Curcumin attenuates collagen-induced inflammatory response through the "gut-brain axis".
BACKGROUND
Previous 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.


METHODS
The 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.


RESULTS
Oral 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.


CONCLUSIONS
Our 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.
['Dou|Yannong|Y|', 'Luo|Jinque|J|', 'Wu|Xin|X|', 'Wei|Zhifeng|Z|', 'Tong|Bei|B|', 'Yu|Juntao|J|', 'Wang|Ting|T|', 'Zhang|Xinyu|X|', 'Yang|Yan|Y|', 'Yuan|Xusheng|X|', 'Zhao|Peng|P|', 'Xia|Yufeng|Y|', 'Hu|Huijuan|H|', 'Dai|Yue|Y|http://orcid.org/0000-0003-0118-8984']
D000109:Acetylcholine D000818:Animals D000894:Anti-Inflammatory Agents, Non-Steroidal D001169:Arthritis, Experimental D001921:Brain D002478:Cells, Cultured D002795:Choline O-Acetyltransferase D003474:Curcumin D005260:Female D041981:Gastrointestinal Tract D026901:Membrane Transport Proteins D018733:Nicotinic Antagonists D009620:Nodose Ganglion D011897:Random Allocation D051381:Rats D017208:Rats, Wistar D014628:Vagotomy D014630:Vagus Nerve
Curcumin Gut-brain axis Collagen-induced arthritis Unilateral cervical vagotomy α7 nAChR Nodose ganglion neurons