Identification and Characterization of Antimicrobial Peptides From Butterflies: An Integrated Bioinformatics and Experimental Study

Butterflies represent one of the largest animal groups on Earth, yet antimicrobial peptides (AMPs) of this group are less studied in comparison with their moth counterparts. This study employed an integrated bioinformatics approach to survey natural AMPs from publicly available genomic datasets. Numerous AMPs, including cecropins, defensins, and moricins, were identified and subsequently used as templates for the design of a series of synthetic AMPs that mimicked the naturally occurring sequences. Despite differing biological effects among the various sequences, the synthetic AMPs exhibited potent antibacterial and antifungal activities in vitro and in vivo, without inducing hemolysis, which implied their therapeutic potential in infectious diseases. Electron and confocal fluorescence microscopies revealed that the AMPs induced distinct morphological and biophysical changes on microbial cell membranes and nuclei, suggesting that the antimicrobial effects were related to a mechanism of membrane penetration and nucleic acid binding by the peptides. In conclusion, this study not only offers insights into butterfly AMPs but also provides a practical strategy for high-throughput natural AMP discoveries that will have implications for future research in this area.

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Effects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Models

Cells ◽

10.3390/cells11020228 ◽

2022 ◽

Vol 11 (2) ◽

pp. 228

Author(s):

Izabella Lice ◽

José Marcos Sanches ◽

Rebeca D. Correia-Silva ◽

Mab P. Corrêa ◽

Marcelo Y. Icimoto ◽

...

Keyword(s):

Therapeutic Potential ◽

Biological Effects ◽

Experimental Models ◽

Formyl Peptide Receptor ◽

Saline Control ◽

Acute Peritonitis ◽

Formyl Peptide ◽

Leukocyte Influx

Formyl peptide receptors (Fprs) are a G-protein-coupled receptor family mainly expressed on leukocytes. The activation of Fpr1 and Fpr2 triggers a cascade of signaling events, leading to leukocyte migration, cytokine release, and increased phagocytosis. In this study, we evaluate the effects of the Fpr1 and Fpr2 agonists Ac9-12 and WKYMV, respectively, in carrageenan-induced acute peritonitis and LPS-stimulated macrophages. Peritonitis was induced in male C57BL/6 mice through the intraperitoneal injection of 1 mL of 3% carrageenan solution or saline (control). Pre-treatments with Ac9-12 and WKYMV reduced leukocyte influx to the peritoneal cavity, particularly neutrophils and monocytes, and the release of IL-1β. The addition of the Fpr2 antagonist WRW4 reversed only the anti-inflammatory actions of WKYMV. In vitro, the administration of Boc2 and WRW4 reversed the effects of Ac9-12 and WKYMV, respectively, in the production of IL-6 by LPS-stimulated macrophages. These biological effects of peptides were differently regulated by ERK and p38 signaling pathways. Lipidomic analysis evidenced that Ac9-12 and WKYMV altered the intracellular lipid profile of LPS-stimulated macrophages, revealing an increased concentration of several glycerophospholipids, suggesting regulation of inflammatory pathways triggered by LPS. Overall, our data indicate the therapeutic potential of Ac9-12 and WKYMV via Fpr1 or Fpr2-activation in the inflammatory response and macrophage activation.

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Antimicrobial Peptides: a New Frontier in Antifungal Therapy

mBio ◽

10.1128/mbio.02123-20 ◽

2020 ◽

Vol 11 (6) ◽

Author(s):

Giuseppe Buda De Cesare ◽

Shane A. Cristy ◽

Danielle A. Garsin ◽

Michael C. Lorenz

Keyword(s):

Antimicrobial Peptides ◽

Drug Targets ◽

Fungal Infections ◽

Nucleic Acid Binding ◽

Microbial Infections ◽

Cell Wall Inhibition ◽

Resistance Rates ◽

Limited Spectrum

ABSTRACT Invasive fungal infections in humans are generally associated with high mortality, making the choice of antifungal drug crucial for the outcome of the patient. The limited spectrum of antifungals available and the development of drug resistance represent the main concerns for the current antifungal treatments, requiring alternative strategies. Antimicrobial peptides (AMPs), expressed in several organisms and used as first-line defenses against microbial infections, have emerged as potential candidates for developing new antifungal therapies, characterized by negligible host toxicity and low resistance rates. Most of the current literature focuses on peptides with antibacterial activity, but there are fewer studies of their antifungal properties. This review focuses on AMPs with antifungal effects, including their in vitro and in vivo activities, with the biological repercussions on the fungal cells, when known. The classification of the peptides is based on their mode of action: although the majority of AMPs exert their activity through the interaction with membranes, other mechanisms have been identified, including cell wall inhibition and nucleic acid binding. In addition, antifungal compounds with unknown modes of action are also described. The elucidation of such mechanisms can be useful to identify novel drug targets and, possibly, to serve as the templates for the synthesis of new antimicrobial compounds with increased activity and reduced host toxicity.

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Targeting Histone Deacetylases: A Novel Approach in Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2015/303294 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Sorabh Sharma ◽

Rajeev Taliyan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Transcriptional Activation ◽

Histone Deacetylases ◽

Therapeutic Potential ◽

Hdac Inhibitors ◽

Clinical Manifestations ◽

Future Research

The worldwide prevalence of movement disorders is increasing day by day. Parkinson’s disease (PD) is the most common movement disorder. In general, the clinical manifestations of PD result from dysfunction of the basal ganglia. Although the exact underlying mechanisms leading to neural cell death in this disease remains unknown, the genetic causes are often established. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the neurological disease conditions. The acetylation and deacetylation of histone proteins are carried out by opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. In the recent past, studies with HDAC inhibitors result in beneficial effects in bothin vivoandin vitromodels of PD. Various clinical trials have also been initiated to investigate the possible therapeutic potential of HDAC inhibitors in patients suffering from PD. The possible mechanisms assigned for these neuroprotective actions of HDAC inhibitors involve transcriptional activation of neuronal survival genes and maintenance of histone acetylation homeostasis, both of which have been shown to be dysregulated in PD. In this review, the authors have discussed the putative role of HDAC inhibitors in PD and associated abnormalities and suggest new directions for future research in PD.

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microRNAs in Cardiovascular Disease: Small Molecules but Big Roles

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190808160241 ◽

2019 ◽

Vol 19 (21) ◽

pp. 1918-1947 ◽

Cited By ~ 8

Author(s):

Bingqian Yan ◽

Huijing Wang ◽

Yao Tan ◽

Wei Fu

Keyword(s):

Cardiovascular Diseases ◽

Therapeutic Potential ◽

Biological Effects ◽

Aberrant Expression ◽

Therapeutic Trials ◽

Cellular Phenotypes ◽

And Control ◽

Mirna Therapeutics

microRNAs (miRNAs) are an evolutionarily conserved class of small single-stranded noncoding RNAs. The aberrant expression of specific miRNAs has been implicated in the development and progression of diverse cardiovascular diseases. For many decades, miRNA therapeutics has flourished, taking advantage of the fact that miRNAs can modulate gene expression and control cellular phenotypes at the posttranscriptional level. Genetic replacement or knockdown of target miRNAs by chemical molecules, referred to as miRNA mimics or inhibitors, has been used to reverse their abnormal expression as well as their adverse biological effects in vitro and in vivo in an effort to fully implement the therapeutic potential of miRNA-targeting treatment. However, the limitations of the chemical structure and delivery systems are hindering progress towards clinical translation. Here, we focus on the regulatory mechanisms and therapeutic trials of several representative miRNAs in the context of specific cardiovascular diseases; from this basic perspective, we evaluate chemical modifications and delivery vectors of miRNA-based chemical molecules and consider the underlying challenges of miRNA therapeutics as well as the clinical perspectives on their applications.

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The Transcriptional Regulation and Ubiquitination Dependent Regulation of Hnrnpk Oncogenic Function in Prostate Tumorigenesis

10.21203/rs.3.rs-452319/v1 ◽

2021 ◽

Author(s):

Huan-Lei Wu ◽

Sen-Mao Li ◽

Yao-chen Huang ◽

Qi-Dong Xia ◽

Peng Zhou ◽

...

Keyword(s):

Prostate Cancer ◽

Transcriptional Regulation ◽

Clinical Investigation ◽

Biological Effects ◽

Nucleic Acid Binding ◽

Prostate Tumorigenesis ◽

Hnrnp K ◽

Important Player

Abstract Background Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid-binding protein that regulates diverse biological events. Pathologically, hnRNPK proteins are frequently overexpressed and clinically correlated with poor prognosis to various types of human cancers, therefore pursued as attractive therapeutic targets for selective patients. However, both the transcriptional regulation and degradation of hnRNPK in prostate cancer are remain poorly understood. Methods qRT-PCR was used to detect the expression of hnRNPK and miRNA; Immunoblots and immunohistochemical assays were used to determine the levels of hnRNPK and other proteins. Flow cytometry was used to investigate cell cycle stage. MTS and clonogenic assays were used to investigate cell proliferation. Immunoprecipitation was used to analyze the interaction between SPOP and hnRNPK. A prostate carcinoma xenograft mouse model was used to detect the in vivo effects of hnRNPK and miRNA. Results In the present study, we observed that hnRNPK emerged as an important player in carcinogenesis process of PrCa. miR-206 and miR-613 suppressed hnRNPK expression by targeting the 3’-UTR of hnRNPK in PrCa cell lines, where hnRNP K is overexpressed. In biological effects studies, proliferation and colony formation of PrCa cells in vitro, and tumor growth in vivo, were also dramatically suppressed upon reintroduction of miR-206/ miR-613. We have further provided clear evidence that Cullin 3 SPOP as a novel upstream E3 ubiquitin ligase complex that governs hnRNPK proteins stability and oncogenic functions through promoting the degradation of HnRNP K in a poly-ubiquitinaion dependent proteolysis in the prostate cancer setting. Moreover, prostate cancer-associated SPOP mutants fail to interact with and promote the destruction of hnRNPK proteins. Conclusion Our finding reveal new post-transcriptional and post-translational modifications mechanism of hnRNPK regulation via miR-206/ miR-613 and SPOP, respectively. More important, given the critical oncogenic role of hnRNPK and high frequency of SPOP mutation in prostate cancer, our results provide a molecular rationale for the clinical investigation of novel strategies to combat prostate cancer based on SPOP genetic status.

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A Comprehensive Review of Genus Sanguisorba: Traditional Uses, Chemical Constituents and Medical Applications

Frontiers in Pharmacology ◽

10.3389/fphar.2021.750165 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ping Zhou ◽

Jingyan Li ◽

Qi Chen ◽

Long Wang ◽

Jing Yang ◽

...

Keyword(s):

Biological Effects ◽

Chemical Constituents ◽

Influenza Virus Infection ◽

Wild Plant ◽

Future Research ◽

Pharmacological Effects ◽

Comprehensive Review ◽

Traditional Uses

Genus Sanguisorba (family: Rosaceae) comprises nearly 148 species, distributed widely across the temperate and subtropical regions of the Northern Hemisphere. Sanguisorba officinalis L. (S. officinalis) has been used as a hemostatic and scald treating medicine in China for a long time. Numerous studies have demonstrated that plant extracts or monomers from S. officinalis exhibit several pharmacological effects, such as anti-cancer, anti-virus, anti-inflammation, anti-bacteria, neuroprotective and hepatoprotective effects. The other species of genus Sanguisorba are also being studied by researchers worldwide. Sanguisorba minor Scop. (S. minor), as an edible wild plant, is a common ingredient of the Mediterranean diet, and its young shoots and leaves are often mixed with traditional vegetables and consumed as salad. Reports on genus Sanguisorba available in the current literature were collected from Google Scholar, Web of Science, Springer, and PubMed. The Plant List (http://www.theplantlist.org./tpl1.1/search?q=Sanguisorba), International Plant Name Index (https://www.ipni.org/?q=Sanguisorba) and Kew Botanical Garden (http://powo.science.kew.org/) were used for obtaining the scientific names and information on the subspecies and cultivars. In recent years, several in vivo and in vitro experiments have been conducted to reveal the active components and effective monomers of S. officinalis and S. minor. To date, more than 270 compounds have been isolated and identified so far from the species belonging to genus Sanguisorba. Numerous reports on the chemical constituents, pharmacologic effects, and toxicity of genus Sanguisorba are available in the literature. This review provides a comprehensive understanding of the current traditional applications of plants, which are supported by a large number of scientific experiments. Owing to these promising properties, this species is used in the treatment of various diseases, including influenza virus infection, inflammation, Alzheimer’s disease, type 2 diabetes and leukopenia caused by bone marrow suppression. Moreover, the rich contents and biological effects of S. officinalis and S. minor facilitate these applications in dietary supplements and cosmetics. Therefore, the purpose of this review is to summarize the recent advances in the traditional uses, chemical constituents, pharmacological effects and clinical applications of genus Sanguisorba. The present comprehensive review may provide new insights for the future research on genus Sanguisorba.

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Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions

Current Molecular Pharmacology ◽

10.2174/1874467211666181010154139 ◽

2019 ◽

Vol 12 (3) ◽

pp. 184-194 ◽

Cited By ~ 4

Author(s):

Ricardo Jorge Dinis-Oliveira ◽

Carolina Lança Pereira ◽

Diana Dias da Silva

Keyword(s):

Native American ◽

Animal Behavior ◽

Therapeutic Potential ◽

Biological Effects ◽

Signs And Symptoms ◽

Clinical Effects ◽

Pharmacokinetics And Pharmacodynamics ◽

Native American Church

Background: Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly understood. Objective: This article aims to fully review pharmacokinetics and pharmacodynamics of mescaline, focusing on the in vivo and in vitro metabolic profile of the drug and its implications for the variability of response. Methods: Mescaline pharmacokinetic and pharmacodynamic aspects were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Biological effects of other compounds found in peyote were also reviewed. Results: Although its illicit administration is less common, in comparison with cocaine and Cannabis, it has been extensively described in adolescents and young adults, and licit consumption often occurs in religious and therapeutic rituals practiced by the Native American Church. Its pharmacodynamic mechanisms of action are primarily attributed to the interaction with the serotonergic 5-HT2A-C receptors, and therefore clinical effects are similar to those elicited by other psychoactive substances, such as lysergic acid diethylamide (LSD) and psilocybin, which include euphoria, hallucinations, depersonalization and psychoses. Moreover, as a phenethylamine derivative, signs and symptoms are consistent with a sympathomimetic effect. Mescaline is mainly metabolized into trimethoxyphenylacetic acid by oxidative deamination but several minor metabolites with possible clinical and forensic repercussions have also been reported. Conclusion: Most reports concerning mescaline were presented in a complete absence of exposure confirmation, since toxicological analysis is not widely available. Addiction and dependence are practically absent and it is clear that most intoxications appear to be mild and are unlikely to produce lifethreatening symptoms, which favors the contemporary interest in the therapeutic potential of the drugs of the class.

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Evaluation of In vitro Antimicrobial and In vivo Cytotoxic Properties of Peroxo Coordination Complexes of Mg(II), Mn(II), Fe(II) & Ni(II)

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v3i1.184 ◽

1970 ◽

Vol 3 (1) ◽

Author(s):

Kudrat E Zahan ◽

MD. Shamin Hossain ◽

Shuranjan Sarkar ◽

Md. Mukhlesur Rahman ◽

Md. Akhter Farooque ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antifungal Activity ◽

Cytotoxic Activity ◽

Full Text ◽

Brine Shrimp ◽

Coordination Complexes ◽

Antibacterial And Antifungal Activities ◽

Antibacterial And Antifungal

Six newly synthesized nickel peroxo coordination complexes, [Mg2(2-ap)2(O2)(OH), A], [Mn(2-ap) (ED)(O2), B], [Fe(2-ab)(ED)(O2), C], [Fe(2-ap)(ED)(O2), D], [Ni2(2-ab)2(O2)(OH), E] and [Ni2(2-ap)2(O2)(OH), F] showed significant antibacterial and antifungal activities. The minimum inhibitory concentrations (MIC) of these compounds were found in the range of 8-128 µg/ml. Among these compounds, F showed maximum cytotoxicity (LC50 = 3.62 µg/ml) in brine shrimp lethality bioassay. Key words: Peroxo coordination complexes; Antimicrobial activity; antifungal activity; cytotoxic activity. Dhaka Univ. J. Pharm. Sci. Vol.3(1-2) 2004 The full text is of this article is available at the Dhaka Univ. J. Pharm. Sci. website

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Phytochemical, Pharmacological, and Biotechnological Study of Ageratina pichinchensis: A Native Species of Mexico

Plants ◽

10.3390/plants10102225 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2225

Author(s):

Mariana Sánchez-Ramos ◽

Silvia Marquina-Bahena ◽

Laura Alvarez ◽

Angélica Román-Guerrero ◽

Antonio Bernabé-Antonio ◽

...

Keyword(s):

Native Species ◽

Biological Effects ◽

Critical Evaluation ◽

Cell Suspension Cultures ◽

Future Research ◽

Research Perspectives ◽

Crude Extracts ◽

Pure Compounds

Ageratina pichinchensis (Asteraceae) has been used for a long time in traditional Mexican medicine for treating different skin conditions and injuries. This review aimed to provide an up-to-date view regarding the traditional uses, chemical composition, and pharmacological properties (in vitro, in vivo, and clinical trials) that have been achieved using crude extracts, fractions, or pure compounds. Moreover, for a critical evaluation of the published literature, key databases (Pubmed, Science Direct, and SciFinder, among others) were systematically searched using keywords to retrieve relevant publications on this plant. Studies that reported on crude extracts, fractions, or isolated pure compounds of A. pichinchensis have found a varied range of biological effects, including antibacterial, curative, antiulcer, antifungal, and anti-inflammatory activities. Phytochemical analyses of different parts of A. pichinchensis revealed 47 compounds belonging to chromenes, furans, glycosylated flavonoids, terpenoids, and essential oils. Furthermore, biotechnological studies of A. pichinchensis such as callus and cell suspension cultures have provided information for future research perspectives to improve the production of valuable bioactive compounds.

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Traditional Uses, Phytochemistry, and Pharmacology ofOlea europaea(Olive)

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/541591 ◽

2015 ◽

Vol 2015 ◽

pp. 1-29 ◽

Cited By ~ 53

Author(s):

Muhammad Ali Hashmi ◽

Afsar Khan ◽

Muhammad Hanif ◽

Umar Farooq ◽

Shagufta Perveen

Keyword(s):

Therapeutic Potential ◽

Wide Spectrum ◽

Modern Medicine ◽

Future Research ◽

Plant Materials ◽

Benzoic Acid Derivatives ◽

Traditional Uses ◽

Available Information

Aim of the Review.To grasp the fragmented information available on the botany, traditional uses, phytochemistry, pharmacology, and toxicology ofOlea europaeato explore its therapeutic potential and future research opportunities.Material and Methods.All the available information onO. europaeawas collected via electronic search (using Pubmed, Scirus, Google Scholar, and Web of Science) and a library search.Results.Ethnomedical uses ofO. europaeaare recorded throughout the world where it has been used to treat various ailments. Phytochemical research had led to the isolation of flavonoids, secoiridoids, iridoids, flavanones, biophenols, triterpenes, benzoic acid derivatives, isochromans, and other classes of secondary metabolites fromO. europaea. The plant materials and isolated components have shown a wide spectrum ofin vitroandin vivopharmacological activities like antidiabetic, anticonvulsant, antioxidant, anti-inflammatory, immunomodulatory, analgesic, antimicrobial, antiviral, antihypertensive, anticancer, antihyperglycemic, antinociceptive, gastroprotective, and wound healing activities.Conclusions. O. europaeaemerged as a good source of traditional medicine for the treatment of various ailments. The outcomes of phytochemical and pharmacological studies reported in this review will further expand its existing therapeutic potential and provide a convincing support to its future clinical use in modern medicine.

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