Phytochemical profile and hepatoprotective effects of Crotalaria vialattei against antituberculosis drug-induced liver injury

Authors

  • Kaouther Zouioueche 1. Research Unit, Valorization of Natural Resources, Bioactive Molecules, and Physicochemical and Biological Analyses (VARENBIOMOL), University of Constantine 1 Frères Mentouri, Ain El-Bey Road, 25000, Constantine, Algeria; 2. Department of Animal Biology, Faculty of Natural and Life Sciences, University of Constantine 1 Frères Mentouri, Aïn El Bey Road, 25000, Constantine, Algeria https://orcid.org/0009-0002-9108-4424
  • Meriem Laraba 1. Research Unit, Valorization of Natural Resources, Bioactive Molecules, and Physicochemical and Biological Analyses (VARENBIOMOL), University of Constantine 1 Frères Mentouri, Ain El-Bey Road, 25000, Constantine, Algeria; 2. Department of Animal Biology, Faculty of Natural and Life Sciences, University of Constantine 1 Frères Mentouri, Aïn El Bey Road, 25000, Constantine, Algeria https://orcid.org/0000-0003-2069-6570
  • Afifa Bensegueni Department of Anatomic Pathology, Faculty of Medicine, University Salah Boubnider Constantine 3, Constantine, Algeria https://orcid.org/0009-0007-1977-3600
  • Iman Ramli Applied Biochemisty laboratory, University of Constantine 1 Frères Mentouri, Ain El Bey Road, 25000, Constantine, Algeria https://orcid.org/0000-0002-3364-967X
  • Leila Hammoud Research Unit, Valorization of Natural Resources, Bioactive Molecules, and Physicochemical and Biological Analyses (VARENBIOMOL), University of Constantine 1 Frères Mentouri, Ain El-Bey Road, 25000, Constantine, Algeria https://orcid.org/0009-0007-1586-1785
  • Ramazan Erenler Department of Chemistry, Faculty of Arts and Sciences, Tokat Gaziosmanpasa University, 60240 Tokat, Türkiye https://orcid.org/0000-0002-0505-3190
  • İlyas Yıldız Department of Molecular Biology and Genetics, Department of Biotechnology, Institute of Science, Tokat Gaziosmanpaşa University, 60240 Tokat, Türkiye https://orcid.org/0000-0003-1254-1069
  • Imene Messaoud Nacer Laboratory of Biotechnology, Environment and Health, University of Blida 1, Blida, Algeria https://orcid.org/0009-0009-0028-8685
  • Aya Berkane 1. Research Unit, Valorization of Natural Resources, Bioactive Molecules, and Physicochemical and Biological Analyses (VARENBIOMOL), University of Constantine 1 Frères Mentouri, Ain El-Bey Road, 25000, Constantine, Algeria; 2. Department of Biochemistry and Cellular and Molecular Biology, Faculty of Natural and Life Sciences, University of Constantine 1 Frères Mentouri, Aïn El Bey Road, 25000, Constantine, Algeria https://orcid.org/0009-0003-7967-658X
  • Chawki Bensouici Biotechnology Research Center (CRBT), Ali Mendjeli New Town UV 03, Constantine 25000, Algeria https://orcid.org/0000-0003-4612-4642
  • Fadila Benayache Research Unit, Valorization of Natural Resources, Bioactive Molecules, and Physicochemical and Biological Analyses (VARENBIOMOL), University of Constantine 1 Frères Mentouri, Ain El-Bey Road, 25000, Constantine, Algeria https://orcid.org/0000-0002-2282-6343
  • Samir Benayache Research Unit, Valorization of Natural Resources, Bioactive Molecules, and Physicochemical and Biological Analyses (VARENBIOMOL), University of Constantine 1 Frères Mentouri, Ain El-Bey Road, 25000, Constantine, Algeria https://orcid.org/0000-0003-2298-2466
  • Djamila Zama 1. Research Unit, Valorization of Natural Resources, Bioactive Molecules, and Physicochemical and Biological Analyses (VARENBIOMOL), University of Constantine 1 Frères Mentouri, Ain El-Bey Road, 25000, Constantine, Algeria; 2. Department of Animal Biology, Faculty of Natural and Life Sciences, University of Constantine 1 Frères Mentouri, Aïn El Bey Road, 25000, Constantine, Algeria https://orcid.org/0000-0002-4312-7701

DOI:

https://doi.org/10.2298/ABS260110001Z

Keywords:

Crotalaria vialattei, RHZ, polyphenols, antioxidant activity, hepatoprotective effect

Abstract

Paper description:

  • Crotalaria vialattei, is an endemic Algerian plant whose phytochemical composition and biological properties remain poorly documented.
  • The n-butanol extract of vialattei was characterized by LC–MS/MS and evaluated for its antioxidant activity and hepatoprotective effects in a rat model of antituberculosis drug-induced hepatotoxicity.
  • The extract exhibited a phenolic-rich profile, measurable antioxidant activity, and significant protective effects against RHZ-induced hepatic alterations.
  • These findings provide new experimental evidence supporting the potential relevance of vialattei as a source of bioactive compounds with hepatoprotective activity.

Abstract: Tuberculosis is a global public health concern, and its treatment is frequently associated with hepatotoxic side effects. Phytotherapy represents a promising complementary approach. This study aimed to characterize the phenolic profile of the n-butanol extract of Crotalaria vialattei (BCV), evaluate its antioxidant capacity, and assess its hepatoprotective effects against liver damage induced by a fixed-dose antituberculosis drug combination containing rifampin, isoniazid, and pyrazinamide (RHZ). Phytochemical analysis revealed a phenolic-rich extract, identifying 17 polyphenolic compounds. BCV exhibited measurable antioxidant activity in vitro. In vivo, oral administration of RHZ (rifampin 150 mg/kg, isoniazid 75 mg/kg, and pyrazinamide 400 mg/kg) induced marked alterations in hepatic biochemical markers, lipid profile, oxidative status, and liver histoarchitecture. BCV treatment significantly attenuated these changes by improving liver enzyme activities, restoring oxidative balance, and preserving liver architecture. Overall, the BCV extract demonstrates antioxidant-associated hepatoprotective potential against RHZ-induced liver injury and may represent a promising complementary strategy to reduce antituberculosis drug-related hepatotoxicity.

Downloads

Download data is not yet available.

References

Larsen SE, Baldwin SL, Orr MT, Reese VA, Pecor T, Granger B, Dubois Cauwelaert N, Podell BK, Coler RN. Enhanced anti-Mycobacterium tuberculosis immunity over time with combined drug and immunotherapy treatment. Vaccines (Basel). 2018;6(2):30. https://doi.org/10.3390/vaccines6020030

Nader LA, de Mattos AA, Picon PD, Bassanesi SL, de Mattos AZ, Pineiro Rodriguez M. Hepatotoxicity due to rifampicin, isoniazid and pyrazinamide in patients with tuberculosis: is anti-HCV a risk factor? Ann Hepatol. 2010;9(1):70-4. https://doi.org/10.1016/S1665-2681(19)31682-5

Ezhilarasan D. Antitubercular drugs induced liver injury: an updated insight into molecular mechanisms. Drug Metab Rev. 2023;55(3):239-53. https://doi.org/10.1080/03602532.2023.2215478

Gulati K, Reshi MR, Rai N, Ray A. Hepatotoxicity: its mechanisms, experimental evaluation and protective strategies. Am J Pharmacol. 2018;1(1):1004.

Shakya AK. Drug-induced hepatotoxicity and hepatoprotective medicinal plants: a review. Indian J Pharm Educ Res. 2020;54(2):234-50. https://doi.org/10.5530/ijper.54.2.28

Samaila Yaradua S, Alzahrani DA, Bello A. Phylogenetic position of West African species of the genus Crotalaria L. (Crotalarieae, Fabaceae) based on the current infrageneric classification. Pakistan J Bot. 2019;51(4):1453-8. https://doi.org/10.30848/PJB2019-4(37)

Kusar S, Saddiqe Z, Ali F, Bashir S, Zubairi T. GCMS and HPLC profiling, antioxidant and anti-inflammatory activities of Crotalaria medicaginea Lamk. S Afr J Bot. 2024;168:196-208. https://doi.org/10.1016/j.sajb.2024.03.014

Yaqub MS, Basher B, Aslam R. Secondary metabolites of the genus Crotalaria (rattlepods) and their medicinal importance: a review. J Hortic Sci Technol. 2020;3(1):1-7. https://doi.org/10.46653/jhst20030101

Anwar S, Nadeem MF, Pervaiz I, Khurshid U, Akmal N, Aamir K, Rehman MH, Almansour K, Alshammari F, Shaikh MF, Locatelli M, Ahemad N, Saleem H. A comprehensive phytochemical, biological, and toxicological studies of roots and aerial parts of Crotalaria burhia Buch.-Ham: an important medicinal plant. Front Plant Sci. 2022;13:988352. https://doi.org/10.3389/fpls.2022.988352

Quezel P, Santa S. New flora of Algeria and the southern desert regions. Vol 1. Paris: CNRS; 1962. 1170 p.

Müller L, Gnoyke S, Popken AM, Böhm V. Antioxidant capacity and related parameters of different fruit formulations. Lebensm Wiss Technol. 2010;43(6):992-9. https://doi.org/10.1016/j.lwt.2010.02.004

Topçu G, Ay M, Bilici A, Sarıkürkcü C, Öztürk M, Ulubelen A. A new flavone from antioxidant extracts of Pistacia terebinthus. Food Chem. 2007;103(3):816-22. https://doi.org/10.1016/j.foodchem.2006.09.028

Erenler R, Atalar MN, Yıldız İ, Geçer EN, Yildirim A, Demirtas I, Alma MH. Quantitative analysis of bioactive compounds by LC-MS/MS from Inula graveolens. J Integr Anat Med. 2023;4(3):3–10. https://doi.org/10.53445/batd.1278048

Erenler R, Hosaflıoğlu İ, Yıldız İ, Atalar MN, Çelik SM, Alma MH. Quantitative analysis of phenolics in Trifolium pratense L. flowers and evaluation of antioxidant activity by sensory. JNRS. 2024;13(2):165-74. https://doi.org/10.54187/jnrs.1529229

Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1985;181:1199-200. https://doi.org/10.1038/1811199a0

Oyaizu M. Antioxidative activities of products of browning reaction prepared from glucosamine. Jpn J Nutr. 1986;44:307-15. https://doi.org/10.5264/eiyogakuzashi.44.307

Szydłowska-Czerniak A, Dianoczki C, Recseg K, Karlovits G, Szłyk E. Determination of antioxidant capacities of vegetable oils by ferric-ion spectrophotometric methods. Talanta. 2008;76(4):899-905. https://doi.org/10.1016/j.talanta.2008.04.055

Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. J Agric Food Chem. 2004;52(26):7970-81. https://doi.org/10.1021/jf048741x

Laraba M, Tachour SH, Belbache H, Boubekri N, Djebbari R, Benayache F, Benayache S, Zama D. Hepatoprotective potential of the n-butanol extract of Moricandia arvensis from Algeria against doxorubicin-induced toxicity in Wistar albino rats. Adv Tradit Med. 2022. https://doi.org/10.1007/s13596-022-00642-6

Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271-8. https://doi.org/10.1016/0003-2697(78)90342-1

Ellman G. Plasma antioxidants. Arch Biochem Biophys. 1959;82:70-7. https://doi.org/10.1016/0003-9861(59)90090-6

Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol. 1984;105:114-20. https://doi.org/10.1016/S0076-6879(84)05015-1

Mokhtari R, Kazemi Fard M, Rezaei M, Moftakharzadeh SA, Mohseni A. Antioxidant, antimicrobial activities, and characterization of phenolic compounds of thyme (Thymus vulgaris L.), sage (Salvia officinalis L.), and thyme–sage mixture extracts. J Food Qual. 2023;2023:2602454.

Sinana KI, Saftić L, Peršurić Ž, Kraljević-Pavelić S, Quattara Katinan E, Picot-Allain MCN, Mahomoodally MF, Zengin G. A comparative study of the chemical composition, biological and multivariate analysis of Crotalaria retusa L. stem barks, fruits, and flowers obtained via different extraction protocols. S Afr J Bot. 2020;128:101–108. https://doi.org/10.1016/j.sajb.2019.10.019

Falleh H, Hafsi C, Mohsni I, Ksouri R. Evaluation of different procedures for the extraction of phenolic compounds from a medicinal plant. Biol (Basel). 2021;215(3–4):133-42. https://doi.org/10.1051/jbio/2021009

Devendra BN, Srinivas N, Solmon KS. Comparative pharmacological and phytochemical analysis of in vivo and in vitro propagated Crotalaria species. Asian Pac J Trop Med. 2012;5(1):37–41. https://doi.org/10.1016/S1995-7645(11)60242-3

Kumar A, Manickam MS, Sreejith M, Sebastin V. In vitro antioxidant and anthelmintic activity of the extracts of whole plant Crotalaria biflora L. Ann RSCB. 2021;25(4):150-61.

Chen F, Zhang X, Wang J, Wang F, Mao J. P-coumaric acid: advances in pharmacological research based on oxidative stress. Curr Top Med Chem. 2024;24(5):416-36. https://doi.org/10.2174/0115680266276823231230183519

Iannuzzi C, Liccardo M, Sirangelo I. Overview of the role of vanillin in neurodegenerative diseases and neuropathophysiological conditions. Int J Mol Sci. 2023;24:1817. https://doi.org/10.3390/ijms24031817

Karami A, Fakhri S, Kooshki L, Khan H. Polydatin: pharmacological mechanisms, therapeutic targets, biological activities, and health benefits. Molecules. 2022;27(19):6474. https://doi.org/10.3390/molecules27196474

Qadeer K, Memon S. Synthesis, characterisation, and antioxidant study of Cr(III)–rutin complex. Chem Pap. 2014;68(5):614–623. https://doi.org/10.2478/s11696-013-0494-6

Li AN, Li S, Zhang YJ, Xu XR, Chen YM, Li HB. Resources and biological activities of natural polyphenols. Nutrients. 2014;6(12):6020-6047. https://doi.org/10.3390/nu6126020

Tostmann A, Boeree MJ, Aarnoutse RE, de Lange WC, van der Ven AJ, Dekhuijzen R. Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. J Gastroenterol Hepatol. 2008;23(2):192-202. https://doi.org/10.1111/j.1440-1746.2007.05207.x

Panda VS, Ashar HD, Sharan A. Antioxidant and hepatoprotective effects of Garcinia indica fruit rind in antitubercular drug-induced liver injury in rats. Botanics Targets Ther. 2013;3:29-37. https://doi.org/10.2147/BTAT.S42483

Saraswathy SD, Suja V, Prema G, Devi SC. Effect of Liv.100 against antitubercular drugs induced hepatotoxicity in rats. Indian J Pharmacol. 1998;30:233-8.

Jaydeokar AV, Bandawane DD, Bibave KH, Patil TV. Hepatoprotective potential of Cassia auriculata roots on ethanol and antitubercular drug-induced hepatotoxicity in experimental models. Pharm Biol. 2014;52(3):344-55. https://doi.org/10.3109/13880209.2013.837075

Tostmann A, Boeree MJ, Peters WH, Roelofs HM, Aarnoutse RE, van der Ven AJ, Dekhuijzen PN. Isoniazid and its toxic metabolite hydrazine induce in vitro pyrazinamide toxicity. Int J Antimicrob Agents. 2008;31(6):577-80. https://doi.org/10.1016/j.ijantimicag.2008.01.022

Gęgotek A, Rybałtowska-Kawałko P, Skrzydlewska E. Rutin as a mediator of lipid metabolism and cellular signaling pathways interactions in fibroblasts altered by UVA and UVB radiation. Oxid Med Cell Longev. 2017;2017:4721352. https://doi.org/10.1155/2017/4721352

Wang P, Pradhan K, Zhong XB, Ma X. Isoniazid metabolism and hepatotoxicity. Acta Pharm Sin B. 2016;6(5):384-92. https://doi.org/10.1016/j.apsb.2016.07.014

Ansari MI, Dubey N, Ganeshpurkar A. Hepatoprotective potential of vanillic acid against isoniazid–rifampicin-induced liver toxicity. Aspects Mol Med. 2025;5:100087. https://doi.org/10.1016/j.amolm.2025.100087

Paulpriya K, Tresina PS, Mohan VR. Hepatoprotective Effect of Crotalaria longipes Wight & Arn, Ethanol Extract in CCl4 Induced Hepatotoxicity in Wistar Rats. Int J Toxicol Pharmacol Res. 2016;8(1):45-52.

Downloads

Published

2026-04-09

How to Cite

1.
Zouioueche K, Laraba M, Bensegueni A, Ramli I, Hammoud L, Erenler R, Yıldız İlyas, Messaoud Nacer I, Berkane A, Bensouici C, Benayache F, Benayache S, Zama D. Phytochemical profile and hepatoprotective effects of Crotalaria vialattei against antituberculosis drug-induced liver injury. Arch Biol Sci [Internet]. 2026Apr.9 [cited 2026Apr.10];78(1):45-56. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/12041

Issue

Section

Articles

Most read articles by the same author(s)