The Protective Effects of Neoastilbin on Monosodium Urate Stimulated THP-1-Derived Macrophages and Gouty Arthritis in Mice through NF-κB and NLRP3 Inflammasome Pathways

Gouty arthritis (GA) is a frequent inflammatory disease characterized by pain, swelling, and stiffness of joints. Neoastilbin is a flavonoid isolated from the rhizome of Smilax glabra, which possesses various anti-inflammatory effects. However, the mechanism of neoastilbin in treating GA has not yet been clarified. Thus, this study was to investigate the protective effects of neoastilbin in both monosodium urate (MSU) stimulated THP-1-derived macrophages and the animal model of GA by injecting MSU into the ankle joints of mice. The levels of key inflammatory cytokines in MSU stimulated THP-1-derived macrophages were detected by enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome pathways were further detected by Western blotting. In addition, swelling degree of ankle joints, the levels of inflammatory factors, infiltration of inflammatory cells and the expressions of related proteins were determined. Swelling degree and histopathological injury in ankle joints of MSU-injected mice were significantly decreased after being treated with neoastilbin. Moreover, neoastilbin significantly diminished the secretion of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), suppressing the activation of NF-κB and NLRP3 inflammasome pathways in both MSU stimulated THP-1-derived macrophages and the mouse model of GA. In summary, neoastilbin could alleviate GA by inhibiting the NF-κB and NLRP3 inflammasome pathways, which provided some evidence for neoastilbin as a promising therapeutic agent for GA treatment.     

Synthesis of phenol-class azo derivatives of 4-aminosalicylic acid

To explore the better prodrug of 4-aminosalicylic acid（4-ASA）with higher activity and less side effects against the inflammatory bowel disease.4-ASA,after a succession of synthesis process,was conjugated with various carder molecules to get seven azo derivatives of 4-ASA.All compounds were characterized by FT-IR,^1H NMR,^13C NMR spectras in detail.New derivatives of 4-ASA were definituded.     

Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant‐induced arthritis in rats

To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time‐of‐flight mass spectrometry (GC‐TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant‐induced arthritis (AA). Sprague–Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC‐TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures–discriminant analysis. Nine potential biomarkers were identified, including 2,2‐dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l ‐dopa, 1,4‐dihydroxy‐2‐naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright © 2016 John Wiley & Sons, Ltd.     

基于气相色谱-飞行时间质谱技术的佐剂性关节炎大鼠尿液代谢组学的研究

采用弗氏完全佐剂(FCA)诱导佐剂性关节炎(AA)大鼠模型,观察大鼠足趾肿胀度和踝关节组织的病理学形态变化。应用气相色谱-飞行时间质谱(GC-TOF MS)技术检测AA大鼠尿液代谢物谱,并对数据进行主成分分析(PCA)、偏最小二乘法-判别分析(PLS-DA)及正交偏最小二乘法-判别分析(OPLS-DA),探讨可能的发病机制。通过变量重要性投影值(VIP>1)和P值(<0.05),筛选出尿液中的差异代谢物。在模型组大鼠的尿液中共发现异柠檬酸、α-酮戊二酸、柠康酸、肌酸、3-羟基丁酸等20种差异代谢物。推断AA代谢组学的发病机制可能与能量代谢、氨基酸代谢、脂肪酸代谢途径有关。     

A new morphinandienone alkaloid from the stems of Fissistigma tungfangense

A new morphinandienone alkaloid, fissistigmine A (1), together with three known alkaloids (2?4), were isolated and identified from the stems of Fissistigma tungfangense. Among them, fissistigmine A (1) represents the first example of a novel naturally occurring morphinandienone alkaloid with a unique cleavage of the C-9?N-17 bond. All isolated compounds were evaluated for their anti-rheumatoid arthritis activities via examining their anti-proliferative effects on synoviocytes in vitro. Compound 1 exhibited inhibitory effect on the proliferation of synoviocytes with an IC₅₀ value of 114.6 ± 2.2 μM.     

Homotherapy for heteropathy active components and mechanisms of Qiang-Huo-Sheng-Shi decoction for treatment of rheumatoid arthritis and osteoarthritis

Qiang-Huo-Sheng-Shi decoction (QHSSD), a classic traditional Chinese herbal formula, which has been reported to be effective in rheumatoid arthritis (RA) and osteoarthritis (OA). However, the concurrent targeting mechanism of how the aforementioned formula is valid in the two distinct diseases OA and RA, which represents the homotherapy-for-heteropathy principle in traditional Chinese medicine (TCM), have not yet been clarified. In the present study, network pharmacology was adopted to analyze the potential molecular mechanism, and therapeutic effective components of QHSSD on both OA and RA. A total of 153 active ingredients in QHSSD were identified, 142 of which associated with 59 potential targets for the two diseases were identified. By constructing the protein-protein interaction network and the compound-target-disease network, 72 compounds and 10 proteins were obtained as the hub targets of QHSSD against OA and RA. The hub genes of ESR1, PTGS2, PPARG, IL1B, TNF, MMP2, IL6, CYP3A4, MAPK8, and ALB were mainly involved in osteoclast differentiation, the NF-κB and TNF signaling pathways. Moreover, molecular docking results showed that the screened active compounds had a high affinity for the hub genes. This study provides new insight into the molecular mechanisms behind how QHSSD presents homotherapy-for-heteropathy therapeutic efficacy in both OA and RA. For the first time, a two-disease model was linked with a TCM formula using network pharmacology to identify the key active components and understand the common mechanisms of its multi-pathway regulation. This study will inspire more innovative and important studies on the modern research of TCM formulas.     

Novel calorimetric properties of human cartilage samples in rheumatoid arthritis

During recent years, knowledge of rheumatoid arthritis has increased, and management of the disease has improved. A limited number of papers have been published before on the subject of thermal analysis of degenerative cartilage but rheumatoid arthritis (RA) has not been studied previously. A new protocol had to be established before the investigation. The purpose of this study was to further characterize the altered metabolism in human RA cartilage that promotes disease progression. Previously, these methods have not been used for this purpose. The use of thermal analysis could be an effective method for controlling the relationship between biomarkers and disease progression.     

风湿性关节炎动物模型中血啉甲醚荧光强度的同步检测研究

光动力疗法的疗效依赖于治疗过程中靶组织中光敏剂的含量或浓度 ,而药物在组织中的分布特性是受动物机体调控的 ,因此 ,同一个体不同组织对光敏剂吸收的时间特性需要同时进行检测才能排除个体之间的差异。建立了一套空间三通道激光诱导荧光同步检测装置 ,并用该装置研究了活体大耳白兔风湿性关节炎模型滑膜、软骨和皮肤对血啉甲醚吸收的时间特性。研究结果表明 ,炎性滑膜组织对血啉甲醚的吸收量远大于软骨和皮肤 ,这一差别在静脉给药即刻就很明显 ,在静脉给药后 2 0min内 ,滑膜中的光敏剂药物含量约为软骨和皮肤中的 6倍。因此 ,对于借助血啉甲醚 ,用光动力疗法治疗风湿性关节炎并采用体外照射治疗方案时 ,从注药即刻开始 ,前 2 0min左右进行光照治疗可能是较好的选择。     

Synthesis,reactivity, in vitro boron neutron capture therapy assay,and molecular docking of fluorocyclocarboxyboranylamine

The one-pot reaction of Me₃NBH₂CN with Et₃O⁺BF₄⁻ followed by addition of BF₃·Et₂O and water produces a trimethylamine derivative of fluorocyclocarboxyboranylamine, Me₃NBH₂C(O₂BF₂NH₂) ( 1 ) in 36.0% yield. Compound 1 undergoes exchange reaction between the exo-Me₃N moiety and piperidine or pyridine to produce the corresponding piperidine-substituted fluorocyclocarboxyboranylamine ( 2 ) or pyridine-substituted fluorocyclocarboxyboranylamine ( 3 ) in 51.2% or 42.4% yields, respectively. The new compounds were characterized by ¹H, ¹³C, ¹¹B, and ¹⁹F nuclear magnetic resonance spectroscopy; Fourier-transform infrared spectroscopy; and elemental analyses and the crystal structure of 1 was determined to confirm its molecular geometry. The in vitro killing effects of 1 , along with its toxicity measurements and molecular docking interactions with matrix metalloproteinases showed a potential promise of such species as both boron neutron capture therapy and boron neutron capture synovectomy agents in the treatment of tumors and rheumatoid arthritis, respectively, in the presence of slow neutrons.     

Towards Better Sinomenine-Type Drugs to Treat Rheumatoid Arthritis: Molecular Mechanisms and Structural Modification

Sinomenine is the main component of the vine Sinomenium acutum. It was first isolated in the early 1920s and has since attracted special interest as a potential anti-rheumatoid arthritis (RA) agent, owing to its successful application in traditional Chinese medicine for the treatment of neuralgia and rheumatoid diseases. In the past few decades, significant advances have broadened our understanding of the molecular mechanisms through which sinomenine treats RA, as well as the structural modifications necessary for improved pharmacological activity. In this review, we summarize up-to-date reports on the pharmacological properties of sinomenine in RA treatment, document their underlying mechanisms, and provide an overview of promising sinomenine derivatives as potential RA drug therapies.