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Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thomson, a known immunomodulatory agent extensively used in ayurveda, has not been effectively validated for the mechanisms involved in immunomodulation and the identification of the active principles. The bioactive fraction of T. cordifolia (TBF) in methanol was used for nitric oxide (NO) radical scavenging activity, lipoxygenase (LOX) and cyclooxygenase (COX) dual inhibition and cytotoxicity studies. Production of the proinflammatory cytokines, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in dendritic cell (DC) suspensions treated with lipopolysaccharide (LPS) was also studied. The bioactive principles involved were identified with ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometric (UPLC-Q-ToF MS/MS) system. The results indicate significantly higher potency of TBF as compared to positive standards for LOX/COX inhibition with moderate NO radical scavenging activity and the fraction was also found to be non-cytotoxic to monocyte cells. A significant inhibition was also observed in TNF-α and IL-1β production in LPS-treated DC suspensions as compared to standards, rolipram and dexamethasone, respectively. 11 compounds were identified from TBF by MS/MS system. The potent inhibition of LOX and COX enzymes with moderate NO scavenging was indicative of a free radical scavenging-independent mechanism of immunomodulation. Further investigations into the active principles identified would result in the development of lead candidates with potent therapeutic implications. [ABSTRACT FROM AUTHOR]

Background: Guggulutiktaka ghritam is an ayurvedic medicine which has been traditionally used to treat various chronic inflammatory conditions. However, the mechanism of action of the Ayurvedic medication in control of inflammatory conditions has not been clearly evaluated., Objective: In the current study, the effect of the Guggulutiktaka ghritam extract (GTG) on the lipoxygenase pathway and in the production of proinflammatory cytokines involved in the pathogenesis of chronic inflammation was studied., Materials and Methods: The effect of GTG in the production of leukotriene was determined by enzyme inhibition studies on 12- lipoxygenase. The assay was carried out by ferrous oxidation of xylenol orange (FOX assay) and was compared to a positive control nordihydroguaiaretic acid. The effect of GTG on the production of proinflammatory cytokines TNF-α and IL-1β in monocytes were studied. For this, the monocytes were pretreated with various concentrations of GTG and subsequently stimulated with lipopolysaccharide. The cytokines TNF-α and IL-1β produced were quantified by ELISA and the results were compared to positive controls Rolipram and Dexamethasone respectively. The gene expression studies were carried out using qRT-PCR. The IC 50 values were calculated and evaluated statistically., Results: The result indicates that GTG in comparison to the positive control Nordihydroguaiaretic acid significantly reduced the activity of 12- lipoxygenase. Also, there was significant inhibition in the production of proinflammatory cytokines in LPS stimulated monocytes pretreated with GTG as compared to positive control Rolipram and Dexamethasone. There was significant downregulation of IL-1β gene in LPS stimulated monocytes pretreated with GTG as compared to control. These changes are further supported by Raman spectra obtained for GTG treated and untreated cells., Conclusion: The study revealed that GTG is a leukotriene and cytokine inhibitor. The inhibition in the production of cytokines may be due to the down-regulation of genes for TNF-α and IL-1β. The study provides a scientific validation on the possible anti-inflammatory mechanism of action of this traditionally used medicine. Identification of bioactive molecules would aid in developing newer therapeutics for control of chronic inflammation., (Copyright © 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Varanadi Kashayam is an Ayurvedic polyherbal decoction containing 16 ingredients, for which the mechanisms of action involved in controlling chronic inflammatory conditions have not been evaluated. The inhibition of release of proinflammatory cytokines by lipopolysaccharide (LPS)-stimulated monocytes/macrophages is an ideal in vitro model for identifying anti-inflammatory molecules., Aim: The aim of the study is to determine the anti-inflammatory effect of Varanadi Kashayam in THP-1-derived macrophages., Materials and Methods: The efficacy of Varanadi Kashayam on monocyte cell differentiation was determined by quantitative polymerase chain reaction to assess the expression of differentiation markers MMP-9, CD36, CD11b and CD14. Further Varanadi Kashayam treated THP-1 macrophages were induced with LPS and the production of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) were measured and corresponding genes expressions were quantified., Results: The results indicate that Varanadi Kashayam reduced the differentiation of THP-1 monocytes to macrophages and downregulated the expression of cell surface markers. Furthermore, it could decrease the release of proinflammatory cytokines from LPS-induced THP-1 macrophages and downregulated the expression of TNF-α and IL-1β genes., Conclusion: The results obtained from this study suggest a possible mechanism of action of the herbal decoction in inflammatory processes and opens up the possibilities of identifying bioactive lead molecules with anti-inflammatory potentials., Competing Interests: There are no conflicts of interest

Doxorubicin (Dox) has been used for more than four decades to treat cancer, particularly solid tumours and haematological malignancies. However, the administration of this drug is a matter of concern in the clinical community, since Dox therapy is commonly associated with dose-dependent cardiotoxicity. Attempts at alleviating drug generated cardiac damage using naturally occurring compounds with radical scavenging property are a promising area of research. p -Coumaric acid ( p CA) is one such compound which has significant antiradical scavenging effect. This study aims to investigate the effect of pre and co-administration of p CA on mitigating or preventing Dox induced cardiotoxicity in vitro using H9c2 cardiomyoblast cell lines. Addition of p CA and Dox were performed for both treatment and control sets on H9c2 cells. Sulphorhodamine B assay was used to study the cytotoxic effect of p CA and Dox. The effect of the drug on cell morphology, cell viability and nuclear damage was studied using AO/EB and DAPI staining. ROS production was studied using DCFH-DA staining. Mitochondrial membrane potential and intracellular calcium levels were assessed by rhodamine 123 and Fura 2AM staining. p CA showed strong ABTS cation radical scavenging activity and FRAP activity in a dose dependent manner. The results showed that Dox has significant cytotoxic effect in a dose dependent manner while p CA, even at higher concentrations did not display any significant cytotoxicity on H9c2 cells. Both pre treatment and co- administration of p CA reduced the drug induced toxic effects on cell morphology and enhanced the number of viable cells in comparison to the Dox treated cells as evident from the AO/EB and DAPI staining images. The Dox induced ROS production was found to be significantly reduced in p CA pre-treated and co-administered cells. Dox induced changes in mitochondrial membrane potential and intracellular calcium levels were remarkably improved following pre and co-treatment of H9c2 cells with pCA. These results clearly suggest that pre-treatment and co-administration of p CA is a promising therapeutic intervention in managing Dox mediated cardiotoxicity.