Clinical application of biological agents in rheumatoid arthritis

Transplant Immunology, Год журнала: 2025, Номер unknown, С. 102187 - 102187

Опубликована: Янв. 1, 2025

Язык: Английский

---

The protective effect of natural medicines in rheumatoid arthritis via inhibit angiogenesis

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Май 31, 2024

Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia inflammation underlies Delaying or even blocking angiogenesis has emerged as an important target of RA treatment. Natural medicines long history treating RA, numerous reports have suggested that natural strong inhibitory activity on angiogenesis, thereby improving progression RA. could regulate following signaling pathways: HIF/VEGF/ANG, PI3K/Akt pathway, MAPKs NF-κB PPARγ JAK2/STAT3 etc., inhibiting angiogenesis. Tripterygium wilfordii Hook. f. (TwHF), sinomenine, total glucoside Paeonia lactiflora Pall. Are currently most representative all products worthy development utilization. In this paper, main factors affecting were discussed different types inhibit systematically summarized. Their specific anti-angiogenesis mechanisms are also reviewed which aiming provide new perspective options for management targeting

Язык: Английский

---

Hydrogel Doped with Sinomenine-CeO ₂ Nanoparticles for Sustained Intra-articular Therapy in Knee Osteoarthritis

Journal of drug targeting, Год журнала: 2025, Номер unknown, С. 1 - 32

Опубликована: Янв. 2, 2025

Intra-articular injection has emerged as a promising approach for treating knee osteoarthritis (OA), showing notable efficacy and potential. However, the risk of side effects remains concern with commonly used steroid therapies in clinical practice. Here, we developed an intra-articular injectable hydrogel drug depot (SMN-CeO2@G) sustained OA treatment. This system, which carries sinomenine-loaded cerium dioxide nanoparticles (SMN-CeO2), enhances anti-inflammatory anti-apoptotic within joint cavity. SMN-CeO2@G features three-dimensional network structure approximate pore size 10 μm, stably encapsulating SMN-CeO2 (∼75 nm). Under hydrogen peroxide (H2O2) exposure simulated mechanical stress, achieves cumulative SMN release 44.72 ± 7.83% over 48 hours, demonstrating controlled capabilities. At concentration 0.5 μg/mL, significantly proliferation, reduces apoptosis, lowers matrix metalloproteinases-13 (MMP-13) secretion IL-1β-induced ATDC5 chondrocytes. In ATDC5-RAW264.7 co-culture model, effectively reactive oxygen species (ROS) levels, apoptosis (∼20%), MMP13 concentrations (24.3 3.1 ng/mL) chondrocytes, likely due to promotion macrophages M2 polarization. anti-OA vivo studies, single osteophyte formation, promotes subchondral bone normalization, alleviates pain sensitivity, serum IL-1β (59.3 2.4 pg/mL) MMP-13 (23.6 1.7 levels model rats. also prolonged retention synovial fluid, 6.7 2.8% still detectable at 72 hours post-injection, factor crucial therapeutic effect. Overall, presents tool treatment, potential improved outcomes.

Язык: Английский

---

Metabolic profiling and transcriptome analysis of Sinomenium acutum provide insights into the biosynthesis of structurally diverse benzylisoquinoline alkaloids

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 18, 2025

Sinomenium acutum, a traditional medicinal plant, has been utilized for millennia to alleviate various forms of rheumatic pain symptoms. The structurally diverse benzylisoquinoline alkaloids (BIAs) found in S. acutum are the primary contributors its therapeutic efficacy, with sinomenine being principal bioactive constituent. In this study, we employed an integrated transcriptomic and metabolomic approach investigate BIA biosynthesis acutum. Transcriptome sequencing, functional annotation, differential gene expression analysis were combined metabolite profiling predict biosynthetic pathways BIAs screen candidate genes. Metabolomic revealed significant stem-enriched accumulation compared leaves. Furthermore, proposed pathway hypothesized that 34 key genes, including cytochrome P450 (CYP450s), reductases, 2-oxoglutarate-dependent dioxygenases (2-ODDs), O-methyltransferases (O-MTs), might be involved process. This study provides foundation understanding compounds offers critical insights future characterization genetic elements.

Язык: Английский

---

Multiomics analysis of human serum and animal experiments reveals the protective mechanism of Qingre Huoxue Decoction against rheumatoid arthritis

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 7, 2025

Qingre Huoxue Decoction (QRHXD) is a traditional Chinese herbal prescription widely used in clinical practice with significant therapeutic effects on RA; however, its mechanism of action remains unclear. This study aimed to investigate the efficacy and underlying mechanisms QRHXD treating RA through research, multiomics approaches, animal experiments. We conducted 24-week which was primary treatment, collecting serum samples from patients before after treatment for integrated proteomic metabolomic analysis identify potential targets. Bioinformatics differentially expressed proteins (DEPs) differential metabolites (DMs) performed using hierarchical clustering, volcano plots, heat maps, Gene Ontology (GO), Kyoto Encyclopaedia Genes Genomes (KEGG) analysis. To validate identified targets, we constructed collagen-induced arthritis (CIA) mouse model. Clinical research has shown that can improve symptoms relevant indicators patients, including disease activity score-28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen (SJC), visual analogue scale (VAS), patient-reported outcome (PRO), health assessment questionnaire (HAQ). Proteomics metabolomics 83 DEPs 54 DMs, 46 upregulated 37 downregulated proteins, as well 11 43 metabolites. KEGG enrichment revealed are primarily associated fatty acid degradation, ferroptosis, glycerolipid metabolism, related pathways. The DMs AMPK signalling pathway, FoxO glycolysis/gluconeogenesis, MTOR so on. GO indicated were mainly apoptotic mitochondrial changes, modification processes, fatty-acyl-CoA binding, Integrated proteomics analyses increase fructose-1,6-biphosphatase 1 (FBP1) levels reduction AMP-activated kinase (AMPK) RA. inhibited FBP1 activated signalling. Animal experiments validated findings analyses, demonstrating could also delay bone destruction reduce inflammatory factor CIA mice. may RA, attenuate response, by inhibiting activating pathway.

Язык: Английский

---

Sinomenine alleviates neuroinflammation in chronic cerebral hypoperfusion by promoting M2 microglial polarization and inhibiting neuronal pyroptosis via exosomal miRNA-223-3p

Acta Neuropathologica Communications, Год журнала: 2025, Номер 13(1)

Опубликована: Март 5, 2025

Chronic cerebral hypoperfusion (CCH) is a major contributor to vascular dementia, with neuroinflammation playing central role in its pathogenesis. Sinomenine (SINO), natural alkaloid derived from traditional Chinese medicine, has shown significant anti-inflammatory and neuroprotective properties. However, efficacy mechanism of action CCH remain unclear. In this study, we established rat model through bilateral common carotid artery occlusion administered 10 mg/kg SINO daily. Behavioral tests demonstrated that significantly improved cognitive memory functions rats. Histological analysis revealed effectively reduced damage the hippocampal CA1, CA3, DG regions. Mechanistically, promoted microglial polarization M1 M2 phenotype, markedly inhibiting release pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α. Further exploration showed exosomes SINO-treated microglia were enriched miRNA-223-3p, which suppressed NLRP3-mediated pyroptosis neurons. While our findings highlight therapeutic potential SINO, further studies are needed validate safety diverse populations chronic settings. summary, study not only demonstrates SINO's regulatory effect on but also unveils novel exosomal miRNA-223-3p delivery, providing solid theoretical foundation for as treatment CCH.

Язык: Английский

---

A sinomenine derivative alleviates bone destruction in collagen-induced arthritis mice by suppressing mitochondrial dysfunction and oxidative stress via the NRF2/HO-1/NQO1 signaling pathway

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107686 - 107686

Опубликована: Март 1, 2025

Bone destruction in rheumatoid arthritis (RA) leads to significant disability, yet effective treatments are limited. Sinomenine (Sino) demonstrates anti-arthritic and bone-protective effects but requires high doses. In this study, we developed a Sino derivative, SINX, evaluated its efficacy RA. Safety assessments mice confirmed suitability for further study. vitro, SINX inhibited osteoclast differentiation by reducing TRAP-positive cells, disrupting F-actin ring formation, suppressing bone resorption pits, alongside downregulating osteoclast-specific genes. It also showed strong anti-inflammatory properties inflammatory cytokine levels. vivo, using collagen-induced (CIA) mouse model, improved integrity joint inflammation, maintaining trabecular density, preventing erosion. Histological micro-CT analyses effects, including suppressed activity reduced resorption-related gene expression. Mechanistically, ameliorated mitochondrial dysfunction, decreased ROS levels, activated the NRF2/HO-1/NQO1 pathway, enhancing antioxidant defenses. Compared Sino, achieved similar results at lower These findings highlight potential of as safe, treatment RA-related destruction.

Язык: Английский

---

Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2604 - 2604

Опубликована: Март 13, 2025

Neuropathic pain (NP) is a type of chronic resulting from injury or dysfunction the nerves spinal cord. Previous studies have shown that combination ligustrazine (LGZ) and sinomenine (SIN) exerts synergistic antinociceptive effect in peripheral central NP models. On this basis, comprehensive analgesic evaluation was performed constriction (CCI)-induced model rats. Sciatic nerve histopathological changes were observed, 22 cytokines chemokines levels analyzed. We also combined network pharmacology metabolomics to explore their molecular mechanisms. Results showed LGZ SIN significantly alleviated pain-like behaviors CCI rats time- dose-dependent manner, demonstrating superior therapeutic effects compared alone. It improved pathological damage sciatic regulated inflammatory cytokine levels. Network identified shared distinct pain-related targets for SIN, while revealed 54 differential metabolites plasma, 17 CSF associated with intervention SIN. Finally, through an integrated analysis core metabolites, tyrosine metabolism, phenylalanine arginine proline metabolism as potential key metabolic pathways underlying treatment. In conclusion, our study provides evidence support clinical application treatment NP.

Язык: Английский

---

Natural product-integrated microneedle patch for rheumatoid arthritis treatment through anti-inflammation and angiogenesis suppression

Biomaterials Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

A microneedle patch (B/S-TM@MN) was developed to encapsulate ROS-responsive micelles loaded with berberine and sinomenine, which enhanced the overall anti-arthritis outcome through simultaneous anti-inflammation anti-angiogenesis.

Язык: Английский

---

Therapeutic Potential of Phytocompounds in Rheumatoid Arthritis: Molecular Insights and Clinical Applications

Pathology - Research and Practice, Год журнала: 2025, Номер unknown, С. 155945 - 155945

Опубликована: Март 1, 2025

Язык: Английский

---