Intestinal and Blood-Brain Barrier Dysfunction in Lupus: Emerging Mechanisms and Modulation by Cinnamon

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with evolving pathogenesis. Biological barriers, especially intestinal and blood-brain barriers (BBBs) with their tight junctions (TJ), are gaining attention in recent years as key players in disease initiation and progression. Among natural products targeting these barriers, cinnamon is emerging as a multi-targeted modulator of TJ. This narrative review integrates current evidence about gut and brain barrier dysfunction in lupus pathogenesis and highlights, on the basis of animal studies, the potential of cinnamon as a therapeutic candidate to restore barrier integrity and attenuate immune and neuroinflammation associated with lupus. Experimental evidence from lupus models supports the role of TJ disruption in disease pathogenesis. The alteration of TJ protein distribution in the epithelial barrier is correlated with an increased permeability of the intestinal barrier and changes in the microbiota composition in lupus, with consequent alteration in the gut-liver axis, liver inflammation and oxidative stress. Pre-clinical studies have demonstrated the restorative effect of cinnamon on gut TJ and permeability, microbiota and the gut-liver axis. Moreover, accumulating data suggest BBB disruption in lupus, correlated with neuroinflammation and behavioral disturbances. A murine model demonstrates the protective effect of cinnamon on BBB, especially via TJ localization, with the alleviation of neuropsychiatric alterations. Future perspectives should focus on cinnamon's effect on the gut-brain axis and translational studies.