Carbon nanospheres mediated delivery of nuclear matrix protein SMAR 1 to direct experimental autoimmune encephalomyelitis in mice

Owing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. Here, we demonstrate a novel carbon nanosphere (CNP) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein SMAR1. A truncated part of SMAR1 ie, the DNA binding domain was conjugated with hydrothermally synthesized CNPs. When administered intravenously, the conjugate suppressed experimental animal encephalomyelitis in T cell specific conditional SMAR1 knockout mice (SMAR-/-). Further, CNP-SMAR1 conjugate delayed the onset of the disease and reduced the demyelination significantly. There was a significant decrease in the production of IL-17 after re-stimulation with MOG. Altogether, our findings suggest a potential carbon nanomaterial based therapeutic intervention to combat Th17 mediated autoimmune diseases including experimental autoimmune encephalomyelitis

Anti-diabetic activity and safety assessment of Ayurvedic medicine, <i style="mso-bidi-font-style:normal">Jasada bhasma</i> (zinc ash) in rats<span style="mso-bidi-font-weight:bold"> </span>

811-822Jasada bhasma (zinc ash) is an extensively used Ayurvedic medicine for treating diabetes mellitus. The present communication presents yet unavailable comprehensive scientific data on its physico-chemical nature vis-à-vis anti-diabetic activity and toxicity profile.Zinc ash prepared by traditional method was found to consist of 200-500 nm sized particles, predominantly zinc oxide with hexagonal wurtzite crystal structure.The effective dose range of zinc ash in oral glucose tolerance tests performed using normoglycemic Wistar rats was found to be 3-30 mg/kg. Subsequently anti-diabetic activity was assessed in streptozotocin induced type 1 and type 2 diabetic rats. Four weeks treatment with zinc ash (1, 3, 10 mg/kg) resulted in improved glucose tolerance (16-19%), lowered blood glucose levels (20-33%) and reduced serum insulin levels (27-32%). Systemic absorption was assessed by single dose pharmacokinetic study where serum zinc levels were found to be elevated (3.5 folds) after oral administration of zinc ash. Acute and sub-acute toxicity tests demonstrated safety of zinc ash up to 300 mg/kg doseie. 100 times the efficacy dose in rats.These findings, the first of their kind, provide concrete scientific evidence that justifies usage of zinc ash in diabetes treatment

Anticancer Activity of Indian Stingless Bee Propolis: An In Vitro Study

Indian stingless bee propolis has a complex chemical nature and is reported to possess various medicinal properties. In the present study, anticancer activity of the ethanolic extract of propolis (EEP) was explored by testing the cytotoxic and apoptotic effect in four different cancer cell lines, namely, MCF-7 (human breast cancer), HT-29 (human colon adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), and B16F1 (murine melanoma), at different concentrations. Cytotoxicity was evaluated by MTT assay and Trypan blue dye exclusion assay. EEP at a concentration of 250 g/mL exhibited ≥50% mortality in all cell lines tested (i.e., IC50 value). EEP revealed a concentration and time dependent cytotoxic effect. Apoptosis was estimated by differential staining (ethidium bromide/acridine orange) and TUNEL (deoxynucleotidyl transferase-dUTP nick end labeling) assay. Light microscopy and atomic force microscopy demonstrated morphological features of apoptosis in all the cell lines after treatment with 250 g/mL EEP for 24 h. Thus, early onset of apoptosis is the reason for anticancer activity of Indian stingless bee propolis. Further, the antioxidant potential of Indian stingless bee propolis was demonstrated to substantiate its anticancer activity

Antioxidant and trace element potential of Chyavanpraash and some Ayurvedic preparations

215-223Importance of antioxidants such as vitamin C and zinc in treatment of diabetes mellitus and hypertension is being recognised. There is a growing interest to find naturally occurring antioxidants rather than synthetic ones for their use in medicinal material. Therefore a study was undertaken a) to assess antioxidant and trace metal potential of five brands of Chyavanpraash and eight marketed Ayurvedic preparations (AP) at their prescribed dose level along with their major nine ingredients; b) to measure bioavailable amounts of trace metals; and c) to examine toxicity of lead in these AP. Trivang, Abhrak and Loha bhasma had high levels of copper, cobalt and nickel. Manganese contents were high in Trivang and Abhrak but zero in Lohabhasma. Even though amalaki is one of the main ingredients of Chyavanpraash and Raktavardhak, their vitamin C content was quite low. Tannic acid was marginal in these two preparations. Three types of amalaki showed variable contents of iron, zinc, copper, lead, manganese and ascorbic acid. Tannic acid was highest in small amalaki. Sun drying reduced vitamin C content by seventy five percent of the fresh amalaki. Lohabhasma showed highest bioavailable iron followed by Lohachurna. The bioavailable iron was negligible in Chyavanpraash and Raktavardhaka as compared to Lohabhasma and Abhrak bhasma. Bioavailable zinc content was high in Trivang bhasma and is a promising zinc supplement. Mineral iron treated with Gomutra decreased % iron bioavailability by one third but % zinc bioavailabiliy increased twofold. Lead content was highest in Trivang bhasma. The content of lead in daily dose of Chyavanpraash and Raktavardhak was high, but within the prescribed safe limits for lead. Further the bioavailable amount of lead for all these preparations was also very low

SMAR1-derived P44 peptide retains its tumor suppressor function through modulation of p53

The use of pharmacologically active short peptide sequences is a better option in cancer therapeutics than the full-length protein. Here we report one such 44-mer peptide sequence of SMAR1 (TAT-SMAR1 wild type, P44) that retains the tumor suppressor activity of the full-length protein. The protein transduction domain of human immunodeficiency virus, type 1, Tat protein was used here to deliver the 33-mer peptide of SMAR1 into the cells. P44 peptide could efficiently activate p53 by mediating its phosphorylation at serine 15, resulting in the activation of p21 and in effect regulating cell cycle checkpoint. In vitro phosphorylation assays with point-mutated P44-derived peptides suggested that serine 347 of SMAR1 was indispensable for its activity and represented the substrate motif for the protein kinase C family of proteins. Using xenograft nude mice models, we further demonstrate that P44 was capable of inhibiting tumor growth by preventing cellular proliferation. P44 treatment to tumor-bearing mice prevented the formation of poorly organized tumor vasculature and an increase in hypoxia-inducible factor-1α expression, both being signatures of tumor progression. The chimeric TAT-SMAR1-derived peptide, P44, thus has a strong therapeutic potential as an anticancer drug