Naru-3 inhibits inflammation, synovial hyperplasia, and neovascularization in collagen-induced arthritis in rats. (15th July 2023)

• Record Type: Journal Article
• Authors: Zhao, Haiyue; Duan, Shasha; Shi, Yilu; Zhang, Minjie; Zhang, Lu; Jin, Zhiyuan; Fu, Wenyan; Xiao, Wuping; Bai, Tianhao; Zhang, Xiaoshan; Wang, Yaxi
• Is Part Of: Journal of ethnopharmacology. Volume 311(2023)
• Publication Date: 2023-07-15
• Subjects: Naru-3 -- Rheumatoid arthritis -- Neovascularization -- Contrast-enhanced ultrasound -- Power Doppler imaging; 2D two-dimensional -- AI arthritis index -- AUC area under the curve -- CEUS contrast-enhanced ultrasound -- CIA collagen-induced arthritis -- CMC carboxymethylcellulose -- DMARDs disease-modifying antirheumatic drugs -- ETN etanercept -- H&E hematoxylin and eosin -- IL-1β Interleukin-1 beta -- PDI power Doppler imaging -- PI peak intensity -- RA rheumatoid arthritis -- S slope -- TIC time intensity curve -- TNF tumor necrosis factor -- TTP time to peak -- VEGF vascular endothelial growth factor; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2023.116350
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Naru-3 is a prescribed formulation based on the theory of Mongolian medicine for the treatment of rheumatoid arthritis (RA). Naru-3 consists of three medicinal agents: Aconitum kusnezoffii Reichb (caowu), Terminalia chebula Retz (hezi), and Piper longum L (biba). These medicinal agents are widely distributed in the Mongolian area of China and have been used to treat rheumatism for centuries. Background: Mongolian medicine Naru-3 is commonly prescribed to treat RA, but its mechanism of action is unknown. Methods: A rat collagen-induced arthritis (CIA) model was established to investigate the mechanism of Naru-3. Rats were treated with Naru-3, Etanercept (ETN), and sodium carboxymethylcellulose (CMC) for four weeks. After treatment was terminated, paw thickness, ankle diameter, and arthritis index (AI) were scored. Synovial hyperplasia was evaluated using hematoxylin and eosin (H&E) staining and two-dimensional ultrasonography. Synovitis and neovascularization were assayed using power Doppler imaging (PDI) and contrast-enhanced ultrasonography (CEUS). Levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1, and CD31 in the serum or synovium were detected using ELISA and immunohistochemistry analyses. Results: Naru-3 and ETN alleviated the symptoms of CIA as evidenced by diminished paw thickness, ankle diameter, and AI scores. Mechanistically, Naru-3 inhibited synovial hyperplasia, synovitis, and neovascularization by diminishing systemic and local inflammation, as indicated by the relative expression of CD31, VEGF and IL-1 in the serumor synovium. After four weeks of treatment, no significant neovascularization was observed in the Naru-3 group, but neovascularization and synovitis occurred in the ETN group, as demonstrated by H&E staining, PDI, and CEUS examination. Conclusion: Naru-3 inhibited inflammation, synovial hyperplasia, and neovascularization and alleviates RA in our CIA rat model. No symptom recurrence was observed four weeks after drug treatment. Graphical abstract: Image 1 Highlights: This paper illustrats the mechanisms of action of Naru-3 in the treatment of RA through inhibition of synovial neovascularization. No symptom recurrence is observed four weeks after Naru-3 treatment. CEUS for evaluating synovial neovascularization provides reference for clinical visualization evaluation of drug efficacy.