Toxicology International (Formerly Indian Journal of Toxicology)

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Genotoxicity of Beta-Sitosterol, Betulinic Acid, Biochanin A, and Ursolic Acid, Potential Anthelmintic Phyto-Compounds


Affiliations
1 Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya, India
2 PG and Research Department of Zoology, B. Borooah College, Guwahati – 781007, Assam, India
     

   Subscribe/Renew Journal


Beta-sitosterol, betulinic acid, biochanin A and ursolic acid are known to possess anthelmintic properties. This study was undertaken to assess the genotoxic potentials of these phytocompounds in albino rats. Animals were orally administered with 1 and 10 mg/ml of the above phyto-compounds for a period of 14 days. All the animals were subjected to mitotic arrest before sacrifice and then bone marrow cells were collected from both the femurs and processed to observe the chromosomal aberrations. The results revealed that ursolic acid induced the maximum number of statistically significant abnormalities (p ≤ 0.05) followed by betulinic acid and biochanin A. Beta-sitosterol was found to be the safest of all the tested phytocompounds as far as chromosomal abnormalities in short term oral studies are concerned as it did not lead to major changes at genomic level. Although these phyto-compounds are considered potential anthelmintics, their long-term use may cause genotoxic effects to the users.

Keywords

beta sitosterol, betulinic acid, biochanin A, genotoxicity, ursolic acid.
User
Subscription Login to verify subscription
Notifications
Font Size

  • Gurib-Fakim A. Medicinal plants: Traditions of yesterday and drugs of tomorrow. Mol Aspects Med. 2006; 27:1–93. PMid: 16105678. https://doi.org/10.1016/j. mam.2005.07.008

  • Arome D, Chinedu E. The importance of toxicity testing. J Pharm Biosci. 2013; 4:146–8.

  • Almeida DRP, Johnson D, Hollands H, Smallman D, Baxter S, Eng KT, Kratky V, Hove MW, Sharma S, El-Defrawy S. Effect of prophylactic nonsteroidal anti-inflammatory drugs on cystoid macular edema assessed using optical coherence tomography quantification of total macular volume after cataract surgery. J Cataract Refract Surg. 2008; 34:64–9. PMid: 18165083. https://doi.org/10.1016/j.jcrs.2007.08.034

  • Metzler M, Kulling S, Pfeiffer E, Jacobs E. Genotoxicity of estrogens. Z Lebensm Unters Forsch. 1998; 206:367–73. https://doi.org/10.1007/s002170050275

  • Jung YJ, Youn JY, Ryu JC, Surh YJ. Salsolinol, a naturally occurring tetrahydroisoquinoline alkaloid, induces DNA damage and chromosomal aberrations in cultured Chinese hamster lung fibroblast cells. Mutat Res. 2001; 474:25–33. PMid: 11239960. https://doi.org/10.1016/ s0027-5107(00)00156-1

  • Baeshen NA, Elkady AI, Yaghmoor SS, Ashmaoi HMA, Kumosani TA. Evaluation of the cytotoxicity and genotoxicity of alkaloid-rich and alkaloid-free aqueous extracts of Rhazya stricta leaves. Bothalia J. 2014; 44:43–69.

  • Dey A, Hazra AK, Mukherjee A, Nandy S, Pandey DK. Chemotaxonomy of the ethnic antidote Aristolochia indica for aristolochic acid content: Implications of anti-phospholipase activity and genotoxicity study. J Ethnopharmacol. 2021; 266:113416. PMid: 32980485. https://doi. org/10.1016/j.jep.2020.113416

  • Ahmadi A, Gandomi H, Derakhshandeh A, Misaghi A, Noori N. Phytochemical composition and in vitro safety evaluation of Ziziphora clinopodioides Lam. ethanolic extract: Cytotoxicity, genotoxicity and mutagenicity assessment. J Ethnopharmacol. 2021; 266:113428. PMid: 33011368. https://doi.org/10.1016/j.jep.2020.113428

  • Ribeiro RCL, Botelho ELL, Donadel G, Ames ML, Nunes B, Tramontini S, Soares AA, Alberton O, Jacomassi E, Junior AG. Genotoxicity study of Vitex megapotamica (Spreng.) Moldenke. J Med Food. 2021; 24:762–5. PMid: 33535021. https://doi.org/10.1089/jmf.2020.0159

  • Wolfreys AM, Hepburn PA. Safety evaluation of phytosterol esters. Part 7. Assessment of mutagenic activity of phytosterols, phytosterol esters and the cholesterol derivative, 4-cholesten-3-one. Food Chem Toxicol. 2002; 40:461–70. PMid: 11893405. https://doi.org/10.1016/ S0278-6915(01)00099-0

  • Kutkowska J, Strzadala L, Rapak A. Hypoxia increases the apoptotic response to betulinic acid and betulin in human non-small cell lung cancer cells. Chem-Biol Interact. 2021; 333:109320. PMid: 33181113. https://doi.org/10.1016/j. cbi.2020.109320

  • Cunha AB, Batista R, Castro MA, David JM. Chemical strategies towards the synthesis of betulinic acid and its more potent antiprotozoal analogues. Molecules. 2021; 26:1081. PMid: 33670791 PMCid: PMC7922983. https://doi.org/10.3390/molecules26041081

  • Ma X-Y, Zhang M, Fang G, Cheng C-J, Wang M-K, Han Y-M, Hou X-T, Hao E-W, Hou Y-Y, Bai G. Ursolic acid reduces hepatocellular apoptosis and alleviates alcoholinduced liver injury via irreversible inhibition of CASP3 in vivo. Acta Pharmacol Sin. 2021; 42:1101–10. PMid: 33028983 PMCid: PMC8209164. https://doi.org/10.1038/ s41401-020-00534-y

  • Naß J, Abdelfatah S, Efferth T. Ursolic acid enhances stress resistance, reduces ROS accumulation and prolongs life span in C. elegans serotonin-deficient mutants. Food Funct. 2021; 12:2242–56. PMid: 33596295. https://doi. org/10.1039/D0FO02208J

  • Zhou Y, Xu B, Yu H, Zhao W, Song X, Liu Y, Wang K, Peacher N, Zhao X, Zhang H-T. Biochanin A attenuates ovariectomy-induced cognition deficit via antioxidant effects in female rats. Front Pharmacol. 2021; 12:603316. PMid: 33815102 PMCid: PMC8010695. https://doi. org/10.3389/fphar.2021.603316

  • Hu K-X, Shi X-C, Xu D, Laborda P, Wu G-C, Liu F-Q, Laborda P, Wang S-Y. Antibacterial mechanism of Biochanin A and its efficacy for the control of Xanthomonas axonopodis pv. glycines in soybean. Pest Manag Sci. 2021; 77:1668–73. PMid: 33202090. https://doi.org/10.1002/ ps.6186

  • Abeesh P, Guruvayoorappan C. Preparation and characterization of beta sitosterol encapsulated nanoliposomal formulation for improved delivery to cancer cells and evaluation of its anti-tumor activities against Daltons Lymphoma Ascites tumor models. J Drug Deliv Sci Technol. 2021; 2021:102832. https://doi.org/10.1016/j.jddst.2021.102832

  • Vijaya, Yadav, AK. In vitro anthelmintic assessment of selected phytochemicals against Hymenolepis diminuta, a zoonotic tapeworm. J Parasit Dis. 2016; 40:1082–6. PMid: 27605841 PMCid: PMC4996173. https://doi.org/10.1007/ s12639-014-0560-1

  • Kavithaa K, Paulpandi M, Ramya S, Ramesh M, Balachandar V, Ramasamy K, Narayanasamy A. Sitosterol-fabricated chitosan nanocomplex induces apoptotic cell death through mitochondrial dysfunction in lung cancer animal model: an enhanced synergetic drug delivery system for lung cancer therapy. New J Chem. 2021; 45:9251–63. https://doi. org/10.1039/D1NJ00913C

  • OECD. Guidelines for the Testing of Chemicals, Section 4: Health Effects Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents. OECD Publications; 2008. https://doi.org/10.1787/9789264070684-en

  • Dolan LC, Hofman-Huther H, Amann N. Hydroxytyrosol: lack of clastogenicity in a bone marrow chromosome aberration study in rats. BMC Res Notes. 2014; 7:9–23. PMid: 25515426 PMCid: PMC4301881. https://doi. org/10.1186/1756-0500-7-923

  • Sankar R, Maheshwari R, Karthik S, Shivashangari KS, Ravikumar V. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles. Mater Sci Eng C Mater Biol Appl. 2014; 44:234–9. PMid: 25280701. https://doi. org/10.1016/j.msec.2014.08.030

  • Dolan DWP, Zupanic A, Nelson G, Hall P, Miwa S, Kirkwood TBL. Integrated stochastic model of DNA damage repair by non-homologous end joining and p53/p21- mediated early senescence signalling. PLoS Computational Biol. 2015; 11:e1004246. PMid: 26020242 PMCid: PMC4447392. https://doi.org/10.1371/journal.pcbi.1004246

  • Zong D, Callen E, Pegoraro G, Lukas C, Lukas J, Nussenzweig A. Ectopic expression of RNF168 and 53BP1 increases mutagenic but not physiological non-homologous end joining. Nucleic Acids Res. 2015; 43:4950–61. PMid: 25916843 PMCid: PMC4446425. https://doi.org/10.1093/ nar/gkv336

  • Cassidy A, Bingham S, Setchell KD. Biological effects of a diet of soy protein rich in isoflavones on the menstrual cycle of premenopausal women. Am J Clin Nutr. 1994; 60:333– 40. PMid: 8074062. https://doi.org/10.1093/ajcn/60.3.333

  • Li H, He N, Li X, Zhou L, Zhao M, Jiang H, Zhang X. Oleanolic acid inhibits proliferation and induces apoptosis in NB4 cells by targeting PML/RARα. Oncol Lett. 2013; 6:885–90. PMid: 24137431 PMCid: PMC3796429. https:// doi.org/10.3892/ol.2013.1497

  • Gogoi R, Sarma N, Loying R, Pandey SK, Begum T, Lal M. A comparative analysis of bark and leaf essential oil and their chemical composition, antioxidant, anti-inflammatory, antimicrobial activities and genotoxicity of North East Indian Cinnamomum zeylanicum Blume. Nat Prod J. 2021; 11:74–84. https://doi.org/10.2174/22103155096661911191 11800

  • Hadi NSA, Bankoglu EE, Schott L, Leopoldsberger E, Ramge V, Sievers OKH, Stopper H. Genotoxicity of selected pyrrolizidine alkaloids in human hepatoma cell lines HepG2 and Huh6. Mutat Res Genet Toxicol Environ Mutagen. 2021; 861–62. PMid: 33551105. https://doi.org/10.1016/j. mrgentox.2020.503305

  • Deshpande SS, Kewatkar SM, Paithankar VV. Anticlastogenic activity of flavonoid rich extract of Cassia auriculata Linn. on experimental animal. Indian J Pharmacol. 2013; 45:184–6. PMid: 23716897 PMCid: PMC3660933. https://doi.org/10.4103/0253-7613.108314

  • McClain RM, Wolz E, Davidovich A, Pfannkuch F, Edwards JA, Bausch J. Acute, subchronic and chronic safety studies with genistein in rats. Food Chem Toxicol. 2006; 44:56–80. PMid: 16213646. https://doi.org/10.1016/j.fct.2005.05.021

  • Prasad S, Yadav VK, Srivastava S, Shukla Y. Protective effects of lupeol against benzo[a]pyrene induced clastogenicity in mouse bone marrow cells. Mol Nutr Food Res. 2008; 52:1117–20. PMid: 18496817. https://doi.org/10.1002/mnfr.200700420

  • Fujita M, Sasanuma H, Yamamoto KN, Harada H, Kurosawa A, Adachi N, Omura M, Hiraoka M, Takeda S, Hirota K. Interference in DNA replication can cause mitotic chromosomal breakage unassociated with double- stranded breaks. PLoS One. 2013; 8:e60043. PMid: 23573231 PMCid: PMC3616066. https://doi.org/10.1371/ journal.pone.0060043


Abstract Views: 250

PDF Views: 0




  • Genotoxicity of Beta-Sitosterol, Betulinic Acid, Biochanin A, and Ursolic Acid, Potential Anthelmintic Phyto-Compounds

Abstract Views: 250  |  PDF Views: 0

Authors

Vijaya Mishra
Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya, India
Arun K. Yadav
Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya, India
Amar Deep Soren
PG and Research Department of Zoology, B. Borooah College, Guwahati – 781007, Assam, India

Abstract


Beta-sitosterol, betulinic acid, biochanin A and ursolic acid are known to possess anthelmintic properties. This study was undertaken to assess the genotoxic potentials of these phytocompounds in albino rats. Animals were orally administered with 1 and 10 mg/ml of the above phyto-compounds for a period of 14 days. All the animals were subjected to mitotic arrest before sacrifice and then bone marrow cells were collected from both the femurs and processed to observe the chromosomal aberrations. The results revealed that ursolic acid induced the maximum number of statistically significant abnormalities (p ≤ 0.05) followed by betulinic acid and biochanin A. Beta-sitosterol was found to be the safest of all the tested phytocompounds as far as chromosomal abnormalities in short term oral studies are concerned as it did not lead to major changes at genomic level. Although these phyto-compounds are considered potential anthelmintics, their long-term use may cause genotoxic effects to the users.

Keywords


beta sitosterol, betulinic acid, biochanin A, genotoxicity, ursolic acid.

References





DOI: https://doi.org/10.18311/ti%2F2023%2Fv30i2%2F30946