Exploring the Neuroprotective Properties of Capsanthin - Antioxidant Defense and Inflammatory Responses

Sep 30, 2026

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Capsanthin is a xanthophyll carotenoid with strong antioxidant potential. The study tests whether capsanthin protects RA-differentiated SH-SY5Y neuron-like cells from glutamate-induced excitotoxic stress by evaluating cell viability, ROS production, antioxidant defense markers, mitochondrial ATP status, inflammatory cytokine release, and apoptosis-related endpoints. Glutamate elevates oxidative stress, shifts cytokines toward a pro-inflammatory pattern, lowers ATP, and promotes pro-apoptotic gene expression, while capsanthin attenuates ROS, stabilizes antioxidant enzymes, reduces pro-inflammatory cytokines, supports anti-inflammatory signaling, and preserves ATP to mitigate neuronal damage.

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Abstract

Introduction

Article Exploring the Neuroprotective Properties of Capsanthin: Antioxidant Defense and Inflammatory Responses Ramóna Pap 1, *, Edina Pandur 1, Gergely Jánosa 1, Adrienn Horváth 1, Kitti Tamási 1, Katalin Sipos 1, Attila Agócs 2 and József Deli 2,3 Academic Editors: Begoña Olmedilla-Alonso and Elena Rodríguez Rodríguez Received: 14 November 2025 Revised: 15 December 2025 Accepted: 16 December 2025 Published: 19 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary; [pandur.edina@gytk.pte.hu](pandur.edina@gytk.pte.hu) (E.P.); [janosa.gergely@gytk.pte.hu](janosa.gergely@gytk.pte.hu) (G.J.); [horvath.adrienn2@pte.hu](horvath.adrienn2@pte.hu) (A.H.); [tamasi.kitti@gytk.pte.hu](tamasi.kitti@gytk.pte.hu) (K.T.); [sipos.katalin@gytk.pte.hu](sipos.katalin@gytk.pte.hu) (K.S.) 2 Department of Biochemistry and Medical Chemistry, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary; [attila.agocs@aok.pte.hu](attila.agocs@aok.pte.hu) (A.A.); [deli.jozsef@gytk.pte.hu](deli.jozsef@gytk.pte.hu) (J.D.) 3 Department of Pharmacognosy, Faculty of Pharmacy, University of Pécs, Rókus u. 2, H-7624 Pécs, Hungary * [Correspondence: pap.ramona@pte.hu](Correspondence: pap.ramona@pte.hu) Abstract Background/Objectives: Capsanthin is a xanthophyll carotenoid from Capsicum species with an extended conjugated polyene chain that underlies both its orange–red color and strong antioxidant potential. In this study, we investigated whether capsanthin protects RA-differentiated SH-SY5Y neuron-like cells against glutamate-induced stress. Methods: Neuronal dysfunction was induced by glutamate exposure, and capsanthin treatment was evaluated using cell viability, reactive oxygen species (ROS) production, antioxidant defense markers, inflammatory cytokines, mitochondrial energy status, and apoptosis-related endpoints. Antioxidant responses were assessed using superoxide dismutase, catalase, glutathione peroxidase activities, and total antioxidant capacity. Cytokine release (TNFα, IL-6, IL-8, IL-4, IL-10) was quantified by ELISA. Mitochondrial function was monitored using ATP content. Apoptosis-associated genes (BAX, BCL-2, CASP3, and CASP9) were analyzed using SYBR Green-based RT-qPCR, complemented by caspase-9 ELISA and caspase-3 Western blotting. Results: Glutamate increased oxidative stress and shifted the cytokine profile toward a pro-inflammatory state, accompanied by reduced ATP levels and a pro-apoptotic transcriptional pattern. Capsanthin significantly attenuated glutamate-induced ROS production, stabilized antioxidant enzyme activities and total antioxidant capacity, reduced pro-inflammatory cytokines while supporting anti-inflammatory signaling, and preserved ATP levels. Conclusions: Overall, capsanthin mitigated excitotoxic stress by maintaining redox balance, limiting inflammatory responses, and protecting mitochondrial energy metabolism in neuron-like cells, supporting its potential as a neuroprotective candidate for glutamate-induced neuronal stress. Keywords: capsanthin; glutamate; oxidative stress; inflammation; antioxidants; neuron 1. Introduction Carotenoids are natural lipid-soluble isoprenoid pigments found in plants, algae, fungi, and some bacteria, and they possess well-documented antioxidant and anti-inflammatory properties [1] . Beyond reactive oxygen species (ROS) scavenging, they are able to modulate membrane properties andredox-sensitive signaling pathways that influence inflammation and cell survival [2,3] . These features are relevant to neurodegenerative conditions, where oxidative stress and neuroinflammatory signaling often converge with excitotoxic mechanisms driven by glutamate [4] . Glutamate is the ma

FAQs

What is the main objective of the capsanthin study?

To determine whether capsanthin protects RA-differentiated SH-SY5Y neuron-like cells against glutamate-induced stress by addressing oxidative, inflammatory, mitochondrial, and apoptotic pathways.

How is glutamate-induced neuronal dysfunction modeled?

Neuronal dysfunction is induced by glutamate exposure, which triggers oxidative stress, pro-inflammatory cytokine shifts, reduced mitochondrial ATP, and pro-apoptotic signaling.

Which outcomes show capsanthin’s protective effect?

Capsanthin reduces glutamate-driven ROS production, stabilizes antioxidant defense activities and total antioxidant capacity, lowers pro-inflammatory cytokines while supporting anti-inflammatory signaling, and preserves ATP levels, helping limit apoptotic progression.

Sep 30, 2026

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