Barleria prionitis L. extracts ameliorate doxorubicin-induced acute kidney injury via modulation of oxidative stress, inflammation, and apoptosis

10.1016/j.jtcme.2023.05.007

Sachinthi S. Amarasiri；Anoja P. Attanayake；Liyanage D.A.M. Arawwawala；Lakmini K.B. Mudduwa；Kamani A.P.W. Jayatilaka

Barleria prionitis ； Biomarkers ； Doxorubicin-induced acute kidney injury ； Nephroprotective mechanisms ； In vitro antioxidant studies

Journal of Traditional and Complementary Medicine

13卷5期（2023 / 09 / 01）

500 - 510

英文

Background and aim: Doxorubicin (DOX) is a chemotherapeutic drug with potential nephrotoxic effects on patients who are on cancer chemotherapy. An interest has been observed in using natural products to ameliorate the potential side effects of DOX. The present study is to investigate the cellular mechanisms underlying the protective effects of Barleria prionitis L. (BP) (Acanthaceae) extracts, DOX-induced acute kidney injury (AKI). Experimental procedure: Hexane (25 mg/kg/day), ethyl acetate (80 mg/kg/day), n-butanol (70 mg/kg/ day), and water (120 mg/kg/day) extracts of BP, were administered to DOX-induced (5 mg/kg (2500 μL/ kg), ip) Wistar rats for four consecutive weeks. At the end of the study, investigations were carried out for the assessment of biomarkers of nephrotoxicity, oxidative stress, inflammation, and apoptosis. Results: Treatments with BP extracts significantly reversed DOX-induced elevations in serum and urine biochemical markers of nephrotoxicity (serum creatinine; 21-33%, blood urea nitrogen; 26-58%, β_2- microglobulin; 19-22% and urine total protein; 47-67%). There was a reduction in the levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde in kidney homogenates of rats treated with the n-butanol extract (by 43, 62, and 24%) and water extract (by 57%, 85%, and 26%) (p < 0.05). Immunohistochemical expression of the pro-apoptotic B-cell associated X protein was reduced while the anti-apoptotic B-cell lymphoma gene product 2 protein was increased in kidney tissues after the treatments with BP extracts. Conclusions: The selected BP extracts significantly ameliorated DOX-induced AKI. The findings would open new vistas for the development of a drug using the BP extracts to minimize DOX-induced AKI in cancer patients.

1. Ali, N,AlAsmari, AF,Imam, F(2021).Protective effect of diosmin against doxorubicin-induced nephrotoxicity.Saudi J Biol Sci,28,4375-4383.
2. Altınkaynak, Y,Kural, B,Akcan, BA(2018).Protective effects of L-theanine against doxorubicin-induced nephrotoxicity in rats.Biomed Pharmacother,108,1524-1534.
3. Amarasiri, SS,Attanayake, AP,Arawwawala, LDAM,Jayatilaka, KAPW,Mudduwa, LKB(2020).Protective effects of three selected standardized medicinal plants used in Sri Lankan traditional medicine on adriamycin induced nephrotoxicity in Wistar rats.J Ethnopharmacol,259,112933.
4. Anon(1985).Anon. Ayurveda Pharmacopoeia. Colombo: Sri Lanka: Department of Ayurveda; 1985..
5. Awdishu, L,Mehta, RL(2017).The 6R's of drug induced nephrotoxicity.BMC Nephrol,18(1),124.
6. Bancroft, JD,Gamble, M(2004).Theory and Practice of Histological Techniques.New York:Churchill Livingstone.
7. Banerjee, S,Banerjee, S,Jha, GK,Bose, S(2021).Barleria prionitis L.: an illustrative traditional, phytochemical and pharmacological review.Nat Prod J,3,258-274.
8. Benzer, F,Kandemir, FM,Kucukler, S,Comaklı, S,Caglayan, C(2018).Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in Wistar rats: by modulating inflammatory cytokines, apoptosis, oxidative stress and oxidative DNA damage.Arch Physiol Biochem,124,448-457.
9. Blois, M(1958).Antioxidant determinations by the use of a stable free radical.Nature,181,1199-1200.
10. Chinnappan, SM,George, A,Thaggikuppe, P(2019).Nephroprotective effect of herbal extract Eurycoma longifolia on paracetamol-induced nephrotoxicity in rats.Evid Based Complement Alt Med,2019,1-6.
11. Chu, CD,Powe, NR,McCulloch, CE(2021).Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use among hypertensive US adults with albuminuria.Hypertension,77(1),94-102.
12. Eid, SY,Althubiti, MA,Wink, M,El-Readi, MZ(2020).The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes.Phytomedicine,77,153280.
13. Farnsworth, NR(1996).Biological and phytochemical screening of plants.J Pharmaceut Sci,55,225-276.
14. Gabelova, A,Kozics, K,Kapka-Skrzypczak, L,Kruszewski, M,Sramkova, M(2019).Nephrotoxicity: topical issue.Mutat Res Genet Toxicol Environ Mutagen,845,402988.
15. Gangaram, S,Naidoo, Y,Dewir, YH,El-Hendawy, S(2022).Phytochemicals and biological activities of Barleria (Acanthaceae).Plants,11(1),82.
16. Heidari-Soreshjani, S,Asadi-Samani, M,Yang, Q,Saeedi-Boroujeni, A(2017).Phytotherapy of nephrotoxicity induced by cancer drugs: an updated review.J Nephropathol,6,254-263.
17. Heravi, NE,Hosseinian, S,Yazd, ZN(2018).Doxorubicin-induced renal inflammation in rats: protective role of Plantago major.Avicenna J Phytomed,8,179-187.
18. Hübschmann, HJ(2015).Handbook of GC-MS: Fundamentals and Applications.John Wiley and Sons.
19. Iahtisham-Ul-Haq,Butt, MS,Randhawa, MA,Shahid, M(2019).Nephroprotective effects of red beetroot-based beverages against gentamicin-induced renal stress.J Food Biochem,e12873.
20. Insaf, A,Raju, PN(2019).Potential of pure phytoconstituents and herbs in theprotection of drug induced nephrotoxicity.Indian J Pharm Educ Res,53,400-413.
21. Khadse, CD,Kakde, RB(2011).Anti-inflammatory activity of aqueous extract fractions of Barleria prionitis L. roots.Asian J Plant Sci Res,1,63-68.
22. Lahlou, M(2013).The success of natural products in drug discovery.Pharmacol Pharm,4,17-31.
23. Liur, YQ,Wang, XL,He, DH,Cheng, YX(2020).Protection against chemotherapy-and radiotherapy-induced side effects: a review based on the mechanisms and therapeutic opportunities of phytochemicals.Phytomedicine,80,153402.
24. Mohan, M,Kamble, S,Gadhi, P,Kasture, S(2010).Protective effect of Solanum torvum on doxorubicin-induced nephrotoxicity in rats.Food Chem Toxicol,48,436-476.
25. Mohebbati, R,Shafei, MN,Beheshti, F(2017).Mixed hydroalcoholic extracts of Nigella sativa and Curcuma longa improves adriamycin-induced renal injury in rat.Saudi J Kidney Dis Transplant,28,1270-1281.
26. Nair, AB,Jacob, S(2016).A simple practice guide for dose conversion between animals and human.J Basic Clin Pharm,7,27-31.
27. National Institutes of Health(1985).Guide for the Care and Use of Laboratory Animals.National Academies.
28. Prsa, P,Karademir, B,Biçim, G(2019).The potential use of natural products to negate hepatic, renal and neuronal toxicity induced by cancer therapeutics.Biochem Pharmacol,173,113551.
29. Qi, Y,Xiao, H,Xu, C,Tian, X,Wu, H,Shen, W(2012).Cyprinus carpio decoction improves nutrition and immunity and reduces proteinuria through nephrin and CD2AP expressions in rats with adriamycin-induced nephropathy.Evid Based Complement Alt Med,2012,1-8.
30. Rajasekaran, M(2019).Nephroprotective effect of Costus pictus extract against doxorubicin-induced toxicity on Wistar rat.Bangladesh J Pharmacol,14,93-100.
31. Rokade, SS,Joshi, KA,Mahajan, K(2017).Novel anticancer platinum and palladium nanoparticles from Barleria prionitis.Glob J Nanomed,2(5),555600.
32. Safhi, MM(2018).Nephroprotective effect of zingerone against CCl4-induced renal toxicity in Swiss albino mice: molecular mechanism.Oxid Med Cell Longev,2018,1-7.
33. Sherma, J(ed.),Fried, B(ed.)(2003).Handbook of Thin-Layer Chromatography.CRC press.
34. Siddhuraju, P,Becker, K(2003).Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves.J Agric Food Chem,51,2144-2155.
35. Singleton, VL,Orthofer, R,Lamuela-Raventos, RM(1999).Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin- Ciocaltue reagent.Methods Enzymol,299,152-178.
36. Tiong, HY,Huang, P,Xiong, S,Li, Y,Vathsala, A,Zink, D(2014).Drug-induced nephrotoxicity: clinical impact and preclinical in vitro models.Mol Pharm,11(7),1933-1948.
37. Wu, Q,Li, W,Zhao, J(2021).Apigenin ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation.Biomed Pharmacother,137,111308.
38. Zhu, F,Du, B,Xu, B(2018).Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: a review.Crit Rev Food Sci Nutr,58(8),1260-1270.