Hepatorenoprotective effects of Lepidium draba L. extracts against cyclophosphamide-induced oxidative injuries in rats via reducing apoptosis and inflammation

Yu-Lai You , Sheng Zheng , Cheng-Jian Zhao , Ye-Fei Chang , Pei Liu , Xue-Li Zeng , Lian Liu

Asian Pacific Journal of Tropical Biomedicine ›› 2025, Vol. 15 ›› Issue (2) : 53 -64.

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Asian Pacific Journal of Tropical Biomedicine ›› 2025, Vol. 15 ›› Issue (2) : 53 -64. DOI: 10.4103/apjtb.apjtb_518_24
Original Article

Hepatorenoprotective effects of Lepidium draba L. extracts against cyclophosphamide-induced oxidative injuries in rats via reducing apoptosis and inflammation

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Abstract

Objective: To investigate the protective effects of Lepidium draba L. (L. draba) on cyclophosphamide (CP)-induced hepatotoxicity and nephrotoxicity in rats.

Methods: A total of 36 rats were divided into six groups as follows: the sham control group, the CP group (CP 100 mg/kg i.p. on days 1, 7, 14, 21, 28, and 35), the CP groups treated with L. draba extract (100, 200 and 400 mg/kg of L. draba extract for 28 d), and the L. draba extract alone group (400 mg/kg of L. draba extract for 28 d). Serum parameters of renal and hepatic function, as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured. Moreover, Bax, Bcl-2, and caspase-3 gene expression and histopathological changes were assessed.

Results: L. draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide, TBARS, IL-6, TNF-α, and IL-Ιβ levels, as well as increasing superoxide dismutase, catalase and glutathione peroxidase activities, and FRAP, MIF, and TGF-β levels. In addition, the extract downregulated the expression of pro-apoptotic genes (Bax and caspase-3) and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes.

Conclusions: L. draba extract can protect hepatic and renal structure and function against CP-induced toxicities, and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.

Keywords

Lepidium draba / Cyclophosphamide / Oxidative stress / Antioxidant / Apoptosis / Hepatotoxicity / Nephrotoxicity

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Yu-Lai You, Sheng Zheng, Cheng-Jian Zhao, Ye-Fei Chang, Pei Liu, Xue-Li Zeng, Lian Liu. Hepatorenoprotective effects of Lepidium draba L. extracts against cyclophosphamide-induced oxidative injuries in rats via reducing apoptosis and inflammation. Asian Pacific Journal of Tropical Biomedicine, 2025, 15(2): 53-64 DOI:10.4103/apjtb.apjtb_518_24

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

This study was supported by the Basic Research Joint Special General Project of Yunnan Provincial Local Universities (part) (No: 202301BA070001-029, 202301BA070001-044) and Yunnan Province High-level Scientific and Technological Talents and Innovation Team Selection Special Young and Middle-aged Academic and Technical Leaders Reserve Talent Project (No: 202405AC350067).

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

YY contributed in writing draft. SZ and CZ conducted the experimental design and protocol preparation. YC and PL performed statistical analysis and laboratory tests. XZ reviewed the manuscript draft. LL developed the conceptualization and supervised the project.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

[1]

Xu B, Ganesan K, Mickymaray S, Alfaiz FA, Thatchinamoorthi R, Al-Aboody M. Immunomodulatory and antineoplastic efficacy of common spices and their connection with phenolic antioxidants. Bioact Comp Health Dis 2020; 3(2): 15-31.

[2]

Cauli O. Oxidative stress and cognitive alterations induced by cancer chemotherapy drugs: A scoping review. Antioxidants 2021; 10(7): 1116.

[3]

Shen S, Dean DC, Yu Z, Duan Z. Role of cyclin-dependent kinases (CDKs) in hepatocellular carcinoma: Therapeutic potential of targeting the CDK signaling pathway. Hepatol Res 2019; 49(10):1097-1108.

[4]

Hu L, Chen M, Chen X, Zhao C, Fang Z, Wang H, et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate Cell Death Dis 2021; 11(4): 1-17.

[5]

Karim S, Shaik RA. Geraniol alleviates cyclophosphamide-induced cardiotoxicity in mice. Asian Pac J Trop Biomed 2024; 14(10): 427-435.

[6]

Kim SH, Lee IC, Baek HS, Shin IS, Moon C, Bae CS, et al. Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats. Food Chem Toxicol 2014; 64: 110-118.

[7]

Ettaya A, Dhibi S, Samout N, Elfeki A, Hfaiedh N. Hepatoprotective activity of white horehound (Marrubium vulgare) extract against cyclophosphamide toxicity in male rat. Canadian J Physiol Pharmacol 2016; 94(4): 441-447.

[8]

Jiang W, Liu J, Li P, Lu Q, Pei X, Sun Y, et al. Magnesium isoglycyrrhizinate shows hepatoprotective effects in a cyclophosphamide-induced model of hepatic injury. Oncotarget 2017; 8(20): 33252-33264.

[9]

Lata S, Singh S, NathTiwari K, Upadhyay R. Evaluation of the antioxidant and hepatoprotective effect of Phyllanthus fraternus against a chemotherapeutic drug cyclophosphamide. Appl Biochem Biotechnol 2014; 173(8): 2163-2173.

[10]

Abulyazid I, Abd Elhalim SA, Sharada HM, Aboulthana WM, Abd Elhalim ST. Hepatoprotective effect of carob pods extract (Ceratonia siliqua L.) against cyclophosphamide induced alterations in rats. Int J Current Pharm Rev Res 2017; 8(2): 149-162.

[11]

Duléry R, Mohty R, Labopin M, Sestili S, Malard F, Brissot E, et al. Early cardiac toxicity associated with posttransplant cyclophosphamide in allogeneic stem cell transplantation. Cardio Oncol 2021; 3(2): 250-259.

[12]

Gadisa DA, Assefa M, Wang SH, Yimer G. Toxicity profile of doxorubicin-cyclophosphamide and doxorubicin-cyclophosphamide followed by paclitaxel regimen and its associated factors among women with breast cancer in Ethiopia: A prospective cohort study. J Oncol Pharm Pract 2020; 26(8): 1912-1920.

[13]

Alrefaei AE, Alzahrani MA, Alsuhaim SA. Cyclophosphamide related toxicity; a systematic review. IJMDC 2022; 6(5): 740-747.

[14]

Darband SG, Kaviani M, Yousefi B, Sadighparvar S, Pakdel FG, Attari JA, et al. Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer. J Cell Physiol 2018; 233(9): 6544-6560.

[15]

Ali Q, Khalil R, Nadeem M, Azhar MM, Hafeez MM, Malik A. Antibacterial, antioxidant activities and association among plant growth related traits of Lepidium draba. Biologic Clin Sci Res J 2020; 2020(11): 1-5.

[16]

Benakashani F, Allafchian A, Jalali SAH. Green synthesis, characterization and antibacterial activity of silver nanoparticles from root extract of Lepidium draba weed. Green Chem Lett Rev 2017; 10(4): 324-330.

[17]

Gao XC, Lv JW, Li CN, Zhang NX, Tian LL, Han XY, et al. Screening of the active component promoting Leydig cell proliferation from Lepidium meyenii using HPLC-ESI-MS/MS coupled with multivariate statistical analysis. Molecules 2019; 24(11): 2101.

[18]

Razavi R, Molaei R, Moradi M. Biosynthesis of metallic nanoparticles using mulberry fruit (Morus alba L.) extract for the preparation of antimicrobial nanocellulose film. Applied Nanosci 2020; 10(2): 465-476.

[19]

Wang Y, Bai L, Li H, Yang W, Li M. Protective effects of Lepidium draba L. leaves extract on testis histopathology, oxidative stress indicators, serum reproductive hormones and inflammatory signaling in oxymetholone-treated rat. Andrologia 2021; 53(11): e14239.

[20]

Arena AC, Jorge BC, Silva MC, De Barros AL, Fernandes AAH, Nóbrega RH, et al. Acrocomia aculeata oil: Beneficial effects on cyclophosphamide-induced reproductive toxicity in male rats. Andrologia 2018; 50(6): e13028.

[21]

López-Froilán R, Hernández-Ledesma B, Cámara M, Pérez-Rodríguez ML. Evaluation of the antioxidant potential of mixed fruit-based beverages: A new insight on the folin-ciocalteu method. Food Anal Methods 2018; 11(10): 2897-2906.

[22]

Mamou A, Eloutassi N, Alshawwa SZ, Al Kamaly O, Kara M, Bendaoud M, et al. Total phenolic content and antioxidant and antimicrobial activities of Papaver rhoeas L. organ extracts growing in taounate region, Morocco. Molecules 2022; 27(3): 854.

[23]

Akbaribazm M, Khazaei MR, Khazaei F, Khazaei M.Doxorubicin and Trifolium pratense L. (Red clover) extract synergistically inhibits brain and lung metastases in 4T1 tumor-bearing BALB/c mice. Food Sci Nutr 2020; 8(10): 5557-5570.

[24]

Khaksari M, Esmaili S, Abedloo R, Khastar H. Palmatine ameliorates nephrotoxicity and hepatotoxicity induced by gentamicin in rats. Arch Physiol Biochem 2021; 127(3): 273-278.

[25]

Kawade N, Murai A, Suzuki W, Tokuda Y, Kobayashi M, Horio F. Ascorbic acid deficiency increases hepatic expression of acute phase proteins through the intestine-derived IL-6 and hepatic STAT3 pathway in ODS rats. J Nutr Biochem 2019; 70: 116-124.

[26]

Atli G. How metals directly affect the antioxidant status in the liver and kidney of Oreochromis niloticus? An in vitro study. J Trace Elem Med Biol 2020; 62. doi: 10.1016/j.jtemb.2020.126567.

[27]

Najafi H, Mohamadi Yarijani Z, Changizi-Ashtiyani S, Mansouri K, Modarresi M, Seyed Madani H, et al. Protective effect of Malva sylvestris L. extract in ischemia-reperfusion induced acute kidney and remote liver injury. PLoS One 2017; 12(11). doi: 10.1371/journal.pone.0188270.

[28]

Wang J, Zhu P, Toan S, Li R, Ren J, Zhou H. Pum2-Mff axis fine-tunes mitochondrial quality control in acute ischemic kidney injury. Cell Biol Toxicol 2020; 36(4): 365-378.

[29]

Ibrahim RE, Amer SA, Farroh KY, Al-Gabri NA, Ahmed AI, El-Araby DA, et al. The effects of chitosan-vitamin C nanocomposite supplementation on the growth performance, antioxidant status, immune response, and disease resistance of Nile tilapia (Oreochromis niloticus) fingerlings. Aquaculture 2021; 534. doi: 10.1016/j.aquaculture.2020.736269.

[30]

Kusuyama J, Alves-Wagner AB, Conlin RH, Makarewicz NS, Albertson BG, Prince NB, et al. Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health. Cell Metab 2021; 33(5): 939956.

[31]

Fish L, Zhang S, Johnny XY, Culbertson B, Zhou AY, Goga A, et al. Cancer cells exploit an orphan RNA to drive metastatic progression. Nat Med 2018; 24(11): 1743-1751.

[32]

Clèries R, Galvez J, Espino M, Ribes J, Nunes V, de Heredia ML. Boots Ratio: A web-based statistical analysis of fold-change in qPCR and RT- qPCR data using resampling methods. Comput Biol Med 2012; 42(4): 438-445.

[33]

Goudarzi M, Khodayar MJ, Hosseini Tabatabaei SMT, Ghaznavi H, Fatemi I, Mehrzadi S. Pretreatment with melatonin protects against cyclophosphamide-induced oxidative stress and renal damage in mice. Fund Clin Pharmacol 2017; 31(6): 625-635.

[34]

Abdelfattah-Hassan A, Shalaby SI, Khater SI, El-Shetry ES, Abd El Fadil H, Elsayed SA. Panax ginseng is superior to vitamin E as a hepatoprotector against cyclophosphamide-induced liver damage. Complement Ther Med 2019; 46: 95-102.

[35]

Iqubal A, Syed MA, Ali J, Najmi AK, Haque MM, Haque SE. Nerolidol protects the liver against cyclophosphamide-induced hepatic inflammation, apoptosis, and fibrosis via modulation of Nrf2, NF-κB p65, and caspase-3 signaling molecules in Swiss albino mice. Biofactors 2020; 46(6): 963-973.

[36]

Lixin X, Lijun Y, Songping H. Ganoderic acid A against cyclophosphamide-induced hepatic toxicity in mice. J Biochem Mol Toxicol 2019; 33(4). doi: 10.1002/jbt.22271.

[37]

Wang Y, Bai L, Zhang J, Li H, Yang W, Li M. Lepidium draba L. leaves extract ameliorated cyclophosphamide-induced testicular toxicity by modulation of ROS-dependent Keap1/Nrf2/HO1, Bax/Bcl2/p53/caspase-3, and inflammatory signaling pathways. J Food Biochem 2021; 45(12): e13987.

[38]

Yan X, Qi M, Li P, Zhan Y, Shao H. Apigenin in cancer therapy: Anti-cancer effects and mechanisms of action. Cell Biosci 2017; 7(1): 1-16.

[39]

Kashyap D, Mittal S, Sak K, Singhal P, Tuli HS. Molecular mechanisms of action of quercetin in cancer: Recent advances. Tumor Biol 2016; 37(10): 12927-12939.

[40]

Al-Numair KS, Chandramohan G, Veeramani C, Alsaif MA. Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats. Redox Rep 2015; 20(5): 198-209.

[41]

Vijayaprakash S, Langeswaran K, Kumar SG, Revathy R, Balasubramanian MP. Nephro-protective significance of kaempferol on mercuric chloride induced toxicity in Wistar albino rats. Biomed Aging Pathol 2012; 3(3): 119-124.

[42]

Chyad AH. Evaluation of anticancer, analgesic and anti-inflammatory activities of the ethanolic extract of Lepidium draba Linn. leaves. Adv Anim Vet Sci 2017; 5(1): 7-13.

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