Curcumin attenuates collagen-induced inflammatory response through the “gut-brain axis”

Abstract

BackgroundPrevious studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin.MethodsThe collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund’s adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings. Unilateral cervical vagotomy (VGX) was performed before the induction of CIA. The ChAT, AChE activities, and serum cytokine levels were determined by ELISA. The expression of the high-affinity choline transporter 1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) were determined by real-time PCR and immunohistochemical staining. The neuronal excitability of the vagus nerve was determined by whole-cell patch clamp recording.ResultsOral administration of curcumin restored the imbalance between the sympathetic and parasympathetic tones in CIA rats and increased ChAT activity and expression of ChAT and VAChT in the gut, brain, and synovium. Additionally, VGX eliminated the effects of curcumin on arthritis and ACh biosynthesis and transport. Electrophysiological data showed that curcumin markedly increased neuronal excitability of the vagus nerve. Furthermore, selective α7 nAChR antagonists abolished the effects of curcumin on CIA.ConclusionsOur results demonstrate that curcumin attenuates CIA through the “gut-brain axis” by modulating the function of the cholinergic system. These findings provide a novel approach for mechanistic studies of anti-arthritic compounds with low oral absorption and bioavailability.

Immunotoxicity evaluation by subchronic oral administration of clothianidin in Sprague-Dawley rats

“…In fact, anticholinergic agents are used for the treatment of diarrhea, because they slow colonic transit and improve stool consistency and frequency [35]. Increasing evidence indicates that the immune and nervous system maintain extensive interactions [12,57]. Our present results further may suggest that the homeostasis of the immune system may be disrupted via influencing the intestinal functions.…”

The Anti-Cancer Effects of Frondoside A

“…Alternatively, perhaps the immune modulatory effects are mediated by action in the gut and do not require absorption of the compound. A recent study demonstrated that curcumin, another compound with poor oral availability but potent effects on the attenuating arthritis, was mediated by increasing neuroexcitability of the vagus nerve [ 60 ]. It is interesting to speculate that frondoside A might also activate a similar gut/brain axis.…”

Curcumin for the Management of Periodontitis and Early ACPA-Positive Rheumatoid Arthritis: Killing Two Birds with One Stone

“…Curcumin, a traditional remedy and major curcuminoid found in the spice turmeric, has been used for centuries for treating chronic inflammatory diseases [ 16 , 17 , 18 , 19 ]. Recent studies have demonstrated the decisive role of curcumin in treating autoimmune diseases [ 19 , 20 , 21 , 22 ], including experimental autoimmune arthritis, the animal model of rheumatoid arthritis (RA) [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. How curcumin exerts its beneficial effect in experimental arthritis is under investigation [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”