{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:50:29Z","timestamp":1776484229014,"version":"3.51.2"},"reference-count":44,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006111","name":"PT national funds","doi-asserted-by":"publisher","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}],"id":[{"id":"10.13039\/501100006111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The development of new therapeutic options for Parkinson\u2019s disease (PD) requires formulations able to mitigate both brain degeneration and motor dysfunctions. SC-Nanophytosomes, an oral mitochondria-targeted formulation developed with Codium tomentosum membrane polar lipids and elderberry anthocyanin-enriched extract, promote significant brain benefits on a rotenone-induced rat model of PD. In the present work, the effects of SC-Nanophytosome treatment on the skeletal muscle tissues are disclosed. It is unveiled that the rotenone-induced PD rat model exhibits motor disabilities and skeletal muscle tissues with deficient activity of mitochondrial complexes I and II along with small changes in antioxidant enzyme activity and skeletal muscle lipidome. SC-Nanophytosome treatment mitigates the impairment of complexes I and II activity, improving the mitochondrial respiratory chain performance at levels that surpass the control. Therefore, SC-Nanophytosome competence to overcome the PD-related motor disabilities should be also associated with its positive outcomes on skeletal muscle mitochondria. Providing a cellular environment with more reduced redox potential, SC-Nanophytosome treatment improves the skeletal muscle tissue\u2019s ability to deal with oxidative stress stimuli. The PD-related small changes on skeletal muscle lipidome were also counteracted by SC-Nanophytosome treatment. Thus, the present results reinforces the concept of SC-Nanophytosomes as a mitochondria-targeted therapy to address the neurodegeneration challenge.<\/jats:p>","DOI":"10.3390\/ijms242316787","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T03:32:03Z","timestamp":1701055923000},"page":"16787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mitochondrial Dysfunction in Skeletal Muscle of Rotenone-Induced Rat Model of Parkinson\u2019s Disease: SC-Nanophytosomes as Therapeutic Approach"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-2496","authenticated-orcid":false,"given":"Daniela","family":"Mendes","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-7477","authenticated-orcid":false,"given":"Francisco","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Chemistry Center-Vila Real (CQ-VR), Biological and Environment Department, School of Life and Environmental Sciences, University of Tr\u00e1s-os-Montes e Alto Douro, UTAD, P.O. Box 1013, 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5834-5253","authenticated-orcid":false,"given":"Maria Manuel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Chemistry Center-Vila Real (CQ-VR), Chemistry Department, School of Life and Environmental Sciences, University of Tr\u00e1s-os-Montes e Alto Douro, UTAD, 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula Branquinho","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4170-0092","authenticated-orcid":false,"given":"Romeu Ant\u00f3nio","family":"Videira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbadis.2009.08.013","article-title":"Mitochondrial dysfunction in Parkinson\u2019s disease","volume":"1802","author":"Winklhofer","year":"2010","journal-title":"Biochim. et Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ene.14108","article-title":"Parkinson disease","volume":"27","author":"Balestrino","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1016\/j.neuroimage.2011.12.021","article-title":"Functional brain networks and abnormal connectivity in the movement disorders","volume":"62","author":"Poston","year":"2012","journal-title":"NeuroImage"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2174\/1871527316666170124165222","article-title":"Monoamine Oxidase B Inhibitors in Parkinson\u2019s Disease","volume":"16","author":"Dezsi","year":"2017","journal-title":"CNS Neurol. Disord. - Drug Targets"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.2174\/1570159X15666170510143821","article-title":"Levodopa in Parkinson\u2019s Disease: Current Status and Future Developments","volume":"16","author":"Tambasco","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/joim.12191","article-title":"Clinical trials and late-stage drug development for Alzheimer\u2019s disease: An appraisal from 1984 to 2014","volume":"275","author":"Schneider","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3389\/fnmol.2019.00299","article-title":"Targeting Alpha-Synuclein as a Therapy for Parkinson\u2019s Disease","volume":"12","author":"Fields","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10756","DOI":"10.1523\/JNEUROSCI.23-34-10756.2003","article-title":"Mechanism of Toxicity in Rotenone Models of Parkinson\u2019s Disease","volume":"23","author":"Sherer","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/toxsci\/kfl133","article-title":"Obligatory Role for Complex I Inhibition in the Dopaminergic Neurotoxicity of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)","volume":"95","author":"Richardson","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mendes, D., Valent\u00e3o, P., Oliveira, M.M., Andrade, P., and Videira, R.A. (2021). A nanophytosomes formulation based on elderberry anthocyanins and Codium lipids to mitigate mitochondrial dysfunctions. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112157"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.algal.2015.09.020","article-title":"Decoding bioactive polar lipid profile of the macroalgae Codium tomentosum from a sustainable IMTA system using a lipidomic approach","volume":"12","author":"Melo","year":"2015","journal-title":"Algal Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0014-5793(02)03292-1","article-title":"Cardiolipin: A proton trap for oxidative phosphorylation","volume":"528","author":"Haines","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1016\/S0021-9258(18)99608-0","article-title":"Biosynthesis of Cardiolipin in Escherichia coli","volume":"242","author":"Stanacev","year":"1967","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrn3820","article-title":"Polyunsaturated fatty acids and their metabolites in brain function and disease","volume":"15","author":"Bazinet","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jff.2019.03.019","article-title":"A new insight on elderberry anthocyanins bioactivity: Modulation of mitochondrial redox chain functionality and cell redox state","volume":"56","author":"Neves","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mendes, D., Peixoto, F., Oliveira, M.M., Andrade, P.B., and Videira, R.A. (2022). Brain Effects of SC-Nanophytosomes on a Rotenone-Induced Rat Model of Parkinson\u2019s Disease\u2014A Proof of Concept for a Mitochondria-Targeted Therapy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012699"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Maga\u00f1a, J.C., Deus, C.M., Gin\u00e9-Garriga, M., Montan\u00e9, J., and Pereira, S.P. (2022). Exercise-Boosted Mitochondrial Remodeling in Parkinson\u2019s Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123228"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0022-510X(94)90248-8","article-title":"Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson\u2019s disease and multiple system atrophy","volume":"125","author":"Blin","year":"1994","journal-title":"J. Neurol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0022-510X(91)90311-T","article-title":"Respiratory chain abnormalities in skeletal muscle from patients with Parkinson\u2019s disease","volume":"104","author":"Bindoff","year":"1991","journal-title":"J. Neurol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Burtscher, J., Millet, G.P., Place, N., Kayser, B., and Zanou, N. (2021). The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126479"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Nay, K., Smiles, W.J., Kaiser, J., McAloon, L.M., Loh, K., Galic, S., Oakhill, J.S., Gundlach, A.L., and Scott, J.W. (2021). Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084052"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1055\/s-0037-1601869","article-title":"The Phenomenology of Parkinson\u2019s Disease","volume":"37","author":"Hallett","year":"2017","journal-title":"Semin. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chen, M., Wang, Y., Deng, S., Lian, Z., and Yu, K. (2022). Skeletal muscle oxidative stress and inflammation in aging: Focus on antioxidant and anti-inflammatory therapy. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.964130"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s10522-017-9710-z","article-title":"Lipid (per) oxidation in mitochondria: An emerging target in the ageing process?","volume":"18","author":"Ademowo","year":"2017","journal-title":"Biogerontology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12809","DOI":"10.1074\/jbc.M512649200","article-title":"Parkin Protects against Mitochondrial Toxins and beta-Amyloid Accumulation in Skeletal Muscle Cells","volume":"281","author":"Rosen","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.expneurol.2009.03.006","article-title":"Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson\u2019s disease","volume":"218","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.freeradbiomed.2013.04.030","article-title":"Comparative bioenergetic study of neuronal and muscle mitochondria during aging","volume":"63","author":"Li","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jnutbio.2005.05.013","article-title":"Novel mechanisms of natural antioxidant compounds in biological systems: Involvement of glutathione and glutathione-related enzymes","volume":"16","author":"Masella","year":"2005","journal-title":"J. Nutr. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative Stress and Antioxidant Defense","volume":"5","author":"Birben","year":"2012","journal-title":"World Allergy Organ J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1111\/j.1471-4159.2006.03907.x","article-title":"Oxidative stress and neurodegeneration: Where are we now?","volume":"97","author":"Halliwell","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.addr.2009.07.015","article-title":"The energy\u2013redox axis in aging and age-related neurodegeneration","volume":"61","author":"Yap","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1093\/brain\/awac176","article-title":"Lipid pathway dysfunction is prevalent in patients with Parkinson\u2019s disease","volume":"145","author":"Galper","year":"2022","journal-title":"Brain"},{"key":"ref_33","first-page":"121","article-title":"Membrane lipids as signaling molecules","volume":"18","author":"Fernandis","year":"2007","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Xicoy, H., Wieringa, B., and Martens, G.J.M. (2019). The Role of Lipids in Parkinson\u2019s Disease. Cells, 8.","DOI":"10.3390\/cells8010027"},{"key":"ref_35","first-page":"102","article-title":"Effects of lipids on mitochondrial functions","volume":"1862","author":"Doan","year":"2017","journal-title":"Biochim. et Biophys. Acta (BBA) - Mol. Cell Biol. Lipids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1017\/S0007114509992133","article-title":"Membrane fatty acid composition of rat skeletal muscle is most responsive to the balance of dietaryn-3 andn-6 PUFA","volume":"103","author":"Abbott","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_37","first-page":"e2376","article-title":"Assessment of Motor Balance and Coordination in Mice using the Balance Beam","volume":"10","author":"Luong","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jnutbio.2018.02.001","article-title":"Beneficial effects of white wine polyphenols-enriched diet on Alzheimer\u2019s disease-like pathology","volume":"55","author":"Mendes","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mendes, D., Silva, A.M., Oliveira, M.M., Andrade, P.B., and Videira, R.A. (2023). An Experimental Approach to Address the Functional Relationship between Antioxidant Enzymes and Mitochondrial Respiratory Complexes. Methods Protoc., 6.","DOI":"10.3390\/mps6020032"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0003-2697(70)90343-X","article-title":"Spectrophotometric determination of phosphate esters in the presence and absence of orthophosphate","volume":"36","author":"Bartlett","year":"1970","journal-title":"Anal. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.tiv.2004.02.009","article-title":"A comparative study of plant and animal mitochondria exposed to paraquat reveals that hydrogen peroxide is not related to the observed toxicity","volume":"18","author":"Peixoto","year":"2004","journal-title":"Toxicol. Vitr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1210\/endrev\/bnaa016","article-title":"Muscle\u2013Organ Crosstalk: The Emerging Roles of Myokines","volume":"41","author":"Severinsen","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mito.2022.05.001","article-title":"Mitochondria research and neurodegenerative diseases: On the track to understanding the biological world of high complexity","volume":"65","author":"Mendes","year":"2022","journal-title":"Mitochondrion"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S185","DOI":"10.1016\/S1353-8020(09)70811-9","article-title":"The MitoPark Mouse\u2014An animal model of Parkinson\u2019s disease with impaired respiratory chain function in dopamine neurons","volume":"15","author":"Ekstrand","year":"2009","journal-title":"Park. Relat. Disord."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/16787\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:30:54Z","timestamp":1760131854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/16787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":44,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242316787"],"URL":"https:\/\/doi.org\/10.3390\/ijms242316787","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,27]]}}}