Synthesis of naringenin loaded lipid based nanocarriers and their in-vivo therapeutic potential in a rheumatoid arthritis model

2021 ◽  
pp. 102854
Author(s):  
Adil Munir ◽  
Faqir Muhammad ◽  
Yumna Zaheer ◽  
Asim Ali ◽  
Mazhar Iqbal ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Arthritis Model

scholarly journals Simultaneous Determination of 5 Active Components of Periploca forrestii Schltr Extract in Rat Plasma by UPLC-MS and Its Application to Pharmacokinetic Studies in Normal and Adjuvant-Induced Arthritis Model Rats

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098143
Author(s):  
Hui Liu ◽  
Hao Chen ◽  
Xiaoli Qin ◽  
Xue Ma ◽  
Zipeng Gong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chlorogenic Acid ◽  
Intravenous Administration ◽  
Area Under The Curve ◽  
Pharmacokinetic Studies ◽  
Active Components ◽  
Arthritis Model ◽  
Adjuvant Induced Arthritis ◽  
Neochlorogenic Acid

Periploca forrestii Schltr ( P. forrestii) is a herb used in traditional Chinese medicine for its anti-rheumatoid arthritis effect. The aim of this study was to compare the pharmacokinetic properties of the 5 active components of this plant: neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid C, and periplocin between normal rats and adjuvant-induced arthritis model rats. After the intravenous administration (177.78 mg/kg) of P. forrestii extract, samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Compared with normal rats, the area under the curve [(AUC)(0-t), AUC(0-∞)], mean residence time [(MRT)(0-t), MRT(0-∞)] of neochlorogenic acid-treated rats decreased significantly, and drug clearance (CL) and apparent volume of distribution (V) increased significantly; the V of chlorogenic acid-treated rats decreased significantly, and MRT(0-t) significantly increased; the AUC(0-t) and AUC(0-∞) of cryptochlorogenic acid-treated rats decreased significantly, and CL and V increased significantly; the AUC(0-t) and MRT(0-t) of isochlorogenic acid C-treated rats decreased significantly, and V increased significantly; the AUC(0-t) and AUC(0-∞) of periplocin-treated rats increased significantly, and MRT(0-t), MRT(0-∞), CL, and V decreased significantly in model rats. The disease condition of rheumatoid arthritis in rats had a significant effect on the in vivo pharmacokinetics of P. forrestii after the intravenous administration.

Therapeutic Potential of Mesenchymal Stromal Stem Cells in Rheumatoid Arthritis: a Systematic Review of In Vivo Studies

2020 ◽  
Vol 16 (2) ◽  
pp. 276-287 ◽  
Author(s):  
Alexia Karamini ◽  
Athina Bakopoulou ◽  
Dimitrios Andreadis ◽  
Konstantinos Gkiouras ◽  
Aristeidis Kritis
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Stem Cells ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Stromal Stem Cells

Development of novel pH-sensitive nanoparticle-based transdermal patch for management of rheumatoid arthritis

Nanomedicine ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. 603-624 ◽  
Author(s):  
Dildar Khan ◽  
Maimoona Qindeel ◽  
Naveed Ahmed ◽  
Ashraf U Khan ◽  
Salman Khan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transdermal Delivery ◽  
Therapeutic Potential ◽  
Ph Sensitive ◽  
In Vivo Studies ◽  
Transdermal Patch ◽  
Inflammatory Models ◽  
Average Size ◽  
Central Composite

Aim: To formulate and evaluate a pH-responsive nanoparticle (NP)-based patch for efficient transdermal delivery of flurbiprofen against rheumatoid arthritis. Materials & methods: Nanoprecipitation technique was used for preparation of NPs and central composite design was employed for optimization purposes. Optimized NPs were loaded into the transdermal patch by the solvent evaporation method. Results: Prepared NPs exhibited an average size of 69 nm, while NPs loaded onto the transdermal patch showed sustained release and high permeation through the skin. In in vivo studies, the prepared carrier system elucidated high therapeutic potential in both acute and chronic inflammatory models as evident from the results of behavioral, radiological, histopathological and antioxidant analyses. Conclusion: The flurbiprofen-loaded pH-sensitive NP-based transdermal patch has the potential to manage rheumatoid arthritis effectively.

Targeting anticomplement agents

2002 ◽  
Vol 30 (6) ◽  
pp. 1037-1041 ◽  
Author(s):  
R. A. G. Smith
Keyword(s):  
Rheumatoid Arthritis ◽  
Large Scale ◽  
Cell Membranes ◽  
Therapeutic Potential ◽  
Human Subjects ◽  
Outer Cell ◽  
Specific Direction ◽  
Disease Site ◽  
Peptide Derivatives

Biological targeting is normally thought of as a process of specific direction of one molecule (the agent) to another (the target) in vivo. However, an addressive approach in which the agent is concentrated, first within the vasculature and then at a disease site containing one or more targets, may be more suitable for delivering therapeutic quantities of certain drugs. This approach has been applied to complement regulatory molecules expressed in recombinant soluble forms and attached post-translationally to highly soluble synthetic peptide derivatives comprising two addressin units, one with affinity for the membrane bilayer interior and the other for phospholipid headgroups. This combination conferred affinity for outer cell membranes in general, and areas of translocated acidic phospholipid in particular. Large increases in potency in cell-based antihaemolytic assays accompanied modification and were shown to be associated with membrane binding. Modified agents co-localized with glycosylphosphatidyl-inositol-anchored proteins in lipid rafts on cell membranes. One agent, a modified fragment of human complement receptor-1 (APT070), has been prepared on a large scale and has been shown to be an active anti-inflammatory agent when administered locally and systemically in animal models of vascular shock, rheumatoid arthritis and transplantation reperfusion injury. APT070 has been shown to be well tolerated in human subjects when given intravenously and is currently under study in rheumatoid arthritis patients to explore the therapeutic potential of localized complement inhibition in the synovial space.

scholarly journals S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src/FAK Signaling Pathway in Rheumatoid Arthritis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2168
Author(s):  
Chien-Chung Huang ◽  
Tzu-Ting Tseng ◽  
Shan-Chi Liu ◽  
Yen-You Lin ◽  
Yat-Yin Law ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
In Vivo Model ◽  
Endothelial Progenitor ◽  
Chick Chorioallantoic Membrane ◽  
Cartilage Erosion ◽  
The Impact

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. Vascular endothelial growth factor (VEGF) stimulation of endothelial progenitor cells (EPCs) facilitates angiogenesis and the progression of RA. Phosphorylation of sphingosine kinase 1 (SphK1) produces sphingosine-1-phosphate (S1P), which increases inflammatory cytokine production, although the role of S1P in RA angiogenesis is unclear. In this study, we evaluated the impact of S1P treatment on VEGF-dependent angiogenesis in osteoblast-like cells (MG-63 cells) and the significance of SphK1 short hairpin RNA (shRNA) on S1P production in an in vivo model. We found significantly higher levels of S1P and VEGF expression in synovial fluid from RA patients compared with those with osteoarthritis by ELISA analysis. Treating MG-63 cells with S1P increased VEGF production, while focal adhesion kinase (FAK) and Src siRNAs and inhibitors decreased VEGF production in S1P-treated MG-63 cells. Conditioned medium from S1P-treated osteoblasts significantly increased EPC tube formation and migration by inhibiting miR-16-5p synthesis via proto-oncogene tyrosine-protein kinase src (c-Src) and FAK signaling in chick chorioallantoic membrane (CAM) and Matrigel plug assays. Infection with SphK1 shRNA reduced angiogenesis, articular swelling and cartilage erosion in the ankle joints of mice with collagen-induced arthritis (CIA). S1P appears to have therapeutic potential in RA treatment.

scholarly journals Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2627
Author(s):  
Chien-Chung Huang ◽  
Yat-Yin Law ◽  
Shan-Chi Liu ◽  
Sung-Lin Hu ◽  
Jun-An Lin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Therapeutic Potential ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Synovial Cell ◽  
Vegf Expression ◽  
Endothelial Progenitor

Rheumatoid arthritis (RA) is an erosive polyarthritis that can lead to severe joint destruction and painful disability if left untreated. Angiogenesis, a critical pathogenic mechanism in RA, attracts inflammatory leukocytes into the synovium, which promotes production of proinflammatory cytokines and destructive proteases. Adipokines, inflammatory mediators secreted by adipose tissue, also contribute to the pathophysiology of RA. The most abundant serum adipokine is adiponectin, which demonstrates proinflammatory effects in RA, although the mechanisms linking adiponectin and angiogenic manifestations of RA are not well understood. Our investigations with the human MH7A synovial cell line have revealed that adiponectin dose- and time-dependently increases vascular endothelial growth factor (VEGF) expression, stimulating endothelial progenitor cell (EPC) tube formation and migration. These adiponectin-induced angiogenic activities were facilitated by MEK/ERK signaling. In vivo experiments confirmed adiponectin-induced downregulation of microRNA-106a-5p (miR-106a-5p). Inhibiting adiponectin reduced joint swelling, bone destruction, and angiogenic marker expression in collagen-induced arthritis (CIA) mice. Our evidence suggests that targeting adiponectin has therapeutic potential for patients with RA. Clinical investigations are needed.

scholarly journals Isopsoralen ameliorates rheumatoid arthritis by targeting MIF

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Yi Han ◽  
Jinguang Wang ◽  
Shufeng Li ◽  
Yi Li ◽  
Yongli Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Potential ◽  
Mechanistic Study ◽  
Network Pharmacology ◽  
In Vivo Models ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory ◽  
Cellular Thermal Shift Assay

Abstract Background Isopsoralen (IPRN), one of the active ingredients of Psoralea corylifolia Linn, has anti-inflammatory properties. We attempted to investigate the inhibitory effects of IPRN on rheumatoid arthritis (RA) and characterize its potential mechanism. Methods RA fibroblast-like synoviocytes (FLSs) and mice with collagen-induced arthritis (CIA) were used as in vitro and in vivo models to analyze the antiarthritic effect of IPRN. Histological analysis of the inflamed joints from mice with CIA was performed using microcomputed tomography (micro-CT) and hematoxylin-eosin (HE) staining. RNA sequencing (RNA-Seq), network pharmacology analysis, molecular docking, drug affinity responsive target stability (DARTS) assay, and cellular thermal shift assay (CETSA) were performed to evaluate the targets of IPRN. Results IPRN ameliorated the inflammatory phenotype of RA FLSs by inhibiting their cytokine production, migration, invasion, and proangiogenic ability. IPRN also significantly reduced the severity of CIA in mice by decreasing paw thickness, arthritis score, bone damage, and serum inflammatory cytokine levels. A mechanistic study demonstrated that macrophage migration inhibitory factor (MIF), a key protein in the inflammatory process, was the specific target by which IPRN exerted its anti-inflammatory effects in RA FLSs. Conclusion Our study demonstrates the antiarthritic effect of IPRN, which suggests the therapeutic potential of IPRN in RA.

Apolipoprotein B binds to enolase-1 and aggravates inflammation in rheumatoid arthritis

2018 ◽  
Vol 77 (10) ◽  
pp. 1480-1489 ◽  
Author(s):  
Joo Youn Lee ◽  
Min Jueng Kang ◽  
Ji Yong Choi ◽  
Ji Soo Park ◽  
Jin Kyun Park ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Immune Cells ◽  
Knockout Mice ◽  
Apolipoprotein B ◽  
Arthritis Model ◽  
Arthritis Severity ◽  
Serum Transfer

ObjectiveImmune cells from patients with rheumatoid arthritis (RA) express more enolase-1 (ENO1) on their surface than those from healthy subjects, and they elicit an enhanced inflammatory response. This study is aimed to identify the ligands of ENO1 that could promote inflammatory loops in vitro and enhance the arthritis severity in vivo.MethodsENO1-binding proteins in RA synovial fluid were identified by mass spectromety, and affinity to ENO1 was evaluated by means of a ligand blotting and binding assay, surface plasmon resonance and confocal microscopy. Proinflammatory response by the interaction between ENO1 and apolipoprotein B (apoB) was tested in vitro and in vivo using peripheral blood mononuclear cells and a K/BxN serum transfer arthritis model and low-density lipoproteins receptor (LDLR) knockout mice.ResultsApoB in the synovid fluid of patients with RA was identified as a specific ligand to ENO1 with a higher affinity than plasminogen, a known ENO1 ligand. ApoB binding to ENO1 on monocytes elicited the production of tumour necrosis factor-α, interleukins (IL)-1β and IL-6 through both p38 mitogen-activated protein kinase and NF-κB pathways. In the K/BxN serum transfer arthritis model, administration of apoB increased the production of proinflammatory cytokines and exaggerated arthritis severity. The severity of K/BxN serum transfer arthritis in LDLR knockout mice was comparable with wild-type mice.ConclusionsA key component of atherogenic lipids, apoB, aggravated arthritis by potentiating the inflammatory response via its interaction with ENO1 expressed on the surface of immune cells. This suggests a novel mechanism by which lipid metabolism regulates chronic inflammation in RA.

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