Vol. 4, No. 7, p. 53-66 - Jun. 30, 2017
Anticarcinogenic potential of ethanol extract of Indigofera cordifolia Roth. (Fabales: Fabaceae) on diethylnitrosamine induced hepatocarcinogenesis in rats
Raju Senthil Kumar , Gopal Murugananthan and Balasubramanian Rajkapoor
Abstract
Indigofera cordifolia Roth. (Fabales: Fabaceae) has been widely used in Indian system of medicine to treat various disorders. Earlier studies showed that I. cordifolia (EIC) possess antioxidant, free radical scavenging and antitumour activities. The present investigation was designed to evaluate the anticarcinogenic potential of EIC against diethylnitrosamine (DEN) induced hepatocellular carcinoma in male Wistar rats. Hepatocarcinogenesis was induced by a single intraperitoneal administration of DEN (200 mg/kg) and the carcinogenic effect was promoted by phenobarbital given through drinking water for 16 successive weeks. EIC at the dose of 200 and 400 mg/kg/day were administered orally for the entire study period. After the end of experimental period, changes in body weight, the weight of liver, relative liver weight, lipid peroxidation, antioxidant, serum hepatic parameters, tumour markers, DNA, RNA and protein content were analysed. Treatment with EIC significantly increased the body weight (P < 0.01 0.001), reduced the liver weight and relative liver weight (P < 0.01-0.001), restored the altered serum hepatic parameters (P < 0.001), down-regulated the serum tumour markers such as alpha-fetoprotein and carcinoembryonic antigen (P < 0.001) when compared to DEN group. EIC treatment restored the antioxidant enzymes and significantly reduced the lipid peroxidation in DEN-treated animals (P < 0.001). EIC treatment also significantly reduced the elevated levels of nucleic acid levels and restored the protein content in liver tissues (P < 0.001). We investigated the anticarcinogenic potential of EIC against DEN-induced HCC in rats. Chemoprotective effect of the extract might be related with antioxidant, free radical scavenging and reduction of lipid peroxidation. The results suggested that EIC would be a potent anticarcinogenic agent inhibiting DEN-induced hepatic carcinoma.
Keywords
Indigofera cordifolia; Diethylnitrosamine; Serum hepatic parameters; Carcinoembryonic antigen; Alpha-fetoprotein; Chemoprevention.
DOI
10.21472/bjbs.040707
Full text
PDF
References
Borbath, I.; Leclercq, I. A.; Sempoux, C.; Abarca-Quinones, J.; Desaeger, C.; Horsmans, Y. Efficacy of lanreotide in preventing the
occurrence of chemically induced hepatocellular carcinoma in rats. Chem. Biol. Interact., v. 183, p. 238-248, 2010.
Burton, K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic
acid. Biochem. J., v. 62, p. 315-323, 1956.
Chen, B.; Ning, M.; Yang, G. Effect of paeonol on antioxidant and immune regulatory activity in hepatocellular carcinoma rats.
Molecules, v. 17, p. 4672-4683, 2012.
Devasagayam, T. P.; Tarachand, U. Decreased lipid peroxidation in the rat kidney during gestation. Biochem. Biophys. Res. Commun.,
v. 145, p. 134-138, 1987.
El Miniawy, H. M. F.; Ahmed, K. A.; Tony, M. A.; Mansour, S. A.; Khattab, M. M. S. Camel milk inhibits murine hepatic carcinogenesis,
initiated by diethylnitrosamine and promoted by phenobarbitone. Int. J. Vet. Sci. Med., v. 2, p. 136-141, 2014.
El-Serag, H. B.; Rudolph, K. L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, v. 132,
p. 2557-2576, 2007.
Fotsis, T.; Pepper, M. S.; Aktas, E.; Breit, S.; Rasku, S.; Adlercreutz, H.; Wahala, K.; Montesano, R.; Schweigerer, L. Flavonoids,
dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res., v. 57, p. 2916-2921, 1997.
Ghosh, D.; Choudhury, S. T.; Ghosh, S.; Mandal, A. K.; Sarkar, S.; Ghosh, A.; Saha, K. D.; Das, N. Nanocapsulated curcumin: oral
chemopreventive formulation against diethylnitrosamine induced hepatocellular carcinoma in rat. Chem. Biol. Interact., v. 195,
p. 206-214, 2012.
Glory, D. M.; Thiruvengadam, D. Potential chemopreventive role chrysin against n-nitrosdiethylamine induced hepatocellular carcinoma
in rats. Biomed. Prev. Nutr., v. 2, p. 106-112, 2012.
Habig, W. H.; Pabst, M. J.; Jakoby, W. B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J. Biol.
Chem., v. 249, p. 7130-7139, 1974.
Jagadeesh, M. C.; Sreepriya, M.; Bali, G.; Manjulakumari, D. Biochemical studies on the effect of curcumin and embelin during
N-nitrosodiethylamine/phenobarbital induced-hepatocarcinogenesis in wistar rats. Afr. J. Biotechnol., v. 8, p. 4618-4622, 2009.
Jagan, S.; Ramakrishnan, G.; Anandakumar, P.; Kamaraj, S.; Devaki, T. Antiproliferative potential of gallic acid against
diethylnitrosamine-induced rat hepatocellular carcinoma. Mol. Cell. Biochem., v. 319, p. 51 59, 2008.
Jemal, A.; Bray, F.; Center, M. M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA. Cancer J. Clin.,
v. 61, p. 69-90, 2011.
Khatri, D. K.; Juvekar, P.; Juvekar, A. R. Phytochemical investigation and in vitro antioxidant activities Indigofera
cordifolia seed extracts. Intl. J. Pharm. Pharm. Sci., v. 5, p. 71 75, 2013.
Kintzios, S. E. Terrestrial plant-derived anticancer agents and plant species used in anticancer research. Crit. Rev. Plant
Sci., v. 25, p. 79-113, 2006.
Kumar, V.; Kato, N.; Urabe, Y.; Takahashi, A.; Muroyama, R.; Hosono, N.; Otsuka, M.; Tateishi, R.; Omata, M.; Nakagawa, H.;
Koike, K.; Kamatani, N.; Kubo, M.; Nakamura, Y.; Matsuda, K. Genome-wide association study identifies a susceptibility locus
for HCV-induced hepatocellular carcinoma. Nat. Genet., p. 43, p. 455-458, 2011.
Lowry, O. H.; Rosebrough, N. J.; Farr, A. L.; Randall, R. Protein measurement with the Folin phenol reagent. J. Biol. Chem.,
v. 193, p. 265-275, 1951.
Man, S.; Gao, W.; Zhang, Y.; Huang, L.; Liu, C. Chemical study and medical application of saponins as anti-cancer agents.
Fitoterapia, v. 81, p. 703-714, 2010.
Mandal, A.; Das, S.; Mitra, M.; Chakrabarti, R. N.; Chatterjee, M.; Das, N. Vesicular flavonoid in combating diethylnitrosamine
induced hepatocarcinoma in rat model. J. Exp. Ther. Oncol., v. 7, p. 123-133, 2008.
Marklund, S.; Marklund, G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay
for superoxide dismutase. Eur. J. Biochem., v. 47, p. 469-474, 1974.
Pracheta, P.; Sharma, V.; Singh, L.; Paliwal, R.; Sharma, S.; Yadav, S.; Sharma, S. Chemopreventive effect of hydroethanolic
extract of Euphorbia neriifolia leaves against DENA-induced renal carcinogenesis in mice. Asian Pac. J. Cancer
Prev., v. 12, p. 677-683, 2011.
Rajkapoor, B.; Murugesh, N.; Chodon, D.; Sakthisekaran, D. Chemoprevention of N-nitrosodiethylamine induced phenobarbitol promoted
liver tumors in rat by extract of Indigofera aspalathoides. Biol. Pharm. Bull., v. 28, p. 364-366, 2005.
Ramakrishnan, G.; Augustine, T. A.; Jagan, S.; Vinodhkumar, R.; Devaki, T. Effect of silymarin on N-nitrosodiethylamine induced
hepatocarcinogenesis in rats. Exp. Oncol., v. 29, p. 39-44, 2007.
Rotruck, J.; Pope, A. L.; Ganther, H. E.; Swanson, A. B.; Hafeman, D. G.; Hoekstra, W. G. Selenium: biochemical role as a component
of glutathione peroxidase. Science, v. 179, p. 588-590, 1973.
Roy, S. R.; Gadad, P. C. Effect of β-asarone on diethylnitrosamine-induced hepatocellular carcinoma in rats. Indian J. Health
Sci., v. 9, p. 82-88, 2016.
Sarin, R.; Upman, S. Extraction of sterols from in vivo and in vitro tissue cultures of Indigofera cordifolia and
I. linnaei. Intl. J. Adv. Pharm. Res., v. 2, p.122-126, 2011.
Schinder, W. C. Determination of nucleic acid in tissue by pentose analysis. In: Colowick, S. P.; Kaplon, N. O. (Eds.). Methods in
enzymology. New York: Academic Press, 1957. v. 3. p. 680-684.
Shih, W. L.; Yu, M. W.; Chen, P. J.; Wu, T. W.; Lin, C. L.; Liu, C. J.; Lin, S. M.; Tai, D. I.; Lee, S. D.; Liaw, Y. F. Evidence for
association with hepatocellular carcinoma at the PAPSS1 locus on chromosome 4q25 in a family-based study. Eur. J. Hum.
Genet., v. 17, p. 1250-1259, 2009.
Singh, B. N.; Singh, B. R.; Sharma, B. K.; Singh, H. B. Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcino-genesis
by polyphenolics from Acacia nilotica bark. Chem. Biol. Interact., v. 181, p. 20-28, 2009.
Sinha, A. K. Colorimetric assay of catalase. Anal. Biochem., v. 47, p. 389-394, 1972.
Sivaramakrishnan, V.; Shilpa, P. N.; Praveen Kumar, V. R.; Niranjali Devaraj, S. Attenuation of N-nitrosodiethylamine-induced
hepato-cellular carcinogenesis by a novel flavonol-Morin. Chem. Biol. Interact., v. 171, p. 79-88, 2008.
Taha, M. M.; Abdul, A. B.; Abdullah, R.; Ibrahim, T. A.; Abdelwahab, S. I.; Mohan, S. Potential chemoprevention of
diethylnitrosa-mine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the
subtropical ginger (Zingiber zerumbet). Chem. Biol. Interact., v. 186, p. 295-305, 2010. https://dx.doi.org/10.1016/j.cbi.2010.04.029
Tambe, A. D.; Chaudhari, T. B.; Chaudhari, R. S. Wound healing activity of Indigofera cordifolia aerial part extracts
in rats. J. Pharm. Res., v. 3, p. 1417-1419, 2010.
Thangavel, D.; Govindasamy, J.; Kumar, R. S. Anticancer and antioxidant activities of ethanol extract of Indigofera cordifolia
Roth. on Ehrlich Ascites Carcinoma tumour bearing mice. Intl. J. Phytother., v. 5, p. 111-117, 2015.
Thangavel, D.; Govindasamy, J.; Kumar, R. S. In vitro antioxidant and anticancer activities of various extracts of
Indigofera cordifolia Roth. J. Pharm. Biol., v. 4, p. 85-93, 2014.
Weber, G.; Shen, F.; Prajda, N.; Yeh, Y. A.; Yang, H.; Herenyiova, M.; Look, K. Y. Increased signal transduction activity and
down-regulation in human cancer cells. Anticancer Res., v. 16, p. 271-3282, 1996.
Yadav, A. S.; Bhatnagar, D. Chemo-preventive effect of Star anise in N-nitrosodiethylamine initiated and phenobarbital promoted
hepatocarcinogenesis. Chem. Biol. Interact., v. 169, p. 207-214, 2007.