Title:
Rutin from Ruta Chalapensis Mitigates Rotenone-Induced Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis
Author:
Jayanthi P1, Shobana C2*
. 1Department of Biochemistry, School of Life Sciences, Vels Institute of Science, Technology and Advanced Studies, Chennai, Tamil Nadu, India.
2*Associate Professor, Department of Biochemistry, School of Life Sciences, Vels Institute of Science, Technology and Advanced Studies, Chennai, Tamil Nadu, India.
Received: 14th Aug, 2025; Revised: 19th Sep 2025; Accepted: 20th Nov, 2025; Available Online: 30th Nov, 2025
ABSTRACT
This study intends to employ an in vitro model to investigate whether rutin, a plant-derived flavanol glycoside, may protect neurons against oxidative stress, mitochondrial malfunction, and cell death caused by rotenone. According to the MTT viability test, SH-SY5Y cells were assigned to four different experimental groups. The groups comprised rotenone (100 nM), a control, rutin (10 µM) alone, and rutin (10 µM) in combination with rotenone (100 nM). Rotenone caused mitochondrial malfunction, oxidative stress, and cytotoxicity in SH-SY5Y cells. Rutin, however, markedly reduced the intensity of these effects. The protective effect of rutin against rotenone was evident from its ability to boost Bcl-2 expression and inhibit Bax and caspase-3 activation. Rutin was found to protect cells by modulating the production of p-AKT, p-GSK-3 beta, and p-PI3K. Through regulation of PI3K/Akt/GSK-3β signaling, rutin suppressed oxidative toxicity, preserved mitochondrial integrity, and limited rotenone-induced apoptosis. Additional research in rats is required to fully determine rutin’s effectiveness as a prospective Parkinson’s disease therapy.
Keywords: Rutin, Ruta chalepensis, Rotenone, Mitochondrial dysfunction, Oxidative stress, PI3K/Akt/GSK-3β pathway.
How to cite this article: Jayanthi P, Shobana C. Rutin from Ruta chalapensis mitigates rotenone-induced mitochondrial dysfunction, oxidative stress, and apoptosis.. Int J Drug Deliv Technol. 2025;15(4): 66-73
Source of support: Nil.
Conflict of interest: None
REFERENCES
- Ong WY, Farooqui T, Koh HL. Protective effects of ginseng on neurological disorders. Front Aging Neurosci. 2015;7.
- Janakiraman U, Manivasagam T, Thenmozhi AJ, Essa MM, Barathidasan R, SaravanaBabu C, et al. Influences of chronic mild stress on impairments and neurochemical variables in MPTP/probenecid neurotoxicity. PLoS One. 2016;11.
- Gandhi S, Wood NW. Molecular pathogenesis of Parkinson’s disease. Hum Mol Genet. 2005;14(18):2749–55. doi:10.1093/hmg/ddi308
- Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003;39(6):889–909. doi:10.1016/S0896-6273(03)00568-3
- Venkatesh GV, Rajasankar S, Ramkumar M, Dhanalakshmi C, Manivasagam T, Thenmozhi AJ, et al. Agaricus blazei extract attenuates rotenone-induced apoptosis in SH-SY5Y cells. Nutr Neurosci. 2016;1–11.
- Radad K, Rausch WD, Gille G. Rotenone induces cell death by increasing ROS and inhibiting mitochondrial respiration. Neurochem Int. 2006;49(4):379–86. doi:10.1016/j.neuint.2006.02.003
- Kavitha M, Manivasagam T, Essa MM, Tamilselvam K, Selvakumar GP, Karthikeyan S. Mangiferin attenuates rotenone-induced apoptosis via mitochondrial protection. Neurochem Res. 2014;39(4):668–76. doi:10.1007/s11064-014-1249-7
- Dhanalakshmi C, Manivasagam T, Nataraj J, Thenmozhi AJ, Essa MM. Neurosupportive role of vanillin against rotenone toxicity in SH-SY5Y cells. Evid Based Complement Alternat Med. 2015;626028.
- Dhanalakshmi C, Janakiraman U, Manivasagam T, Thenmozhi AJ, Essa MM, Kalandar A, et al. Vanillin attenuated behavioural impairments and oxidative stress in rotenone-induced Parkinson’s model. Neurochem Res. 2016;41(8):1899–910. doi:10.1007/s11064-016-1901-5
- Fox SH, Katzenschlager R, Lim SY, Ravina B, Seppi K, Coelho M. Evidence-based review: treatments for motor symptoms of Parkinson’s disease. Mov Disord. 2001;3:42–80.
- Selvakumar GP, Janakiraman U, Essa MM, Thenmozhi AJ, Manivasagam T. Escin attenuates impairments in chronic MPTP/probenecid mouse model of Parkinson’s disease. Brain Res. 2014;1585:23–36. doi:10.1016/j.brainres.2014.03.010
- Tamilselvam K, Braidy N, Manivasagam T, Essa MM, Prasad NR, Karthikeyan S, et al. Neuroprotective effects of hesperidin on rotenone-induced apoptosis. Oxid Med Cell Longev. 2013;102741.
- Xicoy H, Wieringa B, Martens GJ. The SH-SY5Y cell line in Parkinson’s disease research. Mol Neurodegener. 2017;12:10.
- Mosmann T. Rapid colorimetric assay for cellular growth and survival (MTT). J Immunol Methods. 1983;65(1–2):55–63.
- Sherer TB, Kim JH, Betarbet R, Greenamyre JT. Rotenone induces dopaminergic neurodegeneration. Exp Neurol. 2003;179(1):9–16.
- Wang H, Joseph JA. Quantifying oxidative stress using DCFH-DA. Free Radic Biol Med. 1999;27(5–6):612–6.
- Scaduto RC Jr, Grotyohann LW. Measurement of mitochondrial membrane potential using rhodamine 123. Biophys J. 1999;76(1):469–77.
- Ribble D, Goldstein NB, Norris DA, Shellman YG. AO/EB staining for apoptosis detection. Nat Protoc. 2005;1:259–67.
- Su CH, Kuo CL, Lu KW, Yu FS, Ma YS, Yang JL, et al. DAPI-based nuclear morphology assessment. Biotechniques. 2017;62:111–6.
- Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121–6.
- Hu S, et al. ImageJ-based densitometric analysis of Western blots. Mol Biol Rep. 2009; 36:2721–5.
- Duncan DB. Multiple range and multiple F tests. Biometrics. 1955;11(1):1–42
Back Download PDF