MULTI-MODAL ASSESSMENT OF NEPHROPROTECTIVE PROPERTIES OF MICHELIA CHAMPACA: IN VITRO AND IN VIVO INVESTIGATIONS
Main Article Content
Keywords
Nephroprotective activity, Michelia champaca, In silico, HEK-293 cells, gentamicin-induced nephrotoxicity
Abstract
This research aims to investigate the in vitro and in vivo nephroprotective activity of Michelia champaca leaves extracts in gentamicin-induced nephrotoxicity rats. The flavonoid and phenols-rich fractions of Michelia champaca leaves extract were subjected to in silico methods based on in vitro investigations, using renal target proteins. The results of the in vitro antioxidant study of extracts were tested for cytoprotective MTT assay and anti-inflammatory efficacy by protein denaturation assay using human embryonic kidney cells (HEK293). The in vivo nephroprotective potential of the extract was evaluated at a lower dose of 250 mg/kg and a higher dose of 500 mg/kg body weight in gentamicin-induced nephrotoxicity in rats with histopathological investigations. The Michelia champaca hydroalcoholic extract (MCHAE) shows remarkable binding affinity with bonding interactions of flavonoids and phenolics-based ligands observed with the target proteins that provided early information. The in vitro cell lines study revealed no cytotoxicity and better anti-inflammatory effect on HEK293 cells with cytoprotective and nephroprotective efficacy of MCHAE. The in vivo nephroprotective activity improved at a dose of 500mg/kg of MCHAE than Michelia champaca ethanolic extract (MCEE). Histopathological investigations revealed the improvement in gentamicin-induced renal toxicity by the MCHAE orally treated group compared to other groups. These results of MCHAE are more effective than MCEE and have a marked in vitro antioxidant, and cytoprotective effect in HEK293 cell lines, with good interaction scores of ligands in molecular docking studies with nephroprotective potential benefits in gentamicin-induced nephrotoxicity in rats.
References
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11. Abdou RM, El-Maadawy WH, Hassan M, El-Dine RS, Aboushousha T, El-Tanbouly ND, et al. Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: A mechanistic study. J Ethnopharmacol. 2021;273.
12. George B, Joy MS, Aleksunes LM. Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy. Exp Biol Med. 2018 Feb 1;243(3):272–82.
13. Irvine AR, van Berlo D, Shekhani R, Masereeuw R. A systematic review of in vitro models of drug-induced kidney injury. Curr Opin Toxicol. 2021;27(June):18–26.
14. Wilmer MJ, Ng CP, Lanz HL, Vulto P, Suter-Dick L, Masereeuw R. Kidney-on-a-Chip Technology for Drug-Induced Nephrotoxicity Screening. Vol. 34, Trends in Biotechnology. Elsevier Ltd; 2016. p. 156–70.
15. Downes KJ, Hayes M, Fitzgerald JC, Pais GM, Liu J, Zane NR, et al. Mechanisms of antimicrobial-induced nephrotoxicity in children. J Antimicrob Chemother. 2020 Jan 1;75(1):1–13.
16. Al-Kuraishy H, Al-Gareeb A, Al-Nami M. Irbesartan attenuates gentamicin-induced nephrotoxicity in rats through modulation of oxidative stress and endogenous antioxidant capacity. Int J Prev Med. 2020 Jan 1;11(1).
17. Jain A, Nahata A, Singhai AK. Effect of tephrosia purpurea (L.) pers. leaves on gentamicin-induced nephrotoxicity in rats. Sci Pharm. 2013;81(4):1071–87.
18. Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: An integrative point of view. Vol. 79, Kidney International. Nature Publishing Group; 2011. p. 33–45.
19. Abdelrahman RS. Protective effect of apocynin against gentamicin-induced nephrotoxicity in rats. Hum Exp Toxicol. 2018 Jan 1;37(1):27–37.
20. Israa M, Mokhtar Y, Thanaa S, Osama M. The protective role of tannic acid against possible hepato-nephrotoxicity induced by silver nanoparticles on male rats. Sanamed. 2019;14(2):131–45.
21. Cao YL, Lin JH, Hammes HP, Zhang C. Flavonoids in Treatment of Chronic Kidney Disease. Molecules. 2022;27(7):1–23.
22. Tolouian R, Tolouian A, Dastan F, Farhangi V, Peymani P, Saeifar S, et al. Antioxidants and cisplatin nephrotoxicity; an updated review on current knowledge. J Nephropharmacology. 2023;12(1):1–5.
23. Kiliś-Pstrusińska K, Wiela-Hojeńska A. Nephrotoxicity of herbal products in europe—a review of an underestimated problem of nephrotoxicity of herbal products. Int J Mol Sci. 2021;22(8).
24. Gamaan M, Zaky H, Ahmed H. Gentamicin-induced nephrotoxicity: A mechanistic approach. Azhar Int J Pharm Med Sci. 2023;0(0):0–0.
25. Delavar MA, Soheilirad Z. Drug and herbal medicine-induced nephrotoxicity in children; review of the mechanisms. J Ren Inj Prev [Internet]. 2020;9(3):e21–e21. Available from: https://doi.org/10.34172/jrip.2020.21
26. Fontecha-Barriuso M, Martín-Sanchez D, Martinez-Moreno JM, Cardenas-Villacres D, Carrasco S, Sanchez-Niño MD, et al. Molecular pathways driving omeprazole nephrotoxicity. Redox Biol [Internet]. 2020;32(February):101464. Available from:
https://doi.org/10.1016/j.redox.2020.101464
27. Zygler A, Słomińska M, Namieśnik J. Soxhlet extraction and new developments such as soxtec. Compr Sampl Sample Prep Anal Tech Sci. 2012;2:65–82.
28. Luque de Castro MD, Ruiz Jiménez J, García Ayuso LE. Environmental Applications | Soxhlet Extraction. Ref Modul Chem Mol Sci Chem Eng. 2013;(June):1–8.
29. Mukherjee PK. Extraction and Other Downstream Procedures for Evaluation of Herbal Drugs. Quality Control and Evaluation of Herbal Drugs. 2019. 195–236 p.
30. Paul D P, Danielle R, Kevin R. Handbook of Antioxidant Methodology: Approaches to Activity Determination. 2021.
31. Prakash J, Geetha KN, Jeyaprakash K, Nagaraja YP. A preliminary pharmacognostical study on leaves and flowers of Michelia champaca L. Magnoliaceae. J Appl Nat Sci [Internet]. 2011;3(2):228–31. Available from: www.ansfoundation.org
32. Karthikeyan V, Palanisamy S. Pharmacognostical, Phyto-Physicochemical Profile of the Leaves of Michelia champaca Linn Antitubercular activity of medicinal Plants View project [Internet]. Available from: www.ijppr.humanjournals.com
33. Jan S, Khan MR, Rashid U, Bokhari J. Assessment of Antioxidant Potential, Total Phenolics and Flavonoids of Different Solvent Fractions of Monotheca Buxifolia Fruit. Osong Public Heal Res Perspect [Internet]. 2013;4(5):246–54. Available from:
http://dx.doi.org/10.1016/j.phrp.2013.09.003
34. Adebiyi OE, Olayemi FO, Ning-Hua T, Guang-Zhi Z. In vitro antioxidant activity, total phenolic and flavonoid contents of ethanol extract of stem and leaf of Grewia carpinifolia. Beni-Suef Univ J Basic Appl Sci [Internet]. 2017;6(1):10–4. Available from: http://dx.doi.org/10.1016/j.bjbas.2016.12.003
35. Robert B, Brown EB. No 主観的健康感を中心とした在宅高齢者における 健康関連指標に関する共分散構造分析Title. 2004. 1–14 p.
36. Ali BM, Boothapandi M, Sultan Nasar AS. Nitric oxide, DPPH and hydrogen peroxide radical scavenging activity of TEMPO terminated polyurethane dendrimers: Data supporting antioxidant activity of radical dendrimers. Data Br [Internet]. 2020;28:104972. Available from: https://doi.org/10.1016/j.dib.2019.104972
37. Riley R, Chapman V. © 1958 Nature Publishing Group. 1958;
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Aug 16, 2022
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Durgesh T. Gautam, T. Venkatachalam, & S. R. Senthilkumar. (2022). MULTI-MODAL ASSESSMENT OF NEPHROPROTECTIVE PROPERTIES OF MICHELIA CHAMPACA: IN VITRO AND IN VIVO INVESTIGATIONS. Journal of Population Therapeutics and Clinical Pharmacology, 29(03), 501–516. https://doi.org/10.53555/jptcp.v29i03.3972
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Author Biographies
Durgesh T. Gautam
1Research scholar, JKKMMRF’s Annai JKK Sampoorani Ammal College of Pharmacy Ethirmedu, Valayakaranoor, Post Komarapalayam, Namakkal Dist. The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, 638 183 India. Contact number: +91-9595436648 ORCID id: https://orcid.org/0000-0002-7669-9618
T. Venkatachalam
Professor; Department of Pharmaceutical Chemistry, JKKMMRF’s Annai JKK Sampoorani Ammal College of Pharmacy Ethirmedu, Valayakaranoor, Post Komarapalayam, Namakkal Dist. The Tamil Nadu Dr. MGR Medical University, Chennai, Tamil Nadu, 638 183 India.
Contact number: +91-9843441716 https://orcid.org/0000-0002-9897-5757
S. R. Senthilkumar
3Professor, Department of Pharmaceutics, Arulmigmu Kalasalingam College, College of Pharmacy, Anand Nagar, Krishnankoil Srivilliputhur (via) Virudhunagar (Dt.), The Tamil Nadu Dr. MGR University, Tamil Nadu State – 626 126 India. Contact number: +91-9443353226