Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and an irreversible lung disorder characterized by the accumulation of fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be one of the possible sources for a substantial increase in the number of fibroblasts/myofibroblasts in IPF lungs. Tannic acid (TA), a natural dietary polyphenolic compound has been shown to possess diverse pharmacological effects. However, whether TA can inhibit TGF-β1-mediated EMT in lung epithelial cells remains enigmatic. Both the human adenocarcinomic alveolar epithelial (A549) and normal bronchial epithelial (BEAS-2B) cells were treated with TGF-β1 with or without TA. Results showed that TA addition, markedly inhibited TGF-β1-induced EMT as assessed by reduced expression of N-cadherin, type-1-collagen, fibronectin, and vimentin. Furthermore, TA inhibited TGF-β1-induced cell proliferation through inducing cell cycle arrest at G0/G1 phase. TGF-β1-induced increase in the phosphorylation of Smad (Smad2 and 3), Akt as well as that of mitogen activated protein kinase (ERK1/2, JNK1/2, and p38) mediators was effectively inhibited by TA. On the other hand, TA reduced the TGF-β1-induced increase in TGF-β receptors expression. Using molecular docking approach, FTIR, HPLC and Western blot analyses, we further identified the direct binding of TA to TGF-β1. Finally, we conclude that TA might directly interact with TGF-β1, thereby repressing TGF-β signaling and subsequent EMT process in lung epithelial cells. Further animal studies are needed to clarify its potential therapeutic benefit in pulmonary fibrosis.

A B S T R A C TRheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune inflammatory disease with unknown etiology accomplished with increased cardiovascular risks. RA is characterized by the clinical findings of synovial inflammation, autoantibody production, and cartilage/bone destruction, cardiovascular, pulmonary and skeletal disorders. Pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and IL-10 were responsible for the induction of inflammation in RA patients. Drawbacks such as poor efficacy, higher doses, frequent administration, low responsiveness, and higher cost and serious side effects were associated with the conventional dosage forms for RA treatment. Nanomedicines were recently gaining more interest towards the treatment of RA, and researchers were also focusing towards the development of various anti-inflammatory drug loaded nanoformulations with an aid to both actively/passively targeting the inflamed site to afford an effective treatment regimen for RA. Alterations in the surface area and nanoscale size of the nanoformulations elicit beneficial physical and chemical properties for better pharmacological activities. These drug loaded nanoformulations may enhances the solubility of poorly water soluble drugs, improves the bioavailability, affords targetability and may improve the therapeutic activity. In this regimen, the present review focus towards the novel nanoparticulate formulations (nanoparticles, nanoemulsions, solid lipid nanoparticles, nanomicelles, and nanocapsules) utilized for the treatment of RA. The recent advancements such as siRNA, peptide and targeted based nanoparticulate systems for RA treatment were also discussed. Special emphasis was provided regarding the pathophysiology, prevalence and symptoms towards the development of RA.

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An improved derivatized RP-HPLC method with PDA detection has been developed and validated for the simultaneous estimation of tranexamic acid and mefenamic acid in combined tablet dosage form. The method employs precolumn derivatization using 0.2% methanolic ninhydrin at primary amino group of tranexamic acid to form ruhemann purple product. Mefenamic acid could not react with ninhydrin. The chromatographic estimation was achieved using phenomenex C-18 (250 X 4.6 mm, 5 µm) analytical column and the mobile phase consisting of methanol and 20 mmol-1 acetate buffer (75:25, v/v) pH adjusted to 4.0 using ortho phosphoric acid at a flow rate of 1.0 mLmin-1. The UV detection was carried out at 370 nm using photodiode array detector. The retention time of tranexamic acid and mefenamic acid were found to be 3.9 and 12.4 min. Tranexamic acid and mefenamic acid calibration curves were linear with correlation coefficient of 0.9973 and 0.9985 at a concentration ranging from 5µgmL-1 to 25 µgmL-1. Recovery was between 98.5%-100.5% for tranexamic acid and 99.7%-104.3% for mefenamic acid. Limit of detection and quantification were 54.0ngmL-1 and 62.6 ngmL-1 for tranexamic acid, 12.3ngmL-1 and 37.1 ngmL-1 for mefenamic acid. The developed method is very sensitive as both peaks were well separated from its derivatizing agent peak with a short analysis time of 15 minutes.

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