<i>In Vitro</i>Evaluations and<i>In Vivo</i>Toxicity and Efficacy Studies of MFM501 against MRSA

Johari, Saiful Azmi; Mohtar, Mastura; Mohamad, Sharifah Aminah Syed; Mohammat, Mohd Fazli; Sahdan, Rohana; Mohamed, Azman; Ridhwan, Mohamad Jemain Mohamad

doi:10.1155/2017/8032865

Cited by 10 publications

(16 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A hydroxylated codonopsinine derivative ( Fig. 3 ), MFM501, has bacteriostatic activity against more than 40 clinical MRSA strains targeting cellular membranes and is tolerated by mice with no toxic effects ( 252 , 253 ). Friar's cowl ( Arisarum vulgare ; Araceae) contains the antibacterial and antifungal compound ( R )-bgugaine.…”

Section: Alkaloidsmentioning

confidence: 99%

Amino acid–derived defense metabolites from plants: A potential source to facilitate novel antimicrobial development

Parthasarathy

Borrego

Savka

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

For millennia, humanity has relied on plants for its medicines, and modern pharmacology continues to reexamine and mine plant metabolites for novel compounds and to guide improvements in biological activity, bioavailability, and chemical stability. The critical problem of antibiotic resistance and increasing exposure to viral and parasitic diseases has spurred renewed interest into drug treatments for infectious diseases. In this context, an urgent revival of natural product discovery is globally underway with special attention directed toward the numerous and chemically diverse plant defensive compounds such as phytoalexins and phytoanticipins that combat herbivores, microbial pathogens, or competing plants. Moreover, advancements in “ omics ,” chemistry, and heterologous expression systems have facilitated the purification and characterization of plant metabolites and the identification of possible therapeutic targets. In this review, we describe several important amino acid–derived classes of plant defensive compounds, including antimicrobial peptides ( e.g. , defensins, thionins, and knottins), alkaloids, nonproteogenic amino acids, and phenylpropanoids as potential drug leads, examining their mechanisms of action, therapeutic targets, and structure–function relationships. Given their potent antibacterial, antifungal, antiparasitic, and antiviral properties, which can be superior to existing drugs, phytoalexins and phytoanticipins are an excellent resource to facilitate the rational design and development of antimicrobial drugs.

show abstract

Section: Alkaloidsmentioning

confidence: 99%

Amino acid–derived defense metabolites from plants: A potential source to facilitate novel antimicrobial development

Parthasarathy

Borrego

Savka

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In the future, our group will conduct research on the pharmacokinetics of citral to improve its efficiency in vivo . In the same mouse model experiment, the ED 50 of the experimental drug was much higher than that of citral (injection, 0.09 g kg −1 ; oral administration, 0.26 g kg −1 ).…”

Section: Discussionmentioning

confidence: 84%

Effect and mechanism of citral against methicillin‐resistant Staphylococcus aureus in vivo

et al. 2019

View full text Add to dashboard Cite

BACKGROUND: Citral is an active component of many plant extracts, and it is a safe additive used in food and cosmetics. A previous study showed that citral has a good antibacterial effect against methicillin-resistant Staphylococcus aureus (MRSA) in vitro, but its in vivo anti-infective activity has not been studied. Anti-MRSA activity and the preliminary mechanism of citral against MRSA were investigated in MRSA-infected KM mice. The ED 50 was calculated using Karber's method. Groups were selected for inflammatory and oxidative stress level tests, and lung and liver tissues were counterstained with HE for detection of pathological changes. Cytokines and oxidative factors were evaluated using the ELISA method (one-way ANOVA computed using SPSS 19.0.). RESULTS: With the increase in the concentration of citral, the survival rate of MRSA-infected mice increased accordingly. The ED 50 values of citral for intramuscular injection and intragastric administration were 0.09 and 0.26 g kg −1 respectively. Citral significantly reduced cytokines (IL-1 , IL-6, TNF-) and oxidative factors (malondialdehyde and hydroxyl radicals) of MRSA-infected mice, whereas it increased gluthtione and superoxide dismutase levels. Citral can reduce the lung inflammatory infiltrates infected by MRSA. CONCLUSIONS: Citral exerted a dose-dependent anti-MRSA effect and ameliorated MRSA-induced abnormal changes in inflammation and oxidative stress. This indicates that citral has the potential for development as a new anti-MRSA drug. Histopathological examination of diseased tissueHistopathological changes in the lung and liver of mice were examined after hematoxylin and eosin staining (Figs 4 and 5). As shown in Fig. 4, mouse liver tissue did not show significant J Sci Food Agric 2019; 99: 4423-4429

show abstract

“…10month-old healthy mice of the C57BL/6 strain, with body weight of 30 to 40 g, will be employed in the experiments. The mice will be housed individually within polypropylene cages with stainless steel grills for a period of 5 days in a controlled environment [31]. Temperature will be standardized to 22 ± 3 °C with relative humidity of 30% to 70%, and a 12-hour light and 12-hour dark cycle will be fixed [31].…”

Section: In Vivo and Ex Vivo Preparationmentioning

confidence: 99%

Potential Application of Silver Nanoparticles Encapsulated in Branched Amphiphilic Peptide Capsules to Circumvent Antibiotic Resistance in Methicillin-Resistant Staphylococcus Aureus: A Research Protocol

et al. 2020

View full text Add to dashboard Cite

Introduction: Antibiotic resistance is a major global health concern as many fatalities occur each year due to severe infections associated with it, such as sepsis. This research protocol hopes to address the issue of antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) by using an alternative antibiotic therapy. Silver nanoparticles (AgNPs), which have antibiotic properties and low antibiotic resistance potential, will be administered in conjunction with stable and biocompatible branched amphiphilic peptide capsules (BAPCs). Surface functionalized ligands will be attached to the peptide capsules to target iron receptors essential to MRSA survival. By targeting its iron receptors, the bacteria will be unable to mutate in such a way that would attenuate its uptake of this antibiotic. Methods: Testing will begin in vitro on MRSA cultures to assess the minimum inhibitory concentration of the various AgNP treatment groups. Constraints determining the minimum inhibitory concentration include a minimum 3-hour delay in bactericidal effect from application, and a 95% eradication efficacy. Drug efficacy will be evaluated via ex vivo and in vivo mice experiments, with off-target toxicity effects measured via BAPC targeted immunohistochemistry, and both serological and organ-based tests. Repeated in vivo treatments will be performed against a control to measure the relative antibiotic resistance advantages this treatment proposes. As this protocol requires the use of mice, ethics approval from the Canadian Council on Animal Care will be obtained prior to experimentation. Results: It is expected that the AgNPs will be successfully encapsulated within the structurally-sound BAPCs and that the AgNPs will eradicate a significant amount of the MRSA present in the human body with minimal side effects. The in vitro, ex vivo and in vivo tests are likely to yield results that demonstrate that the most effective protocol in eradicating MRSA is to use AgNPs in BAPCs in conjunction with a vancomycin treatment. The proposal will likely satisfy the criteria for appropriate AgNP doses, which includes bactericidal effect in a time frame of hours, over 95% efficacy, and statistically significant reproducibility. Discussion: Successful BAPC mediated delivery of AgNPs prove the potential for targeted antibiotic application against multidrug bacteria with lower risk of antibiotic resistance compared to conventional antibiotics. This proof of concept protocol demonstrates the potential for applying rational design of BAPCs as a delivery vector. Certain limitations, including off-target toxicity and redundant targeting are issues to be cognizant of and controlled. Conclusion:This novel therapy can be considered as a preliminary step in overcoming antibiotic resistance. With appropriate modifications to the functional ligands attached to the BAPCs, the proposed drug mechanism could be applied to treat other bacterial strains.

show abstract

In VitroEvaluations andIn VivoToxicity and Efficacy Studies of MFM501 against MRSA

Cited by 10 publications

References 33 publications

Amino acid–derived defense metabolites from plants: A potential source to facilitate novel antimicrobial development

Amino acid–derived defense metabolites from plants: A potential source to facilitate novel antimicrobial development

Effect and mechanism of citral against methicillin‐resistant Staphylococcus aureus in vivo

Potential Application of Silver Nanoparticles Encapsulated in Branched Amphiphilic Peptide Capsules to Circumvent Antibiotic Resistance in Methicillin-Resistant Staphylococcus Aureus: A Research Protocol

Contact Info

Product

Resources

About