Phytochemical profile and hepatoprotective effects of Crotalaria vialattei against antituberculosis drug-induced liver injury
DOI:
https://doi.org/10.2298/ABS260110001ZKeywords:
Crotalaria vialattei, RHZ, polyphenols, antioxidant activity, hepatoprotective effectAbstract
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
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
How to Cite
Issue
Section
License
Copyright (c) 2026 KAOUTHER ZOUIOUECHE, Meriem Laraba, Afifa Bensegueni, Iman Ramli, Leila Hammoud, Ramazan Erenler, İlyas Yıldız, Imene Messaoud Nacer, Aya Berkane, Chawki Bensouici, Fadila Benayache, Samir Benayache, Djamila Zama

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.