The anti arthritic and anti inflammatory activity of NN-32, a cytotoxic protein from Indian spectacle cobra snake (Naja naja) venom has been studied in Freund's complete adjuvant (FCA) induced arthritis and carrageenan induced anti inflammatory model. NN-32 treatment showed significant decrease in physical and urinary parameters, serum enzymes, serum cytokines levels as compared to arthritic control group of rats. NN-32 treatment recovered carrageenan induced inflammation as compared to control group of rats. The findings showed that the cytotoxic protein NN-32 shares anti arthritic and anti inflammatory activity and thus NN-32 may target complex pathophysiological processes like cancer- arthritis-inflammation. © 2014 Elsevier Ltd. All rights reserved.

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University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

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The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

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It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

Toxicon

A cytotoxin NN-32 (6.7 kDa) from Indian cobra (Naja naja) venom inhibited human leukemic U937 cell growth as observed by Trypan blue dye exclusion method and cytotoxicity was confirmed by MTT assay. NN-32 induced apoptosis of U937 cell and cell cycle arrest of sub-G1 phase were revealed by FACS analysis. Increased Bax/Bcl-2 ratio, increased caspase 3 and 9 activities, cleaved PARP, decreased VEGF, MMP-2 and MMP-9 activities were observed after NN-32 treatment of U937 cell. Antileukemic activity of NN-32 on U937 cell may be due to activation of apoptosis, arresting cell cycle and antiangiogenesis activities. © 2013.

Inhibition of leukemic U937 cell growth by induction of apoptosis, cell cycle arrest and suppression of VEGF, MMP-2 and MMP-9 activities by cytotoxin protein NN-32 purified from Indian spectacled cobra (Naja naja) venom

Limited efficacy of current first-line treatment for leukemia calls attention for further development of efficient strategies. Recently, much attention has been given to nanoparticle-based drug delivery systems loaded with dual drugs to improve current disease therapies by overcoming toxicity. In the present study, we document to explore an approach to conjugate gold nanoparticles (GNPs) with protein toxin (NKCT1), a protein toxin from the Indian cobra (Naja kaouthia) venom, and to establish its antileukemic activity. GNP was prepared by NaBH4 reduction method. UV-vis spectroscopy of GNP showed the absorbance at 530 nm for plasma resonance. Dynamic light scattering (DLS) size of GNPs was 2-8 nm and the GNP-NKCT1 was 68-122 nm. CD spectra of GNP-NKCT1 showed change in percentage of β-turn as compared with NKCT1. GNP-NKCT1 significantly inhibited leukemic cell growth in dose- and time-dependent manner by two- to threefold more than NKCT1. For human leukemic lymphoma cell line and human myelogenous leukemic cell line, the IC50 dose was found to be 1.2 and 0.75 μg/ml, respectively, observed by trypan blue exclusion method and tetrazolium bromide reduction assay. Flow cytometric analysis showed appreciable number of both cell lines in early and late apoptotic stages and arrested cell cycle in the G1 phase by GNP-NKCT1. Resilient power of leukemic cell line after wound healing and migration or invasive power of the cell line was significantly low in GNP-NKCT1-treated plate than the control plate. These analyses reveal that GNP-NKCT1 possesses significant and selective anticancer activity, likely by inducing programmed cell death through mitochondrial and/or lysosomal pathway. © 2013 Springer-Verlag Wien.

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Cancer Nanotechnology

Antileukemic potential of PEGylated gold nanoparticle conjugated with protein toxin (NKCT1) isolated from Indian cobra (Naja kaouthia) venom

Aim of the study was to evaluate the anti-arthritic activity of aqueous black tea extract against experimental arthritis model and in clinical study. Black tea leave (Assam, CTC, India) was collected commercially from authenticated tea supplier. BTE was prepared withMilliQ water and expressed in terms of dry weight. Rheumatoid arthritis was developed in male albino rats by FCA injection into the sub planter surface of hind foot and divided into five groups: Group-1 (Gr.1): Sham control; Group-2 (Gr.2): Arthritic control, Group-3 (Gr.3): Standard anti-arthritic drug Indomethacin, Group-4 (Gr.4) & Group-5 (Gr.5): BTE (high and low dose). Anti-arthritic activity of BTE was examined in animal models through physical, urinary, serum parameters and clinical serum samples. Histological studies of joints were done. Clinical study with BTE performed on the rheumatoid arthritis patients and the serum cytokines (IL-10, IL-6, IL-4) was done. Data was expressed in terms of mean ± SEM (n06). The data were subjected to one way analysis of variance (ANOVA) followed by Tukey's test using Graph Pad InStat3 software to establish statistical significance. Physical, urine, serum parameters and anti-oxidant markers, changed significantly in FCA induced arthritic rats but restored in BTE treated groups. Histological studies of joints showed restoration of the structural architecture of the joint after BTE treatment. Clinical study showed decreased cytokines level in the BTE treated group of patients as compared with the arthritis control group of patients. Data was expressed in terms of mean ± SEM (n06). The data were subjected to one way analysis of variance (ANOVA) followed by Tukey's test to establish statistical significance (*p<0.05, **p<0.01, ***p<0.001). The findings showed BTE had anti-arthritic activity in both experimental and clinical study. Further studies required to ascertain the action of BTE extract at molecular level. © Institute of Oriental Medicine, Kyung Hee University 2012.

Oriental Pharmacy and Experimental Medicine

Anti arthritic activity of aqueous extract of Indian black tea in experimental and clinical study

A cytotoxic and antioxidant protein (NN-32) from the Indian spectacled cobra Naja naja venom was identified and its probable mode of action on murine Ehrlich ascites carcinoma (EAC) was established. The venom purified through ion exchange chromatography produced several peaks, among which fraction 32 produced cytotoxic-cardiotoxic properties. This fraction (NN-32) showed a single peak (retention time 38.3 min) by HPLC using C4 column. The molecular mass determined by MALDI-MS, found to be 6.7 kDa and the first ten N-terminal sequence was determined (LKCNKLVPLF) by Edmann degradation method using applied Biosystem procise sequencer. It was observed that the sequence shared 100% homology with other cytotoxin cardiotoxin identified from the venom of Naja species. NN-32 showed cytotoxicity on EAC cells, increased survival time of inoculated EAC mice, reduced solid tumor volume and weight. NN-32 increased proapoptotic protein caspase 3 and 9 activity and Bax-Bcl2 ratio. It also increased the antioxidant markers glutathione, glutathione peroxidase, glutathione transferase, superoxide dismutase and catalase activity. NN-32 increased serum IL-10 level and decreased murine keratinocyte-derived chemokine level. The cardiotoxicity of NN-32 was established on isolated guinea pig auricle, where 100% irreversible blockade of auricular contraction was observed. Thus, it may be concluded that, NN-32 induced anticancer activity in EAC mice was partly mediated through its apoptogenic - antioxidant property. © 2011 Elsevier Ltd.

Cytotoxic and antioxidant property of a purified fraction (NN-32) of Indian Naja naja venom on Ehrlich ascites carcinoma in BALB/c mice

A lethal cardiotoxic-cytotoxic protein (mol. wt. 6.76 kDa) has been purified from the Indian monocellate cobra (Naja kaouthia) venom by ion-exchange chromatography and HPLC. CD spectra indicated the presence of 23% α helix, 19% β sheets and 35% coil. Complete amino acid sequence was determined by MALDI, which showed similar homology with cardiotoxins/cytotoxins isolated from venom of other Naja species. Intraperitoneal LD 50 was 2.5 mg kg -1 in BalbC male mice. In vitro cardiotoxicity studies on isolated guinea pig auricle showed that the molecule produced auricular blockade that was abolished after trypsin treatment. Cytotoxicity studies on human leukemic U937 and K562 cells showed that it significantly inhibited cell proliferation in a dose and time dependent manner, as observed by trypan blue exclusion method and tetrazolium bromide reduction assay. IC 50 on U937 and K562 cells were 3.5 μg/ml and 1.1 μg/ml respectively. Morphometry and cell sorting studies indicated apoptosis induction in toxin treated leukemic cells. Apoptosis was caspase 3 and 9 dependent and the treated leukemic cells were arrested in sub-G1 stage. There was an increase in Bax-Bcl2 ratio, decrease in HSP (Heat shock protein) 70 and HSP90 and induction of PARP cleavage after NK-CT1 treatment. The toxin showed low cytotoxic effect on normal human leukocytes as compared with imatinib mesylate. Further detailed cytotoxic and cardiotoxic effects at the molecular level are in progress. © 2010 Elsevier Ltd.

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ISSN	0041-0101