In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria.

BACKGROUND: Melittin is one of the most studied antimicrobial peptides, and several in vitro experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between in vitro and in vivo studies. METHODS: In the first step, in vitro toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR) Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and KPC-producing Klebsiella pneumonia (KPC-KP) pathogens were tested using both in vitro and in vivo methods. RESULTS: Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50 value of 4.98 mg/kg in BALB/c mice. In vitro antimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads. CONCLUSIONS: These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent.

BACKGROUND: Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. OBJECTIVE: This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. METHODS: Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. RESULTS: The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl (p=0.026) and 40 mg/100 µl (p=0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl (p=0.000) and 300 µl/100 µl (p=0.030). CONCLUSION: The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.

Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent

BACKGROUND: Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified. OBJECTIVE: This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect. METHODS: Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies. RESULTS: The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl (p=0.026) and 40 mg/100 µl (p=0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl (p=0.000) and 300 µl/100 µl (p=0.030). CONCLUSION: The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.

Inhibitory effects of melittin on osteosarcoma xenografts in nude mice and its action on vasculogenic mimicry / 肿瘤

Objective: To investigate the antitumor effects of melittin on UMR-106 cells with osteosarcoma xenografts in nude mice and its action on vasculogenic mimicry (VM) in vitro and in vivo. Methods: A three-dimensional cell culture system was formed on matrigel coats in vitro. Inhibitory action of melittin on the VM of UMR-106 cells was observed in vitro. Osteosarcoma was orthotopically transplanted in nude mice. The mice were randomly divided into three groups: normal saline (NS)-treated group, melittin group (320 μg/kg) and DDP-treated group(2 mg/kg). The drug was administered intratumorally for 10 d. The tumor volume and weight inhibition ratio were calculated, respectively. The VM density in tumor tissues was detected by CD34 and PAS double staining in vivo. The expressions of hypoxia-inducible factor-1α(HIF-1α) and matrix metalloproteinase-2 (MMP-2) proteins were determined by immunohistochemical staining and Western blot. Results: Melittin broke down the mesh and round architectonic of VM in osteosarcoma in vitro. The tumor weight inhibition ratio was 38.92% and the volume inhibition ratio was 43.04%. The VM density and the expressions of HIF-1α and MMP-2 proteins were decreased in the melittin group than that in the NS-treated group (P <0.01). Conclusion: Melittin markedly inhibites the growth of osteosarcoma UMR-106 xenografts in nude mice. The mechanism may be due to down-regulation of HIF-1α and MMP-2 expression and the inhibition of VM.

Apisin injection's clincal results to tuberculous excudatire / 中国基层医药

Objective To review the clinical results of apisin to tuberculous exudatire pleurisy.Methods 60 patients with tuberculous exudatire plearisy were divided into two grups:conteol group and study group.In the control group,they were given 2HRIE/4HR.In the study group,the apisin was dripped into pleural cavity on the base of treat tuberculosis.Results The two group efficacious rate were 100%.The study group's efficacious rate was 90%.The controt group's efficcious.Rate was 63%.There was significant difference between the two groups(P

Protective effect of mastoparan-1 on acute lung injury of mice with endotoxemia / 解放军医学杂志

Objective To assess the protective effect of mastoparan-1(MP-1) on acute lung injury in mouse model with endotoxemia(ETM) induced by lipopolysaccharide(LPS),and to investigate the possible mechanism of protcetive effect.Methods The endotoxemia murine model was reproduced by tail vein injection of LPS(5mg/kg) in mice.Animals were randomly divided into normal control group(n=8),endotoxemia group(n=48) and MP-1-treatment group(MP-1 was injected in 3mg/kg at the same time of LPS injection,n=48).Animals of the latter two groups were sacrificed at 2,6,12,24,48 and 72 hours after injection,and then the blood and lung tissue samples were collected.Plasma LPS was assayed using kinetic turbidimetric limulus test,TNF-? and IL-6 were measured by appropriate ELISA kits,TLR4,TNF-? and IL-6 mRNA expressions in lung tissues were analyzed by real-time RT-PCR,myeloperoxidase(MPO) activity of lung tissues was determined by spectrophotometric method,and the pathological changes in lung tissues were observed under microscope.Result The plasma levels of LPS,TNF-? and IL-6 in the mice of endotoxemia group were increased at 2-48 hours after LPS injection(P