Inhibition of HSP70 release by geniposide improves angiogenesis in moist heat arthralgia spasm syndrome collagen induced arthritis rats / 中国药理学通报

Aim To investigate the relation between the effect of geniposide (GE) in improving angiogenesis in arthralgia spasm syndrome collagen induced arthritis (CIA) rats and the modulation of heat shock proteins 70 (HSP70) release. Methods A CIA model was constructed by multiple intradermal injections of complete Freund's adjuvant (CFA) and an equal volume mixture of chicken type II collagen (CCII) into the dorsal and caudal root regions of rats, on the basis of which a rheumatic fever stimulus was given to build up a moist heat arthralgia spasm syndrome in CIA rats. After successful modeling, the groups were randomly grouped, and the administered groups were gavaged with GE (60, 120 mg · kg

Baicalin inhibits PDK1 to mediate glucose metabolism reprogramming and intervene rheumatoid arthritis synovial inflammation / 药学学报

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

Microdialysis combined with metabonomics in exploring metabolic disturbance of adjuvant arthritis rats and intervention effect of Achyranthes bidentata saponins / 中国药理学通报

Aim To use microdialysis technology combined with ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology to study the effect of Achyranthes bidentata saponins (ABS) on rheumatoid arthritis (RA) and its mechanisms. Methods SD rats were randomly divided into adjuvant arthritis (AA) model group, blank control group and ABS administration group. AA rat model was induced by Freund's complete adjuvant. UPLC-Q-TOF/MS was used to collect joint cavity microdialysis fluid sample information of each group of rats. Results On 6th day after administration of ABS, an inhibitory effect on the paw swelling, improved the arthritis score (P < 0. 05), and better the pathological morphology of the synovial tissues were found in AA rats. Nineteen potential biomarkers were discovered and identified. Pathway enrichment analysis revealed that they mainly involved purine metabolism, pyrimidine metabolism, fatty acid biosynthesis and steroid hormone biosynthesis pathway. Conclusions Microdialysis combined with metabolomics can reveal the metabolic mechanism of ABS intervention on RA, laying a foundation for further study of the mechanism of ABS.

Role of sphingosine-1-phosphate and its signaling pathway in inflammation-related diseases / 中国药理学通报

Sphingosine 1-phosphate(SIP) is an important signal molecule produced by the metabolism of cell membrane sphingomyelin. SIP can be transported to the extracellular domain, and plays a role in activating a series of downstream signals, such as Ras/RafyERK, PI3K/AKT, by acting on SIP receptors. It can also act as a second messenger directly on intracellular targets such as HDAC, TRAF2. Its mediated signaling pathway plays a role in many physiological and pathological processes such as cell proliferation and migration, inflammatory cytokine infiltra tion, angiogenesis and autoimmunity. This article explores the role of SIP and its signaling pathways in inflammation-related diseases from the extracellular and intracellular roles of SIP, and reviews the research progress of SI P signaling pathway related drugs.