pseudomonas aeruginosa ( p. aeruginosa ) is an aerobic gram - negative bacterium ; that is ubiquitous , exist in aqueous habitats , and take advantage of humid environments .
it is also saprophytic and naturally resistant to antibiotics ( beta - lactams , hydrophilic ) , and may become an opportunistic pathogen responsible for serious infections when favorable circumstances exist .
because it is environmentally present in soils , plants ( including fruits and vegetables ) , aqueous habitats and humid environments , it has an ability to acquire resistance to antibiotics , and has multiplicity of virulence factors ( diffusible or constituent ) that baffle the host s defenses and allow the development of infections in susceptible patients , such as malnourished patients ; burn victims , trauma patients , patients suffering from diabetes , cystic fibrosis , cancer , human immunodeficiency virus ( hiv ) , and blood disorders , patients undergoing mechanical ventilation or long - term corticosteroid therapy ; patients in whom carrier surveyed peripheral and central catheters are being used .
aeruginosa infections are most often acquired in a hospital , but are sometimes community acquired ; factors limiting p. aeruginosa proliferation on the skin are dryness of the skin s surface and normal flora ( gram + cocci ) .
the bacterium p. aeruginosa can grow or become permanent on the skin in case of the traumatic rupture of the skin barrier ; chronic wounds such as leg ulcers , extensive burns , diabetes include ulcers , oozing dermatitis , and wet or macerated lesions the disappearance of gram + cocci normal flora caused by the use of systemic or topical antimicrobials .
the first signs of infection of a chronic wound or ulcer are the production of greenish pus and the appearance of a characteristic aromatic odor .
these are vesicular or bullous lesions with a content of serum are hemorrhagic based on an erythematous and edematous base and can initially have the clinical appearance of multiform erythema .
these lesions can change very quickly in a few days to ulceration , and they then take the appearance of a so - called ecthyma gangrenosum [ 3 - 6 ] .
one can also have abscesses or single or multiple subcutaneous nodules that can change very quickly to necrosis and ulceration .
biofilm formation seems to facilitate the survival of p. aeruginosa in the environment and in their hosts .
bacterial biofilms are structured masses of bacterial cells coated with a hydrated polymeric matrix of their own synthesis .
the biofilm bacteria can withstand the immune response of the host and are much more resistant to antibiotics and disinfectants than planktonic bacterial cells . the ability to form a biofilm
the presence of biofilms during infections therefore requires new methods of prevention , diagnosis and treatment .
the existence of biofilms and antibiotic resistance has emerged as one of the greatest threats to global health and , brings an additional level of complexity to the control of chronic ulcers .
the  black beast  of burn centers , pseudomonas , is responsible for 10% of bloodstream infections and 28% of deaths .
therefore , alternative antimicrobial strategies are urgently needed , and this situation has led to a re - evaluation of the therapeutic use of ancient remedies , such as herbal extracts and herbal - based products .
these include proteins , lipids and carbohydrates that are used for subsistence and reproduction ; in not only the plant itself but also the animals that feed on them .
in addition , plants synthesize an extraordinary range of other compounds , called secondary metabolites , whose functions are far from being unanimously accepted .
antibiotics  as they protect plants against fungi , bacteria , animals and even other plants .
phenol compound are involved in plant - plant interactions ( allelopathy , and inhibitions of both germination and growth ) .
these compounds include lignin , flavonoids , phenylpropanoids , anthocyanins and  nitrogen compounds including alkaloids and glycosides .
recently , phenol compounds have drawn much attention due to their antioxidants properties and their potential beneficial implications for human health , such as the treatment and the prevention of cancer , cardiovascular disease and other inflammatory diseases .
polyphenol are composed of various phenol compounds such as phenolic acid , catechins , flavonoids , and tannins .
they usually have antiseptic , antibacterial actions . the simplest is phenol ( an antimicrobial ) present in thyme oil .
other phenols have analgesics , anti - inflammatory , cholesterol - lowering , hypotensive , anticoagulant , anti - allergenic , hypotensive , and hepato - protective effects
these substances can be yellow ( origin of the word flav ) , red , blue or purple .
the main properties of flavonoids are their veinotonic , protective ( vessels ) , anti - cholesterol or antioxidants effects [ 11 , 12 ] .
. these complex compounds may be soluble in water or alcohol , are the flavonoid family .
they are common both in gymnosperms and angiosperms . within angiosperms , tannins are more common in dicotyledons than they are in monocotyledons .
tannins are mainly used externally , particularly to treat patients with injuries , wounds or hemorrhoids .
catechin is a molecule of the flavonoid family ; the name comes from the fact that this molecular compounds found in the fruits of acacia catechu
. catechins are astringent juices from various sources and involve decoction of the fruit of areca catechu l. ( palms ) , and the wood of the acacia catechu .
the fermentation of the leaves being stopped soon after harvest , they are barely oxidized , which is the reason that green tea retains most of its original catechins , which gives them their slightly bitter and astringent taste .
interesting amounts of catechins also exist in chocolate , red wine , apples and grapes .
five catechins molecules are : catechins , epicatechin , epigallocatechin , epicatechin gallate and epigallocatechin gallate molecules .
the latter is the most abundant and most active of all the catechins . according to numerous studies , catechins have , in addition to their antioxidant properties , a protective role in the prevention of certain chronic diseases such as diabetes and osteoporosis .
several studies that have been conducted in recent years have manifested the antibiotic activities of some phenol compounds in natural plants extracts , including acacia catechu ( l.f . )
honey , maple saps , phoenix dactylifera l. ( dates ) extract and pomegranate which are well known for their high levels of antioxidants and polyphenols have also shown promise as novel antimicrobial agents .
phenol compounds have recently attracted much interest due to their antioxidants properties and their potential beneficial implications for human health , such as their use in the treatment and the prevention of cancer , cardiovascular diseases and inflammatory diseases .
the effectiveness of these above substances ; has been demonstrated in several studies [ 16 - 19 ] .
however , no effort has been made to evaluate the synergic effects of combined natural sweeteners on enhancing the antibiotic activities of natural plants extracts .
the topical formulations that on certain vitamins and nutrients , are rich in phenol compounds , and are applied directly to wounds are more effective for reducing the risk of infection and for stimulating healing .
meanwhile , phenol - rich compounds ; provides a number of essential minerals such as zinc , potassium , iron , magnesium and calcium ( table 1 ) .
in order to obtain a natural antibiotic for the dressing and the treatment of chronic wounds , we conducted this study to find an innovative strategy for using natural medicine derived from phenol - rich compounds that have been tested on bacterial strains of a reference such p. aeruginosa .
this research was conducted through 2015 at the laboratories of dubai pharmacy college united arab emirates ( uae ) .
the processing of the plants performed in this study was the same as the traditional method used by the people in the iranian bakhtiari tribe , as mentioned in ref .
the phenol - rich compound sweet gel was prepared by blending four natural herbal extract acacia catechu ( l.f . )
willd , castanea sativa , ephedra sinica stapf , and momia in to combination of sweet gel medium , including honey , maple saps , date syrup , pomegranate extract and azadirachta indica gum as a stabilizer .
the combinations were screened by using a well - diffusion assay with cloxacillin as a control .
suspension assays were used to determine the antimicrobial activities of the medium gel alone and of the medium gel in combination with the four natural herbal extract .
the test organism was p. aeruginosa . in this study , eight plant species were used as shown in ( table 2 ) and 3 .
the ingredients of the sweet gel compound are presented in ( table 4 ) , bacterial strains and growth conditions .
the inhibition of bacterial growth was studied by using the well - diffusion method with nutrient agar , as commonly practiced in medical bacteriology , and was purchased from himedia laboratories , india .
plates were inoculated with 100 l of each pathogenic microorganism adjusted to standardized inoculum ( 1.5  10 cfu / ml ) in triplicates and were spread with sterile swabs .
eight mm wells were drilled into the agar by using a sterile stainless steel borer . for the preparation of phenol - rich compound herbal extracts , one gram of aslan crude
extract ( table 3 ) was added to 10 ml of distilled water to form 10% aslan ( w / v ) , which was heated and stirred until all ingredients had dissolved .
it was then mixed with an equal amount of sweet gel , which included honey , date , maple syrup and pomegranate in specific percentages , as shown in ( table 3 ) , after which neem gum as much as 5 percent of the total weight , was added as stabilizer .
one drop of each sample solution ( 50 ul ) was applied to each well on the plate by using a pasteur pipette .
the petri dishes thus prepared were left at room temperature for ten minutes to allow diffusion of the extract into the agar .
anti - bacterial activity was indicated by an inhibition zone surrounding the well ( including the well diameter ) containing the plant extract .
the diameters of the zones of inhibition were measured in millimeters and interpreted based on published standards .
anti - bacterial activity was recorded if the zone of inhibition was greater than 8 mm .
the interpretation of the anti - bacterial activity results was done according to the diameter of the zone of inhibition as follows : zones with diameters < 9 mm zone were considered inactive , zones with diameters from 9 to 12 mm were considered partially active , zones with diameters from 13 to 18 mm were considered active , and zones with diameters from > 18 mm were considered very active . the means and standard deviations of the diameters of the inhibition zones were calculated .
data were evaluated using the ibm spss software program ( version 19 ; ibm spss inc .
were compared at the 95% confidence interval , and the results were expressed as means  standard deviations .
differences between the control group and the herbal extract groups were the criteria for the anti - bacterial activities . the t - test ( paired tests ) was used to detect differences between the treatment groups and the control group .
the table 5 shows the zones of inhibition for the individual ingredients in the phenol - rich compound that were used against p. aeruginosa and that produced a greater inhibition of pseudomonas spp .
table 6 shows that the phenol - rich compound sweet gel produced a greater inhibition of pseudomonas spp . than cloxacillin did .
also , the table shows that phenol - rich compound sweet gel had a greater inhabitation had a greater inhabitation on pseudomonas spp .
based on the results for the antibacterial effects , we can state that phenol - rich compound sweet gel is a good candidate for the prevention and the treatment of chronic ulcers .
our findings showed that the phenol - rich compound sweet gel had a significant antiseptic effective against pseudomonas spp . and were in agreement with those of previous studies [ 15 - 19 ] that found that phenol compound exhibited fairly good antimicrobial activities against both gram - negative and gram - positive bacteria and that remarkable activity was exhibited by p. aeruginosa .
also , the greater inhibition due to the compound compared to the inhabitation due to the individual ingredients on pseudomonas spp . indicates significant synergic effects .
however , no effort has been made so far to evaluate the synergic effects of combined natural sweeteners on enhancing the antibiotic activities of natural plants extracts .
phenol compounds rich in minerals and trace elements are involved in many biological processes in wound healing : several studies revealed a higher postoperative morbidity , delayed healing , and more frequent secondary infections in malnourished patients with amputations than in non - malnourished patients .
zinc as a trace element is quantitatively the most important one and is involved in the construction of over 200 enzymes with effects as follow : improving cell growth and differentiation , fibroblast proliferation , collagen synthesis , strengthening the immune system and increasing steroid receptors [ 21 , 22 ] .
. it also promotes collagen synthesis , improves oxygen delivery to tissue , and is a component of many enzyme systems .
chronic iron deficiency or anemia is associated with an extended period of healing and other painful complications .
copper is considered one of the most effective nutrients for improving the wound healing rate .
some studies shown that copper can destroy several bacterial strains ; hence , it is interesting for use in dressings and bandages devices .
globally , copper strengthens bones , organs and connective tissues , and provides better overall immune response .
this is because copper , iron and zinc use the same routes to cross the intestinal barrier and reach the bloodstream . therefore excessive inputs of a given mineral salt can interfere with the absorption of others .
no significant benefit for wound healing is seen with nutritional supplements such as vitamins c , a , e , and zinc in a non - deficient individuals . [ 25 - 28 ] in contrast to oral administration , topical administration of zinc
appears to be superior due to its action in reducing super infections and necrotic material via enhanced local defense systems and collagenolytic activity ; and to the sustained release of zinc ions , which stimulates epithelialization of wounds in normozincemic individuals .
zinc oxide in paste bandages ( unna boot ) protects and soothes inflamed peri - wound skin .
zinc from these formulations is transported through the skin although the systemic effects seem insignificant .
the topical administration formula that focuses on certain vitamins and nutrients applied directly on the wounds is more effective as a supplements to reduce the risk of infection and to stimulate healing .
furthermore , phenolrich compounds , provides a number of essential minerals , such as zinc , potassium , iron , magnesium and calcium ( table 1 ) . in previous studies [ 29 - 31 ] on phenol compounds , no contraindications and side effects
have been reported to date for any of the ingredient used in our study , even though all of the benefits seem to have been reported .
the topical use of phenol - rich compound sweet gel should be safer than that of the other formulations , but to be on the safe side , more clinical studies and toxicology studies need to be conducted .
the antibiotic effect of phenol- rich compounds is due to the presence of hydrophilic components , such as polyphenols , polysaccharides , flavonoids and tannins in one or more parts of the plant .
thus is an innovative approach to fighting the antibiotic - resistant pseudomonas . our results and those of previous studies provide pharmacology and microbiology information to explain the advantages of the phenol - rich compound sweet gel and its mechanisms of action as a bioactive dressing material in treating chronic ulcer :  sterilization of wounds  rapid autolytic debridement  inhibition of potential pathogens of wounds and enzymes that destroy tissue ,  stimulations of tissues growth to speed healing ,  protection against cross - contamination ,  reduction of scars ,  anti - inflammatory effect : reductions of infections , deodorization of wounds , reducing edema and against maceration due reduced of exudate ,  provision of moist healing environment without risk of surrounding skin maceration and preventions of adhesion of the dressings to the wound , thus preventing pain and tissue damage when dressing is changed .
the increase in the number of bacterial infections resistant to current antibiotics is an extremely worrying phenomenon , especially in the hospital setting ( nosocomial infections ) .
therefore new strategies and innovative antibiotics for use against these particularly virulent microorganisms need to be developed if a therapeutic impasse is to be avoided .
this work evaluated the synergic effects of combined natural sweeteners on enhancing the antibiotic sensitivities of natural plants extracts and found the phenol - rich compounds sweet gel to be an alternative medicine and bioactive dressing material , for the treatment of patients with various types of wounds , including burns , venous leg ulcers , ulcers of various etiologies , diabetes induced ulcers on the feet , unhealed sampling sites grafts , abscesses , boils , surgical wounds , necrosis process , post - operative and neonatal wound infection .
based on these results , that compound should be considered an alternative to the usual methods of cure . on burns
its antibacterial and anti - inflammatory properties allow a moist healing environment that protects the wounds from deterioration and fibrosis to be maintained .
united states department of agriculture , national nutrient database for standard reference , the national agricultural library , release 28 , slightly revised may , 2016 , software v.2.5.4 .
 objectives : the purpose of this study was to obtain a natural antibiotic from phenol - rich compounds ; for the dressing and the treatment of chronic wounds.methods:the phenol - rich compound sweet gel was prepared by blending four natural herbal extracts , acacia catechu ( l.f . ) , momia ( shilajit ) , castanea sativa , and ephedra sinica stapf , with combination of a sweet gel medium , including honey , maple saps , phoenix dactylifera l. ( date ) , pomegranate extract and azadirachta indica gum as a stabilizer . 
 the combinations were screened by using a well - diffusion assay with cloxacillin as a control . 
 pseudomonas spp . 
 was tested with our novel antimicrobial compound . 
 the zones of inhibition in agar culture were measured for each individual component and for the compound , and the results were compared with those of the control group which had been treated with cloxacillin . 
 data were expressed as means  standard deviations . 
 quantitative analyses were performed using the paired t-test.results:the antibiotic effect of the phenol - rich compound sweet gel was statistically shown to be more significant than that of cloxacillin against pseudomonas aeruginosa ( p < 0.05).conclusion : our novel approach to fighting the antibiotic resistance of pseudomonas proved to be successful . 
 the phenol - rich compound sweet gel was found to be suitable for use as an alternative medicine and bioactive dressing material , for the treatment of patients with various types of wounds , including burns , venous leg ulcers , ulcers of various etiologies , leg ulcers on the feet of diabetic , unhealed graft sampling sites , abscesses , boils , surgical wounds , necrotic process , post - operative and neonatal wound infection , and should be considered as an alternative to the usual methods of cure . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusion