Mangiferin from Pueraria tuberosa reduces inflammation via inactivation of NLRP3 inflammasome.

Recent reports have demonstrated the role of phyto-constituents in modulating inflammatory responses. Mangiferin isolated from Mangifera indica is known to induce potent anti-oxidative, anti-diabetic and anti-inflammatory activity. However, the molecular mechanism of its anti-inflammatory activity is not properly understood. In this study we have isolated Mangiferin from the tubers of Pueraria tuberosa (PT-Mangiferin) and analysed the mechanism of its potent anti-inflammatory effects in LPS stimulated RAW 264.7 mouse macrophage cell line and in a carrageenan induced air pouch model. PT-Mangiferin was non-toxic to primary cells but showed significant toxicity and apoptotic effect on cancerous cells. It significantly reduced the production of pro-inflammatory mediators (COX-2, iNOS and TNF-α) in LPS stimulated RAW 264.7 cells. Further, it has also reduced the generation of ROS and inhibited LPS induced NF-kB translocation in these cells. Additionally, PT-Mangiferin significantly reduced inflammation in a mouse air pouch model by inhibiting the infiltration of monocytes and neutrophils and reducing the production of cytokines. These effects were mediated via inactivation of NLRP3 inflammasome complex and its downstream signalling molecules. Taken together these results suggest that PT-Mangiferin is potent anti-inflammatory compound that reduces inflammation and holds promise in development of herbal based anti-inflammatory therapeutics in future.

Biocompatible silver nanoparticles reduced from Anethum graveolens leaf extract augments the antileishmanial efficacy of miltefosine.

Despite the existence of chemotherapy, there is no effective cure for leishmaniasis. In the light of recommended therapeutic regimen is attributed for toxicity and development of clinical resistance, exploration of an efficient method of drug delivery could be one of the option in reducing the dosage and toxicity of drugs. This work is aimed in such fashion to study the enhanced antileishmanial activity of miltefosine with silver-nanoparticles (AgNPs) synthesized by using Anethum graveolens (dill) leaf extract as reducing agent. AgNPs were synthesized in a single step process and characterized by UV-visible, X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FTIR) to understand the crystal structure and functional groups on their surface. TEM analysis showed that the synthesized AgNPs are of an average size of 35 nm. By performing MTT assay, we found that, AgNPs (between 20 and 100 µM) are biocompatible in nature through pertaining >80% viability of macrophages. Furthermore, AgNPs alone (50 µM) have not shown antileishmanial effect on promastigote stage of Leishmania parasite but in combination with miltefosine (12.5 µM and 25 µM), it magnifies the leishmanicidal effect of miltefosine by ∼2-folds (i.e. AgNPs cut down the IC50 of miltefosine about to half). Scanning electron microscopic (SEM) observation for morphological aberration and genomic DNA fragmentation in promastigotes confirmed the enhanced effect of meltefosine in combination with AgNPs (50 µM AgNPs plus 12.5 µM miltefosine). Similarly, this combination has likely shown a slight augmentation (p = 0.057) of miltefosine (2.5 µM) leishmanicidal efficacy on amastigote stage of the parasite in infected human macrophages by reducing their intracellular growth.

Chebulagic acid from Terminalia chebula causes G1 arrest, inhibits NFκB and induces apoptosis in retinoblastoma cells.

BACKGROUND: Plants are the valuable source of natural products with important medicinal properties. Most of the approved anti cancer drugs have a natural product origin or are natural products. Retinoblastoma is the most common ocular cancer of children. Although chemotherapy is the preferred mode of therapy, a successful treatment for retinoblastoma requires enucleation. Chebulagic acid (CA) from Terminalia chebula was shown to have anti-proliferative properties in the studies on cancerous cell lines. Due to anti cancer properties of CA and due to limitation in treatment options for retinoblastoma, the present study is undertaken to understand the role of CA on the proliferation of retinoblastoma cells. METHODS: Anti proliferative potential of CA was determined by MTT assay. The expression levels of various cell death mediators in retinoblastoma cells with CA treatment were assessed by Western blotting. Flowcytometer analysis was used to estimate the mitochondrial membrane potential (MMP) and to determine the percentage of cells undergoing apoptosis. RESULTS: The present study showed CA inhibited the proliferation of retinoblastoma cells in a dose dependent manner. CA modulated MMP, induced release of Cytochrome c, activated caspase 3 and shifted the ratio of BAX and Bcl2 towards cell death. G1 arrest, noticed in CA treated cells, is mediated by the increase in the expression of CDK inhibitor p27. CA treatment also decreased the levels of NFκB in the nucleus. This decrease is mediated by suppression in degradation of IκBα. CONCLUSION: CA has shown significant anti proliferative potential on retinoblastoma cells. Our findings clearly demonstrate that CA induces G1 arrest, inhibits NFκB and induces apoptosis of retinoblastoma cells.