Effect of Rumex Abyssinicus on preneoplastic lesions in dimethylhydrazine induced colon carcinogenesis in rats

BMC Complementary and Alternative Medicine

Eyasu Makonnen²  Getnet Yimer²  Biniyam Girma¹ 

[1] Pharmacology and Toxicology Course Team, School of Pharmacy, College of Health Sciences, Jimma University, Jimma, Ethiopia;Department of Pharmacology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia

关键词: Virtual screening;    Docking;    Aberrant crypt foci;    Rumex abyssinicus;    Colon cancer;    Chemoprevention;   

Others  :  1233246
DOI  :  10.1186/s12906-015-0883-1

 received in 2015-05-08, accepted in 2015-09-28,  发布年份 2015

【 摘 要 】

Background

Cancer as a multistage process can be reversed or blocked by using chemopreventive agents. Colon cancer chemoprevention has been widely investigated using cyclooxygenase inhibitors and many other chemicals of synthetic or natural origin. This particular study was carried out to assess the colon cancer chemopreventive effect of hydro-methanol extract of Rumex abyssinicus rhizome on rats.

Method

Colon cancer chemopreventive potential of hydro-methanol extract of Rumex abyssinicus rhizome was determined based on the number and multiplicity of aberrant crypt foci (ACF). Fifteen DMH (1, 2-dimethylhydrazine) treated and five untreated Wistar female rats were used. DMH was administered subcutaneously 30 mg/kg, after its pH was adjusted to 6.5–7. Treatment groups started receiving extract after six weeks of weekly DMH injections. The rats were divided in to four groups: Group 1 received only oral normal saline, Group 2 received DMH and normal saline, Group 3 and 4 received DMH plus 250 mg/kg and 500 mg/kg extract, respectively. Specific phytoconstituents of the plant, which were reviewed from original articles, were virtually evaluated for cyclooxygenase-2 (COX-2) inhibition. The binding energies and interactions of the phytochemicals from Rumex abyssinicus against COX-2 were determined by Autodock4.2.

Results

There was a statistically significant reduction (p-value < 0.05) in the number of aberrant crypt (AC) and aberrant crypt foci (ACF) at both administered doses. However, significant association (p-value > 0.05) was not observed in reducing crypt multiplicity. The docking process resulted in estimated binding energies [−6.83 kcal/mol to −7.9 kcal/mol] which are closer to the positive controls or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) [−4.55 kcal/mol to −10.84 kcal/mol]. The phytochemical-COX-2 interaction indicated the involvement of key amino acid residues in inhibition of cyclooxygenase like ARG120, TYR355, TYR385, SER530 and GLY526.

Conclusions

Rumex abyssinicus had demonstrated a chemopreventive potential at post-initiation stage. As the virtual screening data suggested, COX-2 inhibition by the anthraquinones in the extract could be one mechanism for the observed chemopreventive effect.

【 授权许可】

   
2015 Girma et al.

【 图 表 】

Fig. 1.

【 参考文献 】

• [1]Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009; 22(4):191-7.
• [2]Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007; 255:170-81.
• [3]Repetto L, Granetto C, Venturino A, Aapro M. Screening and chemoprevention. Crit Revin Oncol Hematol. 1998; 27:111-5.
• [4]Rao CV, Reddy BS. NSAIDs and chemoprevention. Curr Cancer Drug Tar. 2004; 4:29-42.
• [5]Gravitz L. First line of defense. Nature. 2011; 471:5-7.
• [6]Wargovich MJ. Colon cancer chemoprevention with ginseng and other botanicals. J Korean Med Sci. 2001; 16Supp:S81-6.
• [7]Raju NJ, Yesuf EA. Evaluation of anthelmentic activities of Rumex abyssinicus JACQ and Rumex nervosus VAHL (Polygonacea). International Journal of Pharmaceutical Sciences Review and Research. 2010; 5(2):55-7.
• [8]Fatima N, Zia M, Rehman R, Rizvi ZF, Ahmad S, Mirza B et al.. Biological activities of Rumex dentatus L.: evaluation of methanol extracts. Afr J Biotechnol. 2009; 8(24):6945-51.
• [9]Rao KNV, Sunitha C, Banji D, Sandhya S, Mahesh V. A study on the nutraceuticals from the genus Rumex. Hygeia Hygeia JD Med. 2011; 3(1):76-88.
• [10]Fassil Y, Bezabeh A, Abegaz B, Botta B, Monache GD, Monache FD. Anthracene derivatives from Rumex abyssinicus. J Nat Prod. 1985; 48(1):148.
• [11]Zinaye B, Fiseha A. Phytochemical investigation on the root of Rumex abyssinicus (MAKMAKO). AAU electronic library 2008.
• [12]Munavu RM, Mudamba LO, Ogur JA. Isolation and characterization of the major anthraquinone pigments from Rumex abysinica. Planta Med. 1984; 50(1):111.
• [13]Grover J, Kumar V, Singh V, Bairwa K, Sobhia ME, Jachak SM. Synthesis, biological evaluation, molecular docking and theoretical evaluation of ADMET properties of nepodin and chrysophanol derivatives as potential Cyclooxgenase (COX-1, COX-2) inhibitors. Eur J Med Chem. 2014; 80:47-56.
• [14]Gautam R, Jachak Sm. Anti-inflammatory and cyclooxygenase (COX)-2 inhibitory activities of Rumex nepalensis Spreng. Planta Med. 2008; 74: doi:. 10. 1055/s-0028-1084318 webcite
• [15]Getie M, Gebre-Mariam T, Rietz R, Hohne C, Huschaka C, Schmditke M et al.. Evaluation of the anti-microbial and anti-inflammatory activities of medicinal plants Dodonea viscose, Rumex nervosus, and Rumex abyssinicus. Fitoterapia. 2003; 74:139-43.
• [16]Tamokou JD, Chouna JR, Fischer-Fodor E, Chereches G, Barbos O, Damian G et al.. Anticancer and antimicrobial activities of some antioxidant-rich Cameroonian medicinal plants. PLoS ONE. 2013; 8(2): Article ID e55880
• [17]Worku N, Mossie A, Stich A, Daugschies A, Trettner S, Hemdan NYA, et al. Evaluation of the in vitro efficacy of Artemisia annua, Rumex abyssinicus, and Catha edulis Forsk extracts in cancer and Trypanosoma brucei cells. ISRN Biochem. 2013; Article ID 910308, 10 pages. doi:10.1155/2013/910308.
• [18]Wegiera M, Smolarz HD, Bogucka-Kocka A. Rumex L. species induce apoptosis in 1301, EOL-1 and H-9 cell lines. Acta Poloniae Pharmaceutica. 2012; 69(3):487-99.
• [19]Daniel H, Lutfun N, Brhanachari V, Gadria M, Saif EN, Satyajitd DS. Biodiversity of Rumex obtusifolius (poygonacea). Arch Biol sci. 2010; 62(2):387-92.
• [20]Tamimi RM, Lagiou P, Adami HO, Trichopoulos D. Prospects for chemoprevention of cancer. J Intern Med. 2002; 251:286-300.
• [21]Mekonnen T, Urga K, Engidawork E. Evaluation of the diuretic and analgesic activities of the rhizomes of Rumex abyssinicus Jacq in mice. J Ethnopharmacol. 2010; 127:433-9.
• [22]Moreira APB, Sabarense CM, Dias CMGC, Lunz W, Natali AJ, Glória MB et al.. Fish oil ingestion reduces the number of aberrant crypt foci and adenoma in 1,2-dimethylhydrazine-induced colon cancer in rats. Braz J Med Biol Res. 2009; 42:1167-72.
• [23]Tanwar L, Vaish V, Sanyal SN. Chemoprevention of 1,2-dimethylhydrazine-induced colon carcinogenesis by a non-steroidal anti-inflammatory drug, etoricoxib, in rats: inhibition of nuclear factor kappa-B. Asian Pac J Cancer Prev. 2009; 10:1141-6.
• [24]Bird RP. Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: Preliminary findings. Cancer Lett. 1987; 37:147-51.
• [25]Nursamsiar, Musfiroh I, Muchtaridi, Ibrahim S, Tjahjono DH. Interaction study of curculigoside A and its aglycone as cyclooxygenase inhibitors using computational modelling. Int J Pharm Pharm Sci. 2013; 5(suppl 4):702-5.
• [26]Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004; 1(4):337-41.
• [27]Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY et al.. Structural basis for selective inhibition of cyclooxygenase 2 by antiinflammatory agents. Nature. 1996; 384:644-8.
• [28]Warner T, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci USA. 1999; 96:7563-8.
• [29]Bird RP, Good CK. The significance of aberrant crypt foci in understanding the pathogenesis of colon cancer. Toxicol Lett. 2000; 112–113:395-402.
• [30]Ehrlich VA, Huber W, Grasl-Kraupp B, Nersesyan A, Knasmueller S. Use of preneoplastic lesions in colon and liver in experimental oncology. Radiol Oncol. 2004; 38:205-16.
• [31]Smith TK, Lund EK, Johnson IT. Inhibition of dimethylhydrazine-induced aberrant crypt foci and induction of apoptosis in rat colon following oral administration of the glucosinolatesinigrin. Carcinogenesis. 1998; 19:267-73.
• [32]Sengottuvelan M, Viswanathan P, Nalini N. Chemopreventive effect of trans-resveratrol - a phytoalexin against colonic aberrant crypt foci and cell proliferation in 1,2-dimethylhydrazine induced colon carcinogenesis. Carcinogenesis. 2006; 27:1038-46.
• [33]Wargovich MJ, Jimenez A, McKee K, Steele VE, Velasco M, Woods J et al.. Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis. 2000; 21:1149-55.
• [34]Dorai T, Aggarwal BB. Role of chemopreventive agents in cancer therapy. Cancer Lett. 2004; 215:129-40.
• [35]Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS et al.. A novel mechanism of Cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003; 278(46):45763-9.
• [36]Landa P, Kutil Z, Temml V, Vuorinen A, Malik J, Dvorakova M et al.. Redox and non-redox mechanism of in vitro Cyclooxygenase inhibition by natural quinones. Planta Med. 2012; 78:326-33.
• [37]Robinson S, Chapman K, Hudson S, Sparrow S, Spencer-Briggs D, Danks A et al.. Guidance on dose level selection for regulatory general toxicology studies for pharmaceuticals. NC3Rs/LASA, London; 2009.