehicle, EtOH) was also prepared. After, 4 mL of the artificial seawater was added to each test tube and 10 BSs were introduced into each tube. Thus, there were a total of sixty shrimps per dilution. Then, the volume was adjusted with artificial seawater up to 5 mL per test tube. The number of surviving shrimps was counted and recorded after 24 h. LC50 values were obtained from the best-fit line plotted concentration versus percentage lethality. The regression equation and the coefficient of correlation were then derived from the curve. LC50 of <100 ppm was considered as active, whereas LC50 value of >1000 μg/mL is nontoxic.[30],[31]

High-pressure liquid chromatography analysis

High-pressure liquid chromatography (HPLC) was performed on a Waters 2795 instrument equipped with binary LC pump, a Water 996 Photodiode Array detector, and a Spherisorb S5 ODS2, analytical column (Waters, 250 mm × 4.6 mm × 5 μm); solvent A: acetonitrile, solvent B: 2% acetic acid as eluent gradient: (acetonitrile – 2% acetic acid [4: 96, v/v, 0 min; 12:88, v/v, 20 min; 20:80, v/v, 30 min; 50:50, v/v, 45 min; and 4: 96, v/v, 60 min; flow rate of 1.0 mL/min, λ 260 nm]). 20 mg of the EELSm was dissolved with MeOH (10 mL) and a sample of 20 μL was injected. Rutin was identified by comparison of its retention time (34.1 min; 72.1% of rutin/mg of extract) using commercial rutin as standard. The calibration curve of rutin was constructed by injecting, in triplicates, five concentrations of stock solutions (0.01, 0.03, 0.06, 0.09, and 0.12 mg/mL). The regression equation and the coefficient of correlation were then derived from the curve.

In addition, the flavonoids, quercitrin, isoquercitrin, and quercetin were identified but were not tested.

Statistical analysis

The plot of percentage of inhibition against concentration was made; the best straight line was determined by regression analysis, and the EC50 or IC50 or LC50 was calculated. All data were expressed as mean ± standard deviation of six measurements. Statistical analysis of data was performed using ANOVA one-way. A probability value of P < 0.05 was considered statistically significant. Differences between groups were analyzed by Bonferroni and Dunnett post hoc test. Analyses were performed using GraphPad Prism Version 5.03 (GraphPad Software Inc., La Jolla, CA, USA).


   Results and Discussion Top


Antilymphoma, cytotoxic, and toxic properties [Table 1] of the ethanol extract of leaves from S. molle and its major flavonoid, rutin, were studied on induced lymphoma mice model systems. According to the results, the EELSm showed strong antilymphoma activity on athymic CD-1 nu/nu mice inoculated with U-937 cell line with EC50 from 52.2 mg/kg on the growth of the solid tumors. In contrast, the antilymphoma effect on CD-1 mice was moderate with EC50 from 99.4 mg/kg. In the case of major flavonoid rutin, it showed strong antilymphoma properties in both mice with EC50 values of 9.5 mg/kg for nu/nu mice and 6.8 mg/kg for CD-1 mice. In CD-1 mice model, rutin was less active than methotrexate (EC50 0.86 mg/kg). In these contexts, it is important to point out that at rutin showed important antilymphoma activity on nu/nu mice and methotrexate caused 100% of mortality at doses tested.
Table 1: Antilymphoma, cytotoxic, and toxic properties of the ethanol extract of the leaves from Schinus molle and rutin

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The EELSm and rutin showed cytotoxicity on U-937 cells with IC50 values of 172.0 and 9.6 μg/mL, respectively. In relation with the BSLT, it was used to predict of cytotoxic activity.[30] In these sense, the extract and rutin showed strong lethality on BS larvae with LC50 values of 22.2 and 5.8 μg/mL, respectively. The cytotoxic activity on BSs of rutin and the EELSm was major than of methotrexate a standard anticancer drug, used as positive control. This significant lethality of the EELSm and rutin to BS is an indicative of their potential cytotoxic effects.[30],[31]

It is important to point out that, previously, of S. molle leaf and fruit essential oil, several terpenoids had been reported such as preisocalamendiol, shyobunol, lupenone, β-myrcene, limonene, α-pinene, β-phellandrene, and α-phellandrene. These compounds have been associated with its antioxidant, antimicrobial, tranquilizing, insecticidal, and anticancer properties.[3],[32],[33],[34],[35],[36],[37],[38] In this sense, the anticancer properties have been associated with the presence of the cyclic monoterpene, α-phellandrene. It monoterpene-induced DNA damage and affect DNA repair protein expression in WEHI-3 murine leukemia cells.[3],[32],[33],[34],[35],[36],[37] In the case of ethanolic and methanolic extracts from the aerial parts from S. molle, several flavonoids had been isolated such as 2''-O-α-L-rhamnopyranosyl-hyperin 6''-O-gallate, 2''-O-alpha-L-rhamnopyranosyl-hyperin, quercetin 3-O-β-D-neohesperidoside, quercetin 3-O-β-D-galacturonopyranoside, isoquercitrin, hyperin, isoquercitrin 6''-gallate, hyperin 6''-O-gallate, (+)-catechin, and rutin.[6],[11] These flavonoids have been associated with its antioxidant, antidepressant-like, and cytotoxic effects.[6],[11],[12],[22] In the case of rutin (3′,4′, 5, 7-tetrahydroxy-flavone-3-rutinoside), it is a glycosyl flavone that is widely consumed from plant-derived beverages and foods as traditional medicine worldwide. Till date, over 130 registered therapeutic medicinal preparations are containing rutin in their formulations. To date, it is reported that more than seventy plant species contain rutin. The major commercial sources of rutin include Ruta graveolens L. (Rutaceae), Sophora japonica L. (Fabaceae), Maranta leuconeura E. Morren (Marantaceae), Orchidantha maxillarioides (Ridl.) Schum (Lowiaceae), Strelitzia reginae Banks ex Aiton (Strelitziaceae), Eucalyptus spp. (Myrtaceae), Canna indica L. (Cannaceae), Canna edulis Ker Gawl. (Cannaceae), and Labisia pumila (Blume) Mez (Primulaceae); these species contain up to 1.5% of rutin. Rutin has a wide range of pharmacological activities such as anti-inflammatory, neuroprotective, antiulcerogenic, antimicrobial, antiviral, antiparasitic, antiurolithiatic, antihyperglycemic, antitumoral, and antioxidant.[39],[40],[41],[42],[43],[44] Antitumor effects have been demonstrated on nude mice bearing SW 480 tumors, skin carcinogenesis in Swiss albino mice, murine leukemia (WEHI-3), and colonic neoplasia.[3],[24],[25],[36] Furthermore, it has shown antitumor effects in models such as NK/Ly ascites and B16F10 cells.[24] To our knowledge, this is the first report of antilymphoma activity of the EELSm and rutin. Since that the EELSm and rutin tested in this study exhibited antilymphoma properties in two induced lymphoma mice model systems and cytotoxic activity against U-937 cells. The results presented here confirm the antitumor properties of the EELSm and rutin and extend these studies. Rutin may be useful in cancer prevention as chemopreventive agent that can inhibit initiation and also to act as blocking and suppressing agent.[24],[37] In addition, it can help attenuated effects caused by antitumor agents as cisplatin.[39]

On the other hand, the results obtained in BSLT to EELSm and rutin showed a good correlation with antilymphoma and cytotoxic properties using U-937 cells. EELSm showed strong lethality on BS larvae with LC50 value of 22.2 μg/mL [Table 1], it is in agreement with the previously reported to essential oils obtained from the leaves of S. molle (LC50 of 47.4 μg/mL).[40],[41] In these sense, BSLT may be a biological model for the preliminary selection of antilymphoma components from medicinal plants. Artemia salina has been suggested for use as a model for several preliminary evaluations of pharmacological activities such as insecticidal, antioxidant, cytotoxic, antimutagenic, antimicrobial, and antitumor activity.[30],[31],[40],[41]

Ethanol extract of S. molle leaves collected in Mexico was obtained by maceration and characterized by HPLC analysis [Figure 1] and [Table 2] allowing the identification of rutin as major active constituent. The ethanol extract was chromatographed and resolved by HPLC, using a Spherisorb S5 ODS2 analytical column. Rutin was identified by comparison with authentic sample (Sigma) available in our laboratory. Considering the major constituent, the literature reveals that the ethanol extract of the aerial parts from S. molle had high concentrations of rutin.[5] In agreement with this result, the HPLC analysis revealed that rutin is the major constituent of the EELSm. These results support traditional medicinal use of S. molle as antitumoral [2] and also suggest that rutin may play an important role in anticancer properties of S. molle. Additional studies to evaluate antilymphoma properties of flavonoids such as quercitrin, isoquercitrin, quercetin, and other compounds will be carried out to explain the antilymphoma effects of the EELSm. Furthermore, of the EELSm and rutin will be studied in cellular proliferation, viability, apoptosis, proteomic, and genomic approach to confirm their potential uses as therapeutic agents.
Figure 1: Chromatographic profile of ethanol extract of the leaves from Schinus molle

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Table 2: Flavonoids by high-pressure liquid chromatography analysis of ethanol extract of the leaves from Schinus molle

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Acknowledgment

We are grateful to the scholarship of IMSS Foundation A. C. given to Dr. Normand Garcia Hernandez, and IMSS for contract/grant sponsor FIS/IMSS/PROT/MD11/1005, FIS/IMSS/PROT/G13/1213, FIS/IMSS/PROT/G15/1470, and FIS/IMSS/PROT/G16/1576. We are grateful to the research scholarship of IMSS Foundation A. C. given to Dr. Normand Garcia Hernandez.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Orwa C, Mutua A, Kindt R, Jamnadass R, Anthony S. Agroforestree Database: A Tree Reference and Selection Guide Version 4.0 Available from: http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp 2009. [Last accessed on 2016 Dec 8].  Back to cited text no. 1
    
2.
Biblioteca Digital de la Medicina Tradicional Mexicana. Available from: http://www.medicinatradicionalmexicana.unam.mx 2009. [Last accessed on 2016 Dec 8].  Back to cited text no. 2
    
3.
Batista LC, Cid YP, De Almeida AP, Prudêncio ER, Riger CJ, De Souza MA, et al. In vitro efficacy of essential oils and extracts of Schinus molle L. Against Ctenocephalides felis felis. Parasitology 2016;143:627-38.  Back to cited text no. 3
    
4.
Taylor A, Oyedeji OO, Aremu O, Oyemitan I, Gwebu ET, Oyedeji AO, et al. Assessment of the analgesic, anti-inflammatory and sedative effects of the dichloromethanol extract of Schinus molle . Eur Rev Med Pharmacol Sci 2016;20:372-80.  Back to cited text no. 4
    
5.
Machado DG, Bettio LE, Cunha MP, Santos AR, Pizzolatti MG, Brighente IM, et al. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. In mice: Evidence for the involvement of the serotonergic and noradrenergic systems. Eur J Pharmacol 2008;587:163-8.  Back to cited text no. 5
    
6.
Marzouk MS, Moharram FA, Haggag EG, Ibrahim MT, Badary OA. Antioxidant flavonol glycosides from Schinus molle . Phytother Res 2006;20:200-5.  Back to cited text no. 6
    
7.
Yueqin Z, Recio MC, Máñez S, Giner RM, Cerdá-Nicolás M, Ríos JL, et al. Isolation of two triterpenoids and a biflavanone with anti-inflammatory activity from Schinus molle fruits. Planta Med 2003;69:893-8.  Back to cited text no. 7
    
8.
Molina-Garza ZJ, Bazaldúa-Rodríguez AF, Quintanilla-Licea R, Galaviz-Silva L. Anti-Trypanosoma cruzi activity of 10 medicinal plants used in Northeast Mexico. Acta Trop 2014;136:14-8.  Back to cited text no. 8
    
9.
Ferrero A, Minetti A, Bras C, Zanetti N. Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats. J Ethnopharmacol 2007;113:441-7.  Back to cited text no. 9
    
10.
Ferrero AA, Chopa CS, González JO, Alzogaray RA. Repellence and toxicity of Schinus molle extracts on Blattella germanica . Fitoterapia 2007;78:311-4.  Back to cited text no. 10
    
11.
Machado DG, Bettio LE, Cunha MP, Santos AR, Pizzolatti MG, Brighente IM, et al. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. In mice: Evidence for the involvement of the serotonergic and noradrenergic systems. Eur J Pharmacol 2008;587:163-8.  Back to cited text no. 11
    
12.
Ruffa MJ, Ferraro G, Wagner ML, Calcagno ML, Campos RH, Cavallaro L, et al. Cytotoxic effect of argentine medicinal plant extracts on human hepatocellular carcinoma cell line. J Ethnopharmacol 2002;79:335-9.  Back to cited text no. 12
    
13.
Bras C, Domínguez S, Codón S, Minetti A, Ferrero A. Consequences of subchronic exposure to ethanolic extract from fruits and leaves of Schinus molle var. Areira L. In mice. J Ethnopharmacol 2010;132:321-7.  Back to cited text no. 13
    
14.
Bras C, Gumilar F, Gandini N, Minetti A, Ferrero A. Evaluation of the acute dermal exposure of the ethanolic and hexanic extracts from leaves of Schinus molle var. Areira L. In rats. J Ethnopharmacol 2011;137:1450-6.  Back to cited text no. 14
    
15.
Capasso A, Piacente S, Cumanda J, De Tommasi N, Ragucci M, Pizza C. Flavonol glycosides from Croton menthodorus reduce in vitro morphine withdrawal. Pharm Biol 1998;36:310-4.  Back to cited text no. 15
    
16.
Arima H, Ashida H, Danno G. Rutin-enhanced antibacterial activities of flavonoids against Bacillus cereus and Salmonella enteritidis . Biosci Biotechnol Biochem 2002;66:1009-14.  Back to cited text no. 16
    
17.
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA, et al. Flavonoids: A review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001;74:418-25.  Back to cited text no. 17
    
18.
Calzada F, Meckes M, Cedillo-Rivera R. Antiamoebic and antigiardial activity of plant flavonoids. Planta Med 1999;65:78-80.  Back to cited text no. 18
    
19.
Escandón-Rivera S, González-Andrade M, Bye R, Linares E, Navarrete A, Mata R, et al. A-glucosidase inhibitors from Brickellia cavanillesii . J Nat Prod 2012;75:968-74.  Back to cited text no. 19
    
20.
Ahmad A, Javed MR, Rao AQ, Husnain T. Designing and screening of universal drug from neem (Azadirachta indica ) and standard drug chemicals against influenza virus nucleoprotein. BMC Complement Altern Med 2016;16:519.  Back to cited text no. 20
    
21.
Sharma I, Khan W, Ahmad S. In vitro and ex vivo approach for anti-urolithiatic potential of bioactive fractions of gokhru with simultaneous HPLC analysis of six major metabolites and their exploration in rat plasma. Pharm Biol 2017;55:701-11.  Back to cited text no. 21
    
22.
Makowska-Was J, Galanty A, Gdula-Argasinska J, Tyszka-Czochara M, Szewczyk A, Nunes R, et al . Identification of predominat phytochemical compouds and cytotoxic activity of wild olive leaves (Olea europea L. ssp.sylvestris) harvested in South Portugal. Chem Biodivers 2017;14. doi: 10.1002/cbdv.201600331.  Back to cited text no. 22
    
23.
Calzada F, Solares-Pascasio JI, Ordoñez-Razo RM, Velazquez C, Barbosa E, García-Hernández N, et al. Antihyperglycemic activity of the leaves from Annona cherimola miller and rutin on alloxan-induced diabetic rats. Pharmacognosy Res 2017;9:1-6.  Back to cited text no. 23
    
24.
Alonso-Castro AJ, Domínguez F, García-Carrancá A. Rutin exerts antitumor effects on nude mice bearing SW480 tumor. Arch Med Res 2013;44:346-51.  Back to cited text no. 24
    
25.
Savita D. Anticancer effect of rutin isolated from the methanolic extract of Triticum aestivum Straw in mice. Med Sci 2014;2:153-60.  Back to cited text no. 25
    
26.
Zvikas V, Pukeleviviene V, Ivanauskas L, Romanovskaja D, Jakstas V. Evaluation of phenolic antioxidant content in organically and conventionally grown buckwheat herb crop and its regrowth. J Sci Food Agric 2017;97:3278-83. doi: 10.1002/jsfa.8176.  Back to cited text no. 26
    
27.
Norma Oficial Mexicana NOM-062-ZOO-1999. Especificaciones Técnicas Para la Producción, Cuidado y Uso de Los Animales de Laboratorio. México City, México: Diario Oficial de la Federación; 2001.  Back to cited text no. 27
    
28.
Zahedpanah M, Shaiegan M, Ghaffari SH, Nikbakht M, Nikugoftar M, Mohammadi S, et al. Parthenolide induces apoptosis in committed progenitor AML cell line U937 via reduction in osteopontin. Rep Biochem Mol Biol 2016;4:82-8.  Back to cited text no. 28
    
29.
Christina AJ, Joseph DG, Packialakshmi M, Kothai R, Robert SJ, Chidambaranathan N, et al. Anticarcinogenic activity of Withania somnifera dunal against dalton's ascitic lymphoma. J Ethnopharmacol 2004;93:359-61.  Back to cited text no. 29
    
30.
Meyer BN, Ferrigni NR, Putnam JE, Jacobsen LB, Nichols DE, McLaughlin JL, et al. Brine shrimp: A convenient general bioassay for active plant constituents. Planta Med 1982;45:31-4.  Back to cited text no. 30
    
31.
Asaduzzaman M, Sohel R, Hasan R, Hossain M, Das N. Cytotoxic (brine shrimp lethality bioassay) and antioxidant investigation of Barringtonia acutangula (L.). Int Pharm Sci Res 2015;6:1179-85.  Back to cited text no. 31
    
32.
Lin JJ, Yu CC, Lu KW, Chang SJ, Yu FS, Liao CL, et al. A-phellandrene alters expression of genes associated with DNA damage, cell cycle, and apoptosis in Murine leukemia WEHI-3 cells. Anticancer Res 2014;34:4161-80.  Back to cited text no. 32
    
33.
Lin JJ, Wu CC, Hsu SC, Weng SW, Ma YS, Huang YP, et al. Alpha-phellandrene-induced DNA damage and affect DNA repair protein expression in WEHI-3 Murine leukemia cells in vitro . Environ Toxicol 2015;30:1322-30.  Back to cited text no. 33
    
34.
Bendaoud H, Romdhane M, Souchard JP, Cazaux S, Bouajila J. Chemical composition and anticancer and antioxidant activities of schinus molle L. And Schinus terebinthifolius raddi berries essential oils. J Food Sci 2010;75:C466-72.  Back to cited text no. 34
    
35.
Díaz C, Quesada S, Brenes O, Aguilar G, Cicció JF. Chemical composition of Schinus molle essential oil and its cytotoxic activity on tumour cell lines. Nat Prod Res 2008;22:1521-34.  Back to cited text no. 35
    
36.
St-Gelais A, Mathieu M, Levasseur V, Ovando JF, Escamilla R, Marceau H, et al. Preisocalamendiol, shyobunol and related oxygenated sesquiterpenes from Bolivian Schinus molle essential oil. Nat Prod Commun 2016;11:547-50.  Back to cited text no. 36
    
37.
Kasmi A, Hammami M, Raoelison EG, Abderrabba M, Bouajila J, Ducamp C. Chemical composition and behavioral effects of five plant essential oils of the green pea aphid Acyrthosiphon pisum (harris) (homoptera: aphididae). Chem Biodivers 2017;14. doi: 10.1002/cbdv.201600464.  Back to cited text no. 37
    
38.
Martins Mdo R, Arantes S, Candeias F, Tinoco MT, Cruz-Morais J. Antioxidant, antimicrobial and toxicological properties of Schinus molle L. Essential oils. J Ethnopharmacol 2014;151:485-92.  Back to cited text no. 38
    
39.
Deschner EE, Ruperto J, Wong G, Newmark HL. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis 1991;12:1193-6.  Back to cited text no. 39
    
40.
Lin JP, Yang JS, Lu CC, Chiang JH, Wu CL, Lin JJ, et al. Rutin inhibits the proliferation of Murine leukemia WEHI-3 cells in vivo and promotes immune response in vivo . Leuk Res 2009;33:823-8.  Back to cited text no. 40
    
41.
Pensak J, Hiroyuki A, Warintorn R. Anti-cancer activity of rutin encapsulated in low methoxyl pectin beads. Int J Pharm Sci 2014;6:199-202.  Back to cited text no. 41
    
42.
Vyas D, Laput G, Vyas AK. Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis. Onco Targets Ther 2014;7:1015-23.  Back to cited text no. 42
    
43.
Déciga-Campos M, Rivero-Cruz I, Arriaga-Alba M, Castañeda-Corral G, Angeles-López GE, Navarrete A, et al. Acute toxicity and mutagenic activity of Mexican plants used in traditional medicine. J Ethnopharmacol 2007;110:334-42.  Back to cited text no. 43
    
44.
Chua LS. A review on plant-based rutin extraction methods and its pharmacological activities. J Ethnopharmacol 2013;150:805-17.  Back to cited text no. 44
    


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