Vardenafil and cilostazol can improve vascular reactivity in rats with diabetes mellitus and rheumatoid arthritis co-morbidity

Wahba, Mariam Gamal Fahmy; Messiha, Basim Anwar Shehata; El‐Daly, Mahmoud; Abo-Saif, Ali A.

doi:10.1016/j.lfs.2019.05.024

Cited by 5 publications

(4 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…57 Furthermore, several studies illustrated the connection between systemic inflammation and cardiovascular dysregulations, such as endothelial dysfunction and myocardial toxicity, which might explain the increased blood pressure of untreated CFA-arthritis rats observed in our results. [58][59][60][61][62] Indeed, histological examination of myocardial tissue of these rats showed signs of mild cardiomyopathy. Interestingly, RA rats that received the different anti-inflammatory treatments showed normal blood pressure values.…”

Section: Discussionmentioning

confidence: 99%

Functional Role of Novel Anthranilic Acid Derivatives as Anti-inflammatory Agents

Morsy¹,

Patel²,

Parmar³

et al. 2022

Ind. J. Pharm. Edu. Res

View full text Add to dashboard Cite

Background:The discovery of new cyclooxygenase (COX) inhibitors with high efficacy and safety would greatly aid in developing anti-inflammatory drugs. This study evaluated the anti-inflammatory activity and the expected side effect of two synthesized anthranilic acid derivatives (JS-3 and JS-4). Materials and Methods: The COX selectivity of compounds was assessed in a whole blood assay. The results were confirmed by molecular docking studies. In vivo anti-inflammatory activity was tested in complete Freund's adjuvant (CFA)-induced rheumatoid arthritis (RA) in rats. The safety profile was determined by administering a dose three times the therapeutic dose. Results: In vitro COX-2 selectivity of JS-4 was higher than JS-3 (13.70 vs. 5.56). Docking studies supported the higher selectivity of both derivatives against COX-2 than mefenamic acid. Treatment of CFA-arthritic rats with both compounds showed significant (P < 0.01) decreases in paw volume, paw thickness, arthritic index, and inflammatory parameters such as rheumatoid factor, interleukin (IL)-1β, IL-6, prostaglandin (PG) E 2 , PGI 2 , and TXB 2 compared to untreated RA animals. JS-3 and JS-4 improved knee joint histopathology and protected against RA-induced pathological changes: splenomegaly, thymomegaly, and cardiomyopathy. Both derivatives produced minimal effects on liver and renal functions, without any ulcerogenic effects. Conclusion: These results suggest that JS-4 is a potential and safe candidate for managing RA without renal, liver, gastrointestinal, or cardiovascular toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Functional Role of Novel Anthranilic Acid Derivatives as Anti-inflammatory Agents

Morsy¹,

Patel²,

Parmar³

et al. 2022

Ind. J. Pharm. Edu. Res

View full text Add to dashboard Cite

show abstract

“…P‐selectin plays an important role in the progress of immune endothelial dysfunction. The adhesion of leukocytes to vascular endothelial cells is mediated by the binding of P‐selectin and leukocyte P‐selectin glycoprotein ligand‐1 (Lam, Da, Guillory, & Cruz, ; Wahba, Messiha, El Daly, & Abo‐Saif, ). ET‐1 and NO are a pair of antagonistic bioactive factors, which play an important role in the regulation of cardiovascular system function.…”

Section: Discussionmentioning

confidence: 99%

“…P-selectin plays an important role in the progress of immune endothelial dysfunction. The adhesion of leukocytes to vascular endothelial cells is mediated by the binding of Pselectin and leukocyte P-selectin glycoprotein ligand-1(Lam, Da, Guillory, & Cruz, 2018;Wahba, Messiha, El Daly, & Abo-Saif, 2019).…”

mentioning

confidence: 99%

Salvia miltiorrhiza stem‐leaf active components of salvianolic acids and flavonoids improved the hemorheological disorder and vascular endothelial function on microcirculation dysfunction rats

Sun

Zhu

et al. 2020

Phytotherapy Research

View full text Add to dashboard Cite

Microcirculation, which connects macrocirculation and cells between arterioles and venules, plays a major role in the early onset of a variety of diseases. In this article, a dextran‐induced microcirculation dysfunction (MCDF) model rats were adopted to evaluate the effects and mechanism of Salvia miltiorrhiza stem‐leaf extracts based on plasma and urine metabonomics. The results showed the effective components of S. miltiorrhiza stem‐leaf could significantly improve the hemorheology and coagulation index of MCDF rats and callback the expression of endothelin‐1 (ET‐1), induciblenitric oxide synthase (iNOS), vascularendothelial growth factor (VEGF), P‐Selectin, thromboxane A2, 6‐keto‐PGF1α, TNF‐α, and interleukin‐1β to control group in MCDF rats. The decrease of microvessel density (MVD) in lung and thymus caused by MCDF was upgraded by Salvia miltiorrhiza stem‐leaf. Based on the plasma and urine metabolic data, 20 potential biomarkers were identified. These biomarkers are mainly related to linoleic acid metabolism, glutathione metabolism, pantothenate and coenzyme A biosynthesis, pentose and glucuronate interconversions, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, beta‐alanine metabolism, and citrate cycle. The results indicated that the effective components of S. miltiorrhiza stem‐leaf can improve the hemorheological disorder and vascular endothelial function. Meanwhile, the effective components can regulate potential biomarkers and correlated metabolic pathway, which can provide guidance for the research and development of new drugs for MCDF.

show abstract

“…The phosphodiesterase (PDE) inhibitors Vardenafil and cilostazol can induce vasodilation and maintain endothelial integrity. Vardenafil and cilostazol can up-regulate vascular eNOS to exhibit protective effects against vascular reactivity defects and endothelial dysfunction in RA patients [78]. All-trans retinoic acid (ATRA) is a vitamin A derivative with various immunomodulatory effects through inhibiting NF-κB translocation and iNOS expression in peripheral blood mononuclear cells [79].…”

Section: Conventional Dmardsmentioning

confidence: 99%

Nitric Oxide Synthases in Rheumatoid Arthritis

et al. 2023

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. However, the specific mechanism of RA has not been thoroughly clarified over the past decade. Nitric oxide (NO), a kind of gas messenger molecule with many molecular targets, is demonstrated to have significant roles in histopathology and homeostasis. Three nitric oxide synthases (NOS) are related to producing NO and regulating the generation of NO. Based on the latest studies, NOS/NO signaling pathways play a key role in the pathogenesis of RA. Overproduction of NO can induce the generation and release of inflammatory cytokines and act as free radical gas to accumulate and trigger oxidative stress, which can involve in the pathogenesis of RA. Therefore, targeting NOS and its upstream and downstream signaling pathways may be an effective approach to managing RA. This review clearly summarizes the NOS/NO signaling pathway, the pathological changes of RA, the involvement of NOS/NO in RA pathogenesis and the conventional and novel drugs based on NOS/NO signaling pathways that are still in clinical trials and have good therapeutic potential in recent years, with an aim to provide a theoretical basis for further exploration of the role of NOS/NO in the pathogenesis, prevention and treatment of RA.

show abstract

Vardenafil and cilostazol can improve vascular reactivity in rats with diabetes mellitus and rheumatoid arthritis co-morbidity

Cited by 5 publications

References 67 publications

Functional Role of Novel Anthranilic Acid Derivatives as Anti-inflammatory Agents

Functional Role of Novel Anthranilic Acid Derivatives as Anti-inflammatory Agents

Salvia miltiorrhiza stem‐leaf active components of salvianolic acids and flavonoids improved the hemorheological disorder and vascular endothelial function on microcirculation dysfunction rats

Nitric Oxide Synthases in Rheumatoid Arthritis

Contact Info

Product

Resources

About