Role and uptake of metal-based nanoconstructs as targeted therapeutic carriers for rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a chronic autoimmune systemic inflammatory disease that affects the joints and other vital organs and diminishes the quality of life. The current developments and innovative treatment options have significantly slowed disease progression and improved their quality of life. Medicaments can be delivered to the inflamed synovium via nanoparticle systems, minimizing systemic and undesirable side effects. Numerous nanoparticles such as polymeric, liposomal, and metallic nanoparticles reported are impending as a good carrier with therapeutic properties. Other issues to be considered along are nontoxicity, nanosize, charge, optical property, and ease of high surface functionalization that make them suitable carriers for drug delivery. Metallic nanoparticles (MNPs) (such as silver, gold, zinc, iron, titanium oxide, and selenium) not only act as good carrier with desired optical property, and high surface modification ability but also have their own therapeutical potential such as anti-oxidant, anti-inflammatory, and anti-arthritic properties, making them one of the most promising options for RA treatment. Regardless, cellular uptake of MNPs is one of the most significant criterions for targeting the medication. This paper discusses the numerous interactions of nanoparticles with cells, as well as cellular uptake of NPs. This review provides the mechanistic overview on MNPs involved in RA therapies and regulation anti-arthritis response such as ability to reduce oxidative stress, suppressing the release of proinflammatory cytokines and expression of LPS induced COX-2, and modulation of MAPK and PI3K pathways in Kuppfer cells and hepatic stellate cells. Despite of that MNPs have also ability to regulates enzymes like glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) and act as an anti-inflammatory agent.

Targeting Pathways and Integrated Approaches to Treat Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic symmetrical systemic disorder that not only affects joints but also other organs such as heart, lungs, kidney, and liver. Approximately there is 0.5%-1% of the total population affected by RA. RA pathogenesis still remains unclear due to which its appropriate treatment is a challenge. Further, multitudes of factors have been reported to affect its progression i.e. genetic factor, environmental factor, immune factor, and oxidative factor. Therapeutic approaches available for the treatment of RA include NSAIDs, DMARDs, enzymatic, hormonal, and gene therapies. But most of them provide the symptomatic relief without treating the core of the disease. This makes it obligatory to explore and reach the molecular targets for cure and long-term relief from RA. Herein, we attempt to provide extensive overlay of the new targets for RA treatment such as signaling pathways, proteins, and receptors affecting the progression of the disease and its severity. Precise modification in these targets such as suppressing the notch signaling pathway, SIRT 3 protein, Sphingosine-1-phosphate receptor and stimulating the neuronal signals particularly efferent vagus nerve and SIRT 1 protein may offer long term relief and potentially diminish the chronicity. To target or alter the novel molecules and signaling pathway a specific delivery system is required such as liposome, nanoparticles and micelles and many more. Present review paper discusses in detail about novel targets and delivery systems for treating RA.

Plant-Based Approaches for Rheumatoid Arthritis Regulation: Mechanistic Insights on Pathogenesis, Molecular Pathways, and Delivery Systems.

Rheumatoid arthritis (RA) is classified as a chronic inflammatory autoimmune disorder, associated with a varied range of immunological changes, synovial hyperplasia, cartilage destructions, as well as bone erosion. The infiltration of immune-modulatory cells and excessive release of proinflammatory chemokines, cytokines, and growth factors into the inflamed regions are key molecules involved in the progression of RA. Even though many conventional drugs are suggested by a medical practitioner such as DMARDs, NSAIDs, glucocorticoids, etc., to treat RA, but have allied with various side effects. Thus, alternative therapeutics in the form of herbal therapy or phytomedicine has been increasingly explored for this inflammatory disorder of joints. Herbal interventions contribute substantial therapeutic benefits including accessibility, less or no toxicity and affordability. But the major challenge with these natural actives is the need of a tailored approach for treating inflamed tissues by delivering these bioactive agentsat an appropriate dose within the treatment regimen for an extended periodof time. Drug incorporated with wide range of delivery systems such as liposomes, nanoparticles, polymeric micelles, and other nano-vehicles have been developed to achieve this goal. Thus, inclinations of modern treatment are persuaded on the way to herbal therapy or phytomedicines in combination with novel carriers is an alternative approach with less adverse effects. The present review further summarizes the significanceof use of phytocompounds, their target molecules/pathways and, toxicity and challenges associated with phytomolecule-based nanoformulations.

Mechanistic prospective and pharmacological attributes of quercetin in attenuation of different types of arthritis.

Arthritis is a frequent autoimmune disease with undefined etiology and pathogenesis. Scientific community constantly fascinating quercetin (QUR), as it is the best-known flavonoid among others for curative and preventive properties against a wide range of diseases. Due to its multifaceted activities, the implementation of QUR against various types of arthritis namely, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis (GA) and psoriotic arthritis (PsA) has greatly increased in recent years. Many research evidenced that QUR regulates a wide range of pathways for instance NF-κB, MAK, Wnt/ß-catenine, Notch, etc., that are majorly associated with the inflammatory mechanisms. Besides, the bioavailability of QUR is a major constrain to its therapeutic potential, and drug delivery techniques have experienced significant development to overcome the problem of its limited application. Hence, this review compiled the cutting-edge experiments on versatile effects of QUR on inflammatory diseases like RA, OA, GA and PsA, sources and bioavailability, therapeutic challenges, pharmacokinetics, clinical studies as well as toxicological impacts. The use of QUR in a health context would offer a tearing and potential therapeutic method, supporting the advancement of public health, particularly, of arthritic patients worldwide.

Contribution of strigolactone in plant physiology, hormonal interaction and abiotic stresses.

Strigolactones (SLs) are carotenoid-derived molecules, which regulate various developmental and adaptation processes in plants. These are engaged in different aspects of growth such as development of root, leaf senescence, shoot branching, etc. Plants grown under nutrient-deficient conditions enhance SL production that facilitates root architecture and symbiosis of arbuscular mycorrhizal fungi, as a result increases nutrient uptake. The crosstalk of SLs with other phytohormones such as auxin, abscisic acid, cytokinin and gibberellins, in response to abiotic stresses indicates that SLs actively contribute to the regulatory systems of plant stress adaptation. In response to different environmental circumstances such as salinity, drought, heat, cold, heavy metals and nutrient deprivation, these SLs get accumulated in plant tissues. Strigolactones regulate multiple hormonal responsive pathways, which aids plants to surmount stressful environmental constraints as well as reduce negative impact on overall productivity of crops. The external application of SL analog GR24 for its higher bioaccumulation can be one of the possible approaches for establishing various abiotic stress tolerances in plants.