Venlafaxine alleviates complete Freund's adjuvant-induced arthritis in rats: Modulation of STAT-3/IL-17/RANKL axis

Kamel, Kamel M.; Gad, Amany M.; Mansour, Suzan M.; Safar, Marwa M.; Fawzy, Hala M.

doi:10.1016/j.lfs.2019.03.063

Cited by 21 publications

(15 citation statements)

References 30 publications

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“…Therefore, we also demonstrated that anxiety-and depression-like behaviors of CPMS mice were recovered by venlafaxine treatment, which inhibits the 5-HT/noradrenalin synaptosomal uptake [40]. Venlafaxine also has anti-inflammatory property about abnormal inflammatory responses related to microglia as one of the risk factors causing depressive symptoms [41][42][43]. So, we confirmed that Velafaxine reduced microglial activation (Additional file 1: Fig.…”

Section: Discussionsupporting

confidence: 64%

Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice

2021

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The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the cause of long-lasting depressive states is still unclear. To identify the effects of cumulative mild stress in brain development periods, we generated a young adult depression mouse model exposed to cumulative mild stress (CPMS; cumulative mild prenatal stress, mild maternal separation, and mild social defeat) to mimic early life adversities. CPMS mice exhibited more long-lasting anxiety and depression-like behaviors than groups exposed to single or double combinations of mild stress in young adult age. Using the molecular works, we found that inflammatory cytokines, especially interleukin (IL)-17, upregulated microglial activation in the hippocampus, amygdala, and prefrontal cortex of CPMS mice. In the brains of CPMS mice, we also identified changes in the T helper (Th)-17 cell population as well as differentiation. Finally, anti-IL-17 treatment rescued anxiety and depression-like behavior in CPMS mice. In conclusion, we found that cumulative mild stress promoted long-lasting depressive symptoms in CPMS mice through the upregulation of IL-17. We suggest that the CPMS model may be useful to study young adult depression and expect that IL-17 may be an important therapeutic target for depression in young adults.

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Section: Discussionsupporting

confidence: 64%

Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice

2021

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“…As shown in Figure 5 , IA administration of CFA resulted in marked joint destruction as manifested by the presence of wide areas of articular erosions and irregularities with marked inflammatory cell infiltration, significant loss of chondrocytes and abundant fibrous tissue replacement. These findings that go in line with many investigators (Kamel et al., 2019 ; Weng et al., 2021 ). Similar records were noticed following the administration of piroxicam oral solution and IA suspension with milder inflammatory cells infiltration in the synovial membranes.…”

Section: Resultssupporting

confidence: 91%

Artificial intelligence-assisted development ofin situforming nanoparticles for arthritis therapy via intra-articular delivery

et al. 2022

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Intra-articular (IA) injection is grasping much interest due to the poor drug bioavailability at the targeted site of action which minimizes the effect of the orally administered moiety. Based on the integral role of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of Rheumatoid Arthritis (RA), much effort is exerted to develop novel localized drug delivery systems to increase their bioavailability and minimize their side effects. Artificial intelligence (AI) is acquiring an increasing role in the design of experiments being an effective tool for saving both time and resources. Hence, the aim of this work was to develop, characterize and optimize targeted in-situ forming nano particles (ISNs) for IA delivery of piroxicam using Design ® Expert as an AI-based application where a 3 3 full factorial experimental design was adopted. Morphological investigation, injectability, rheological studies, Fourier Transform Infrared Radiation (FTIR) as well as biological, histopathological, and biochemical examinations were performed to evaluate the optimized-ISNs. The optimized formulation, exhibiting a nano-sized particle size with a dense core, showed significant improvement in the histopathological findings compared to both the oral solution and the placebo. Additionally, the once-a-week IA administration of the optimized-ISNs proved a significant reduction in the protein expression of both STAT-3 and RANKL and the levels of anti-CCP and MCP-1 by almost 54 and 73%, respectively, coupled with a marked decline in the content of IL-17, MMP-3, NF-κB and TNF-α as compared to the positive control. In conclusion, the use of ISNs for intra-articular injection has demonstrated their effectiveness in piroxicam delivery for RA treatment.

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“…64 NE reuptake inhibitors alleviated the inflammatory response through the modulation of the STAT3/IL-17/ RANKL axis. 65 In our in vitro experiments, we used varying concentrations (0, 0.01, 0.1, or 1 μM) of NE to process RAW264.7 cells with or without LPS (1 μg/ml) activation. Our results showed that NE effectively stimulated the LPS-stimulated macrophages to express TNF-α, IL-6, IL-1β, and NGF in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Spinal Cord Stimulation Attenuates Neural Remodeling, Inflammation, and Fibrosis After Myocardial Infarction

He¹,

Sun²,

Jiang³

et al. 2023

Neuromodulation: Technology at the Neural Interface

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Venlafaxine alleviates complete Freund's adjuvant-induced arthritis in rats: Modulation of STAT-3/IL-17/RANKL axis

Cited by 21 publications

References 30 publications

Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice

Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice

Artificial intelligence-assisted development ofin situforming nanoparticles for arthritis therapy via intra-articular delivery

Spinal Cord Stimulation Attenuates Neural Remodeling, Inflammation, and Fibrosis After Myocardial Infarction

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