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Narasin Sale

(Synonyms: 甲基盐霉素) 目录号 : GC63097

An ionophore antibiotic

Narasin Chemical Structure

Cas No.:55134-13-9

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产品描述

Narasin is an ionophore antibiotic isolated from certain Streptomyces sp. and used in veterinary practice as a coccidiostat for gastrointestinal parasites. It has also been shown to inhibit NF-κB signaling via inhibition of IκBα phosphorylation (IC50 = 3.2 ?M) and to stimulate tumor necrosis factor-related apoptosis-induced ligand (TRAIL)-mediated apoptosis in glioma cells via ER stress.1,2

1.Miller, S.C., Huang, R., Sakamuru, S., et al.Identification of known drugs that act as inhibitors of NF-κB signaling and their mechanism of actionBiochem. Pharmacol.79(9)1272-1280(2016) 2.Yoon, M.J., and Kang, Y.J.Monensin, a polyether ionophore antibiotic, overcomes TRAIL resistance in glioma cells via endoplasmic reticulum stress, DR5 upregulation and c-FLIP downregulationCarcinogenesis34(8)1918-1928(2013)

Chemical Properties

Cas No. 55134-13-9 SDF
别名 甲基盐霉素
分子式 C43H72O11 分子量 765.03
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Research Update

Stimulation of Eryptosis by Narasin

Cell Physiol Biochem 2015;37(5):1807-16.PMID:26584281DOI:10.1159/000438543.

Background/aims: Narasin, an ionophore used for the treatment of coccidiosis, has been shown to foster apoptosis of tumor cells. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be triggered by Ca2+ entry with subsequent increase of cytosolic Ca2+ activity ([Ca2+]i), and by ceramide. The present study explored, whether and how Narasin induces eryptosis. Methods: Flow cytometry was employed to estimate phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to Narasin (10 and 25 ng/ml) significantly increased the percentage of annexin-V-binding cells. Forward scatter was decreased by 1 ng/ml Narasin but not by higher Narasin concentrations (10 and 25 ng/ml). Narasin significantly increased Fluo3-fluorescence (10 and 25 ng/ml) and slightly, but significantly increased ceramide abundance (25 ng/ml). The effect of Narasin on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusions: Narasin triggers phospholipid scrambling of the erythrocyte cell membrane, an effect paralleled and partially dependent on Ca2+ entry. Narasin further leads to cell shrinkage and slight increase of ceramide abundance.

Effects of Narasin supplementation frequency on intake, ruminal fermentation parameters, and nutrient digestibility of Bos indicus Nellore steers fed with forage-based diets

Transl Anim Sci 2021 Jul 21;5(3):txab125.PMID:34409265DOI:10.1093/tas/txab125.

The study aimed to evaluate if the frequency of Narasin supplementation impacts dry matter intake, ruminal fermentation parameters, and apparent digestibility of nutrient in Nellore (Bos indicus) steers fed forage-based diets. A total of 32 rumen-cannulated Nellore steers (initial body weight [BW] = 317 ± 27 kg; age =18 ± 1 mo) were assigned to individual pens in a randomized complete block design according to their initial shrunk BW. Within block, steers were randomly assigned to 1 of 4 treatments: 1) forage-based diet without the addition of Narasin (CON; n = 8), 2) CON diet plus 13 ppm of Narasin every 24 h (N24; n = 8), 3) CON diet plus 26 ppm of Narasin every 48 hours (N48; n = 8), or 4) CON diet plus 39 ppm of Narasin every 72 hours (N72; n = 8). The experimental period lasted 30 d, with 18 d for diet adaptation and 12 d for sample collection. The experimental diets contained 95% of Tifton-85 (Cynodon dactylon spp.) haylage and 5% ground corn used as a delivery vehicle for Narasin. Ruminal fluid was obtained from d 25 to 30 at 6 h after feeding to determine ruminal fermentation parameters. Narasin supplementation frequency did not affect (P ≥ 0.22) nutrient intake and total tract apparent digestibility. Steers fed N24 and N48 had reduced (P = 0.02) ruminal acetate concentration compared with CON and N72. Daily supply of Narasin increased (P = 0.01) the molar proportion of propionate compared with CON and N72, and it did not differ between N24 vs. N48, N48 vs. N72, and N72 vs. CON. Also, N48 steers had greater (P = 0.01) rumen propionate concentration compared with CON. The N24 treatment decreased the Ac:Prop (P = 0.01) and AcBut:Prop (P = 0.02) ratio compared with CON and N72, while N48 had reduced (P = 0.01) Ac:Prop and AcBut:Prop ratio when compared with CON steers. Steers fed N24 and N48 had greater (P = 0.04) ruminal short-chain fatty acids compared with CON, but it did not differ (P > 0.11) between N24, N48, and N72. Supplementing Narasin to steers fed forage-based diets decreased (P < 0.01) ruminal ammonia concentration compared with CON steers regardless of supplementation frequency, being the least result observed for N24 steers. Collectively, Narasin supplementation frequency affected fermentation parameters without altering the nutrient intake and total tract apparent digestibility. Hence, decreasing frequency of Narasin supplementation to Nellore steers fed a forage-based diet did not reduce the capacity to modulate rumen fermentation parameters.

Narasin, a novel antiviral compound that blocks dengue virus protein expression

Antivir Ther 2011;16(8):1203-18.PMID:22155902DOI:10.3851/IMP1884.

Background: Dengue virus (DENV) is a mosquito-borne virus that causes a spectrum of human diseases ranging from mild dengue fever to dengue haemorrhagic fever and dengue shock syndrome in severe cases. Currently, there is no effective antiviral therapy or vaccine against DENV infection. Methods: In order to identify potential antiviral agents against DENV, we performed high-throughput cell-based screening on a highly purified natural products library. Among the screening hits, selected compounds which displayed 50-75% inhibition against DENV2 were validated using secondary assays. Time-of-addition studies, dose-dependent assays, real time quantitative reverse transcriptase (RT)-PCR, Western blot and ultrastructural imaging were conducted in an attempt to elucidate the potential antiviral mechanisms of Narasin. Results: In this study, an ionophore, Narasin was selected for detailed analysis due to its strong inhibitory profile against DENV infection with minimal cytotoxicity (50% cytotoxic concentration >1,000 μM). A dose-dependent study revealed Narasin to have an 50% inhibitory concentration of less than 1 μM against all four serotypes of DENV. Time-of-addition studies of narasin-treated, DENV2-infected Huh-7 cells suggested Narasin to be involved in inhibiting the post-entry stages of viral replication during DENV infection. Proteomic and ultrastructural analyses revealed the antiviral mechanism of Narasin as likely to be associated with the disruption of viral protein synthesis. In addition, quantitative RT-PCR studies showed no differences in viral RNA levels between narasin-treated and control DENV2-infected cells. Conclusions: Narasin was identified and characterized as a novel agent that inhibits DENV replication in vitro through non-cytotoxic mechanisms, thus indicating its potential to be further developed as a therapeutic anti-DENV agent.

Narasin effects on energy, nutrient, and fiber digestibility in corn-soybean meal or corn-soybean meal-dried distillers grains with solubles diets fed to 16-, 92-, and 141-kg pigs

J Anim Sci 2017 Sep;95(9):4030-4036.PMID:28991990DOI:10.2527/jas2017.1732.

Three experiments were conducted to determine the effect of Narasin on growth performance and on GE and nutrient digestibility in nursery, grower, and finishing pigs fed either a corn-soybean meal (CSBM) diet or a CSBM diet supplemented with distillers dried grains with solubles (DDGS), in combination with either 0 or 30 mg Narasin/kg of diet. In Exp. 1 (64 gilts, initial BW = 9.0 kg, SD = 1.0 kg) and Exp. 2 (60 gilts. initial BW = 81.1 kg, SD = 6.1 kg), gilts were allotted into individual pens and fed their experimental diets for 24 and 21 d, respectively. On the last 2 d of each experiment, fecal samples were collected to assess apparent total tract digestibility (ATTD) of GE and various nutrients. In Exp. 3, 2 separate groups of 24 gilts (initial BW = 145.1 kg, SD = 7.8 kg) were allotted to individual metabolism crates and fed their experimental diets for 30 d prior to a time-based 6-d total fecal collection period to assess GE and nutrient digestibility. In Exp. 1, there was an interaction between diet type and Narasin addition for G:F and for many of the ATTD coefficients measured. When Narasin was supplemented to the CSBM diet, ATTD of GE, DM, C, S, phosphorus, NDF, and ADF was either not changed or reduced, while when Narasin was supplemented to DDGS diets, these same ATTD parameters were increased (interaction, ≤ 0.05). Even though ADG and ADFI were not affected, G:F was improved in pigs fed the CSBM diet with supplemental Narasin, but was reduced in pigs fed the DDGS diet with supplemental Narasin (interaction, < 0.05). In Exp. 2, there was an interaction between diet type and Narasin supplementation only for ATTD of Ca (interaction, < 0.01), in that Narasin supplementation did not change the ATTD of Ca in pigs fed the CSBM diet, while Narasin supplementation reduced the ATTD of Ca in pigs fed the DDGS containing diet. In Exp. 3, there was an interaction between diet and Narasin only for ATTD of C (interaction, < 0.01) in that Narasin supplementation resulted in an increased ATTD of C in pigs fed the CSBM diet, while Narasin supplementation to the DDGS containing diet resulted in a reduced ATTD of Ca. In general, the data indicate that Narasin interacted with and had its largest effect on pig performance and GE or nutrient digestibility in 9 to 23 kg pigs compared to pigs weighing greater than 80 kg. The data also indicate that the addition of DDGS reduced GE, DM, Ca, and N digestibility, regardless of BW.

Effects of Narasin supplementation on dry matter intake and rumen fermentation characteristics of Bos indicus steers fed a high-forage diet

Transl Anim Sci 2019 Oct 16;4(1):118-128.PMID:32704972DOI:10.1093/tas/txz164.

This study evaluated the effects of Narasin on intake and rumen fermentation characteristics of Bos indicus steers offered a high-forage diet for 140 d. On day 0 of the study, 30 rumen-fistulated Nellore steers [initial body weight (BW) = 281 ± 21 kg] were assigned to 30 individual pens in a randomized complete block design according to their initial BW. Animals were randomly assigned to 1 of the 3 treatments: 1) forage-based diet without Narasin (CONT; n = 10), 2) CONT diet plus 13 ppm of Narasin (13NAR; n = 10), and 3) CONT diet plus 20 ppm of Narasin (20NAR; n = 10). The forage used was Tifton-85 (Cynodon dactylon spp.), whereas the carrier for Narasin was a 50:50 mixture of soybean hull:corn. The experimental period was divided into 5 periods of 28 d each. Throughout the experimental period, total dry matter intake (DMI) was recorded daily, whereas mineral salt intake was recorded weekly. Blood and ruminal fluid samples were collected on day 0 (prior to treatment feeding), 28, 56, 84, 112, and 140 of the study. Moreover, total tract apparent nutrient digestibility was performed for a 5-d period every 28 d. No treatment effects were observed on forage, mineral, concentrate, or total DMI (P ≥ 0.22). Nonetheless, 13NAR tended to have a greater mineral intake vs. 20NAR cohorts (P = 0.08) Narasin-supplemented animals had reduced rumen acetate, Ac:Pr ratio, as well as greater (P ≤ 0.02) rumen propionate concentrations vs. CONT cohorts. Moreover, 13NAR increased rumen propionate and decreased butyrate, Ac:Pr vs. 20NAR cohorts (P ≤ 0.01). Throughout the experimental period, narasin-supplemented animals had reduced ammonia concentrations vs. CONT cohorts (P < 0.01), whereas no differences were observed between 13NAR and 20NAR (P = 0.80). No treatment or dose effects were observed (P ≥ 0.23) on DM, organic matter (OM), protein, neutral detergent fiber (NDF), acid detergent fiber (ADF), and mineral digestibility. Animals fed 13NAR had a reduced mean plasma urea concentration vs. CONT cohorts (P = 0.03), whereas no further differences were observed (P ≥ 0.12). In summary, Narasin supplementation to beef steers offered a high-forage diet did not impact forage, mineral, and total DMI, as well as nutrient digestibility, whereas rumen fermentation characteristics, rumen ammonia, and plasma urea concentrations were positively impacted and lasted throughout the experimental period. Additionally, 13 ppm of Narasin resulted in a reduced Ac:Pr ratio and rumen ammonia when compared to animals supplemented with 20 ppm.