Received: 2 July 2019 Revised: 13 August 2019 Accepted: 21 September 2019

DOI: 10.1002/ptr.6524

REVIEW

Vegetable butters and oils in skin wound healing: Scientific

evidence for new opportunities in dermatology

Nina Poljšak | Samo Kreft | Nina Kočevar Glavač

Faculty of Pharmacy, University of Ljubljana,

Ljubljana, Slovenia The use of vegetable butters and oils shows promising results in the treatment of skin
wounds, as they have an effective impact on the phases of the wound‐healing process
Correspondence
Nina Poljšak, Faculty of Pharmacy, University through their antimicrobial, anti‐inflammatory, and antioxidative activities and by pro-
of Ljubljana Aškerčeva cesta 7, 1000 Ljubljana,
moting cell proliferation, increasing collagen synthesis, stimulating dermal reconstruc-
Slovenia.
Email: nina.poljsak@ffa.uni‐lj.si tion, and repairing the skin's lipid barrier function.
In this article, in vitro and in vivo studies of argan (Argania spinosa), avocado (Persea
americana), black cumin (Nigella sativa), calophyllum (Calophyllum inophyllum), coco-
nut (Cocos nucifera), cranberry (Vaccinium macrocarpon), grape (Vitis vinifera), green
coffee (Coffea arabica), lentisk (Pistacia lentiscus), linseed (Linum usitatissimum),
lucuma (Pouteria lucuma), mango (Mangifera indica), olive (Olea europaea), pomegran-
ate (Punica granatum), pumpkin (Cucurbita pepo), rapeseed (Brassica napus), sea buck-
thorn (Hippophae rhamnoides), and sunflower (Helianthus annuus) oils were
reviewed. In many cases, vegetable oils proved to be more effective than synthetic
wound‐healing compounds used as controls.
The fatty‐acid components of vegetable oils are assumed to play a major role in the
wound‐healing process, in particular polyunsaturated fatty acids such as linoleic acid.
Evidence shows that oils with a higher linoleic to oleic acid ratio are more effective for
lipid barrier repair. However, in depth studies are needed to gain knowledge about
vegetable oils' effects on the skin and vice versa.

K E YW O RD S

fatty acids, skinskin woundskin wound healingvegetable buttersvegetable oils

1 | IN T R O DU C T ION infection, and provide adequate tissue perfusion and oxygenation,

Skin injuries such as wounds are defined as the disruption of skin
integrity (Prisăcaru et al., 2013), which triggers a cascade of events
that leads to a dynamic wound‐healing process in which a variety of
extracellular matrix components act together as a very sophisticated
sequence of events to re‐establish the integrity of the injured skin
(Kováč et al., 2015; Martin, 1997). Wound healing occurs in five
phases: inflammation, neovascularization, the formation of granulation
tissue, re‐epithelisation and the formation of a new extracellular
matrix, and tissue remodelling (Nevin & Rajamohan, 2010). The basic
roles of wound healing are to minimize tissue damage, prevent
proper nutrition, and a moist wound‐healing environment (Pierce &
Mustoe, 1995).
Skin wounds have a negative effect on patients' lives, and the man-
agement and care of such wounds cost the healthcare system a large
amount of money every year (Ashcroft et al., 2003; Lania et al.,
2017; Schreml, Szeimies, Prantl, Landthaler, & Babilas, 2010). A num-
ber of experimental studies are therefore working on new approaches
to skin wound healing, including the study of the potential of
phytopharmacological methods (Ashcroft et al., 2003; Bedi &
Shenefelt, 2002; Buchness, 1998; Eisenberg et al., 1993; Lania et al.,
2017; S. B. Nayak, Isik, & Marshall, 2017; Schreml et al., 2010) to

Phytotherapy Research. 2019;1–16. wileyonlinelibrary.com/journal/ptr © 2019 John Wiley & Sons, Ltd. 1
2 POLJŠAK
replace antibiotic therapy due to serious issues of bacterial resistance
(S. B. Nayak et al., 2017). Phytotherapy in dermatology is the preferred
option for patients over conventional therapy using synthetic medi-
cines, particularly in terms of perceived side effects (Bedi & Shenefelt,
2002; Eisenberg et al., 1993) and has actually been proven to be effec-
tive (Buchness, 1998; Kováč et al., 2015). Medicinal plants have like-
wise been proven to have an effective impact on processes that play
an important role in skin wound healing (Corazza, Borghi, Lauriola, &
Virgili, 2009).
Vegetable butters and oils have shown promising results in in vitro
and in vivo studies. They affect phases of the wound‐healing process
through their bacteriostatic, antimicrobial, anti‐inflammatory, and anti-
oxidative activities and by promoting cell proliferation, increasing col-
lagen synthesis, stimulating dermal reconstruction, and repairing the
skin's lipid barrier function (Cornily et al., 2010; de Oliveira et al.,
2013; Lamaud, Huc, & Wepierre, 1982; Lewinska, Zebrowski, Duda,
Gorka, & Wnuk, 2015; T.‐K. Lin, Zhong, & Santiago, 2017;
Mandawgade & Patravale, 2008; Nasopoulou, Karantonis,
Detopoulou, Demopoulos, & Zabetakis, 2014; Shinagawa, de Santana,
Torres, & Mancini‐Filho, 2015; Vaughn, Clark, Sivamani, & Shi, 2018).
Fatty acids were shown to play major role in the wound‐healing pro-
cess (Cardoso, Souza, Ferro, Favoreto, & Pena, 2004; de Oliveira
et al., 2013; McDaniel, Belury, Ahijevych, & Blakely, 2008). Linolenic,
linoleic, and oleic acids are precursors for the synthesis of inflamma-
tory or anti‐inflammatory mediators and are part of the structure of
cell membrane phospholipids, ceramides, and sebum, that is, important
components of the lipid barrier (Hankenson, Watkins, Schoenlein,
Allen, & Turek, 2000; Lewinska et al., 2015; Ruthig & Meckling‐Gill,
1999).
2 | VEGETABLE BUTTERS AND OILS IN
W OU N D H E A L I N G
Vegetable butters and oils are lipids composed of triglycerides (gener-
ally as high as 99%) and unsaponifiable matter (generally from 0.5% to
2%). Glycerol fraction calculated from the molar mass of triglycerides
ranges from 10% to 15%.
Presented in this section is a review of individual vegetable butters
and oils that were studied in in vitro, in vivo, and/or clinical studies of
skin wound healing. Special emphasis was placed on finding a connec-
tion between the triglyceride composition and the effects expressed
on the skin. When testing vegetable oils in vitro for the dermal treat-
ment of skin wounds, it was observed that polyunsaturated fatty acids
affect the production of inflammatory mediators and stimulate epithe-
lial cell proliferation (Ruthig & Meckling‐Gill, 1999). The presented
vegetable butters and oils were therefore divided into the following
groups: saturated fatty acid‐based butters/oils, monounsaturated fatty
acid‐based butters/oils, and polyunsaturated fatty acid‐based oils. The
fatty acid composition of triglycerides is presented as a proportion of
individual fatty acids, expressed in percentages (Table 1). It should be
noted that, in general, differences in the triglyceride composition are
ET AL.
expected to range from 5% to 10% for vegetable butters and oils of
different origin.
3 | S A T U R A T E D F A T T Y A C I D‐ B A S E D
BUTTERS/OILS
3.1 | Coconut oil
Coconut oil obtained from the seeds of mature coconuts (Cocos
nucifera L., Arecaceae) is an edible oil with various applications, includ-
ing as an ingredient in dermal formulations. Coconut oil is composed of
lauric (48%), myristic (18%), palmitic (9%), caprylic (8%), capric (7%),
oleic (6%), linoleic (2%), and stearic (3%) acids. Because it mostly con-
sists of saturated fatty acids (78% in total), it is characterized as an oxi-
datively stable vegetable oil (Janeš & Kočevar Glavač, 2018). Its
content in dried seeds ranges between 30% and 60% (Fontanel,
2013; Janeš & Kočevar Glavač, 2018).
Applying cold‐pressed coconut oil to skin wounds in young rats
once a day for 10 days resulted in faster epithelization, which in turn
resulted in faster wound healing than was observed in the untreated
wounds of a control group. A histopathological examination of exci-
sion wounds revealed increased neovascularization, fibroblast prolifer-
ation, pepsin‐soluble collagen synthesis, and a significant increase in
the collagen content in wounds treated with the oil. They also healed
much faster, as indicated by a decrease in the time required for com-
plete epithelization and higher levels of glycosaminoglycans, proteins,
hexose, sialic acid, and elastin in the granulation tissue (Nevin &
Rajamohan, 2010).
3.2 | Mango butter
Butter from the seeds of mango (Mangifera indica L., Anacardiaceae),
also referred to as mango oil, is valued for its significant potential as
a cosmetic ingredient. It is considered a possible replacement for
cocoa butter and mineral‐based emollients (Cornily et al., 2010; Dhara,
Bhattacharyya, & Ghosh, 2010). The content of mango oil in dried
seeds ranges between 4% and 13% (Fontanel, 2013; Janeš & Kočevar
Glavač, 2018). Its fatty acid profile consists mainly of oleic (42%),
stearic (40%), and palmitic (8%) acids, which account for up to 50%
of the saturated fatty acid profile (Dhara et al., 2010; Janeš & Kočevar
Glavač, 2018). Literature presents its bacteriostatic and anti‐
inflammatory activities, indicating its use as a curative and protective
ingredient (Cornily et al., 2010).
A foot care cream was formulated as an oil/water emulsion system
containing 25% (w/w) of mango butter and olein fraction and 60% (w/
w) of an aqueous phase (Mandawgade & Patravale, 2008). A primary
irritation study on intact rabbit skin was performed using a draize‐
repeated insult patch test. The foot care cream was applied once a
day for 7 days. No irritation or sensitivity was observed. The same
was shown in an 8‐week clinical study on human volunteers. The com-
plete repair of cracked skin was observed in all volunteers. Antiseptic,
healing, soothing, and cooling activities were observed in most
TABLE 1 Vegetable oils, their fatty acid composition, and unsaponifiable matter content; individual fatty acids were only included when their content was at least 10% in at least one of the listed
oils
POLJŠAK

Lauric
ET AL.

acid Myristic Palmitic Stearic PalmitoleicOleic Erucic Linoleic α‐Linolenic Punicic unsaponifiable
[%] acid [%] acid [%] acid [%] acid [%] acid [%] acid [%] acid [%] acid [%] acid [%] Saturated Monounsaturated Polyunsaturated matter
Chain length: number of C18:1, C 22:1, C18:2, C18:3, C 18:3, fatty acids fatty acids fatty acids [g/100g oil]
unsaturated bonds C12:0 C14:0 C16:0 C18:0 C16:1, ω−7 ω−9, cis ω‐9 ω−6, cis ω−3, cis ω‐5 (SFA) [1] (MUFA) [1] (PUFA) [1] [1], [2]

Cocos nucifera [1] 48 18 9 3 6 2 78 6 2 0.02–1.5

Mangifera indica [1], [3] 8–9 40–41 41–43 7 48–50 41–43 7 0.9–3
Olea europaea [1], [4] 12 2 1 73 9 14 74 9 0.6–3
Prunus amygdalus dulcis 5.2–7.4 0.2–2.2 0.3–0.6 65–77.8 13.5– 0–0.7
oil [26], [27] 25.5
Prunus armeniaca kernel 5.6–7.7 1–2 0.6–1.2 64–73 19.5– 0.2–0.4
oil [28] 22.8
Persea americana [1], [5] 16–24 7 47–60 13–14 1 16 67 15 0.4–12.2
Brassica napus [1], [6] 4 1 46–63 15 19–20 10 5 65 29 0.5–5
Butyrospermum Parkii 3–5 30–45 40–60 4.5–7 0.1–0.2
Butter [22]
Pistacia lentiscus [7] 24 1.4 1.2 51 21 26 53 21 1–5.6
Hippophae rhamnoides 29–36 1 36–48 4‐6 10–12 1 37 48 13 0.–0.9
pericarp oil [1], [8]
Lupinus Albus Oil [24] 7–18.5 1.5–4 0.3–0.8 41–53 0.5‐1.5 10–20 4.8–9.2
[25]
Argania spinosa [1], [9] 14 6 45 35 20 45 35 0.7–1
Calophyllum inophyllum 13–15 14–17 40 28‐31 32 40 28 0.7–2
[1], [10]
Punica granatum [1], 3 3 7 3 80 6 8 83 0.7–5
[11], [12]
Hippophae rhamnoides 7 2 13 36 38 9 15 74 1.2–2
seed oil [1]
Linum usitatissimum[1], 7 5 15–20 14–18 50–60 12 16 72 0.2–1.1
[6], [13]
Vitis vinifera [1], [14], 7 4 17–20 66–75 11 17 71 0.3–2
[15]
Soybean [23], [24] 10–13 3–5 18–27.5 50–57 7–10
Vaccinium macrocarpon 5 1 25 38–45 22–30 6 25 68 1.9
[1], [16]

(Continues)
3
 4 POLJŠAK ET AL.

patients. The emollient effect of the emulsion left the skin looking

Note. The content of individual components is based on the results of different scientific sources listed in the reference section. It is possible that results vary from study to study, as environmental factors have a
unsaponifiable
smooth and hydrated. In an in vivo study of wound repair in Wistar

not available
[g/100g oil]
rats, the foot‐care cream showed significantly better wound closure

0.6–1.5

0.6–2.5

0.7–1.2
7.6–15
matter

[1], [2]
than two control creams. Moreover, complete re‐epithelization was
seen after a single daily application for 10 days. The results also indi-

significant effect on plant metabolism. Therefore, the sum of the percentages of saturated fatty acid, monounsaturated fatty acid, and polyunsaturated fatty acid content is not always 100%.
Polyunsaturated

cated minimum scar formation, whereas the skin was free of marks
fatty acids

after the treatment of skin ruptures and lesions with the foot‐care
(PUFA) [1]

cream (Mandawgade & Patravale, 2008).

58–61

The unsaponifiable matter in mango butter, which is mainly com-

57

52
48

47
39
posed of tocopherols, phytosterols, and triterpenes (Dhara et al.,
Saturated Monounsaturated

2010), significantly reduced wrinkles and skin roughness, whereas

its repairing and protecting properties open up possibilities for the
(MUFA) [1]
fatty acids fatty acids

formulation of sensitive skincare products (Mandawgade & Patravale,

21‐23

2008). Mango butter‐based cream was shown to provide emolliency,

31

20
11

34
28
which rebuilds the skin's protective lipid barrier and actively replen-
ishes moisture (Janeš & Kočevar Glavač, 2018; Mandawgade &
(SFA) [1]
17–19

Patravale, 2008).
10

28
38

17
28
acid [%]
Punicic

C 18:3,

4 | M O N O U N S A T UR A T E D FA T T Y
ω‐5

A C I D ‐B A S E D B U T T E R S / O I L S
α‐Linolenic

ω−3, cis
acid [%]
C18:3,

4.1 | Olive oil

6–8

0.4
2

2
2

Olive oil is obtained from the fruits of the olive tree (Olea europaea L.,
ω−6, cis
acid [%]
Linoleic

50–59

47–51
C18:2,

50‐53

45.3

Oleaceae). It has been used for a long time in several cultures as a skin
55

46

39

and hair cosmetic ingredient. More than 200 different chemical com-
acid [%]
C 22:1,

pounds have been identified in olive oil, the dried fruit content of
Erucic

ω‐9

which ranges from 30% to 44% (Fontanel, 2013). The main proportion
is accounted for by triglycerides of oleic acid (73% to 78%) as the pre-
C16:1, ω−7 ω−9, cis
acid [%]

19–21

20–24

26–34
C18:1,

dominant fatty acid (Berasategi, Barriuso, Ansorena, & Astiasarán,

Oleic

36.8
30

11

28

2012; Janeš & Kočevar Glavač, 2018). Olive oil functions as an antiox-
idant due to phenols (e.g., hydroxytyrosol and oleuropein), which were
Palmitoleic
acid [%]

shown to have higher antioxidative properties than vitamin E (Visioli,

Bellomo, & Galli, 1998). The consumption of olive oil exhibits anti‐
inflammatory properties (Nasopoulou et al., 2014).
acid [%]
Stearic

The healing of pressure ulcers improved after the daily oral appli-
C18:0

3.7

cation of cold‐pressed olive oil for 14 days in an in vivo study on

1

4
8

6
9

mice. This was achieved through anti‐inflammatory effects, the

acid [%]
Palmitic

11–13

11–15
C16:0

reduction of oxidative damage, and the promotion of dermal recon-

9.4
17

30

19

struction. Olive oil was found to reduce the synthesis of nitric oxide
6

and reactive oxygen species and reduce oxidative damage. Collagen

Myristic
acid [%]

C14:0

deposition, myofibroblastic differentiation, and wound contraction

11

were also accelerated by the oral administration of olive oil

Lauric

C12:0

(Donato‐Trancoso, Monte‐Alto‐Costa, & Romana‐Souza, 2016).

acid
[%]

In a randomized, double‐blind, comparator‐controlled, parallel‐

Chain length: number of

group clinical study, 60 patients with chronic wounds were treated

Triticum vulgare (wheat)

Cucurbita pepo [1], [20]

Coffea arabica [1], [19]
Nigella sativa [1], [18]

Pouteria lucuma [21]

(Continued)

twice a day through either the application of a cream containing aloe

unsaturated bonds

Helianthus annuus

Sesamum Indicum

vera and olive oil (composition not available) or phenytoin cream, as

germ Oil [29]

the standard treatment, for a period of 30 days. The wound size,

[1], [17]

Oil [24]

depth, and edges, together with the associated pain, were signifi-
TABLE 1

cantly reduced by both treatments. However, the aloe vera and olive
oil cream was more effective (Panahi et al., 2015).
POLJŠAK ET AL.
The healing effect of cold‐pressed olive oil was evaluated in com-
parison with the lyophilized powder of sea buckthorn leaf aqueous
extract and a silver sulfadiazine and saline (control) group on full‐
thickness burn wounds in rats. Wound contraction was observed for
28 days and occurred faster in groups treated with olive oil, sea buck-
thorn extract, and a mixture of sea buckthorn extract and olive oil than
in the silver sulfadiazine and saline group. Using a mixture of olive oil
and sea buckthorn extract, a synergistic effect was observed, which
resulted in improved wound‐healing characteristics and antibacterial
effects (Edraki et al., 2014).
A traditional Iranian olive oil ointment (a mixture of olive oil, ses-
ame oil, and honey) was tested in a randomized controlled clinical
study including 30 patients. The control group was treated with a
mafenide acetate ointment (8.5%). It was concluded that the olive oil
ointment was a useful treatment for burns, as it prevented infections
and accelerated tissue repair. The mean time of granulation tissue for-
mation in the olive oil ointment group was 12 days, whereas it was
17 days for the mafenide acetate group (Zahmatkesh, Manesh, &
Babashahabi, 2015).
The positive effects of olive oil in promoting wound healing are
probably the result of the modulation of early phases such as inflam-
mation and the stimulation of dermal reconstruction (Nasopoulou
et al., 2014). Evidence suggest, however, that dermally applied olive
oil disrupts the stratum corneum integrity and impairs the skin's nor-
mal lipid barrier function (Danby et al., 2013; Darmstadt et al., 2002;
Jiang & Zhou, 2003) by changing the lipid ordering (T.‐K. Lin et al.,
2017), which is assumed to be due to oleic acid.
4.2 | Avocado oil
Avocado oil is obtained from the pericarp of the avocado fruit. The
avocado tree (Persea americana Mill., Lauraceae) was domesticated
in Meso‐America (Chen, Morrell, Ashworth, de la Cruz, & Clegg,
2008) but has since spread throughout the world in tropical and Med-
iterranean climates. The content of avocado oil in the dried pericarp
ranges from 40% to 80% (Fontanel, 2013; Janeš & Kočevar Glavač,
2018). The main fatty acids in avocado oil triglycerides are monounsat-
urated and polyunsaturated fatty acids (76%), such as oleic (47 to 60%)
and linoleic acids (13.5%), but there is also up to approximately 24% of
palmitic acid (de Oliveira et al., 2013; Janeš & Kočevar Glavač, 2018).
Studies primarily focus on the effects of avocado extract and avocado
oil and their use in wound healing, psoriasis, wrinkles, and stretch
marks (de Oliveira et al., 2013; B. S. Nayak, Raju, & Chalapathi Rao,
2008). The unsaponifiable matter of avocado oil was proven to induce
the regeneration of the epidermis and improve scleroderma (de
Oliveira et al., 2013).
The wound‐healing activity of hexane‐extracted avocado oil on
incisional and excisional skin wound models in Wistar rats was evalu-
ated in an in vivo study. The oil was dermally applied once a day for
14 days. The results showed that avocado oil, used alone or in a der-
mal formulation (50% avocado oil in petrolatum), increased collagen
synthesis and reduced the number of inflammatory cells throughout
5
the wound‐healing process (de Oliveira et al., 2013; Lamaud et al.,
1982).
4.3 | Rapeseed oil
Rapeseed (Brassica napus L., Brassicaceae) is a source of vegetable oil
for both nonfood and food uses (L. Lin et al., 2013). The oil content of
dried seeds ranges from 34% to 60% oil (Fontanel, 2013; Janeš &
Kočevar Glavač, 2018). Nowadays, canola oil (rapeseed oil low in
erucic acid) is the third most important vegetable oil by volume after
palm and soybean oils (L. Lin et al., 2013). Rapeseed oil mostly com-
poses of monounsaturated fatty acids (63%) and consists of 46% to
63% oleic acid, 19% to 20% linoleic acid, and 10% α‐linoleic acid (Janeš
& Kočevar Glavač, 2018; Lewinska et al., 2015).
The biological effects of cold‐pressed rapeseed oil were tested
in vitro on fibroblast cells, in comparison with linseed oil (for the latter,
see the linseed oil section; Lewinska et al., 2015). A scratch wound‐
healing assay was performed to study the ability of the oils to promote
wound healing in vitro. Rapeseed oil stimulated fibroblast proliferation
and promoted the migration of fibroblasts to the wounded area, indi-
cating a wound‐healing activity. For all studied parameters, however,
the observed effects were more pronounced when using linseed oil
(Lewinska et al., 2015).
4.4 | Lentisk oil
Lentisk (Pistacia lentiscus L., Anacardiaceae) is an evergreen shrub or
tree that grows in several Mediterranean regions (Wissal et al.,
2013). The fruits, galls, resin, and leaves of the lentisk have been tradi-
tionally used for skin problems (Abdeldjelil, Bensegueni, Messaï,
Agabou, & Benazzouz, 2014) since the time of the ancient Greeks
(Charef, Yousfi, Saidi, & Stocker, 2008). The content of the oil in the
dried fruit ranges from 10% to 50% (Fontanel, 2013). Lentisk oil tri-
glycerides are mainly composed of monounsaturated fatty acids
(52.4%), followed by saturated fatty acids (26.4%) and polyunsaturated
fatty acids (21.2%). The major fatty acid is oleic (51.1%), followed by
linoleic acid (20.7%; Wissal et al., 2013).
A study on six adult male New Zealand rabbits was performed to
assess the efficacy of cold‐pressed lentisk oil for the healing of deep
third‐degree burn wounds,. Each animal received four burn wounds
on the back. The first wound was not treated, whereas the others
were treated immediately after the burning procedure using Vaseline,
Madecassol cream (1% of dry extract of Centella asiatica containing
40% asiaticoside and 60% madecassic acid; 1g/100g cream), or lentisk
oil. After 4 days of treatment, the results showed that both the lentisk
oil and the Madecassol cream significantly accelerated wound healing
compared with wounds treated with Vaseline and the untreated
wounds. Wound contraction was significantly better and the healing
time faster in the lentisk oil group (30 days) than those of all other
groups (33.5 days for Madecassol group, 34.7 days for Vaseline group,
and 37.2 days for the untreated group; Djerrou et al., 2010).
6 POLJŠAK
4.5 | Sea buckthorn pericarp oil
Sea buckthorn (Hippophae rhamnoides L., Elaeagnaceae) is a branched
and thorny shrub native to Europe and Asia. Its leaf extract is known
for its extensive use in traditional oriental medicine for the treatment
of asthma, skin diseases, gastric ulcers, and lung disorders (Nitin K.
Upadhyay, Kumar, Siddiqui, & Gupta, 2011). The oil is produced from
the seeds and fruit pericarp. The oil content in dried seeds is between
7% and 15%, where in fresh seeds, the content is around 4% to 8%.
The oil content in the pericarp ranges from 2% to 3% (Fontanel,
2013; Janeš & Kočevar Glavač, 2018).
The two oils have very different chemical compositions. Sea buck-
thorn pericarp oil is a rich source of saturated palmitic acid (29% to
36%) and omega‐7 unsaturated palmitoleic acid (36% to 48%), which
is known to promote the epithelization of the skin and mucosal tissue.
There are also significant contents of linoleic (10% to 12%) and oleic
(4% to 6%) acids (Ito et al., 2014; Janeš & Kočevar Glavač, 2018). Peri-
carp oil has a typical orange colour due to its extremely high content of
carotenoids (Janeš & Kočevar Glavač, 2018). On the other hand, sea
buckthorn seed oil contains high amounts of α‐linolenic fatty acid
(38%), together with linoleic (36%), oleic (13%), and palmitic (7%) acids
and a significant amount of carotenoids. Because seed oil contains
more polyunsaturated fatty acids, studies of that oil are discussed sep-
arately in the polyunsaturated fatty acid‐based oil section.
Burn patients in China were treated with a sea buckthorn pericarp
oil dressing, whereas the control group was treated with petrolatum.
Patients treated with sea buckthorn pericarp oil showed statistically
significant faster wound healing, exudation reduction, pain relief, and
faster epithelial growth than the control group (Wang, Luo, & He,
2006). Pericarp oil was proven to act as an antioxidant, anti‐
inflammatory, and regenerative agent (Janeš & Kočevar Glavač, 2018).
4.6 | Argan oil
Argan oil is obtained from the seeds of the argan tree (Argania spinosa
L., Sapotaceae). It has been traditionally used in Morocco for centuries
in diets and cosmetics and against skin infections (Guillaume &
Charrouf, 2011). The oil content in dried seeds ranges from 50% to
55% (Fontanel, 2013; Janeš & Kočevar Glavač, 2018). The oil is rich
in oleic (45%), linoleic (35%), and palmitic (14%) acids, with 45% mono-
unsaturated and 35% polyunsaturated fatty acids (Boucetta, Charrouf,
Derouiche, Rahali, & Bensouda, 2014; Janeš & Kočevar Glavač, 2018).
Argan oil has also been recognized to be effective in enhancing the
healing of burns in an in vivo experiment using rats after dermal applica-
tion for 14 days. The group receiving argan oil showed significantly
increased mRNA levels of transforming growth factor beta 1 and had a
greater contraction rate than the silver sulfadiazine group. Histopatho-
logical assessments showed improved healing in both groups compared
with the control group with no topical agent (Avsar et al., 2016).
The daily dermal application of argan oil for 60 days on postmeno-
pausal women was shown to restore the impaired barrier function of
the skin, as it significantly reduced transepidermal water loss (Boucetta
et al., 2014).
ET AL.
4.7 | Calophyllum oil
Calophyllum (Calophyllum inophyllum L., Calophyllaceae) is an ever-
green tree found on the seashores and islands of the Indian and Pacific
Oceans. Oil obtained from the seeds, also called Tamanu oil, is tradi-
tionally used dermally in French Polynesia to treat skin injuries (burns,
scars, and infected wounds) and diseases (dermatosis, urticaria, and
eczema; Ansel et al., 2016; Léguillier et al., 2015). In Vietnam, the oil
has been used as a traditional medicine to treat burns, skin‐related
and rheumatic diseases, and insomnia (Nguyen et al., 2017). The oil
content of dried seeds ranges from around 30% to 75% (Fontanel,
2013; Janeš & Kočevar Glavač, 2018). It is composed mostly of unsat-
urated fatty acids (71%), as well as saturated fatty acids (29%). The
most represented fatty acids in triglycerides are oleic (40%), linoleic
(28% to 31%), stearic acid (14% to 17%), and palmitic (13% to 15%)
acids (Crane, Aurore, Joseph, Mouloungui, & Bourgeois, 2005; Janeš
& Kočevar Glavač, 2018). Calophyllum oil is characterized by its spe-
cific composition of unsaponifiable matter, which accounts for around
2% of calophyllum oil (Crane et al., 2005).
Five calophyllum oils from Indonesia, Tahiti, the Fiji Islands, and
New Caledonia were studied for their cytotoxic, wound‐healing, and
antibacterial properties. The oils accelerated in vitro wound closure
in a scratch test assay on human keratinocytes and expressed antibac-
terial effects (Léguillier et al., 2015).
Another study investigated the effect of cold‐pressed calophyllum
oil emulsion (the oil was emulsified with an equal amount of commer-
cial monolinolein and sterically stabilized using a polyethylene and
polypropylene oxide triblock copolymer) on human skin cells (epider-
mal keratinocytes and dermal fibroblasts). The results showed
increased cell proliferation, glycosaminoglycan and collagen produc-
tion, and wound‐healing capacity on a scratched fibroblast monolayer
(Ansel et al., 2016).
The unsaponifiable matter of calophyllum oil contains diverse bio-
active compounds, including coumarins, xanthones, flavonoids, ste-
roids, and triterpenoids (Praveena, 2013; Tsai et al., 2012).
Calophyllolide, a coumarin, was reported to have anti‐inflammatory,
anticoagulant, antimicrobial, and anticancer properties (Nguyen et al.,
2017). In a mouse model, calophyllolide reduced fibrosis formation
and promoted wound closure through anti‐inflammatory mechanisms,
such as the regulation of inflammatory cytokines, a reduction in tissue
myeloperoxidase, and the activation of macrophages (Nguyen et al.,
2017).
5 | P O L Y U N S A T U R A T E D FA T T Y
ACID‐BASED OILS
5.1 | Pomegranate oil
Pomegranate oil comes from the seeds of Punica granatum L,
Lythraceae, an ancient fruit tree species traditionally cultivated in the
Near and Middle East (Baumann, 2007; Ismail, Sestili, & Akhtar,
2012). Dry seeds contain from 4% to 27% (Fernandes et al., 2015;
POLJŠAK ET AL.
Fontanel, 2013 ; Janeš & Kočevar Glavač, 2018) of oil, which is mainly
composed of polyunsaturated fatty acids (86% to 90%; Liu et al.,
2018). The main fatty acid in triglycerides is punicic acid (77% to
84%), a conjugated linolenic acid typical for pomegranate oil (Amri
et al., 2017; Fernandes et al., 2015; Janeš & Kočevar Glavač, 2018).
Punicic acid inhibits prostaglandin and leukotriene biosynthesis and
acts as a cytotoxin for cancer w2a cells (Schubert, Lansky, & Neeman,
1999). Pomegranate oil is also valued for its content of polyphenolic
compounds and for its antioxidative and anti‐inflammatory properties
(T.‐K. Lin et al., 2017).
The penetration enhancement effect of pomegranate oil, compared
with isopropyl palmitate, on the transdermal absorption of resveratrol
was studied on the abdominal skin of pigs. Pomegranate oil acceler-
ated resveratrol permeation through the skin better than isopropyl pal-
mitate (Liu et al., 2018).
Cold pressed pomegranate oil was examined for its effects on
human epidermal keratinocytes and human dermal fibroblasts. The
oil was shown to stimulate keratinocyte proliferation in a monolayer
culture. There was no effect, however, on the fibroblast function. In
a skin organ culture, a mild thickening of the epidermis, without the
loss of ordered differentiation, was noted. In contrast, an aqueous
extract of pomegranate exocarp was shown to stimulate dermal fibro-
blast proliferation and collagen synthesis while inhibiting the major
collagen‐degrading enzyme in the skin. An aqueous extract did not
stimulate keratinocyte proliferation. The results suggested that pome-
granate seed oil promotes the regeneration of the epidermis (Aslam,
Lansky, & Varani, 2006).
5.2 | Sea buckthorn seed oil
The sea buckthorn plant and its oils were previously described in the
sea buckthorn pericarp oil section. Here, only seed oil studies are
presented.
An in vivo animal study on five adult sheep with flame burns inves-
tigated the efficacy of sea buckthorn seed oil on burn wound healing
for 21 days. The results showed that complete epithelization time
was shorter than that of the untreated group. It was concluded that
the oil has significant wound‐healing activity in full‐thickness burns
and split thickness harvested wounds (Ito et al., 2014).
The safety and efficacy of supercritical CO2 extracted sea buck-
thorn seed oil on a burn wound model in rats were studied. The oil
was coapplied orally and dermally for 7 days on experimental burns.
Wounds in the control group were untreated, whereas wounds in
the reference group were treated with a silver sulfadiazine ointment.
Sea buckthorn seed oil improved the wound‐healing process: There
were significant increases in wound contraction, hydroxyproline,
hexosamine, DNA, and total protein contents and an expression of
matrix metalloproteinases (MMP‐2 and 9), collagen Type‐III, and vascu-
lar endothelial growth factor in the granulation tissue. Antioxidative
properties were also observed, as seen in a significant increase in
reduced glutathione level and the reduced production of reactive oxy-
gen species in the granulation tissue. There was no associated toxicity
or side effects (N.K. Upadhyay et al., 2009).
7
5.3 | Linseed oil
Linseed or flax (Linum usitatissimum L., Linaceae) is a widely used crop
plant in the food and textile industries. Dried seeds contain between
30% and 45% of linseed oil (Fontanel, 2013; Janeš & Kočevar Glavač,
2018), which is mainly composed of polyunsaturated fatty acids (70%):
50% to 60% α‐linolenic, 17% linoleic, and 15% to 20% oleic acid (Janeš
& Kočevar Glavač, 2018; Lewinska et al., 2015). Its high omega‐3 to
omega‐6 fatty acid ratio is responsible for the oil's beneficial health
effects (Basch et al., 2007).
As mentioned in the rapeseed oil section, the biological effects of
cold‐pressed linseed oil were tested in vitro on fibroblast cells, in com-
parison with rapeseed oil (Lewinska et al., 2015). Two linseed oils were
used. The fatty acid composition of linseed oil triglycerides was
analysed by gas chromatography with a flame ionization detector
(GC). That analysis showed the following: 50.7% and 58.3% α‐linolenic
acid, 16.5% and 17.8% linoleic acid, and 15.8% and 20.0% oleic acid
(Ramos, Fernández, Casas, Rodríguez, & Pérez, 2009). The results
showed that both oils possess a wound‐healing activity. They pro-
moted cell proliferation and improved the migration of fibroblasts to
the wounded area (Lewinska et al., 2015).
An in vivo study on rabbits was performed to assess the effect of
linseed oil application on the healing of burn wounds, in comparison
with untreated wounds, wounds treated with petrolatum, and those
treated with Cicatryl Bio ointment (composition: allantoin [1%],
guaiazulene [0.007%], p‐chloro‐m‐cresol [0.120%], α‐tocopheryl ace-
tate [0.010%], methylparaben, propylparaben, light liquid paraffin, pet-
rolatum, cetostearyl alcohol, sodium cetearyl sulphate, ethoxylated
fatty acid, glycerol monostearate, macrogol glycol 400, sorbitol, and
purified water). Dermal applications were performed daily for 28 days.
Throughout the study, burns treated with linseed oil were found to be
healing faster and showed significantly higher wound contraction than
the control treatments. Less inflammatory cells, complete epithelial
regeneration with a reduced thickness of the newly formed dermis,
fibrosis, enhanced neovascularisation, and an increased number of col-
lagen fibres, fibroblasts, and myofibroblasts were observed in wounds
treated with linseed oil (Beroual et al., 2017).
The effects of cold‐pressed linseed oil alone and a semisolid formu-
lation containing cold pressed linseed oil (petrolatum as a vehicle with
1%, 5%, or 10% linseed oil) on skin wounds in incisional and excisional
rat wound models were studied for 14 days. Re‐epithelialization of
100% was seen for the semisolid formulation with 1% and 5% linseed
oil, whereas re‐epithelialization was only 65%, 50%, and 33.33%,
respectively, in animals treated with linseed oil alone, with a semisolid
formulation containing 10% linseed oil and in the petrolatum control
group, (Franco et al., 2012). It is therefore possible that higher concen-
trations of linseed oil actually slow the healing effect.
In another study on rats, partial‐thickness burns were dermally
treated daily with pumpkin, linseed or prickly pear cold‐pressed oils,
saline (control group), or Cytol Basic emulsion (reference group; com-
position: aqua, glyceryl stearate, grape oil, propylene glycol, stearic
acid, squalane, mineral oil, triethanolamine, allantoin, cetyl palmitate,
tocopheryl acetate, disodium EDTA, retinyl palmitate, and fragrance).
8 POLJŠAK
A histological examination showed that the oils caused complete tis-
sue healing, whereas complete healing was also achieved in the refer-
ence group. However, thick retracted sclerotic tissue was observed,
together with the persistence of intradermal inflammation. The persis-
tence of an active inflammatory lesion with necrosis of the epidermis
and the dermis associated with inflammatory cell infiltration in the
underlying tissue was observed in the control group. The dermis of
the control group revealed the presence of edema and hyperemia of
capillary blood vessels. The use of vegetable oils showed significant
improvements over the control and reference groups during the study
for both general wound appearance and crusting. The collagen content
in the skin of the group treated with prickly pear was found to be sig-
nificantly greater than that in all other groups (Bardaa et al., 2016).
5.4 | Grape oil
Another widely used edible berry is the grape, a fruit of the deciduous
woody vines of the flowering plant Vitis vinifera L., Vitaceae, wine
grape. Its dried seeds contain from 10% to 16% grape oil (Fontanel,
2013; Janeš & Kočevar Glavač, 2018). In cold pressed grape oil, linoleic
acid (polyunsaturated fatty acid) is the most abundant fatty acid in tri-
glycerides, with a content ranging from 66% to 75%, followed by oleic
(20%), palmitic (7%), and stearic (4%) acids (Garavaglia, Markoski,
Oliveira, & Marcadenti, 2016; Janeš & Kočevar Glavač, 2018; Moalla
Rekik et al., 2016).
A study using an excision wound model on rats showed the effi-
cacy of grape oil to reduce wound size, increase the content of
hydroxyproline in the granulation tissue, and promote the formation
of a dense matrix of collagen fibres. Triglycerides or the respective
fatty acids, as well as polyphenol compounds (191mg/kg; Moalla Rekik
et al., 2016), may be responsible for wound healing. The results were
significant compared with control groups (petrolatum and antibiotic
mupirocin). However, the observed effects were more pronounced
when using cranberry oil (Shivananda Nayak et al., 2011).
Uniform excision wounds were made on rats' dorsum. The animals
were randomly divided into five groups treated with CICAFLORA
cream, grape oil (19.8% oleic acid and 69.3% linoleic acid), sesame oil
(40.2% oleic acid and 41.9% linoleic acid), and fenugreek oil (19.2%
oleic acid, 37.7% linoleic acid, and 27.4% α‐linolenic acid) and an
untreated group. The post‐healing biopsies of wounds treated with oils
showed the best tissue regeneration compared with both control
groups. The groups treated with oils and CICAFLORA cream showed
better wound contraction compared with untreated wounds. Polyun-
saturated fatty acids in oils were assumed to act as inflammatory medi-
ators and increase neovascularization, extracellular remodelling, and
migration and cell differentiation, whereas the antibacterial and antiox-
idative activities of vegetable oils may contribute synergistic effects
(Moalla Rekik et al., 2016).
5.5 | Cranberry oil
Cranberry (Vaccinium macrocarpon Aiton, Ericaceae) is a low‐creeping
shrub with small evergreen leaves and dark pink flowers. The fruit is a
ET AL.
red edible berry that is an important commercial crop in North America
(Fontanel, 2013; Janeš & Kočevar Glavač, 2018). Cold‐pressed oil from
cranberry seeds contains about 8% saturated fatty acids and 67%
polyunsaturated fatty acids in triglycerides, with 38% to 45% linoleic
and 22% to 30% α‐linolenic acids (Chemistry, 2006; Janeš & Kočevar
Glavač, 2018).
Cold‐pressed cranberry oil was evaluated for its wound‐healing
activity in comparison with cold‐pressed grape oil (for the latter, see
the grape oil section; Shivananda Nayak et al., 2011). An excision
wound model in rats was used. Petrolatum served as a control,
whereas antibiotic mupirocin ointment served as a reference. Animals
treated with cranberry oil showed a significant reduction in wound size
and a significant increase in the content of hydroxyproline in the gran-
ulation tissue, whereas a histological examination of the granulation
tissue showed a dense collagen fibre matrix, indicating increased colla-
gen deposition. It was also assumed that polyphenols in the
unsaponifiable matter may significantly contribute to the overall
wound‐healing activity of cranberry oil due to their proven antimicro-
bial, anti‐inflammatory, and antioxidative effects (Gupta, Singh, &
Raghubir, 2002; Shivananda Nayak et al., 2011).
5.6 | Sunflower oil
The common sunflower (Helianthus annuus L., Asteraceae), first
domesticated in the Americas, is a large annual forb grown as a crop
for its edible oil and fruits. Sunflower oil is used worldwide in food
and cosmetics. Its content in the dried achene is approximately 50%
(Fontanel, 2013; Janeš & Kočevar Glavač, 2018). It mainly consists of
linoleic (55%) and oleic (30%) acids in triglycerides (Janeš & Kočevar
Glavač, 2018; Sugawara & Nikaido, 2014). However, it should be men-
tioned that there are three different types of sunflower oil on the mar-
ket: low oleic (original), mid‐oleic (NuSun), and high‐oleic sunflower oil.
As indicated by their names, they mostly differ in their triglyceride
fatty acid composition. Original sunflower oil consists of approximately
70% linoleic acid and 20% oleic acid, whereas NuSun consists of 26%
linoleic acid and 65% oleic acid, and high‐oleic oil consists of 9%
linoleic acid and 82% oleic acid (Sugawara & Nikaido, 2014).
Clinical studies have reported the beneficial effects of sunflower oil
in the treatment of atopic dermatitis (Eichenfield, McCollum, & Msika,
2009; Foster, Hardy, & Alany, 2010). After applying six drops of the oil
twice a day for 5 weeks on the forearm of adult skin, the oil demon-
strated the ability to preserve the stratum corneum integrity and pre-
vent transepidermal water loss without inducing erythema, compared
with untreated skin. Sunflower oil was also shown to reduce the sever-
ity of atopic dermatitis and hydrate the skin (Danby et al., 2013).
To study the effects of sunflower oil in the treatment of skin
wounds, two 4‐cm2 wounds on each side of the thoracic region were
surgically made on 18 male lambs. They were treated with sunflower
oil (65% linoleic acid), whereas sterilized Vaseline was used as a con-
trol. Wounds were checked on the 7th, 14th, and 21st day. The dermal
application of sunflower oil accelerated the healing process at the 7th
and 21st days. The results were statistically significant: The wound
area was smaller and wound contraction was higher, whereas
POLJŠAK ET AL.
granulation tissue increased faster, and the epidermis was completely
recovered, compared with control wounds (Marques et al., 2004).
5.7 | Black cumin oil
Black cumin (Nigella sativa L., Ranunculaceae) is an annual herbaceous
plant that grows in the Mediterranean, Iran, Pakistan, and India. Black
cumin seeds are widely used in traditional Islamic medicine and for
culinary purposes worldwide (Ali & Blunden, 2003). The oil content
of dried seeds is around 30% to 40% (Fontanel, 2013; Janeš & Kočevar
Glavač, 2018). Its triglyceride composition typically consists of approx-
imately 83% unsaturated fatty acids and 17% saturated fatty acids,
with the predominant acids being linoleic (50% to 59%), oleic (20%
to 24%), and palmitic (11% to 13%) acids (Gharby et al., 2015; Janeš
& Kočevar Glavač, 2018). The seeds also contain volatile substances
(essential oil), among which thymoquinone is assumed to be responsi-
ble for the biological activity of essential oil. Thymoquinone is also
present in black cumin oil (Ali & Blunden, 2003). The seed oil has been
reported to possess anti‐inflammatory, analgesic, antipyretic, antimi-
crobial, and antineoplastic activities (Ali & Blunden, 2003).
In Indonesia, black cumin oil and aloe vera are typically used to
treat diabetic ulcers. Their efficacy in wound healing was compared
in a rat model of diabetic ulcers. The oil was used to produce a gel
(total composition: water, black cumin oil (10%), propylene glycol,
carbomer, triethanolamine, methyl paraben, and propyl paraben). Aloe
vera juice (Aloes folii succus) was prepared from fresh leaves. Wounds
treated with aloe vera juice were significantly smaller, inflammation
reduction was better, fibroblast infiltration was more abundant, and
wound re‐epithelialization was better than wounds treated with black
cumin oil gel (Sari, Purnawan, Kurniawan, & Sutrisna, 2018).
5.8 | Green coffee oil
Coffee oil is typically obtained from green coffee (Coffea arabica L.,
Rubiaceae) seeds. The oil content of dried seeds is between 11% and
16% (Fontanel, 2013; Janeš & Kočevar Glavač, 2018). The main fatty
acids in triglycerides are linoleic (46%), palmitic (30%), oleic (11%),
stearic (8%), and α‐linolenic acids (2%), accounting for 48% of polyun-
saturated fatty acids (Janeš & Kočevar Glavač, 2018; Wagemaker,
Carvalho, Maia, Baggio, & Guerreiro Filho, 2011). Green coffee oil
has a high content of unsaponifiable matter (approximately 15%),
which is responsible for lowering the oil's melting point from 40°C to
42°C (refined oil; Stevenson et al., 2007) to 8°C (nonrefined oil;
Hartman, Lago, Tango, & Teixeira, 1968).
Cold‐pressed green coffee oil was found to significantly increase
the synthesis of extracellular matrix compounds by human skin fibro-
blasts in vitro. This observed mechanism of action is due to the up‐
regulation of the production of growth factors, such as transforming
growth factor beta 1 and granulocyte‐macrophage colony‐stimulating
factor. In addition, iAQP‐3 mRNA expression was increased, thereby
improving skin hydration (Velazquez Pereda et al., 2009).
Local effects on the skin and systemic effects associated with the
dermal use of coffee oil for wound healing in rats were evaluated using
9
the oil from green coffee and roasted seeds. A 10‐day topical treat-
ment using both oils led to systemic actions and faster incision wound
healing. Animals treated with roasted coffee seed oil showed faster
wound healing, higher insulin‐like growth factor‐1, interleukin (IL)‐6,
and IL‐23 mRNA expression in the early stages of wound healing,
higher IL‐12 in the later stages, and lower serum levels of interferon
(IFN)‐γ. The oil also produced higher serum IFN‐α levels throughout
the experiment, and lower levels of IL‐4, adiponectin and IFN‐γ. Treat-
ment with green coffee seed oil led to higher IL‐6 and IL‐23 mRNA
expression in the early stages of wound treatment. Using second‐
harmonic generation microscopy, a higher collagen density was
observed for treatments using both oils than in treatments using saline
and mineral oil dermal treatments (Lania et al., 2017).
5.9 | Pumpkin seed oil
Pumpkin (Cucurbita pepo L., Cucurbitaceae) is an annual climber, and
its strongly dichromatic (Kreft & Kreft, 2007) seed oil is valued as a rich
source of diverse bioactive compounds (Stevenson et al., 2007). Dried
pumpkin seeds contain from 40% to 50% of oil, which is used in diets
and cosmetics and is high in polyunsaturated fatty acids (Fontanel,
2013; Janeš & Kočevar Glavač, 2018). An analysis of cold‐pressed oil
from pumpkin seeds showed mainly oleic (26% to 34%), linoleic (47%
to 51%), and palmitic acids (11% to 15%) in triglycerides (Bardaa
et al., 2016; Janeš & Kočevar Glavač, 2018) and tocopherols (Fontanel,
2013; Janeš & Kočevar Glavač, 2018) and phytosterols (Bardaa, Ben
Halima, et al., 2016; Janeš & Kočevar Glavač, 2018) among
unsaponifiable matter.
In an in vivo study, uniform wounds were made on the skin of 18
rats. Treatments were carried out every 2 days until the first group
was completely healed after 11 days. The results of macroscopic, mor-
phometric, and histological data showed that the skin wounds in rats
treated with pumpkin oil healed significantly better than those treated
with a saline solution or the reference group treated with Cicaflora
cream (emulsion with 10% of Mimosa tenuiflora extract). Full re‐
epithelialization was noticed in the group treated with pumpkin seed
oil (Bardaa, Ben Halima, et al., 2016).
5.10 | Lucuma oil
Lucuma is the fruit of the evergreen tree Pouteria lucuma (Ruiz & Pav.)
Kuntze, Sapotaceae, native to Peru, Chile, and Ecuador. Triglycerides
in the lucuma seed consist of linoleic (39%), oleic (28%), palmitic
(19%), stearic (9%), and γ‐linolenic (3%) acids, characterizing the oil
as high in polyunsaturated fatty acids (39%) (Rojo et al., 2010).
The effect of heptane extracted lucuma oil on fibroblast migration,
angiogenesis, inflammation, bacterial and fungal growth, and wound
healing has been studied. The results showed that lucuma oil signifi-
cantly promoted migration and vinculin expression in human fibro-
blasts and decreased lipopolysaccharide‐induced nitric oxide
production but did not have significant antibacterial or antifungal
effects. Two in vivo studies were carried out to examine lucuma oil's
effect on angiogenesis and wound healing. In the first study, tail fin
10
regeneration in transgenic zebrafish larvae, expressing enhanced green
fluorescent protein in vascular endothelial cells, was used to study ves-
sel sprouting and wound healing. In the second study, the closure of
wounds was evaluated in mice after the daily dermal application of for-
mulations containing 1.0%, 2.5%, or 5.0% lucuma oil for 10 consecu-
tive days. Wound closure was significantly faster than that achieved
in untreated wounds (Rojo et al., 2010).
6 | MECHANISMS OF ACTION
R E S P O N S I B L E F O R W O U N D ‐ HE AL ING
EFFECTS
Given the chemical composition of vegetable butters and oils, biologi-
cal effects in wound healing are expected to be expressed by triglycer-
ides, free fatty acids, glycerol, and the components of unsaponifiable
matter. These substances have been shown to directly or indirectly
affect the wound‐healing process. In published research, in which such
mechanisms were investigated, the main focus was on the triglyceride
fraction, particularly fatty acids.
Maintaining proper skin moisture and strengthening the lipid bar-
rier function of injured skin is of great importance during the wound‐
healing process. Vegetable butters and oils have been proven to effec-
tively express emollient action and thereby indirectly improve skin
hydration (Janeš & Kočevar Glavač, 2018). The prevention of the
increased transdermal water loss of the injured skin is another effect
confirmed in several studies reviewed in the previous section
(Boucetta et al., 2014; Danby et al., 2013; Mandawgade & Patravale,
2008; Velazquez Pereda et al., 2009). Direct substantiation of the
observed hydrating effect may be found in research (Patzelt et al.,
2012) showing that dermally applied vegetable oils remain on the skin
surface and form a thin semiocclusive layer that significantly decreases
transepidermal water loss. Interestingly, penetration into deeper parts
of the skin was excluded; vegetable oils were only capable of penetrat-
ing the first upper layers of the stratum corneum (Patzelt et al., 2012).
Vegetable butters and oils also show more specific mechanisms of
action. Different authors have suggested that these mechanisms are
expressed by free fatty acids. As a first example, we will focus on
the antimicrobial action. Medium‐chain saturated fatty acids have
been shown to have an antimicrobial activity (Huang, Alimova, Myers,
& Ebersole, 2011; Yoon, Jackman, Valle‐González, & Cho, 2018),
which was discovered as early as 1972 (Kabara, Swieczkowski, Conley,
& Truant, 1972). Monolaurin, a monoglyceride derived from lauric acid,
has also been shown to have an antimicrobial activity (Preuss, Echard,
Enig, Brook, & Elliott, 2005). In addition, medium‐chain monoglycer-
ides have emerged as nontraditional preservatives for use in cosmetics
(Fang, Yu, Zhang, & Wang, 2016; Herbert et al., 2013; Kočevar Glavač
& Lunder, 2018). These findings correspond to study results for coco-
nut oil, which show faster wound healing (Nevin & Rajamohan, 2010).
Coconut oil has more than 60% medium‐chain saturated fatty acids in
triglycerides (Janeš & Kočevar Glavač, 2018), of which the most abun-
dant is lauric acid (Table 1). A mice study using orally administered
hydrogenated coconut oil for 4 weeks showed that coconut oil was
POLJŠAK ET AL.
able to stimulate immune response and eliminate bacterial infection
(Puertollano, 2001). The second example discusses the role of antiox-
idative action. Reactive oxygen species (ROS) are produced during the
course of normal metabolism (the respiratory chain) and in infected,
inflamed, and wounded tissues (Schäfer & Werner, 2008). They partic-
ipate in pathogen destruction and angiogenesis and therefore play a
positive role in the wound‐healing process (Schäfer & Werner, 2008).
However, imbalance in the production of ROS in the inflammation
phase, resulting in excessive levels of ROS, generates oxidative dam-
age in lipids, proteins, and nucleic acids and leads to additional tissue
damage (Donato‐Trancoso et al., 2016; Schäfer & Werner, 2008). It
has been proposed that the antioxidative action prevents cell damage,
promotes DNA synthesis, increases vascularity, increases the strength
of collagen fibres, and improves the viability of collagen fibrils. Antiox-
idative and antimicrobial activities therefore contribute to the
improved wound‐healing process (Bardaa, Ben Halima, et al., 2016).
It is therefore reasonable to propose that vegetable butters and oils
are effective in the (supportive) therapy of wounds, as glycerides, free
fatty acids, and the compounds of unsaponifiable matter express anti-
microbial, antioxidative, and anti‐inflammatory activities.
The basis for the biological activity of vegetable butters and oils in
wound healing originates from similarities with the skin's lipids. The
three major lipids of the stratum corneum are ceramides (50%), choles-
terol (25%), and free fatty acids (10%; Janeš & Kočevar Glavač, 2018),
whereas sebum lipids comprise triglycerides (45%), wax esters (25%),
squalene (12%), free fatty acids (10%), cholesterol and other sterol
esters (4%), and diglycerides (2%; Pappas, 2009). Most fatty acids in
the stratum corneum are long‐chain saturated fatty acids (with more
than 20 carbon atom chains), whereas oleic and linoleic acids were
found to be the only unsaturated free fatty acids. The physiological
ratio between oleic and linoleic acids is 3:1 (Menon, Cleary, & Lane,
2012).
Due to similarities in the chemical composition of vegetable butters
and oils, and the skin's lipids, the proposal of Schliemann‐Willers et al.,
Darmstadt et al., and Vaughn et al. (Darmstadt et al., 2002;
Schliemann‐Willers, Wigger‐Alberti, Kleesz, Grieshaber, & Elsner,
2002; Vaughn et al., 2018) seems to be logical: They suggested that
the specific ratio between individual fatty acids may determine a veg-
etable butter's or oil's effect on lipid barrier repair. In particular, they
stressed that the ratio of oleic to linoleic acid is crucial. Oleic acid is
considered to be detrimental to the integrity of the lipid barrier
because it increases skin permeability (De Paepe, Roseeuw, & Rogiers,
2002; Elias, Brown, & Ziboh, 1980; Hansen & Jensen, 1985; Jiang &
Zhou, 2003; McIntosh, 2003; Colin Prottey, Hartop, & Press, 1975;
Tanojo, Boelsma, Junginger, Ponec, & Bodde, 1998; Viljoen, Cowley,
du Preez, Gerber, & du Plessis, 2015; Wertz, 2000), whereas linoleic
acid maintains the skin's integrity (Darmstadt et al., 2002; Hanley
et al., 1997). However, no specific ratio of oleic to linoleic acid or
between other fatty acids has been proposed yet to make a distinction
between positive and negative lipid barrier effects, as in‐depth studies
are still lacking.
Most of the vegetable triglycerides reviewed in this article are
composed mainly of unsaturated fatty acids in triglycerides (Table 1).
POLJŠAK ET AL.
Monounsaturated fatty acids are predominant in olive, avocado, and
rapeseed oils, and polyunsaturated fatty acids are predominant in sun-
flower, linseed, pomegranate, sea buckthorn, cranberry, grape, and
black cumin oils, whereas the proportions of monounsaturated and
polyunsaturated fatty acids are more similar in argan and pumpkin oils.
The main monounsaturated and polyunsaturated fatty acids found in
the reviewed vegetable oils are oleic, linoleic, linolenic, and punicic
acids.
6.1 | Oleic and linoleic acids
Oleic acid is chemically classified as a long‐chain monounsaturated
omega‐9 fatty acid (18:1, cis‐9‐octadecenoic acid). It is known as a skin
penetration enhancer, as it decreases the order of the stratum
corneum lipids and induces permeability defects, through the separa-
tion of lipid lamellar domains and/or by increasing lipid fluidity (Jiang
et al., 2000; Viljoen et al., 2015). It may also replace linoleic acid, which
is a functional component of acylceramides (C Prottey, Hartop, Black,
& McCormack, 1976). Linoleic acid (18:2, cis, cis‐9,12‐octadecadienoic
acid) is an essential omega‐6 fatty acid. In the human skin, it is found in
the phospholipids of cell membranes and in ceramides in the stratum
corneum, where it is involved in the regulation of transepidermal water
loss (Kihara, 2016; Rabionet et al., 2013; Whelan & Fritsche, 2013).
Negative effects of olive oil on the stratum corneum were con-
firmed in a randomized controlled clinical study involving 19 adults
who applied six drops of olive or sunflower oil to the forearm skin
twice a day for 4 weeks (Danby et al., 2013). Parameters of the stra-
tum corneum integrity and cohesion, intercorneocyte cohesion,
moisturisation, skin surface pH, and erythema were evaluated. Olive
oil (76.3% oleic and 4.6% linoleic acid) caused a significant reduction
in the stratum corneum integrity and thickness and induced mild ery-
thema, whereas the opposite effects were shown for the sunflower
oil group (27.3% oleic and 60.9% linoleic acid; Danby et al., 2013).
Two randomized controlled clinical studies contradict these findings.
However, they were conducted on a population of newborns. The
effect of sunflower oil on the maturation of the lipid barrier in prema-
ture babies was studied using measurements of transepidermal water
loss, stratum corneum hydration, skin pH, and sebum, compared with
a control (no vegetable oil). Sunflower oil was applied daily for 10 days
after birth on the skin of the forehead, abdomen, thigh, and buttocks.
It was concluded that oil application may impede the skin's lipid barrier
development, as transepidermal water loss increased significantly on
the abdomen, thigh, and buttocks, whereas stratum corneum hydra-
tion decreased (Kanti et al., 2014). In another study (Cooke et al.,
2016), olive oil (72.8% oleic and 10.8% linoleic acid) was applied on
full‐term baby skin twice a day for 4 weeks. Sunflower oil (29.3% oleic
and 59.2% linoleic acid) was applied to the reference group, and no
vegetable oil was used in the control group. The results showed signif-
icantly improved hydration in both oil groups, but there was a signifi-
cantly altered lipid lamellae structure compared with the control
group. No significant differences were seen in transepidermal water
loss, skin surface pH, and erythema. In the conclusion, the authors
11
stressed that the study was not powered for clinical significance and
that further research is needed to provide guidelines on baby skin care.
Despite the aforementioned negative effects, olive oil (used alone
or in combination) has been shown to be beneficial in wound healing,
as reviewed in the previous section (Donato‐Trancoso et al., 2016;
Edraki et al., 2014; Lupiáñez‐Pérez et al., 2013; Panahi et al., 2015;
Zahmatkesh et al., 2015). The main mechanism of action is assumed
to be the modulation of inflammation and stimulation of dermal recon-
struction (Nasopoulou et al., 2014). Inflammation may also be the key
process of linoleic acid activity, as it is a precursor of arachidonic acid.
The latter is metabolized into prostaglandins, thromboxanes, and leu-
kotrienes, that is, inflammatory mediators that accelerate inflammation
and enhance local neovascularization, migration and the differentiation
of fibroblasts, and the remodelling of the extracellular matrix, all of
which to the accelerated dynamics of wound healing (Bardaa, Ben
Halima, et al., 2016). Another explanation of oleic and linoleic fatty
acids' mechanism of action is through the activation of the peroxisome
proliferator‐activated receptor alpha (PPARα). PPARα is a nuclear
receptor expressed by keratinocytes. It is involved in regulating
keratinocyte proliferation, inflammation, and lipid barrier homeostasis
in response to a range of lipid metabolites. It also stimulates lipid bar-
rier development and the repair of the functional epidermis in rats and
mice (Hanley et al., 1997). It has been shown that both oleic acid and
linoleic acid accelerate the skin's lipid barrier development. However,
linoleic acid was shown to be a 10 times more potent PPARα activator
(Darmstadt et al., 2002; Hanley et al., 1997). These findings may pres-
ent a rationale for further research to confirm and establish specific
ratios of individual fatty acids in order to distinguish between their
negative and positive effects on the integrity of the skin's lipid barrier,
despite inconsistent clinical outcomes.
Finally, it is important to emphasize that, in order to express their
effects on the skin, free fatty acids must be hydrolyzed from the tri-
glyceride backbone. There is, however, to the best of our knowledge,
no information about the extent of the enzymatic hydrolysis of
dermally applied triglycerides. Lipase hydrolysis has been shown to
occur intensively in the pilosebaceous units that produce glycerol
and free fatty acids from sebum glycerides (Fluhr et al., 2003). The
existence of lipase hydrolysis by the skin's flora of microorganisms is
well known (dos Santos Rodrigues et al., 2014; Freinkel & Shen,
1969; Ro & Dawson, 2005), and there is evidence that triglyceride
hydrolysis also occurs within the stratum corneum (Fluhr et al., 2003;
Scheimann, Knox, Sher, & Rothman, 1960). However, only limited
quantitative data are available (Freinkel & Shen, 1969). It is therefore
reasonable to assume that dermally applied triglycerides, including
vegetable butters or oils, undergo similar degradation and enable
released free fatty acids to express the associated effects.
7 | CONCLUSION
Phytotherapy in dermatology is becoming an interesting alternative for
wound healing. It has been proven that therapies using vegetable but-
ters or oils are effective, with few side effects. The fatty acids of
12
triglycerides are assumed to play an important role in the skin wound‐
healing process, whereas the compounds of unsaponifiable matter may
significantly contribute to antimicrobial, antioxidative, and anti‐
inflammatory activities. In the context of overall effects, it is therefore
reasonable to recommend the use of unrefined vegetable butters and
oils because unsaponifiable matter is removed during the refining
process.
Research in this area is very rare, but increased interest has been
noted recently. This will provide us important knowledge and solid
bases for creating medical guidelines for the treatment and care of
wounded skin using vegetable butters and oils. Overall, researching
the effects of vegetable oils and their use for wound healing seems
to be supported by sound scientific rationale, as such oils are afford-
able, easily accessible, and express several important effects.
FU ND I N G I N FORM AT I ON
There were no sources of funding for this manuscript.
CONFLICT OF INTE REST
Authors declare no conflicts of interest.
OR CI D
Nina Poljšak https://orcid.org/0000-0001-6271-762X
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How to cite this article: Poljšak N, Kreft S, Kočevar Glavač N.
Vegetable butters and oils in skin wound healing: Scientific evi-
dence for new opportunities in dermatology. Phytotherapy
Research. 2019;1–16. https://doi.org/10.1002/ptr.6524