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

Abstract

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.

• Authors: Yannong Dou, Jinque Luo, Xin Wu, Zhifeng Wei, Bei Tong, Juntao Yu, Ting Wang, Xinyu Zhang, Yan Yang, Xusheng Yuan, Peng Zhao, Yufeng Xia, Huijuan Hu, Yue Dai
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 15 Issue 1 Pg. 6 (Jan 06 2018) ISSN: 1742-2094 [Electronic] England
• PMID: 29306322 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Membrane Transport Proteins
• Nicotinic Antagonists
• choline transporter
• Choline O-Acetyltransferase
• Curcumin
• Acetylcholine

Topics

• Acetylcholine (antagonists & inhibitors, metabolism)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Arthritis, Experimental (drug therapy, metabolism, pathology)
• Brain (drug effects, metabolism)
• Cells, Cultured
• Choline O-Acetyltransferase
• Curcumin (pharmacology, therapeutic use)
• Female
• Gastrointestinal Tract (drug effects, metabolism)
• Membrane Transport Proteins (metabolism)
• Nicotinic Antagonists (pharmacology)
• Nodose Ganglion (drug effects, metabolism)
• Random Allocation
• Rats
• Rats, Wistar
• Vagotomy (trends)
• Vagus Nerve (surgery)