ArticlePDF Available


Avocado (Persea americana) oil is rich in nutrient waxes, proteins and minerals, as well as vitamins A, D and E. It is an excellent source of enrichment for dry, damaged or chapped skin. This study aimed to evaluate the wound-healing activity of fruit extract of Persea americana in rats. The effect of topical and oral administration of Persea americana fruit extract (300 mg/kg/day) on excision and dead space wound models was evaluated. The rats used in the excision wound model were divided into four groups of five each and received either topical or oral treatment. The rats used in the dead space wound model were divided into two groups of five each and were treated orally. Healing was assessed by the rate of wound contraction, period of epithelialisation, granulation tissue weight and hydoxyproline content. In the excision wound model, complete healing (full epithelialisation) was observed on average on day 14 in the rats who receive oral or topical treatment. In contrast, the controls took approximately 17 days to heal completely. The extract-treated wounds were found to epithelialise faster than the controls (p < 0.001). Wet and dry granulation tissue weight and the hydroxyproline content of the tissue obtained from extract-treated animals used in the dead space wound model were significantly higher (p < 0.05) compared with the controls. Rate of wound contraction, epithelialisation time together with the hydroxyproline content and histological observations support the use of Persea americana in the management of wound healing.
Wound healing activity of Persea
Americana (avocado) fruit: a
preclinical study on rats
B.S. Nayak, MSc, PhD,
job title? Department of
Preclinical Sciences,
Biochemistry Unit,
Faculty of Medical
Sciences, The University
of the West Indies, St.
Augustine, Trinidad;
S.S. Raju, MBBS, MD, job
title? Department of
Pharmacology, School of
Medical Sciences, RAK
Medical and Health
Sciences University, Ras-
al-khaimah, United Arab
A.V. Chalapathi Rao,
MBBS, MD, Department
of Para clinical sciences,
Pathology unit, Faculty of
Medical Sciences, The
University of the West
Indies, St. Augustine,
ound healing comprises a
complex but well-coordinat-
ed cascade of biochemical
events that follow injury to
the skin and other soft tis-
sues. It is categorised into three phases: inflamma-
tion, proliferation and remodelling. The initial
inflammatory reaction is followed by the prolifera-
tive phase, which is characterised by angiogenesis,
collagen deposition, granulation tissue formation,
epithelialisation and wound contraction.1-4 (Sta-
delmann et al 1998; Iba et al 2004; Quinn
1998; Midwood et al 2004) The extracellular
matrix (okay?) and collagen are remodelled in the
final phase to provide integrity and strength to the
healed tissue (reference?). Factors that impair
wound healing include poor blood supply, lack of
nutrients, systemic disease, infections and the pres-
ence of foreign bodies. The ability to identify and
address these factors will help facilitate healing. Var-
ious nutritional factors and botanical influences,
including carbohydrate, protein, lipid sources (such
as? I assume you mean natural oils, waxes
etc?), vitamins, minerals and other trace elements,
play an important role during the different phases
of wound healing (references?). Adequate dietary
protein is vital for wound healing, and tissue levels
of the amino acids arginine and glutamine may
influence wound repair and immune function.5
(Agrawal et al 2003) Botanical extracts from
sources including Aloe vera, Centella asiatica and the
enzyme bromelain from pineapple have also been
shown to improve healing times and wound out-
comes.6,7 (MacKay and Miller 2003; Douglas et
al 2003 - author, we need the full reference
details for Douglas, seems to be the same as
MacKay and Miller at the moment - thank
Avocado oil (Persea americana) is rich in unsapon-
ifiables (sterolins - please define briefly) com-
prised of biologically active compounds, such as
sterols, tocopherols, squalene and lipidic furans and
also contains vitamins A, C, D and E, proteins, beta-
carotene, lecithin, fatty acids and potassium.8
(Swisher 1988)
The use of avocado oil is considered to be benefi-
cial (by who? how widely accepted is this? or
should we say it has been found to reduce
l Objective: Avocado (Persea americana) oil is rich in nutrient waxes, proteins and minerals, as well as
vitamins A, D and E. It is an excellent source of enrichment for dry, damaged or chapped skin. This study
aimed to evaluate the wound-healing activity of fruit extract of Persea americana in rats.
l Method: The effect of topical and oral administration of Persea americana fruit extract (300mg/kg/day)
on excision and dead space wound models was evaluated. The rats for excision wound model were
divided into two groups, five each for topical and oral treatment. The rats for dead space wound models
were treated orally. Healing was assessed by the rate of wound contraction, period of epithelialisation,
granulation tissue weight and hydoxyproline content.
l Results: Complete healing (full epithelialisation) was observed on average on day 14 in both oral and
topical extract-treated animals. Whereas, controls wound took around 17 days. The extract treated
wounds were found to epithelialise faster as compared with controls (p<0.001). Wet and dry granulation
tissue weight and hydroxyproline contents of the tissue obtained from extract treated animals were
significantly higher (p<0.05) as compared with controls.
l Conclusion: Rate of wound contraction, epithelization time together with the hydroxyproline
content and histological observations support the use of P.americana in the management of wound
l Declaration of interest: None.
Persea americana; hydroxyproline; epithelialisation
pic credit
age spots etc? but was this in a clinical
study?) in reducing age spots, healing scars and
moisturising the upper layers of the skin.7 (Douglas
et al 2003) A mixture of avocado and soybean
unsaponifiables has also been found to aid wound
healing, possibly by stimulating the deposition and
repair of extracellular matrix components.9,10 (Mar-
garet et al 1982; Boumediene et al 1999)
However, there is no scientifically proven data to
support either the collagen-enhancing or wound-
healing activities of Persea americana. This study
therefore set out to explore the effects of Persea
americana fruit on wound-healing parameters
including collagen synthesis.
Fruit paste preparation
The Persea americana fruit (avocado) of 600g in
weight was taken and washed thoroughly with
deionised water, and then ground into a paste
(extract) using an electric blender. Special care was
taken during the procedure, and no water was added
to the extract to avoid contamination. The extract
was stored at a temperature of 4°C. What concen-
tration/amount of avocado was in the final
paste per animal? How was this standard-
The ethics committee for animal experimentation
(AHC06/07/1) at the University of the West Indies
approved the study. Healthy, in-house bred, gender-
matched, Sprague Dawley rats weighing 200–250g
were used for the study. They were individually
housed in an animal house and maintained on nor-
mal food and water ad libitum. The rats were anaes-
thetised before and during (to check, is this cor-
rect - both before and during?) infliction of the
experimental wounds. Surgical interventions were
carried out under sterile conditions using ketamine
anaesthesia (120mg/kg body weight). Animals with
signs of infection were excluded from the study and
Dose selection
The male rats were treated with increasing doses (1,
2, 4 and 8g/kg body weight) of the extract for 14
days. Doses of up to 4g/kg body weight did not pro-
duce any sign of toxicity, while the animals remained
physically active and consumed food and water in a
regular way. As 1g/kg body weight showed better
healing (do you mean resulted in faster heal-
ing times?), the dose of 300mg/kg body weight
was selected for our experimental study. Author, I
presume the dose response study was sepa-
rate from the main study? this needs to be
made clear. At the moment, this looks like
the same animals were used in both studies,
which would invalidate the study
Wound-healing activity
Excision and dead space wound models were used
to evaluate the wound-healing activity of Persea
americana. Author, you also need to state the
study duration for the two models - thanks
l Excision wound model Excision wounds were
created on the rats, as described by Morton and
Malone.11 The dorsal fur was shaved with an electric
clipper and the anticipated wound area was drawn
on the back of the animals in methylene blue using
a circular stainless steel stencil. A full-thickness
excision wound measuring 250mm2 and 2mm deep
was created along the markings using toothed
forceps, a surgical blade and pointed scissors. The
wounds were kept open. The animals were divided
into four groups of five each. Author, to check
were these 4 groups used in the excision
wound model only, or were groups 1 and 2
used for the excision wound model and
groups 3 and 4 for the dead space wound
l Group 1: the fruit paste (300mg/kg/day) was
applied topically using a sterile stainless steel appli-
cator on a daily basis (how did you ensure the
correct dosage of paste was applied? And
how was this standardised between animals?
How was this kept place? More detail is
required to ensure validity of the study -
thank you ).
l Group 2 (control): 1% carboxymethyl cellulose
dissolved in deionsied water was applied topically
- also on a daily basis? (Author, why add CMC
to the control wounds? CMC on its own has
been demonstrated to affect wound healing.
Therefore, the rationale for this needs
explaining and referencing. Also, as with
the fruit paste, you need to make clear why
the carboxymethyl cellulose was used, and
how it was made up, applied and kept in
place - thank you).
l Group 3: 300mg of fruit paste (do you mean 1g
of fruit paste was dissolved in 100ml of
drinking water?) was dissolved in the animal’s
pic credit
on which the eschar fell off, without leaving any
residual raw wound, was considered the period of
epithelialisation. The rats were euthansised after the
study (A table or diagram summarising the
experimental protocol would be helpful, as
you can see it’s not quite clear which groups
were used for which model. Thank you).
l Dead space wound model Dead space wounds
were inflicted by implanting sterile cotton pellets
(10mg each), one on either side of the groin and
axilla, on the ventral surface of each rat using the
technique of D’Arcy et al., as described by Turner.12
(Again, you need to make clear which groups
were used for this model) This is a well-
established standard method of obtaining collagen
for histology and hydroxyproline determination
Animals in the test group were given the fruit
extract orally (you mean these animals were
all in group 3?). On the 10th post-wounding day,
granulation tissue that had formed on the implant-
ed cotton pellets was carefully removed under
anaesthesia and its wet weight noted. The tissue was
then dried at 60°C for 12 hours and its weight
recorded; 5ml 6N hydrochloric acid was added to
the dried tissue, which was stored at 110°C for 24
hours. The acid hydrolysate (author, please
check this reads correctly - thanks) was neu-
tralised using 10N sodium hydroxide, and the vol-
ume made up to 10ml. This neutralised hydrolysate
was used to determine hydroxyproline,13 (Neuman
and Logan 1950) which is an index of collagen
content. An additional piece of wet granulation tis-
sue was preserved in 10% formalin for histological
Estimation of hydroxyproline
Dry granulation tissue from both control and treat-
ed group (are these groups 3 and 4?) was used to
estimate the hydroxyproline content. Hydroxypro-
line present in the neutralised acid hydrolysate was
subsequently oxidised by sodium peroxide in the
presence of copper sulphate. Following this, it was
complexed with paradimethylaminobenzaldehyde
to turn it pink, and measured at 540nm by spectro-
photometer.13 (Neuman and Logan 1950)
Histological study
Granulation tissues (from dead space wound model)
were obtained on day 10 from the test and control
group animals (groups 3 and 4?) for the histo-
logical study. For the better appreciation of collagen
deposition Masson’s trichrome stain, which stains
the fibres green, was used. This technique is used for
quantitative determination and to observe cross-
linking of collagen (reference?).
Statistical analysis
The means of wound area measurements between
groups at different time intervals were compared
using a one-way ANOVA, descriptive tests. One-way
ANOVA was used to examine the mean differences
in epithelialisation time, weight of the tissue and
hydroxyproline content between the groups in dead
excision and dead space wound models. Data were
analysed using the SPSS (version 12) and p value
was set <0.05 for all analyses.
In the excision wound model the topically treated
animal wounds were found to fully have epithelial-
ised faster (13.8 ± 0.48 days) than the controls (17 ±
0.00 days). This difference was statistically signifi-
cant (p<0.001).
Animals given the oral extract also achieved full
epithelialisation significantly faster (13.0 ± 0.54
days) than the controls, who received plain drink-
ing water (16.6 ± 1.1 days). Again, this was sta-
tistically significant correct? (p<0.001).
In the dead space wound model, the tissue
obtained from the extract-treated animals (which
group?) showed significantly increased levels of
hydroxyproline content (68.0 ± 12.1mg/g tissue)
compared with the controls (30.0 ± 16.2mg/g tis-
sue). The wet (120.0 ± 25.84mg/100g rat) and dry
(28.40 ± 6.20mg/100g rat) weight of the granulation
tissue of animals treated with the fruit extract was
higher when compared with wet (57.6 ± 9.70mg/100g
rat) and dry (11.80 ± 0.9 mg/100g rat) weights of
tissue from animals received placebo control (what
placebo? you state plain drinking water).
This was statistically significant in both cases
The histological study of the granulation tissue
obtained on 10th day from the experimental ani-
mals (which group?) showed increased well-
organised collagen and more fibroblasts (Fig 1) when
compared with a section of granulation tissue from
the controls which showed inflammatory cells,
scanty collagen fibres and fibroblasts (Fig 2).
These results show that avocado extract significant-
ly increased the rate of wound contraction/epitheli-
alisation, and the weight of the granulation tissue.
The latter is predominantly composed of fibroblasts,
collagen, oedema and new small blood vessels. The
increased rate of wound contraction is indicative of
increased collagen synthesis. The heavier weight of
the dry granulation tissue from excision wounds of
the extract-treated animals suggests it had a higher
collagen content. It is possible that the proinflam-
matory activity of the constituents of avocado fruit
could attract macrophages to the wound site. Mac-
rophages stimulate the chemotaxis and prolifera-
13 Neuman, R.E., Logan, M.
A. The determination of
hydroxyproline. J Biol
Chem 1950; 184: 1,
14 Lu, Q.Y., Arteaga, J.R.,
Zhang, Q. et al. Inhibition of
prostate cancer cell growth
by an avocado extract: role
of lipid-soluble bioactive
substances. J Nutr Biochem
2005; 16: 1, 23-30.
15 Pacetti, D., Boselli, E.,
Lucci, P., Frega, N.G.
Simultaneous analysis of
glycolipids and phospholids
molecular species in
avocado (Persea Americana
Mill) fruit. J Chromatogr A
2007; 1150: 1-2, 241-251.
16 Pereira, L.M., Hatanaka,
E., Martins, E.F. et al. Effect
of oleic and linoleic acids
on the inflammatory phase
of wound healing in rats.
Cell Biochem Funct 2007;
26: 2, 197-204.
17 Balkan, M., Beyzadeoglu,
M., Oysul, K. et al. Retinoic
acid and intestinal wound
healing in intra-operatively
irradiated rat. Acta Chir
Belg 2006; 106: 1, 73-76.
18 Tom, W.L., Peng, D.H.,
Allaei, A. et al. The effect of
short-contact topical
tretinoin therapy for foot
ulcers in patients with
diabetes. Arch Dermatol
2005; 141: 11, 1373-1377.
19 Muehlberger, T., Moresi,
J.M., Schwarze, H. et al. The
effect of topical tretinoin
on tissue strength and skin
components in a murine
incisional wound model. J
Am Acad Dermatol 2005;
52: 4, 583-588.
20 Lateef, H., Abatan, O.I.,
Aslam, M.N. et al. Topical
pretreatment of diabetic
rats with all-trans retinoic
acid improves healing of
subsequently induced
abrasion wounds. Diabetes
2005; 54: 3, 855-861.
21 Musalmah, M., Nizrana,
M.Y., Fairuz, A.H. et al.
Comparative effects of
palm vitamin E and alpha-
tocopherol on healing and
wound tissue antioxidant
enzyme levels in diabetic
rats. Lipids 2005; 40: 6, 575-
22 Alleva, R., Nasole, E., Di
Donato, F. et al. alpha-Lipoic
acid supplementation
inhibits oxidative damage,
accelerating chronic wound
healing in patients
undergoing hyperbaric
oxygen therapy. Biochem
Biophys Res Commun
2005; 333: 2, 404-410.
23 Stipcevic, T., Piljac, A.,
pic credit
tion of fibroblasts, and attract endothelial cells to
the wound and stimulate their proliferation to pro-
mote angiogenesis (reference?).
Avocado fruit is a rich source of monounsaturated
fatty acids and contains the highest content of
lutein (70% of the measured carotenoids) of com-
monly eaten fruits, as well as significant amounts of
related carotenoids and (should we mention
vitamin A as well?) vitamin E,14 (Lu et al 2005)
various phospholipids and glycolipids.15 (Pacetti
et al 2007) Because the avocado also contains a
significant amount of monounsaturated fat, these
bioactive carotenoids are likely to be better absorbed
into the bloodstream.15 (Lu et al 2005) Vitamin A
is required for epithelial formation, cellular differ-
entiation and immune function, and vitamin E is
the major lipid-soluble antioxidant in the skin.
Monounsaturated fatty acids,16 (Pereira et al
2007) topical and systemic carotenoids17-20 (Bal-
kan et al 2006; Tom et al 2005; Muehlberget
et al 2005; Lateef et al 2005) and vitamin E21
(Musalmah et al 2005) promote wound healing.
Derivatives of phospholipids and glycolipids also
have wound-healing properties.22-25 (Alleva et al
2005; Stipcevic et al 2006; Xu et al 2007; Linet
al 2006)
We hypothesise that carotenoids and, to a certain
extent, monounsaturated fatty acids might have
accelerated (okay?) the epithelialisation rate in the
excision wound model. Phospholipids are essential
co-factors in the blood coagulation cascade and
platelet activation, and it is possible that the phos-
pholipids of avocado fruit might have facilitated the
initial phase of cutaneous repair by initiating hae-
mostasis and the development of (okay?) a provi-
sional matrix for cell migration.
One known, (2R)-(12Z,15Z)-2-hydroxy-4-oxohe-
neicosa-12,15-dien-1-yl acetate (please double
check this is written correctly - thanks), and
two novel compounds, persenone A and B, isolated
from avocado fruit have been identified as inhibi-
tors of superoxide (O2-) and nitric oxide (NO) gen-
eration in cell culture systems.26 (Kim et al 2000)
Avocado has good hypochlorous acid, but not
hydrogen peroxide, scavenging ability.27 (Murcia
et al 2001) While there has been controversy over
the role of free radicals in wound healing,28
(Juranek and Bezek 2005) the efficacy of honey
is well correlated with its antioxidant properties.29
(Henriques et al 2006)
Avocados also have 60% more potassium than
bananas and are rich in vitamins B and K.14 (Lu et
al 2005) Vitamin B promotes wound healing.30
(Neiva et al 2005) However, the role of potassium
and vitamins K and D on wound healing is not
known (according to our reviewer, this is not
true. There is evidence that vitamin D is
involved in regulation of SAMs (fibronec-
Author, you need to fully acknowledge the
study limitations
Avocado fruit promotes wound healing and the
constituents present in the avocado fruit extract
may be responsible for promoting the collagen for-
mation at the proliferative stage of wound healing.
Its wound healing promoting activity could be due
to its antioxidant, antimicrobial, vitamins or some
unknown activities. However, it needs to be studied
further to isolate the active ingredients that pro-
mote wound healing, before considering it for clini-
cal use.
Fig 1: Experimental group granulation tissue with
more collagen (Masson’s trichrome stain) a =
inflammatory cells, b= fibroblast, c= collagen fibres
Fig 2. Control group granulation tissue with less
collagen (Masson’s trichrome stain) a = inflammatory
cells, b= fibroblast, c= collagen fibres
Piljac, G. Enhanced healing
of full-thickness burn
wounds using di-
rhamnolipid. Burns 2006;
32: 1, 24-34.
24 Xu, K.P., Yin, J., Yu, F.S.
Lysophosphatidic acid
promoting corneal
epithelial wound healing by
transactivation of
epidermal growth factor
receptor. Invest
Ophthalmol Vis Sci 2007;
48: 2, 636-643.
25 Lin, C.I., Chen, C.N.,
Chen, J.H., Lee, H.
Lysophospholipids increase
IL-8 and MCP-1
expressions in human
umbilical cord vein
endothelial cells through an
IL-1-dependent mechanism.
J Cell Biochem 2006; 99: 4,
26 Kim, O.K., Murakami, A.,
Nakamura, Y. et al. Novel
nitric oxide and superoxide
generation inhibitors,
persenone A and B, from
avocado fruit. J Agric Food
Chem 2000; 48: 5, 1557-
27 Murcia, M.A., Jiménez,
A.M., Martínez-Tomé, M.
Evaluation of the
antioxidant properties of
Mediterranean and tropical
fruits compared with
common food additives. J
Food Prot 2001; 64: 12,
28 Juránek, I., Bezek, S.
Controversy of free radical
hypothesis: reactive oxygen
species: cause or
consequence of tissue
injury? Gen Physiol Biophys
2005; 24: 3, 263-278.
29 Henriques, A., Jackson,
S., Cooper, R., Burton, N.
Free radical production and
quenching in honeys with
wound healing potential. J
Antimicrob Chemother
2006; 58: 4, 773-777.
30 Neiva, R.F., Al-Shammari,
K., Nociti, F.H. Jr et al.
Effects of vitamin-B
complex supplementation
on periodontal wound
healing. J Periodontol 2005;
76: 7, 1084-1091.
... Naturally occurring compounds from plants, fungi and microbes are still used in pharmaceutical preparations in pure or crude forms. Medicinal plants are increasingly being used in most parts of the world as: analgesic and anti-inflammatory, anticonvulsant (Oyewole and Amabeoku, 2006), hypoglycemic and hypocholesterolemic (Brai et al., 2007), wound healing and reducing cancer risk (Nayak et al., 2008). Herbal remedies have increasingly become attractive alternatives to prevent or treat hypercholesterolemia, especially for those with cholesterol at the borderline levels. ...
... Excellent safety profile, cost effectiveness and multiple beneficial effects on improving wellbeing, have collectively contributed to the emerging trend of increasingly usage of herbal supplements. A number of studies have shown that the reduction of LDL-cholesterol with medicinal plants will reduce the incidence of cardiovascular diseases and overall death rate (Nayak et al., 2008). ...
Full-text available
This study presents results of the antimicrobial properties of Nauclea latifolia leaves commonly called African Peach. The ethanolic extract of the leaves at different concentrations was tested on some seven pathogenic bacteria; Escherichia coli, Staphylococcus aureus, Streptococcus iniae, Bacillus subtilis, Pseudomonas aeruginosa, Samonella typhi and Aeromonas hydrophila using agar well diffusion assay. Results reveal that ethanolic extracts of N. latifolia had better antibacterial potentials than the methanolic extracts. Nauclea latifolia leaves showed the highest antibacterial activity in the ethanolic extracts on Bacillus subtilis with a zone of inhibition of 27.5 ± 0.25 mm while the lowest antibacterial activity was recorded on Escherichia coli with a zone of inhibition of 9.18 ± 0.04 mm. No antibacterial activity was recorded in the control (distilled water). The results signify that the alcoholic extracts of N. latifolia leaves can serve as a cheap source of raw material in the production biomedical products.
... These constituent like Vitamins A and E, proteins, beta-carotene, lecithin, fatty acids and potassium which acts as nutrient wound healing. [27] 3. ...
... Debridiment agent convert proline to hydro proline and it act as antimicrobial on the wound infection. [27] 5. ...
Full-text available
The prevalence of diabetic Foot ulcer is increasing day by day among global population. The most frequent underlying etiologies are neuropathy, trauma, deformity, high plantar pressures, and peripheral arterial disease. The disease etiology suggest that Gram-positive bacteria, such as Staphylococcus aureus and beta-hemolytic streptococci, are the most common pathogens in previously untreated mild and moderate infection. Diabetic foot ulcer (DFU) is one of the important complications, since the major deaths in diabetes are due to DFU, which arises as a consequence of complicated and multi-factorial pathologies. This review is based on plant related drugs, as available antibiotics resistance is global concern. For the treatment of disease with single strategy might unlikely less effective and also the overall costs of these therapies are high. The use of many commonly used herbs and spices are claimed to have wound healing effects with various mechanisms since long time. The treatment with herbal drugs can improve the quality of life of Diabetic foot ulcer patients with less adverse effects.
... It is considered as one of the healthiest fruits due to its rich nutritional composition, which includes vitamins, minerals, proteins and monounsaturated fatty acids (Dreher & Davenport, 2013). Its unique phytochemical content has paved the way for this fruit to be researched for medicinal applications, and so far different parts of the fruit have been studied for their antioxidant, anticancer, anti-inflammatory, antimicrobial, antidiabetic, hypolipidemic, hepatoprotective, antihemolytic and wound healing activities (Nayak et al.,2008;Rodriguez-Carpena et al., 2011;Pahua-Ramos et al., 2012;Nabavi et al., 2013;Alkhalaf et al., 2019;Umoh et al., 2019). However, there is no literature data currently exists on the anti-QS activity of any parts of avocado. ...
The emergence of bacteria resistant to conventional antibiotics and the inability of these antibiotics to treat bacterial biofilm-induced infections cause millions of deaths every year. This situation has prompted scientists to develop alternative strategies to combat infectious diseases. Among these, researches on phytochemicals to reduce bacterial virulence in Pseudomonas aeruginosa have gained momentum in recent years. The main reasons behind this are the production of virulence factors and biofilm formation, all of which are under the control of quorum sensing (QS) system. Hence, inhibition of the QS pathways is an eligible strategy for the control of microbial pathogenesis. For the first time in the present study, the methanolic seed extract of avocado was evaluated for its anti-QS activity against P. aeruginosa PAO1. The results of the experiments carried out proved that the extract has inhibitory activity on the regulation of virulence and biofilm formation. Phytochemical analysis resulted in the identification of epicatechin, catechin, chlorogenic acid, caffeic acid, quercetin, kaempferol, vanillin, ferulic acid in the extract. Then, the mechanism of action for the extract was investigated through molecular docking. Docking outcomes demonstrated that the major components, catechin, epicatechin, chlorogenic acid, could bind to the receptors of QS competitively. Hence, the mode of action for the extract might be through the inhibition of the QS. Considering the computational analysis results and the literature, it is thought that the anti-QS activity of the extract prepared from avocado seeds may be related to the synergistic effect of the phytochemicals it contains.
... Depending on the part of the plant used, P. americana have been reported to possess several pharmacological activities which cannot all be listed here. These include: anti-bacterial and antimicrobial activity (Jiménez et al., 2013;Hinojosa and Linder, 2010), antiviral activity (De Almeida et al., 1998), anti-malarial activity (Komlaga et al., 2015), analgesic and anti-inflammatory activity (Adeyemi et al., 2002), hypoglycemic and antidiabetic activity (Anita et al., 2005), cardiovascular activity (Carvajal et al., 2014), anticancer activity (Butt et al., 2006), hypotensive activity (Dzeufi et al., 2014), wound healing activity (Nayak et al., 2008). Previous phytochemical studies of P. americana seed indicated the presence of Saponins, steroids, terpenoids, tannins, cardiac glycosides, phenols, carbohydrates, cynogenetic glycosides and alkaloids (Idris et al., 2009;Arukwe et al. 2012). ...
Ethnopharmacological relevance Persea americana Miller (Lauraceae) known as “pear” in Cameroon is comestible by the fruit. The leaves of the plant are traditionally used in the treatment of microbial infections, malaria, diabetes, high blood pressure, to stimulate uterine contractions and relief painful menstruations. The leaves and stem bark are also used to cure malaria and typhoid fever. Fresh pulps are used to lower cholesterol, prevents mental strain and cardiovascular diseases whilst the seeds are used against intestinal worms and skin infections. Aim of the study This study aimed to investigate the antibacterial activity and wound healing efficacy of methanol extract of Persea americana seed on an excision wound infected with Staphylococcus aureus using a rat model and characterise the mode of action of this extract. Materials and methods The antibacterial activities of the methanol extract were done against a panel of bacteria using broth microdilution method. The phytochemical analysis as well as the antioxidant activities were evaluated using colorimetric methods. The mode of action of P. americana was studied by targeting bacterial membranes, cytoplasmic contents, and the formation of biofilms. The therapeutic effect of the methanol extract was evaluated on an excision wound infected with Staphylococcus aureus. Results The methanol extract of P. americana seed displayed antibacterial properties MIC varying from 64 to 128 μg/mL which can be linked to its total phenolic, flavonoid and tannin contents. The antibacterial activity of the extract is due to the bacterial biofilm inhibition and the perturbation of the bacterial membrane through the leakage of intracellular materials, the inhibition of H⁺-ATPases pumps. The gel based on P. americana extract showed a significant increase in the percentage of wound closure and had a significant reduction of the number of Colony Forming Units (CFU) of S. aureus at the infection site. The plant has antioxidant activity for wound healing which is lower than vitamin C. The toxicological report showed that the gel-based extract had negligible irritation on the skin and non-irritating to the eye, and therefore can be consider safe for use. Conclusion The present study revealed the antibacterial and wound healing properties of the MEPa and could possibly be used to tackle bacterial infections.
... Fatty acids extracted from avocado oil have several functions, including promoting collagen synthesis, reducing inflammation, and wound healing [37]. In the brain tissue of diabetic rats, the seed oil attenuates oxidative stress and prevents mitochondrial dysfunction [38]. ...
Full-text available
As a general sensory disorder, hearing loss was a major concern worldwide. Autophagy is a common cellular reaction to stress that degrades cytoplasmic waste through the lysosome pathway. Autophagy not only plays major roles in maintaining intracellular homeostasis but is also involved in the development and pathogenesis of many diseases. In the auditory system, several studies revealed the link between autophagy and hearing protection. In this review, we aimed to establish the correlation between autophagy and hair cells (HCs) from the aspects of ototoxic drugs, aging, and acoustic trauma and discussed whether autophagy could serve as a potential measure in the protection of HCs.
... received potassium dichromate at a dose of 30 mg/kg/day by oral gavage (Ounassa, 2010), together with P. americana pulp extract at a dose of 300 mg/kg/day for 28 days (Nayak, Raju, & Chalapathi Rao, 2008). ...
Full-text available
The current study has been designed to assess the role of Persea americana (P. americana) pulp extract on potassium dichromate-induced hepatotoxicity in rats. P. americana pulp extract administration improved the hepatic vascular congestion, blood extravasation, inflammatory cellular infiltration, Kupffer cell hyperplasia, and nuclear changes. It also significantly ameliorated hepatic interstitial and peri-portal fibrosis and caused retrieval of the PAS-positive reaction in the liver parenchyma and around the central vein with restoration of the glycogen granules. P. americana also significantly attenuated the immunohistochemical expression of NF-kβ p65 and its downstream inflammatory cytokines IL6 and TNFα in the liver parenchyma. The antioxidant effect of P. americana was evidenced by significant modulation of the three major components of the thioredoxin (Trx) antioxidant system, the Trx, the thioredoxin reductase (TrxR), and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase along with significant increase in the level of superoxide dismutase and glutathione, and decrease in the lipid peroxidation product malondialdehyde. P. americana pulp extract also caused significant elevation of hepatic protein phosphatase 5 with subsequent down-regulation of Apoptosis signal-regulating kinase1 (ASK1) and its downstream signaling targets MAPK kinase 4 (MKK4), p38 mitogen-activated protein kinases (p38-MAPKs), the c-JUN N-terminal kinase (JNK), and the extracellular signal-regulated kinase 1/2 (ERK 1/2). Also, In conclusion, P. americana pulp extract has anti-oxidative and anti-inflammatory effects against potassium dichromate-induced hepatotoxicity.
Full-text available
The study compares the toxicity of 53 selected medicinal plants commonly used in the Philippines to treat various diseases. It uses as a benchmark Vitex negundo L., which was approved by the Philippine Food and Drug Administration as an herbal drug for cough and asthma after passing clinical trials for safety and efficacy. The methods were chosen for their simplicity and accessibility even for resource-limited laboratories. Extracts (95% ethanol) of the medicinal parts of the plants were (1) chemically profiled using qualitative phytochemical tests that detect the presence of key classes of bioactive compounds; and (2) evaluated for toxicity using the brine shrimp (Artemia sp.) lethality assay (BSLA). General phytochemical screening revealed the presence of tannins in 50 plant extracts, alkaloids in 43, glycosides in 33, flavonoids in 31, steroids in 21, triterpenoids in 20, anthraquinones in 10, and saponins in 8. Extracts from eight plants had LC50 values lower than the potassium dichromate control (approximately 12 µg/mL) and were considered highly toxic; extracts from 21 plants had LC50 values between 12 µg/mL and 100 µg/mL and were considered moderately toxic; extracts from 19 plant extracts, including Vitex negundo and some common vegetables, had LC50 values between 100 µg/mL and 500 µg/mL, and were considered mildly toxic and likely to have reasonable safety margins; five plant extracts, including common vegetables, had LC50 values above 500 μg/mL and were considered essentially nontoxic. No apparent correlation could be found between toxicity and chemical diversity or a specific class of phytochemicals present. Our findings may serve as a guide for herbal drug and nutraceutical development, especially in prioritizing plants for more detailed safety studies.
The process of wound healing imposes a great challenge in the Medicare and pharmaceutical systems globally due to variety in the types of wound, its severity, degree of various microbial infections, interplay of the cellular and molecular complexes and different time taken in order to heal completely. Some of the physiological conditions with chronic diseases like diabetes, peripheral vascular disorders, or even aging result in the delayed wound healing. Owing to such complex conditions of wound management, there is urgent need to come up with efficient strategies. Human beings since ages have been using the traditional plant-based medication as the first line preference for managing adverse physiological conditions. The present chapter aims to analyze about the enormous potential of various plants for wound management using present ethnobotanical knowledge prevailing amongst us. Apart from this, different wound healing models, and pharmacological validation, and scientific proofs are also reviewed for wound healing activity. Therefore, the content of this chapter bridges the ethnobotanical knowledge to the researchers and pharmaceutical systems to further validate and develop efficient wound treatment systems using herbal products.
Full-text available
For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species (ROS), due to their potentially harmful effect towards cellular constituents, is one of the most frequently cited in biomedical sciences. In fact, the ROS-mediated alterations of biomacromolecules are considered to be essential events in the etiopathogenesis of those diseases where involvement of ROS has been indicated. ROS easily react in vitro with most biological molecules, causing their degradation and destruction. This may implicitly suggest that, when excessively produced in vivo, ROS are deleterious to integral components of the cell and cause their dysfunctions. Some experimental data indicate that ROS-mediated lipid peroxidation, protein oxidation and oxidative alterations to nucleic acids are crucial events of unfavorable actions of ROS. Yet the most convincing evidence, i.e. unambiguous inhibition of tissue injury by pretreatment with antioxidants, has not been provided. On the contrary, there are quite a few papers reporting failure in applying antioxidants to heal those pathologies where the causal role of ROS was supposed. Other papers reported serious complications arising from antioxidant therapy, which is quite in contradiction to its expected effect. On the other hand, an increasing number of recent findings have provided evidence of a key role of ROS in both intracellular signaling and intercellular communication, processes involved in maintaining homeostasis. Hence, some investigators consider excessive production of ROS to be rather a "smoke after the fire" than "a deleterious fire" itself, suggesting the occurrence of overproduced ROS as being the consequence of some primary damage. The present paper aims at summarizing some pros and cons of various opinions with an attempt to help better understand the involvement of ROS in tissue injury.
Full-text available
Honey-impregnated wound dressings are now available on drug tariff in the UK, though the modes of action of honeys with antibacterial and wound healing properties are not entirely clear. The action of some but not all of these honeys is linked to the production of hydrogen peroxide on dilution of the honey with wound exudate. The present study investigates both free radical production and the antioxidant potential of some honeys, properties which may have a role to play in wound healing. Free radical production and quenching of three honey types (manuka, antibacterial but non-peroxide-producing; pasture, antibacterial peroxide-producing; commercial heat processed, non-antibacterial) was investigated by electron paramagnetic resonance (EPR) spectroscopy; quenching was also examined using a superoxide quenching assay. All honeys tested had antioxidant potential, with manuka able to completely quench added radicals within 5 min of spiking. Only the peroxide-producing honey (pasture PS9) was found to form radicals on dilution. The ability to modulate production and quenching of free radicals may contribute to the demonstrated ability of some honeys to help in resolving the state of inflammation typifying chronic wounds.
Full-text available
To identify the underlying mechanisms by which lipid mediator lysophosphatidic acid (LPA) acts as a growth factor in stimulating extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3K) during corneal epithelial wound healing. Epithelial debridement wounds in cultured porcine corneas and scratch wounds in an epithelial monolayer of SV40-immortalized human corneal epithelial (THCE) cells were allowed to heal in the presence or absence of an epidermal growth factor receptor (EGFR) inhibitor (tyrphostin AG1478), a matrix metalloproteinase inhibitor (GM6001), or a heparin-binding EGF-like growth factor (HB-EGF) antagonist (CRM197) with or without LPA. EGFR activation was analyzed by immunoprecipitation using EGFR antibodies and Western blotting with phosphotyrosine antibodies. Phosphorylation of ERK and AKT (a major substrate of PI3K) was analyzed by Western blotting with antibodies specific to the phosphorylated proteins. Wound- and LPA-induced shedding of HB-EGF was assessed by measuring the release of alkaline phosphatase (AP) in a stable THCE cell line that expressed HB-EGF with AP inserted in the heparin-binding site. In organ and cell culture models, LPA enhanced corneal epithelial wound healing. LPA-stimulated and spontaneous wound closure was attenuated by AG1478, GM6001, or CRM197. Consistent with the effects on epithelial migration, these inhibitors, as well as the Src kinase inhibitor (PP2), retarded LPA-induced activation of EGFR and its downstream effectors ERK and AKT in THCE cells. Unlike exogenously added HB-EGF, LPA stimulated moderate EGFR phosphorylation; the level of phosphorylated EGFR was similar to that induced by wounding. However, LPA appeared to prolong wound-induced EGFR signaling. The release of HB-EGF assessed by AP activity increased significantly in response to wounding, LPA, or both, and the release of HB-EGF-AP induced by LPA was inhibited by PP2 and GM6001. LPA accelerates corneal epithelial wound healing through its ability to induce autocrine HB-EGF signaling. Transactivation of EGFR by LPA represents a convergent signaling pathway accessible to stimuli such as growth factors and ligands of G-protein-coupled receptors in response to pathophysiological challenge in human corneal epithelial cells.
One known, (2R)-(12Z,15Z)-2-hydroxy-4-oxoheneicosa-12,15-dien+ ++-1-yl acetate (1), and two novel compounds, persenone A (2) and B (3), have been isolated from avocado fruit (Persea americana P. Mill), as inhibitors of superoxide (O(2)(-)) and nitric oxide (NO) generation in cell culture systems. They showed marked inhibitory activities toward NO generation induced by lipopolysaccharide in combination with interferon-gamma in mouse macrophage RAW 264.7 cells. Their inhibitory potencies of NO generation (1, IC(50) = 3.6; 2, IC(50) = 1.2; and 3, IC(50) = 3.5 microM) were comparable to or higher than that of a natural NO generation inhibitor, docosahexaenoic acid (DHA; IC(50) = 4.3 microM). Furthermore, compounds 1-3 and DHA markedly suppressed tumor promoter 12-O-tetradecanoylphorbol-13-acetate-induced O(2)(-) generation in differentiated human promyelocytic HL-60 cells (1, IC(50) = 33.7; 2, IC(50) = 1.4; 3, IC(50) = 1.8; and DHA, IC(50) = 10.3 microM). It is notable that they were found to be suppressors of both NO- and O(2)(-)-generating biochemical pathways but not to be radical scavengers. The results indicate that these compounds are unique antioxidants, preferentially suppressing radical generation, and thus may be promising as effective chemopreventive agent candidates in inflammation-associated carcinogenesis.
Several Mediterranean and tropical fruits have been analyzed in order to assess their antioxidant activity compared with that of common food additives (butylated hydroxyanisole [BHA], butylated hydroxytoluene [BHT] and propyl gallate). Among Mediterranean fruits, red grape and plum were more effective (P < 0.05) scavengers of peroxyl radicals than BHA, BHT, and propyl gallate. Of the tropical fruits, banana was the most effective scavenger of peroxyl radicals. Mediterranean and tropical fruits showed very good scavenger activity against hydroxy radicals (OH*), protecting deoxyribose better than BHA and BHT. The HOCI scavenging ability of Mediterranean fruits tested was, in decreasing order, lemon > plum > apricot > white grape > melon > red grape > mandarin > watermelon > peach > medlar > apple > orange > cherry > strawberry. However, the four varieties of pear were poor scavengers (P < 0.05). Among tropical fruits, the order of efficiency as HOCI scavengers was passion fruit > lime > passiflora > kumquat > avocado > pineapple > physalis > papaya fruit > carambola > mango > banana. All Mediterranean fruits showed an effect on hydrogen peroxide except peach. Tropical fruits also had a strong effect on hydrogen peroxide except avocado, which had no effect. The effect of Mediterranean and tropical fruits on the protection factor of refined olive oil, analyzed by the Rancimat method and compared with common food additives, was clear. Watermelon conferred a significantly (P < 0.05) greater protection than the other Mediterranean fruits. Among tropical fruits, physalis had the most stabilizing effect.
Reports have demonstrated that nutrient supplements, in particular vitamin-B complex (Vit-B), can positively influence wound healing processes. However, limited information is available on the effects of Vit-B on periodontal wound healing. A total of 30 patients (13 males, 17 females) presenting with generalized moderate to severe chronic periodontitis were enrolled in this study. All subjects presented > or = two teeth in the same sextant with probing depth (PD) > or =5 mm and bleeding upon probing (BOP) in need of access flap surgery (AFS). This study was a randomized, double-masked, placebo-controlled clinical trial. Subjects were instructed to take one capsule a day of either Vit-B (50 mg of the following: thiamine HCl, riboflavin, niacinamide, d-calcium pantothenate, and pyridoxine HCl; 50 microg each of d-biotin and cyanocobalamin; and 400 mcg of folate) or placebo for 30 days following AFS. Clinical attachment levels (CAL) and N-benzoyl-dl-arginine-2-naphthylamide (BANA) test scores were measured at baseline and at 90 and 180 days following surgical intervention. Assessments of the healing response were also performed using BOP, gingival index (GI), and plaque index (Pl) at baseline and 7, 14, 30, 90, and 180 days. The mean results of each parameter were averaged within a group. Differences between groups were analyzed by using repeated measures analysis of variance (ANOVA). Both groups experienced comparable levels of PD reduction following AFS (test: -1.57 +/- 0.34; control: -1.50 +/- 0.21). Changes in mean CAL were more favorable in Vit-B supplemented subjects (test: +0.41 +/- 0.12; control: -0.52 +/- 0.23; P = 0.024). Stratified data demonstrated significantly better results for the test group in both shallow (test: -0.08 +/- 0.03; control: -1.11 +/- 0.27; P = 0.032) and deep sites (test: +1.69 +/- 0.31; control: +0.74 +/- 0.23; P = 0.037). No significant differences were observed between groups regarding PI, GI, and BOP. BANA test values were significantly reduced in both groups after surgical treatment and no significant differences were noted between groups. Vitamin B-complex supplement in combination with AFS resulted in statistically significant superior CAL gains when compared to placebo.
The effect of supplementing 200 mg/kg body weight palm vitamin E (PVE) and 200 mg/kg body weight α-tocopherol (α-loc) on the healing of wounds in streptozotocin-induced diabetic rats was evaluated. The antioxidant potencies of these two preparations of vitamin E were also evaluated by determining the antioxidant enzyme activities, namely, glutathione peroxidase (GPx) and superoxide dismutase (SOD), and malondialdehyde (MDA) levels in the healing of dermal wounds. Healing was evaluated by measuring wound contractions and protein contents in the healing wounds. Cellular redistribution and collagen deposition were assessed morphologically using cross-sections of paraffin-embedded day-10 wounds stained according to the Van Gieson method. GPx and SOD activities as well as MDA levels were determined in homogenates of day-10 dermal wounds. Results showed that PVE had a greater potency to enhance wound repair and induce the increase in free radical-scavenging enzyme activities than α-Toc. Both PVE and α-Toc, however, were potent antioxidants and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in MDA levels.
The aim of this study was to investigate the properties of di-rhamnolipid [alpha-L-rhamnopyranosyl-(1-2)-alpha-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3] relating to the process of cutaneous wound healing. Di-rhamnolipid was prepared in a eucerin ointment and applied topically on full-thickness burn wounds in normal Sprague-Dawley rats covering 5% of the total body surface area. The rate of wound closure was measured over the period of 45 days. The collagen content was evaluated microscopically, by performing densitometric analysis on Verhoeff's stained histopathological slides of wound biopsies taken at the end of 45th day of di-rhamnolipid treatment. Di-rhamnolipid toxicity was assessed with the subcutaneous multi-dose study in Swiss-Webster mice. The treatment of full-thickness-burn wounds with topical 0.1% di-rhamnolipid accelerated the closure of wounds on day 21 of the treatment by 32% compared to the control (p < 0.05). On day 35, the wounds closed in all animals-treated with 0.1% di-rhamnolipid ointment while some rats in the control group had open wounds on days 35 and even 45. Histologic comparisons have shown that di-rhamnolipid significantly decreased collagen content in burn wounds (47.5%, p < 0.05) as compared to the vehicle-treated (control) wounds. Di-rhamnolipid was well-tolerated. The results of this study raise the possibility of potential efficacy of di-rhamnolipid in accelerating normal wound healing and perhaps in overcoming defects associated with healing failure in chronic wounds.
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both low-molecular-weight lysophospholipid (LPL) ligands which are recognized by the Edg family of G protein-coupled receptors (GPCRs). In endothelial cells, these two ligands activate Edg receptors resulting in cell proliferation and cell migration. Interleukin-8 (IL-8) is a C-X-C chemokine and acts as a chemoattractant of neutrophils, whereas monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine and functions mainly as a chemoattractant of monocytes/macrophages. Both factors are secreted from endothelial cells and have been implicated in the processes leading to atherosclerosis. We examined the effects of LPLs on the expression of IL-8 and MCP-1, key regulators of leukocyte recruitment in human umbilical cord vein endothelial cells (HUVECs). Work illustrated in this article showed that LPA and S1P enhanced IL-8 and MCP-1 mRNA expressions, and protein secretions in dose- and time-dependent fashions. Maximal mRNA expression appeared at 16 hr post-ligand treatment. Using prior treatments with chemical inhibitors, LPLs enhanced IL-8 and MCP-1 expressions through a Gi-, Rho-, and NFkappaB-dependent mechanism. In a chemotaxis assay system, LPL treatments of endothelial cells enhanced monocyte recruitment through upregulating IL-8 and MCP-1 protein secretions. Pre-incubation with AF12198, an IL-1 receptor antagonist or IL-1 functional blocking antibody both suppressed the enhanced effects elicited by LPLs of IL-8 and MCP-1 mRNA expressions in HUVECs. These results suggest that LPLs released by activated platelets might enhance the IL-8- and MCP-1-dependent chemoattraction of monocytes toward the endothelium through an IL-1-dependent mechanism, which may play an important role in facilitating wound-healing and inflammation processes.