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Andrographolide Reduces Neuroinflammation and Oxidative Stress in Aged Octodon degus

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Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder in which superior brain functions, such as memory and cognition, are impaired. Currently, no effective treatment is available for AD. Although andrographolide (ANDRO), a compound extracted from the herb Andrographis paniculata, has shown interesting effects in models of several diseases, including AD, its effects on other molecular changes observed in AD, such as neuroinflammation and oxidative stress, have not yet been studied. To evaluate the impact of ANDRO-based intervention on the levels of amyloid-β (Aβ) and neuroinflammatory and oxidative stress markers in the brains of aged Octodon degus, a Chilean rodent, fifty-six-month-old O. degus were treated intraperitoneally with 2 or 4 mg/kg ANDRO. Vehicle-injected and 12-month-old O. degus were used as positive controls. Then, the protein levels of selected markers were assessed via immunohistochemistry and immunoblotting. ANDRO significantly reduced the total Aβ burden as well as astrogliosis and interleukin-6 levels. Moreover, ANDRO significantly reduced the levels of 4-hydroxynonenal and N-tyrosine adducts, suggesting a relevant reduction in oxidative stress within aged O. degus brain. Considering that O. degus has been proposed as a potential “natural” model for sporadic AD due to the development of neuropathological markers that resemble this pathology, our results suggest that ANDRO should be further studied to establish its potential as a therapeutic drug for AD.

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Acknowledgments

We thank the “Lithium in Health and Disease” project from the Sociedad Química y Minera de Chile (SQM).

Funding

This work was supported by a postdoctoral grant from FONDECYT (N° 3,140,395 to DSR and N° 11,160,651 to PC) and by grants from the Basal Center of Excellence in Science and Technology (CONICYT PIA/BASAL FB0002 to FB 0002–2014 (Line 3), CONICYT-AFB 170005 and FONDECYT N° 1,160,724 to NCI).

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  1. Daniela S. Rivera

    Present address: GEMA Center for Genomics, Ecology & Environment, Universidad Mayor, Camino La Piramide, 5750, Huechuraba, Santiago, Chile

Authors and Affiliations

  1. Center of Aging and Regeneration UC (CARE UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda Bernardo O’Higgins 340, P. O. Box 114, -D, Santiago, Chile

    Carolina B. Lindsay, Juan M. Zolezzi, Daniela S. Rivera, Pedro Cisternas & Nibaldo C. Inestrosa

  2. Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile

    Juan M. Zolezzi & Nibaldo C. Inestrosa

  3. Center for Applied Ecology and Sustainability (CAPES), Departamento de Ecología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

    Daniela S. Rivera & Francisco Bozinovic

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Contributions

CL contributed to the western blot analyses and the drafting of this work; JMZ prepared and critically revised the final draft of this manuscript; DSR administered the ANDRO and vehicle solution and manuscript revision; PC contributed to the immunofluorescence analysis and to manuscript revision; NCI and FB contributed to the conception and design of this work as well as the revision of the final manuscript.

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Correspondence to Nibaldo C. Inestrosa.

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Lindsay, C.B., Zolezzi, J.M., Rivera, D.S. et al. Andrographolide Reduces Neuroinflammation and Oxidative Stress in Aged Octodon degus. Mol Neurobiol 57, 1131–1145 (2020). https://doi.org/10.1007/s12035-019-01784-6

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