Nimbolide is an active constituent of Azadirachta indica and is known for its anti‐inflammatory, anti‐oxidant, immune‐modulatory, and anti‐cancer effects. Few studies suggest that nimbolide treatment influences the responses to rheumatoid arthritis, but the underlying molecular mechanisms involved are not yet well established. Therefore, the present study was designed to determine the effect of nimbolide on expression regulation of toll‐like receptors to attenuate rheumatoid arthritis. The rheumatoid arthritis model was established by injecting complete Freund's adjuvant (CFA) intra‐dermally into the sub‐plantar region of the left hind paw of rats. Nimbolide (20 mg/kg) and piroxicam (10 mg/kg) were given to arthritic rats. Rats treated with nimbolide showed a significant reduction in inflammatory cells, rheumatoid factor, ESR, and improved the body weight. The results indicated that nimbolide possesses the capacity to attenuate rheumatoid arthritis by downregulating toll‐like receptors, IL‐17, IL‐23, HSP70, and IFN‐γ expression levels. Nimbolide treatment showed significant reduction in the severity of inflammation and destruction of joints and showed comparable effects to piroxicam, which is a standard non‐steroidal anti‐inflammatory drug used for the treatment of rheumatoid arthritis. It can be concluded that nimbolide can be considered as a potential candidate for therapeutic targeting of the toll‐like receptors pathway in rheumatoid arthritis.

Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund’s adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis.

Asthma is a chronic inflammatory disease of the lower airways, characterize by wheezing cough, chest tightness along with inflammation of airway and shortness of breath. Allergens like environmental substance are predispose asthmatics patients to allergy. Mast cells produced interleukin (IL)- 4 which either activate signal transducer and activator of transcription 6 (STAT-6) pathway that involved in differentiation of na ve T-cells to TH2 or activation of TH2 cells indirectly. The aim of the current context is to present role of IL-4 in asthma and effect as antagonist. IL-4 results in increased mucus production and involve in IgE synthesis from B cells. IL4 facilitate chemotaxis and aid in displaying of VCAM-1 which attract eosinophil basophils monocytes T-lymphocytes to blood vessel. IL4 inhibit apoptosis either by preventing decrease in BCL-2 level or binding of FasL to Fas (cd32) receptor which result in acute allergic response. Elevated level of IL-4 has greatly adverse impact on asthmatic patients so by decreasing the level of IL-4 will greatly reduce asthma phenotype.

Background: Asthma is a debilitating chronic inflammatory disease of airway with frequent episodes of exacerbations. It confers great burden on health systems due to associated symptoms like cough, wheeze, chest tightness and shortness of breath. We have explored the effect of an important indoleamine inhibitor on important asthmatic parameters in this study. Aim: Exploration of an alternative pathway of indoleamine inhibition for the treatment of asthma in future. Methods: Forty Wester rats were divided into four groups (normal control, disease control, prednisolone treated, methyltryptophan treated) with ten animals each. Blood samples were collected for eosinophil count. PCR was performed for measuring the IL-5 expression of the lung tissue. Results:1MT significantly reduced the eosinophil levels and mRNA expression of IL-5 through indoleamine inhibition. Conclusion: The pathway of indoleamine inhibition has appeared significant for reducing the inflammation and allergic response in asthma. Further exploration of this pathway can open new dynamics for asthma treatment. Keywords: Asthma, indoleamines, cytokines, eosinophils, inflammation