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Wound-Healing Activity of Some Species of Euphorbia L.


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Some species of Euphorbia have been used as medicinal plants to treat wounds, and skin diseases, around the world. The solvents n-hexane, ethyl acetate, and methanol were used successively to prepare extracts of the aerial parts of E. characias subsp. wulfenii, E. helioscopia, E. macroclada, E. seguieriana subsp. seguieriana, and E. virgata. Linear incision, circular excision wound models and the hydroxyproline assay method were used to assess the wound-healing activity. The inhibition of the increase in capillary permeability induced by acetic acid was used to assay the anti-inflammatory activity. The methanol extract of the aerial parts of E. characias subsp. wulfenii showed statistically significant wound-healing activity with 43.03% tensile strength for the linear incision wound model and a 65.24% reduction in the area of the wound by day 10 for the circular excision model. The tissue treated with this extract was found to contain 35.47 µg/mg of hydroxyproline. The methanol extract of E. characias subsp. wulfenii inhibited inflammation induced by acetic acid with a value of 34.74%. The results showed that the aerial parts of E. characias subsp. wulfenii possess wound-healing and anti-inflammatory activities on different models.
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The article was published by ACG Publications © March-April 2019 EISSN:1307-6167
Rec. Nat. Prod. 13:2 (2019) 104-113
Wound-Healing Activity of Some Species of Euphorbia L.
Serkan Özbilgin
, Esra Küpeli Akkol
, İpek Süntar
, Mehmet Tekin
and Gülçin Saltan İşcan
Department of Pharmacognosy, Faculty of Pharmacy, Ankara University, 06100, Ankara, Türkiye
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330, Ankara, Türkiye
Department of Pharmaceutical Botany, Faculty of Pharmacy, Trakya University, 22030, Edirne,
(Received March 15, 2018; Revised June 08, 2018; Accepted June 10, 2018)
Abstract: Some species of Euphorbia have been used as medicinal plants to treat wounds, and skin diseases,
around the world. The solvents n-hexane, ethyl acetate, and methanol were used successively to prepare extracts
of the aerial parts of E. characias subsp. wulfenii, E. helioscopia, E. macroclada, E. seguieriana subsp.
seguieriana, and E. virgata. Linear incision, circular excision wound models and the hydroxyproline assay method
were used to assess the wound-healing activity. The inhibition of the increase in capillary permeability induced by
acetic acid was used to assay the anti-inflammatory activity. The methanol extract of the aerial parts of E. characias
subsp. wulfenii showed statistically significant wound-healing activity with 43.03% tensile strength for the linear
incision wound model and a 65.24% reduction in the area of the wound by day 10 for the circular excision model.
The tissue treated with this extract was found to contain 35.47 µg/mg of hydroxyproline. The methanol extract of
E. characias subsp. wulfenii inhibited inflammation induced by acetic acid with a value of 34.74%. The results
showed that the aerial parts of E. characias subsp. wulfenii possess wound-healing and anti-inflammatory activities
on different models.
Keywords: Euphorbia; anti-inflammatory; excision; incision; wound-healing. © 2018 ACG Publications. All
rights reserved.
1. Introduction
The Euphorbia genus is the largest of the Euphorbiaceae plant family of about 2000 species,
ranging from annuals to trees. Euphorbia species contain latex and have very different flower states. An
important part of these are mostly originated from Africa or Madagascar. Ninety-one species of
Euphorbia grow in Turkey [1]. Some species of Euphorbia which are commonly known as “sütleğen”
in Turkish or “spurge” in English are used in traditional medicine to treat skin diseases, wounds, warts,
gonorrhea, migraines, and intestinal parasites in Turkey and other parts of the world [2]. The latex of
Euphorbia armena Prokh., and Euphorbia seguieriana subsp. seguieriana Necker, is used to treat
wounds and warts on the skin. The flowers of Euphorbia virgata Waldst. & Kit. are used on eczema [3-
5], Euphorbia fusiformis Buch.-Ham. ex. D.Don, Euphorbia helioscopia L., Euphorbia peplus L.
Euphorbia hirta L., and Euphorbia characias L. are used as antimicrobial and antifungal agents [6-10].
Ethnobotanical studies have shown that other species of this genus, such as Euphorbia macroclada L.
Corresponding author: E-Mail:; Phone:0090-312-2033103 Fax:0090-312-
Ozbilgin, Rec. Nat. Prod. (2019) 13:2 104-113
and Euphorbia coniosperma Boiss., were used to enhence the healing of wound and also against
scorpion and snake bites [4,11].
Plants of the genus Euphorbia have been found to contain diterpenoids with the basic skeletons
of jatrophane, lathyrane, and myrsinane [12]; ingenane, daphnane and tigliane [13]; paraliane, pepluane,
and segetane. The sesquiterpenoids clovandiol, euphanginol, euphorbioside A, and euphorbioside B
have also been reported [14]. The flavonoids kaempferol, myricetin, rutin, quercetin, and their
derivatives and phenolic compounds have been found [15], along with the volatile compounds α-
terpineol, β-caryophyllene, α-humulene, linalool, terpinene, and germacrene-D [16]. Tannins
(euphorbins), triterpenoids (lupeol, lupeol acetate, betulin, and β-amyrin) and phytosterols such as β-
sitosterol have also been reported [17].
Euphorbia species have an increasingly prevalent due to chemical compounds which have
different skeletal structure and their therapeutic importance. The results showed that Euphorbia species
have cytotoxic, antitumor, antibacterial, anti-inflammatory and anti-HIV activities [18]. Euphorbia
species also show analgesic, antidiorrheal, antifeedant, antimicrobial, antiproliferative, antipyretic, and
molluscicidal activities and the ability to modulate multidrug resistance [13-14].
The existing ethnobotanical studies covering traditional uses of Euphorbia species do not
provide scientific proof of their effectiveness. The aim of the present study is to investigate the in vivo
wound-healing and anti-inflammatory potentials of five Euphorbia species, some of which have been
used in traditional medicine. The species E. characias subsp. wulfenii (Hoppe ex W. Koch) A. R. Smith,
E. helioscopia, E. macroclada, E. seguieriana subsp. seguieriana, and E. virgata were chosen. Extracts
of the aerial parts of the selected species were prepared by using n-hexane, ethyl acetate, and methanol.
Linear incision, circular excision wound models and the hydroxyproline assay method were used to
assess the wound-healing activity. The inhibition of the increase in capillary permeability induced by
acetic acid method was used to assay the anti-inflammatory activity.
2. Materials and Methods
2.1. Plant Material
Plants of various species of Euphorbia were collected from different regions of Anatolia, Turkey
(Table 1). Taxonomic identification of the plants was confirmed by Prof. Dr. Hayri Duman at
Department of Biology, Faculty of Sciences, Gazi University, and Assoc. Prof. Mehmet Tekin at
Department of Pharmaceutical Botany, Faculty of Pharmacy, Trakya University. Voucher specimens
have been deposited in the herbarium at the Faculty of Pharmacy of Ankara University (AEF) and in the
herbarium at the Faculty of Science of Cumhuriyet University (CUFH). The localities where the plant
materials were collected and the dates when they were collected are shown along with the assigned
herbarium numbers in Table 1.
Table 1. Locality of the plants sample
Plant species Locality Altitude Date Herbarium No
E. macroclada
Çayyolu village, Yenimahalle,
Ankara 900 m 10.07.2012 AEF 26268
E. helioscopia Çomaklı village, Korkuteli, Antalya 1000 m 14.05.2012 AEF 26269
E. characias subsp.
wulfenii Yazır village, Korkuteli, Antalya 950 m 15.05.2012 AEF 26270
E. virgata Tödürge Lake, Zara, Sivas 1250 m 16.09.2012 M 1326
E. seguieriana subsp.
seguieriana İğneada, Kırklareli 250 m 21.08.2012 M 1321
2.1.1. Extraction
Air-dried and powdered aerial parts of each plant (80 g) were extracted with n-hexane (900mL
x 4) at room temperature during 8 h/day for 4 days with continuous stirring. The residues were dried
and extracted with ethyl acetate (900 mL x 4) at room temperature during 8 h/day for 4 days with
continuous stirring. These residues were dried and extracted with methanol (900 mL x 4) at room
Wound-healing activity of Euphorbia
temperature during 8 h/day for 4 days with continuous stirring. The extracts were filtered and the solvent
was removed to dryness at 50 °C under reduced pressure to yield the crude extracts.
2.2. Biological Activity Tests
2.2.1. Animals
Male Sprague Dawley rats (160–180 g) and Swiss albino mice (20–25 g) were purchased from
Laboratory of Experimental Animals, Kobay, Ankara, Turkey. The animals were acclimated for 3 days
in room conditions and fed a standard pellet diet and water ad libitum. Six animals from each group
were used to evaluate the activity tests. Throughout the experiments, the animals were processed
according to the suggested European ethical guidelines for the care of laboratory animals. The study
was performed according to the international rules covering animal experiments and biodiversity rights
(Gazi University Ethical Council Project Number: G.U.ET-12.049).
2.2.2. Preparation of the Test Samples
The test materials in an ointment base were applied topically to the wounded area of the test
animal to evaluate the wound-healing activity using the incision and excision wound models. The
extracts were mixed thoroughly in a mortar with a mixture of glycol stearate: propylene glycol and liquid
paraffin (3:6:1) to form an ointment with a concentration of 1%. The animals allocated to the control
group were treated topically with the blank vehicle, while the animals in the negative control group were
not treated with anything. Madecassol® (Bayer) (0.5 g) was used topically as a reference drug.
Madecassol® contains a 1% extract of Centella asiatica L. [19].
Test samples suspended in a mixture of distilled water and 0.5% sodium carboxy methyl
cellulose (CMC) were given to the test animals orally to evaluate anti-inflammatory activity. Animals
in the control group received only the vehicle [20]. Indomethacin (10 mg/kg) in 0.5% CMC was used
as a reference drug [21].
2.2.3. Wound Healing Activity Linear Incision Wound Model
Ketasol® (Richterpharma) with a dose of 0.15 cc were used to anesthetize the animals. The
dorsal sides of the rats were shaved and disinfected with 70% ethanol. Two linear-paravertebral
incisions, each 5 cm long and 1.5 cm from the dorsal midline were made through the shaved skin using
a sterile blade. Three surgical sutures were each placed 1 cm apart.
The test ointments, the reference drug, or the ointment base (vehicle) was applied topically on
the wounds once a day for 9 days. The sutures were removed on day ten and the tensile strengths of the
injured and treated skin were measured with a tensiometer (Zwick/Roell Z 0.5, Germany) [22-23]. Circular Excision Wound Model
The circular excision wound model was used to evaluate the wound contraction and wound
closure time. Each animal group was anesthetized using 0.01 cc of Ketasol® (Richterpharma). After the
dorsal parts of the animals had been shaved, a circular wound was created on application area of each
mouse by excising the skin with a 5 mm biopsy punch (Nopa instruments, Germany) and nothing was
applied on the wounds [24]. The test samples, the reference drug (Madecassol®, Bayer), and the vehicle
ointments were applied topically once a day until the wound was completely healed. The wound areas
were photographed every day using a camera (Fuji, S20 Pro, Japan). The wound area was evaluated
using the program AutoCAD. The wound contraction was calculated as a percentage of the reduction in
the area covered by the wound [23,25]. Estimation of Hydroxyproline
Isolated tissues were dried at 60-70 °C in a hot-air oven until a consistent weight was achieved.
Each sample was hydrolyzed with 6 N HCl for 3 h at 130 °C. The solution was adjusted to pH 7 and
Ozbilgin, Rec. Nat. Prod. (2019) 13:2 104-113
subjected to chloramin T oxidation. Absorbance of the colored adduct-product formed with Ehrlich
reagent at 60 °C was read at 557 nm using a Beckmann Dual Spectrometer (Beckman, Fullerton, CA,
USA). Standard hydroxyproline was also run and values reported as µg/mg dry weight of tissue [26,
2.2.4. Anti-inflammatory Activity
The effects of the test samples on the increased vascular permeability induced by acetic acid in
mice was determined according to the Whittle method [28]. Test samples were orally administered with
0.2 mL/20 g body weight doses. 0.1 mL of 4% Evans blue in saline solution was injected to the tails of
each animal thirty minutes later. After 10 min 0.4 mL of 0.5% (v/v) acetic acid was injected
intraperitoneally. The mice were sacrificed 20 min later by dislocation of the neck, and the viscera was
washed with distilled water, then poured into 10 mL volumetric flasks from glass wool. Each flask was
made up to 10 mL with distilled water, 0.1 mL of 0.1 N NaOH solution was added, and the absorption
of the final solution was measured at 590 nm using a Beckmann Dual Spectrometer (Beckman,
Fullerton, CA, USA). The control group was given a mixture of oral water and 0.5% CMC.
2.3. Statistical Analysis of the Data
One-way analysis of variance (ANOVA) and Students-Newman-Keuls post hoc tests were used
to analyze the data. Values of p ˂ 0.05 were considered statistically significant.
3. Results and Discussion
Wound-healing and anti-inflammatory activity results of n-hexane (Hex), ethyl acetate (EtOAc), and
methanol (MeOH) extracts prepared from the aerial parts of E. characias subsp. wulfenii, E.
helioscopia, E. macroclada, E. seguieriana subsp. seguieriana, and E. virgata, are shown in the tables.
Table 2. Effects of the test materials on the linear incision wound model and the hydroxyproline
content of each extract
Material Extract
Tensile strength of wound
(tensile strength %)
Hydroxyproline (µg/mg)
Vehicle 13.34±1.79 (2.30) 12.47±2.15
Negative control 13.04±1.87 (-) 9.66±2.51
E. virgata
14.07±1.38 (5.47)
14.61±1.42 (9.52)
MeOH 16.42±1.56 (23.09) 17.85±2.17
E. macroclada Hex 13.08±1.41 (-) 14.78±2.12
13.87±1.29 (3.97)
E. seguieriana
subsp. seguieriana Hex 14.02±1.46 (5.09) 10.28±2.19
14.58±1.15 (9.30)
16.50±1.39 (23.69)
E. characias
subsp. wulfenii Hex 14.17±1.52 (6.22) 9.67±2.13
16.11±1.79 (20.76)
E. helioscopia Hex 14.27±1.58 (6.97) 11.73±2.07
EtOAc 15.12±1.70 (13.34) 15.08±2.11
SEM: Standard Error of the Mean; Hex- hexane extracts; EtOAc- ethyl acetate extracts; MeOH- methanol
* : p < 0.05;
** : p < 0.01;
*** : p < 0.001
Wound-healing activity of Euphorbia
The methanol extract of E. characias subsp. wulfenii showed more wound-healing activity than
the other extracts, with a 43.03% tensile strength value for the linear incision wound model (Table 2)
and a 65.24% reduction of the wound area at day 10 for the circular excision wound model (Table 3).
The tissue treated with the methanol extract of E. characias subsp. wulfenii was found to contain 35.47
µg/mg of hydroxyproline (Table 2).
Table 3. Effects of the test materials on the circular excision wound model
Material Extract
Wound area (mm
) ± SEM (Contraction %)
0 2 4 6 8 10
Vehicle 19.89±2.31 17.32±2.37
Negative Control 19.21±2.19 17.15±2.24 15.21±2.30 12.96±1.77 7.09±1.57 3.39±1.82
E. virgata
Hex 19.33±2.02 17.48±1.84
EtOAc 19.53±2.11 16.91±1.96
MeOH 19.38±2.25 15.88±1.82
E. macroclada
Hex 19.62±2.28 16.34±1.61
EtOAc 19.45±2.17 15.01±1.45
MeOH 19.47±2.26 14.37±1.58
E. seguieriana
Hex 19.49±2.14 17.42±1.79
EtOAc 20.02±2.03 16.49±1.81
MeOH 19.99±2.22 16.32±1.85
E. characias
subsp. wulfenii
Hex 19.32±2.01 16.85±1.43
EtOAc 19.27±2.10 16.39±1.59
MeOH 21.03±2.11 15.11±1.34
E. helioscopia
Hex 19.57±2.04 17.25±1.28
EtOAc 19.31±2.07 16.81±1.19
MeOH 20.10±2.31 15.71±1.23
Madecassol® 19.81±2.05 14.28±1.30
SEM: Standard Error of the Mean; Hex- hexane extracts; EtOAc- ethyl acetate extracts; MeOH- methanol
* : p < 0.05
** : p < 0.01
*** : p < 0.001
Anti-inflammatory activity test results showed that, the methanol extracts of E. characias subsp.
wulfenii, and E. macroclada inhibited inflammation by 34.74% and 38.81%, respectively (Table 4). The
Ozbilgin, Rec. Nat. Prod. (2019) 13:2 104-113
wound-healing and anti-inflammatory activity tests were consistent. The methanol extract of E.
characias subsp. wulfenii demostrated remarkable bioactivity in both the wound-healing and acute
inflammation models.
Table 4. Inhibitory effect of the test materials on the acetic acid-induced increase in capillary
Material Extract Dose (mg/kg) Evans Blue Concentration
(g/mL) ± SEM Inhibition (%)
Control 12.29±1.25
E. virgata
EtOAc 100 11.85±1.27 3.58
E. macroclada
Hex 100 12.75±1.33 -
EtOAc 100 11.47±1.39 6.67
MeOH 100 7.52±0.93 38.81***
E. seguieriana
subsp. seguieriana
MeOH 100 10.75±1.05 12.53
E. characias subsp.
Hex 100 11.95±1.34 2.77
EtOAc 100 9.24±0.85 24.82
MeOH 100 8.02±0.79 34.74**
E. helioscopia
Hex 100 10.99±0.91 10.58
MeOH 100 9.45±1.02 23.11
Indomethacin 10.0 6.81±0.37 44.59***
SEM: Standard Error of the Mean; Hex- hexane extracts; EtOAc- ethyl acetate extracts; MeOH- methanol
* : p < 0.05
** : p < 0.01
*** : p < 0.001
Collagen is the major protein of the extracellular matrix. It makes the hydroxyproline and its
peptides free up [29]. The rate of collagen synthesis and the maturation process where covalent binding
of collagen fibrils are deterministic for a tensile strength of a wound [30]. In the present study, the tensile
strength of the new tissue is better than the treated groups and the signs of infection were shown at least
on level. The tensile strength is the resistance to breakage shown against stretching. This shows how
much the repaired tissue is resistanted against breaking. For this purpose, the newly repaired tissue was
removed and the tensile strength was measured [22]. Large amounts of hdyroxyproline in tissues
indicate the presence of collagen and accelerated healing [31]. The amount of hyroxyproline indicated
by the wound tensile strength parallels the results of incision wound model in this study.
The first phase of healing is inflammation. However, an elongated inflammatory response
delays healing. For this purpose, anti-inflammatory activity of the extracts was evaluated by using the
Whittle method. This model of inflammation determines the effectiveness of a test material against the
increased capillary permeability induced by acetic acid [32]. In the present study, the methanol extracts
of E. characias subsp. wulfenii, and E. macroclada significantly inhibited this inflammation more than
other groups.
Anti-inflammatory activity has been reported for Euphorbia australis Boiss., E. drummondii
Boiss., E. heyneana Spreng, E. hirta, E. kansui T.N. Liou ex. T.P. Wang, and E. royleana Boiss [33-
37]. E. fusiformis, E. helioscopia, and E. segetalis L. have shown antimicrobial activity [8,38,39].
Antioxidant activity has been attributed to E. helioscopia, E. hirta, E. macroclada, and E. rigida M.
Bieb. [40-42], and wound-healing activity to E. caducifolia Haines., E. hirta, and E. neriifolia L. [43,44].
The results obtained are similar to the wound-healing potential of the latex of E. caducifolia which
accelerated closure of the wound with greater contents of fibroblasts and collagen in the treated animals
[45]. The same type of wound-healing effect has also been observed for E. neriifolia [46]. Ahmed et al.
[47] have suggested that the topical administration of ethyl acetate and methanol extracts of E.
Wound-healing activity of Euphorbia
consobrina N.E.Br., ethyl acetate extract of E. inarticulata Schweinf., and methanol extracts of E.
balsamifera Aiton, and E. schimperi C. Presl. have significant therapeutic effects on the various phases
involved in the process of wound contraction and healing. Badgujar et al. [48] have reported that the
latex of E. nivulia Buch.-Ham. which included alkaloids, cynogenic glycosides, phenolics, saponins,
and tannins significantly reduced the bleeding and whole-blood clotting times. Results of the
ethnobotanical studies show that Euphorbia species have been used such as analgesic, anti-
inflammatory, antifungal, antiviral, cytotoxic, diuretic, laxative, and wound healer agents in traditional
medicine. However, there is not enough satisfactory studies which provide scientific evidence to prove
the effectiveness of these uses.
The aerial parts and latex of Euphorbia species are reputed to have various biological effects
that make them useful in traditional medicines. Giordiani et al. [7] have reported that plants of the
Euphorbia genus showed significant antimicrobial activity against Gram-positive and Gram-negative
bacteria. Such antimicrobial activity is particularly important because of it prevents infection of the
wounded area during the healing process. Free radicals are known to induce cell damage by lipid
peroxidation. Antioxidant activity therefore also contributes to the healing process. The antioxidant
activities of the Euphorbia species, E. heyneana, E. hirta, E. macroclada, and E. rigida have been
investigated [34, 40, 49]. Phytochemicals such as alkaloids, triterpenoids, tannins, phenolic compounds
and flavonoids are also known to support healing process, especially because of antimicrobial and
astringent properties. Flavonoids and their derivatives have been known to prevent or slow down the
progression of cell necrosis by increasing vascular formation of the tissues. Flavonoids are also thought
to be effective compounds responsible for wound contraction and epithelialisation.[50-54]. The genus
Euphorbia has been reported to be a rich source of sesquiterpenoids, glycerols, cerebrosides,
phloracetophenones, steroids, phenolic compounds and flavonoids [14]. In our study, significant wound-
healing and anti-inflammatory effects of the extracts are attributed to flavonoids and quercetin
glycosides. Flavonoid and flavonoid derivative contents of our selected species are consistent with
studies in literature. Previously quercetin-3-O-glucoside, kaempferol, kaempferol-3-O-glucoside,
kaempferol-3-rutinoside and rutin were isolated from E. virgata [13]. Ertaş et al. [55] have reported that
E. macroclada contained rutin, hyperoside, quercetin, apigenin, kaempferol, myricetin, naringenin and
hesperetin. In biological activity study report published by Pisano et al. [56], researchers have been
showed phytochemical profile of E. characias by using LC-MS/MS. Results of the study have been
showed that E. characias contain flavonoids namely quercetin-3-O-glucoside, quercetin-3-O-
rhamnoside, quercetin-3-O-arabinoside and quercetin-3-O-xyloside, which have antioxidant and
antimicrobial activities.
In the present study, results have shown that the methanol extract proposed from the aerial parts
of E. characias subsp. wulfenii possesses the best wound-healing activity of any of the five species of
Euphorbia we tested using three different solvents for extraction and it also outperformed the control
groups. This is attributed to the combined effect of the constituents present in extracts, especially the
flavonoids (see supporting information). The present study provides evidence to support the traditional
use of the aerial parts of E. characias subsp. wulfenii for wound healing.
This work was financially supported by the Ankara University Scientific Research Projects
Coordination Unit [Project Number: 13L3336004].
Supporting Information
Supporting Information accompanies this paper on
Serkan Özbilgin: 0000-0002-3945-6756
Esra Küpeli Akkol: 0000-0002-5829-7869
İpek Süntar: 0000-0003-4201-1325
Ozbilgin, Rec. Nat. Prod. (2019) 13:2 104-113
Mehmet Tekin: 0000-0002-6504-2223
Gülçin Saltan İşcan: 0000-0001-6633-0713
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Full-text available
For thousands of years, nature has been the source of medicine, and a huge number of modern marketed drugs which isolated from natural remidies were discovered depending on its useses in traditional medicine. Wound healing possesses is still the great challenge for the medical community. According to the WHO, more than 80% of world population utilized traditional remedies as alternative medicine for wound healing treatment. This work focus on the Euphorbia species plants (belong to Euphorbiaceae family) which have wound healing activity. Published previous studies on the wound healing property of Euphorbia species plants was gathered by the use of different scientific websites such as Google Scholar, PubMed, Science Direct, and Web of Knowledge. This review identified plants from species of Euphorbia that promote wound healing. The selected plants are with high content of flavonoids, saponins, steroids, triterpenoid and tannins. At the same time these components reportedly promote wound healing by different pharmacological activity like mopping of reactive oxygen species from wounded tissues, inhibition / cidal effects against infections that delay wound healing and anti-inflammatory activities. These plant could be considered as future drug candidates for wound healing for healing of wounds.
Fourteen previously undescribed diterpenoids, including an unusual diterpenoid (1) with a 9,10-seco-jatrophane skeleton, ten jatrophane-type diterpenoids (2−11), two lathyrane-type diterpenoids (12, 13), and an abietane-type diterpenoid (14), together with thirty-six known ones (15−50), were isolated from the whole plants of Euphorbia helioscopia L. The structures of the new isolates were characterized by spectroscopic methods, single-crystal X-ray diffraction analysis, and computational prediction of ECD and chemical shifts. Thirty-nine abundant diterpenoids were evaluated for their enhancement of NK cell-mediated killing of NSCLC cells. As a result, compounds 24, 33, and 41 were found to significantly enhance the killing activity of NK cells towards H1299-luci cells and A549-luci cells at the concentration of 2.5 μM.
Euphorbia helioscopia L. which is called “Zeqi” in China, is a medicinal plant extensively distributed worldwide, especially in China, and has been widely used for decades to treat various diseases including edema, phlegm and cough, malaria, dysentery, scab, tuberculous fistula, osteomyelitis, and cancer. The present review aims to provide up-to-date information on E. helioscopia, including its traditional uses, phytochemistry, quality control, pharmacological research, toxicology, and human studies in exploring future scientific and therapeutic potentials in disease treatment. So far, a total of 173 terpenoids, as well as polyphenols, steroids, lipids, and volatile oils have been isolated and identified from E. helioscopia. Among them, diterpenoids and flavonoids are the most important and abundant bioactive constituents. Modern pharmacological studies have demonstrated that E. helioscopia has outstanding bioactivities especially on antiproliferative and multidrug resistance modulating. Nevertheless, most of these studies were carried out in vitro. The quality control, metabolites identification, in-depth in-vivo studies as well as toxicology and human studies for the crude extracts and active components are still very limited. Consequently, more well-designed pre-clinical and clinical studies are required to justify their reported therapeutic potential.
Full-text available
The aim of the present study was to evaluate antioxidant, antimicrobial, anti-HIV, and cholinesterase inhibitory activities of aqueous and alcoholic extracts from leaves, stems, and flowers of Euphorbia characias . The extracts showed a high antioxidant activity and were a good source of total polyphenols and flavonoids. Ethanolic extracts from leaves and flowers displayed the highest inhibitory activity against acetylcholinesterase and butyrylcholinesterase, showing potential properties against Alzheimer’s disease. Antimicrobial assay showed that leaves and flowers extracts were active against all Gram-positive bacteria tested. The ethanolic leaves extract appeared to have the strongest antibacterial activity against Bacillus cereus with MIC value of 312.5 μ g/mL followed by Listeria monocytogenes and Staphylococcus aureus that also exhibited good sensitivity with MIC values of 1250 μ g/mL. Moreover, all the extracts possessed anti-HIV activity. The ethanolic flower extract was the most potent inhibitor of HIV-1 RT DNA polymerase RNA-dependent and Ribonuclease H with IC 50 values of 0.26 and 0.33 μ g/mL, respectively. The LC-DAD metabolic profile showed that ethanolic leaves extract contains high levels of quercetin derivatives. This study suggests that Euphorbia characias extracts represent a good source of natural bioactive compounds which could be useful for pharmaceutical application as well as in food system for the prevention of the growth of food-borne bacteria and to extend the shelf-life of processed foods.
Full-text available
This study evaluated the chemical composition, antioxidant, anti-inflammatory and anticancer activities of a Euphorbia hirta L. extract. The antioxidant activities of whole E. hirta ethanol extract were determined by electron spin resonance spectrophotometric analysis of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl, and alkyl radical levels and by using an online high-performance liquid chromatography (HPLC)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay. The E. hirta ethanol extract (0.5 mg/mL) exhibited DPPH-scavenging activity of 61.19% ± 0.22%, while the positive control (0.5 mg/mL ascorbic acid) had 100% ± 0.22% activity. The concentration of the extract required to trap 50% of DPPH (IC50) was 0.205 mg/mL. Online HPLC analysis of the extract also showed strong antioxidant activity. The anti-inflammatory activity of the E. hirta extract was assessed in lipopolysaccharide-induced RAW 264.7 macrophages. The anti-inflammatory activity was highest in the presence of 200 µg/mL E. hirta extract, and nitric oxide production was decreased significantly (p < 0.05). The extract also showed selective anticancer activity at a concentration of 100 µg/mL (p < 0.05). These results indicated that E. hirta may warrant further investigation for the development of antioxidant, anti-inflammatory, and anticancer herbal medications.
Full-text available
In this study, it was aimed to investigate the chemical composition and antioxidant activities of two Euphorbia species. The major component of the fatty acid compositions obtained from the petroleum ether extracts was identified as palmitic acid for Euphorbia gaillardotii and Euphorbia macroclada. The main constituents of the essential oils were identified as arachidic acid for E. gaillardotii and tetratetracontane for E. macroclada. Among the 27 studied compounds, hesperidin, rutin, hyperoside and quinic, malic, gallic and tannic acids were found to be the most abundant compounds in the two Euphorbia species. The methanol extracts of E. gaillardotii and E. macroclada showed strong antioxidant activity in all tested methods. Particularly, IC50 values of E. macroclada methanol extract that was the richest in terms of total phenolic-flavonoid contents were found to be lower than α-tocopherol and butylated hydroxytoluene in β-carotene bleaching, 2,2-diphenyl-1-picrylhydrazyl free and ABTS cation radical scavenging methods.
In this study, in vitro inhibitory effects of 33 ethanol extracts obtained from 24 plant species (representing 11 different families) on cyclooxygenase-1 (COX-1) were evaluated. The plant materials selected for this study have been used in aboriginal medicine in Australia and traditional medicine in China for the treatment of various diseases that are considered as inflammation in nature, e.g. asthma, arthritis, rheumatism, fever, edema, infections, snakebite and related inflammatory diseases. All of the selected plants, with one exception, showed inhibitory activity against COX-1, which supports their traditional uses. The most potent COX-1 inhibition were observed from the extracts of Acacia ancistrocarpa leaves (IC50 = 23 g/ml). Ficus racemosa bark, Clematis pickeringii stem, Acacia adsurgens leaves, Tinospora smilacina stem and Morinda citrifolia fruit powder exhibited inhibition of COX-1 with the IC50 of 100, 141, 144, 158 and 163 g/ml, respectively. Aspirin and indomethacin used as the reference COX-1 inhibitors in this study inhibited COX-1 with IC50 of 241 and 1.2 g/ml, respectively. The findings of this study may explain at least in part why these plants have been traditionally used for the treatment of inflammatory conditions in Australian aboriginal medicine and traditional Chinese medicine.
Background Plants of Euphorbiaceae are used in folkloric medicines in variety of ailments and well known for chemical diversity of their isoprenoid constituents. This study was carried out to explore the preliminary wound healing potential of four Euphorbia species (E. consorbina 1, E. consorbina 2, E. inarticulata, E. balsamifera and E. schimperi). Materials and Methods Excision wound surface of the animals were topically treated with ethyl acetate and methanol extracts of plants at a dose of 400 mg/kg body weight for twenty days. Povidone-iodine ointment was used as a reference drug. Wound contraction measurement and period of epithelialization were used to assess the effect of plants extracts on wound repairing. Results The groups treated with methanol extracts of E. balsamifera and E. schimperi showed profound effects, high rate of wound contraction (100%) and decrease in epithelization period 19.00±0.40 and 18.50±0.64 respectively, followed by methanol extracts of E. consorbina 2, ethyl acetate extract of E. inarticulata and ethyl acetate extracts of E. consorbina 2 which showed significant (P <0.001) wound contraction and decrease in epithelization period. Conversely ethyl acetate extract of E. consorbina 1, E. balsamifera and E. schimperi and methanol extract of E. Consorbina 1 and E. Inarticulata treated groups was not showing significant wound healing. Methanol extracts of E. balsamifera and E. schimperi were also tested for their safety margin and found safe up to dose of 2000mg/kg body weight. Conclusion Topical application of methanol extracts of E. balsamifera and E. schimperi have potential wound healing activity which is identical with standard drug Povidone-iodine.
Comprehensive studies of the complexation of polyphenols (vegetable tannins) with other substrates are of great practical significance and utility. Fundamental studies of these phenomena form part of the strategy adopted in Sheffield to pursue an understanding of the possible function and metabolic role of this distinctive group of natural products. With regard to polyphenols, molecular size, conformational mobility and shape, and water solubility are the three principal critera that most strongly influence association with polysaccharides. The differing affinities of polyphenols for polysaccharides result from a balance between a variety of effects- adsorption, sequestration, and solvation. The importance of polyphenol sequestration into “pores” in the polysaccharide structure has been demonstrated by model studies with Schardinger dextrans or cyclodextrins.
Crataeva magna and Euphorbia nerifolia have been shown to possess hepatoprotective activity and antioxidant property. The present works with these plants were undertaken with the premise that the drug promoting hepatoprotective activity and radical scavenging property could have effect on wound healing also. The wound healing property of the methanolic extract of the leaves of Crataeva magna (CNM) and Euphorbia nerifolia (ENM) were chosen to investigate in excision and incision wound models. The methanolic extracts of the two plants at the dose of 500 mg/kg/day by topically applying method. Healing was assessed by the rate of wound contraction, time until complete epithelialization, incision breaking strength, estimation of hydroxyproline and histopathological parameters. Complete wound contraction was shown by both the plants in the study period. In excision and incision wound models, all the test drugs showed significant (P<0.001) wound healing activities compared to the control. Moreover the CNM was found to possess significant wound healing activities than the ENM and had been observed to have equipotent wound healing activity as of the standard drug Framycetin.
Leaves and fruits of Morus nigra L. (Moraceae) are used for the treatment of wounds especially mouth sore in Turkish traditional medicine. The present study was designed to investigate wound healing activity of M. nigra by using incision and excision wound models. Furthermore, anti-inflammatory activity was assessed by Whittle method. Lyophilized fruit extract (MNF) displayed significant wound healing activity, while aqueous leaf extract of M. nigra (MNL) did not. Through biological activity guided fractionation technique, MNF was subjected to successive solvent extraction. Among the subextracts obtained, n-butanol (MNF-n-BuOH) subextract was found to possess wound healing activity. MNF-n-BuOH was subjected Sephadex LH-20 column chromatography to obtain three fractions, which then applied to the same biological activity tests. Compounds 1 and 2 were isolated from the active fraction and their structures were identified as quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside, respectively. The isolates were investigated for their in vitro enzyme inhibitory activities.