RT journal article
T1 Anti-Inflammatory Effects of the Algal Diterpenoid Ruguloptone A by Modulation of M2 Response in Early Diabetic Retinopathy
A1 Cuevas, Belén
A1 Zubía Mendoza, Eva
A1 Martín Loro, Francisco
A1 Arroba Espinosa, Ana Isabel
A2 Anatomía y Embriología Humana
A2 Química Orgánica
K1 diabetic retinopathy
K1 M2 response
K1 algal diterpenoids
K1 inflammation
AB Background/Objectives: Inflammation is a critical contributor to the development of diabetic retinopathy (DR). In the early stages of DR, the compromised permeability of the blood–retina barrier facilitates the infiltration of macrophages and the activation of microglia. These specific retinal immune cells can adopt morphologies M1 or M2, linked to pro- or anti-inflammatory responses, respectively. This dual response represents a new therapeutic target against DR progression. This study aimed to investigate the modulation of the response M1/M2 and the molecular mechanism of two algal diterpenoids, rugukadiol A (RK) and ruguloptone A (RL), in the early inflammatory events associated with DR. Methods: LPS-stimulated microglial (Bv.2) and macrophage (RAW264.7) cells and an ex vivo physiological model of DR were used to analyze the effects of RK and RL on M1 and M2 inflammatory markers. Results: Compounds RK and RL, besides decreasing the expression of the M1 pro-inflammatory factors iNOS, Il6 mRNA, and NLRP3 in LPS-stimulated Bv.2 cells, caused enhancements in Arg-1 mRNA and Il10 mRNA expression consistent with the induction of an M2 anti-inflammatory response. RK promoted p38α-MAPK phosphorylation, suggesting a non-classical activation of p38α related to the induction of anti-inflammatory responses. Consistently, treatment of retinal explants of BB rats in the early stages of DR with RL decreased M1 pro-inflammatory mediators and induced M2 anti-inflammatory markers, with a reduction in gliosis and a phenotype switch from activated to resting microglia. Conclusions: This study provides the first evidence of algal diterpenoids attenuating pro-inflammatory mediators and promoting the resolution of inflammation in a diabetic retinopathy context, thus opening the way to further explore this class of marine natural products and analogs for early DR management.
PB MDPI
SN 1999-4923
YR 2026
FD 2026-05-15
LK http://hdl.handle.net/10498/40525
UL http://hdl.handle.net/10498/40525
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 06-nov-2026