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

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Authors

  • Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya ,IN
  • Department of Zoology, North-Eastern Hill University, Shillong – 793022, Meghalaya ,IN
  • PG and Research Department of Zoology, B. Borooah College, Guwahati – 781007, Assam ,IN

DOI:

https://doi.org/10.18311/ti/2023/v30i2/30946

Keywords:

Beta Sitosterol, Betulinic Acid, Biochanin A, Genotoxicity, Ursolic Acid
Genotoxicity

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.

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Published

2023-05-19

How to Cite

Mishra, V., Yadav, A. K., & Soren, A. D. (2023). Genotoxicity of Beta-Sitosterol, Betulinic Acid, Biochanin A, and Ursolic Acid, Potential Anthelmintic Phyto-Compounds. Toxicology International, 30(2), 155–160. https://doi.org/10.18311/ti/2023/v30i2/30946
Received 2022-08-11
Accepted 2023-01-25
Published 2023-05-19

 

References

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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: 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 DOI: https://doi.org/10.2174/2210315509666191119111800

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 DOI: 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 DOI: 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 DOI: 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; DOI: https://doi.org/10.1002/mnfr.200700420

: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 DOI: https://doi.org/10.1371/journal.pone.0060043