Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, China.
Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA, 19102, USA.
J Neuroinflammation. 2018 Jan 6;15(1):6. doi: 10.1186/s12974-017-1047-7.
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.
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.
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.
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.
先前的研究表明，尽管姜黄素的生物利用度较差，但口服姜黄素仍具有抗关节炎作用。本研究旨在探讨肠-脑轴是否参与姜黄素的治疗作用。
采用 II 型胶原和完全弗氏佐剂乳化液免疫诱导胶原诱导性关节炎（CIA）大鼠模型。通过心电图记录测量交感和副交感神经张力。在 CIA 诱导前进行单侧颈迷走神经切断术（VGX）。通过 ELISA 测定胆碱乙酰转移酶（ChAT）、乙酰胆碱酯酶（AChE）活性和血清细胞因子水平。通过实时 PCR 和免疫组织化学染色测定高亲和力胆碱转运体 1（CHT1）、ChAT 和囊泡乙酰胆碱转运体（VAChT）的表达。通过全细胞膜片钳记录测定迷走神经的神经元兴奋性。
口服姜黄素恢复了 CIA 大鼠交感和副交感神经张力的失衡，并增加了肠道、大脑和滑膜中 ChAT 活性和 ChAT、VAChT 的表达。此外，VGX 消除了姜黄素对关节炎和 ACh 生物合成和转运的影响。电生理数据表明，姜黄素显著增加了迷走神经神经元的兴奋性。此外，选择性 α7 nAChR 拮抗剂消除了姜黄素对 CIA 的作用。
我们的结果表明，姜黄素通过调节胆碱能系统的功能，通过“肠-脑轴”减轻 CIA。这些发现为研究口服吸收和生物利用度低的抗关节炎化合物的作用机制提供了一种新方法。
