Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents

We used established methodologies from network science to identify patterns in medicinal ingredient combinations in a key medieval text, the 15th-century Lylye of Medicynes, focusing on recipes for topical treatments for symptoms of microbial infection. We conducted experiments screening the antimicrobial activity of selected ingredients. These experiments revealed interesting examples of ingredients that potentiated or interfered with each other’s activity and that would be useful bases for future, more detailed experiments. Our results highlight (i) the potential to use methodologies from network science to analyze medieval data sets and detect patterns of ingredient combination, (ii) the potential of interdisciplinary collaboration to reveal different aspects of the ethnopharmacology of historical medical texts, and (iii) the potential development of novel therapeutics inspired by premodern remedies in a time of increased need for new antibiotics.The pharmacopeia used by physicians and laypeople in medieval Europe has largely been dismissed as placebo or superstition. While we now recognize that some of the materia medica used by medieval physicians could have had useful biological properties, research in this area is limited by the labor-intensive process of searching and interpreting historical medical texts. Here, we demonstrate the potential power of turning medieval medical texts into contextualized electronic databases amenable to exploration by the use of an algorithm. We used established methodologies from network science to reveal patterns in ingredient selection and usage in a key text, the 15th-century Lylye of Medicynes, focusing on remedies to treat symptoms of microbial infection. In providing a worked example of data-driven textual analysis, we demonstrate the potential of this approach to encourage interdisciplinary collaboration and to shine a new light on the ethnopharmacology of historical medical texts

Assessment the Effect of Some Reagents on the Planktonic Cells and Biofilms of Red Complex Periodontal Pathogens

The current study aimed to investigate the effectiveness of four regents; two naturals, olibanum and alum, and two standards, ciprofloxacin (CIP) and chlorhexidine (CHX) to affect the growth and biofilm of three types of periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, "the red complex group". Clinical isolates of the red complex pathogens were isolated from chronic periodontitis. They were identified by phenotypic properties and molecular method. The inhibitory activity of the four reagents was tested by microdilution method. Minimal inhibitory concentration (MIC) on the bacterial plankton and minimal biofilm inhibitory concentration (MBIC) on biofilm of the four reagents in a single and combinational use was determined on mono- and polymicrobial populations. Simple linear regression modeling was used to explore the effect of each reagent and determine MICs and MBICs. All reagents showed inhibition activity against the growth of mono- and polymicrobial planktonic population. MIC values on polymicrobial growth were higher than on monomicrobial growth and MBICs were much higher. All reagents had antibacterial activity on a monomicrobial biofilm with greater significant effect on T. denticola then T. forsythia and P. gingivalis. On polymicrobial biofilm, just olibanum continued showing its effect whilst CHX was less effect and both alum and CIP had no effect. Combinational use with Olibanum encouraged the effect of other regents on polymicrobial biofilm. This combination is a promising medicated preparation to combat the subgingival plaque of red complex pathogens

HERBAL PRODUCTS AND ESSENTIAL OILS WITH HIGH ACTIVITY AGAINST STATIONARY PHASE BARTONELLA HENSELAE

Bartonella henselae is a Gram-negative bacterium which is the causative agent of cat scratch disease. Humans infection with B. henselae can result in acute or chronic systemic infections. The current antibiotic therapy to treat Bartonella infections is not very effective, presumably due to the bacterial persistence. This phenomenon gives rise to the importance of identifying more active drugs targeting bacterial persister cells to develop more effective therapies. Herbal products and essential oils are plant extracts containing organic chemical compounds. Many botanical extracts and essential oil components have been documented to have antimicrobial activities. Nowadays it is important to study botanical products with potential antimicrobial activity, especially with the great concern about increasing antibiotic resistance. In this study, we performed a high-throughput screening of two collections of herbal products and essential oils for active hits against stationary phase B. henselae in vitro. The primary screen was conducted using a SYBR Green I/propidium iodide (PI) viability assay, followed by colony forming unit (CFU) assay throughout a seven-day drug exposure to confirm top hits. We successfully identified 3 herbal product extracts that had high activity against stationary phase B. henselae at 0.25% (v/v), derived from Cryptolepis sanguinolenta, Juglans nigra, and Polygonum cuspidatum. In addition, we identified 32 essential oils that had high activity against stationary phase B. henselae, including four essential oils extracted from Citrus plants, three from Origanum, three from Cinnamomum, two from Pelargonium, and two from Melaleuca, as well as frankincense, ylang-ylang, fir needle, mountain savory (winter), citronella, spearmint, elemi, vetiver, clove bud, allspice, and cedarwood essential oils. The time-kill assay showed 13 active hits could eradicate all stationary phase B. henselae in seven days at 0.032% (v/v). Two active ingredients, carvacrol and cinnamaldehyde, of oregano and cinnamon bark essential oils, respectively, were shown to be very active such that they were able to eradicate all the B. henselae cells even at ≤ 0.01% (v/v). The minimum inhibitory concentration (MIC) determination of these active hits indicated they also had good activity against log phase growing B. henselae. These findings may have implications for developing more effective treatments for persistent Bartonella infections

Antibacterial Activity of Commiphora molmol (myrrha) against the yeast

Commiphora molmol (myrrha) is widely used as a traditional medicine around the globe against inflammatory diseases. It is also considered to be effective as anti-fungal, anti-cancer and anti-oxidant agent. The minimum inhibitory concentration, bactericidal activity and heat stability of antibiotic component in myrrha oil extract has been investigated. The MIC was determined in nutrient free buffer and in nutrient rich peptone glucose buffer. The results showed that MIC was 0.6% in nutrient free buffer as no growth was shown by cells, whereas, in peptone glucose media a slight increase in cell count was seen. It can be concluded that it has strong antimicrobial activity on yeast in nutrient free medium as the oil is unable to show antibacterial activity on growing cells. Bactericidal activity of the oil was tested with yeast on both nutrient free phosphate buffer and nutrient rich media. After 15 minutes, 0.6% myrrha has reduced the cell viability by 99% in nutrient free phosphate buffer showing that it specifically kills the non-growing yeast cells compared to growing ones. Heat stability was tested and reported that oil is stable on heating up to 70°C for 90 minutes. Furthermore, the pre-incubation of yeast with myrrha oil extract was studied and results revealed that if pre-incubation take place in nutrient rich medium then there is no effect on viability of cells. Therefore, it can be determined that presence or absence of nutrients is effecting the cell viability. In conclusion, the results of the following study suggest that extract of myrrha can be used as an anti-fungal drug

Chemical Composition and Biological Activities of Essential Oils

Essential oils extracted by the distillation or hydrodistillation of aromatic plants are a complex mixture of volatile compounds with several biological activities. Their efficacy as antimicrobial agents is related to the activity of several natural compounds belonging to different chemical families that can act both in synergy with each other and with other antibiotics. The antibiotic resistance detected among pathogens has been quickly increasing in recent years, and the control of some of these microorganisms is becoming a planetary emergency for human and animal health. The control of the microbial growth is a problem of great importance also for the food industry (food deterioration and shelf life extension) and for the world of cultural heritage (indoor and outdoor phenomena of biodeterioration). Essential oils can play an important role in this scenario, due their recognized broad-spectrum antimicrobial activity. Therefore, the main subject of this Special Issue includes an essential oil-based approach to control microrganisms in areas such as human and veterinary medicine, entomology, food industry and agriculture. In addition, the chemical composition of essential oils from endemic and rare medicinal/aromatic plants, nanoformulations of essential oils, applications in human and veterinary medicine and its use as animal feeding supplements are topics covered in this Special Issu

Essential oils: pharmaceutical applications and encapsulation strategies into lipid-based delivery systems

Essential oils are being studied for more than 60 years, but a growing interest has emerged in the recent decades due to a desire for a rediscovery of natural remedies. Essential oils are known for millennia and, already in prehistoric times, they were used for medicinal and ritual purposes due to their therapeutic properties. Using a variety of methods refined over the centuries, essential oils are extracted from plant raw materials: the choice of the extraction method is decisive, since it determines the type, quantity, and stereochemical structure of the essential oil molecules. To these components belong all properties that make essential oils so interesting for pharmaceutical uses; the most investigated ones are antioxidant, anti-inflammatory, antimicrobial, wound-healing, and anxiolytic activities. However, the main limitations to their use are their hydrophobicity, instability, high volatility, and risk of toxicity. A successful strategy to overcome these limitations is the encapsulation within delivery systems, which enable the increase of essential oils bioavailability and improve their chemical stability, while reducing their volatility and toxicity. Among all the suitable platforms, our review focused on the lipid-based ones, in particular micro- and nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers.This work was supported by a grant from the Italian Ministry of Research [Grant PRIN2017 #20173ZECCM Tracking biological barriers to antigen delivery by nanotechnological vaccines(NanoTechVax)] and by Research Funding for University of Catania (Piano per la Ricerca 2016–2018—Linea Di Intervento 2 “Dotazione Ordinaria” cod. 57722172106). Cinzia Cimino was supported bythe PhD program in Biotechnology, XXXVI cycle, University of Cataniainfo:eu-repo/semantics/publishedVersio

Novel eco-friendly antimicrobial coatings for use in healthcare and sport textiles

Due to an increase in consumer awareness on environmental and health problems that can arise with synthetic materials and processes used within the textile industry there is a need for novel ‘green’ textiles. The rise in antibiotic-resistant microorganisms within recent years has led to 30,000 deaths in the EU every year, this has led to an increased need for novel antimicrobials (Cassini, Alessano et al., 2016). Synthetic biocides like triclosan and silver have been extensively used in the textile industry but new regulations by the EU Directive 98/8/EC, have now enforced the elimination and withdrawal of many commonly used biocides which are toxic and harmful to humans and the environment (Gao and Cranston, 2008; Gouveia, 2010; Kramer et al., 2006). Plant derived antimicrobials like essential oils (EOs) are therefore an attractive eco-friendly alternative for use in textile finishing (Alihosseini, 2016). Although EOs have regained popularity in recent years, with many studies dedicated to the antimicrobial potentials, (especially citrus-based EOs), few have been focused on their use in blends and encapsulation methods for their application on textiles. Due to EOs physicochemical properties, their development of functional fabrics is met with formulation challenges such as volatility and oxidative degradation and must therefore be protected before they can be used functionally. Screening of ten EOs by disk diffusion and subsequent evaluation of minimum inhibitory concentrations (MICs) and fractional inhibitory concentrations (FICs) showed that a 1:2 blend of L. cubeba (litsea) and Citrus Limon (lemon) EO respectively had the most efficacy in synergy, being inhibitory against Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, Pseudomonas aeruginosa and Trichophyton rubrum compared to the individual EOs. The litsea-lemon EO blend was encapsulated (30% concentration) with natural biopolymers chitosan (0.05-1% w/v) and sodium alginate (0.1 % w/v) by using an emulsification method, without the presence of a surfactant. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis revealed citral and limonene to be the major compounds found in the EOs, their presence also confirmed by Fourier Transform Infrared (FTIR) analysis. In vitro, the release of citral and limonene from the emulsion was examined using a dissolution method and the release profiles were characterised by initial burst release, followed by a slow controlled release of citral and limonene from emulsions; 70.11% of limonene was released within 10 min for a 1% w/v chitosan emulsion, whilst only 4.91% of citral was released within the same time. Fresh 1% chitosan-EO blend emulsions were then used to treat cotton and polyester using a soak-pad-dry method. Promising results were observed when time-kill assays were carried out on the treated fabric using the plate count method adapted from BS EN ISO 20743:2013, with 100% reductions observed at zero contact time (CT) for S. epidermidis, at 5 min for S. aureus and E. coli. Mosquito repellency was also assessed for EO-emulsion treated cotton which demonstrated 71.43% repellency to female mosquito Aedes aegypti compared to a repellency of 52.94% by neat EO-impregnated cotton. EOs show promise in their application as antimicrobials for the development of natural and eco-friendly functional textiles and should be further explored as alternatives to current synesthetic based finishing

Piper betle L. (betel quid) shows bacteriostatic, additive, and synergistic antimicrobial action when combined with conventional antibiotics

Piper betle L., commonly chewed as betel quid (paan), has been extensively acclaimed in a panoply of countries for both its nutritive and medicinal values. The present study was geared towards investigating the antibacterial activities of P. betle extracts and its antibiotic modulating activity. A decoction of P. betle (AQE) leaves as used traditionally, as well as ethanolic (EE), ethylacetate (EAE), acetone (ACE), and dichloromethane (DCME) extracts were evaluated using the broth microdilution assay against six bacterial ATCC strains. The minimum inhibitory concentration (MIC), bacteriostatic and bacteriocidal activities of the extracts were evaluated. Additionally, the ability of the extracts to modulate conventional antibiotics (synergistic, additive, indifference, antagonistic) was assessed using a modified Checkerboard method and the fractional inhibitory concentration index (ƩFIC) was calculated. The phytochemical profile of each extract was determined and the Pearson’s correlation coefficient was used to establish any association between the MIC, ƩFIC, and phytochemical content. All the five extracts inhibited at least one of the six bacterial strains tested with EAE and ACE exhibiting the most potent antibacterial activity. The lowest MIC (0.2500 μg/μl) recorded was against Staphylococcus aureus. Piper betle has been further shown to exhibit only bacteriostatic effect. Results from the Checkerboard indicated additive and synergistic effects of P. betle extracts especially in the 50% EAE-50% antibiotic and 50% ACE-50% antibiotic combinations. The greatest synergy was observed against Pseudomonas aeruginosa (ƩFIC 0.09) in the 70% ACE-30% Chloramphenicol combination. Synergy was also observed against S. aureus, Propionibacterium acnes, Staphylococcus epidermidis, and Streptococcus pyogenes. Phytochemical screening revealed that ACE and EAE contain the highest amount of phenols while DCME contains the highest amount of flavonoids. Statistical analysis showed that lower MICs occurred with increasing phenol content (R=−0.392, p ≤ 0.05) and increasing flavonoid content (R=−0.551, p ≤ 0.01). However, no correlation was established between ƩFIC and phytochemical content which could indicate a different mechanism of action employed by the combinations. Data amassed have provided insight into the antibacterial activity, antibiotic modulating activity, and the phytochemical profile of P. betle.http://www.elsevier.com/locate/sajb2017-07-31hb2016Plant Scienc

Substrate Utilization of the Emerging Fungal Pathogen, Candida auris, and the Antifungal Activity of Select Essential Oils

Candida auris is an emerging fungal pathogen that commonly causes nosocomial blood infections in the immunocompromised. Three factors make this emerging pathogen a global threat. First, it is frequently misidentified by commonly used diagnostic platforms. Second, it is able to survive for weeks on fomites. Third, it is almost always drug resistant, sometimes to all three classes of antifungal drugs used to treat Candida infections. The objectives of this study are three-fold. First, two existing methods, population estimation using absorbance-based standard curves and methylene blue viability staining, were investigated as to application in determining Candida auris cell population size and viability, respectively. Both the spectrophotometric study and methylene blue staining were successfully applied to C. auris concentrations. A standard curve plotting absorbance to concentration were constructed for several organisms for standardizing inoculum for subsequent assays. Second, a description of the basic metabolic capabilities of Candida auris to assimilate a variety of chemicals as a sole source of carbon or nitrogen was determined and compared to related yeasts. Candida auris displayed a unique pattern of carbon and nitrogen assimilation as compared to the other, related species. This included several carbon sources that may have future utility in a diagnostic media. Several isolates of C. auris were also examined using the Biolog YT plate for yeast identification, which operates under a similar principle. Although the organism is absent from database and thus misidentified as one of two organisms in all cases, a significant amount of carbon utilization data was added to the results of the previous study. Third, the antifungal activities of select essential oils were tested against C. auris. This was followed by testing the interaction of the three most effective oils with four commonly used antifungal drugs. Several of the essential oils displayed the ability to inhibit the growth or even kill C. auris, Candida lusitaniae, and Saccharomyces cerevisiae when in direct contact. The three most effective oils were those of lemongrass, clove bud and cinnamon bark. These three oils even retained some antifungal activity in vapor-phase. These were also the oils used in combination with fluconazole, amphotericin B, flucytosine and micafungin. While cinnamon bark oil displayed little interaction with the drugs, lemongrass oil displayed positive or neutral interactions with all four drugs, while clove bud oil had mixed results. The combination of clove bud oil and amphotericin B resulted in an antagonistic outcome, whereas it showed no improved effect when combined with micafungin but displayed positive interactions with fluconazole and flucytosine

Invitro and Invivo Evaluation of Antimicrobial Activity of Aqueous Alcoholic Extracts of Enicostemma Littorale and Lagenaria Siceraria

Lagenaria siceraria L. siceraria commonly known as Bottle gourd is official in Ayurvedic Pharmacopoeia. It is one of the excellent fruit for human being made and gifted by the nature having composition of all the essential constituents that are required for normal and good human health. AIM AND OBJECTIVE: The large numbers of bacteria are resistant to antibiotics, it will be more difficult and more expensive to treat human bacterial infections. When antibiotics fail to work, consequences include extra visits to the doctor, hospitalization or extended hospital stays, a need for more expensive antibiotics to replace the older ineffective ones, lost workdays and, sometimes, death. Antibiotic resistance is found all over the world and has become a very serious problem in the treatment of disease. While the real magnitude of the problem is unknown, the monetary cost of treating antibiotic resistant infections worldwide is estimated to be many billions of dollars per year. Some experts predict that, as resistance to antibiotics is increasing at a faster pace than it can be controlled, the future will resemble the pre-antibiotic era. Others are more optimistic that research and careful drug management can reverse the trend if global efforts are focused on recognizing and controlling it. Herbal medicine remains largely an unproven, inexact science. Although the history of herbal medicine provides decades, sometimes centuries, of anecdotal information, scientific study of herbal medicine is relatively new. Compared to the Federal Food and Drug Administration (FDA), which was founded over 100 years ago, NCCAM has only begun to scratch the surface of scientific research. Despite the criticism of herbal medicine among mainstream medical professionals, it is wise to remember that many common drugs were derived from plant-based sources and also used against infections. For example, scientists originally derived aspirin from willow bark; herbalists prescribe white willow for headaches and pain control. Digitalis, a drug prescribed for certain heart conditions, comes from an extract of potentially toxic foxglove flowers. These are just a few examples of why it's important to consider the advantages and disadvantages of herbal treatments. In the present investigation an attempt was made to test the antimicrobial activity of Enicostemma littorale andLagenaria siceraria by using various in vitro and in vivo methods. 1.Minimum Inhibitory Concentration Determination 2.CupPlate Method. RESULTS: The results of Enicostemma littorale at the dose series from 1000 μg/ml to 32.5 μg/ml by using two fold serial dilution method against a range of bacterial strains were studied. The results revealed that the Enicostemma littorale showed a minimum inhibitory concentration (MIC) at 250 μg/ml to 500 μg/ml of the broth against all bacterial strains. The results were comparable with positive control which was showed MIC at 1.8625 μg/ml to 3.625 μg/ml. The similar findings were also observed in zone of inhibition by using cup plate method (Table No. 3). Since the drug showed better activity against various bacterias, it has given us a lead to select S. typi for our further anti bacterial revise. Phytochemical Analysis In Vivo Anti Bacterial Activity: Enicostemma littorale extract on experimental on SI mice was studied. Enicostemma littorale a siceraria at 400mg/kg forbidden the infection maximally on 4th day of treatment. The complete abolition of infection has observed only on 5th day of post infection. The results were compared with gentamycin, which has controlled the infection effectively from 3rd day of treatment and eradication of infection was found maximum on 4th day of treatment. The results indicated that Lagenaria siceraria at 2mg /kg and 400 mg/kg dose levels were showed effective inhibitory action against bacteria on 3rd day onwards in animals. Lagenaria siceraria at 400mg/kg controlled the infection maximally on 4th day of treatment. Whereas complete eradication of infection has observed only on 5th day of post infection. The results were compared with gentamycin, which has controlled the infection effectively from 3rd day of treatment and eradication of infection was found maximum on 4th day of treatment. CONCLUSION: In this context, the Plants are the basic source of knowledge of modern medicine. The relatively lower incidence of adverse reactions to plant preparations, compared to modern conventional pharmaceuticals, coupled with their reduced cost is encouraging both the consuming public and national health care institutions to consider plant medicines as alternative to synthetic drugs. Nowadays herbal drugs are prescribed widely even when their biologically active compounds are unknown because of their effectiveness and minimal side effect in clinical experience large numbers of plants belonging to different families have been studied for their therapeutic properties. In this present study, the antibacterial activity of the herb Enicostemma littorale and Lagenaria siceraria has been planned to prove its activity against various species of microbes by spread plate method. This study has been very beneficial as it has given an evidence of utilizing this species against the particular microbes satisfactorily. Newly, a numeral of antibiotics has lost their efficiency due to the development of resistant strains of bacteria, which has chiefly occurred through the expression of resistance genes. In accumulation to inducing resistance, antibiotics were sometimes associated with opposing effects such as hypersensitivity, immune-suppression & allergic reactions. Therefore, there is a need to develop alternative antimicrobial drugs for the treatment of infectious diseases. This suggests that these mechanism may also provide antibacterial activity against Salmonella and give a reasonable clarification for the higher antibacterial activity of the EtOH extract. On the other hand, the unidentified minor components present have not been elucidated in terms of their activity. Further studies then need to be done. In the future, thorough study is needed to improved ascertain the antibacterial effect of this herb extract