Review Article

Effect of Topical Administration of Fractions and Isolated Molecules from Plant Extracts on Skin Wound Healing: A Systematic Review of Murine Experimental Models

Table 1

(a) Description of the main characteristics of the studies with fractions obtained from plant extracts. (b) Description of the main characteristics of the studies with isolated molecules from plant extracts.
(a)

Reference Country Animal strain Animal number Sex Age Weight Experimental groups Animal number per group Numbers of animals per box Treatment control group Plant species Native/exotic Used parts Fractions Dose Popular indication Wound area Measurement interval Wound area calculation Treatment time

Bastos et al., 2011 [15]BrazilWistar rats124 mo300–320 g431Miconazole and nonionic cream Piper hayneanum (Piperaceae)?L [CHCl3-EtOAc 1 : 1 (haulm, A) and CHCl3-MeOH 1 : 1 (routs, B)?Anti-inflammatory, infectious skin diseases and healing, wounds, hematoma, and ecchymosis6 mm2Daily?15 days

Shukla et al., 1999 [16]IndiaSprague Dawley
rats
??200–220 g3?1Saline solutionCentella asiatica (Apiaceae)??Asiaticoside20 L of 0.2%Healing activity 8 mm27/7 days?14 days

Muralidhar et al., 2011 [17]IndiaWistar
rats
42??150–200 g76?Ointment baseButea monosperma (Fabaceae)NSbPETFR: petroleum ether fraction
BENFR: benzene fraction, CHLFR: chloroform fraction, and ACEFR: acetone fraction
200 mg/kg-Antitumor, antiulcer, antifungal, and antidiarrheal activities500 mm24/4 days?16 days

Süntar et al., 2013 [18]TurkeySprague Dawley
rats
??160–180 g?6?Ointment baseHelichrysum graveolens (Asteraceae)NFHg-hexane; Hg-CH2Cl2; Hg-EtOAc, Hg-BuOH; Hg-R-H2O; Hg-Fr.B1; Hg-Fr.B2, Hg-Fr.B3, Hg-Fr.A, Hg-Fr.B; and Hg-Fr.C 0.5 gAntimicrobial, antioxidant, anti-inflammatory, sedative, antidiabetic, and cytotoxic activities5 mm2DailyReduction in wounded area, using AutoCAD program12 days

Mekonnen, et al., 2013 [19]EthiopiaSwiss mice/Wistar
rats
24?8–10 wk/3–5 mo 30–40 g/180–200 g461Sodium carboxyl methyl cellulose xerogel and nitrofurazoneKalanchoe petitiana (Crassulaceae)NLMethanolic and chloroform fractions were 16%, 8.76%, 7.5%, and 5.6%, respectively?Wound healing, hemorrhoids, and antibacterial activities312 mm2Daily% wound contraction = wound area on day 0 − wound area on day /wound area on day 0 × 10010 days

Pieters et al., 1995 [20]BelgiumWistar
rats
??250–300 g2021Not treatedCroton spp. (Euphorbiaceae)ELxPolyphenolic: PEG ointment, PEG 400 10% 0,5 mL/2x dayWound healing 3 cm Daily?18 days

Korkina et al., 2007 [21]ItalyWistar
rats
40?350–400 g510?Saline solutionSyringa vulgaris (Oleaceae)NFTwo phenylpropanoid glycosides: verbascoside and teupolioside 100 L (0.2 mg/mL) Wound healing, anti-inflammatory, antirheumatic, antipyretic, and antifungal activities 2.25 cm24/4 daysThe recorded wounds were measured by planimetry using special computer program8 days

Bigoniya et al., 2013 [22]IndiaWistar
rats
30?175 ± 10 g56?Vehicle (not related)Euphorbia hirta (Euphorbiaceae)NWpFlavonoid fraction (EHTF)?Antimicrobial, antifungal, antiviral, anti-inflammatory, antiarthritic, and antioxidant activities500 mm24/4 days?20 days

Lodhi et al., 2011 [23]IndiaWistar
rats
30♂♀?150–200 g561Not treatedMartynia annua (Martyniaceae)NLM. annua fraction: MAF-A, MAF-B, and MAF-C??500 mm22/2 days% Wound contraction = healed area/total wound area × 10020 days

Tabandeh et al., 2013 [24]IranWistar
rats
60?200 ± 50 g415?Saline solutionSilybum marianum (Asteraceae)E?Flavonoid silibinin (SB)10% and 20% SB powderHepatoprotective and liver regenerating activities1 cm Daily?30 days

Sonmez et al., 2015 [25]TurkeyWistar
rats
24?180–260 g38?Saline solutionSolanum tuberosum (Solanaceae)??Polysaccharide hemostat (APH)3 mg of wheat meal in group 2 and 3 mg of APH in powder form?2 × 2 × 2 cm3, 7, and 14 daysPercentage of contraction = [100 − (total wound area on the 14th day/total wound area on the 3rd day) × 100]14 days

Karakaş et al., 2012 [26]TurkeyWistar
rats
12?200–250 g212 and 8?Not treatedBellis perennis (Asteraceae)EFn-Butanol fraction?Activities in sore throat, headache, eczema, skin boils, and gastritis 4 mm21, 5, 10, and 30 daysPercentage of wound area = wound area in day/wound area in the first day × 100; percentage of wound healing = 100 − percentage of wound area30 days

Choi et al., 2001 [27]KoreaHairless mice10??210?Vehicle (not related)Aloe vera (Liliaceae)??Glycoprotein fraction named G1G1M1DI210 mg/g ointment
Gentamicin 0.1%, every day
Wound healing, thermal injury healing, anti-inflammation, and immunomodulation activities 154 mm2Daily?8 days

Parente et al., 2011 [28]BrazilWistar
rats
3660 days 160–190 g218 and 61 Distilled waterCalendula officinalis (Asteraceae)EFDCF: dichloromethane fraction at 1%; HCF: hexane fraction at 1%?Anti-inflammatory, first-degree burns, and skin rashes activities1 cm 4, 7, and 14 days?14 days

Olugbuyiro et al., 2010 [29]NigeriaWistar rats16?250–300 g241Gentamicin and saline solutionFlabellaria paniculata (Malpighiaceae)NLChloroform fraction and aqueous fraction100 mg/mL Activities in skin infections, wounds and sores, and dysentery2 × 2 cm7, 12, 14, and 18 days?18 days

Süntar et al., 2010 [30]TurkeySprague-Dawley rats/Swiss mice??160–180 g/20–25 g96?Not treated Sambucus ebulus (Caprifoliaceae)NLPolyamide column fractions from the methanolic extract (Fr A, B, C, D, and E)0,5 gHemorrhoids, rheumatic pain, treating burns, infectious wounds, edema, eczema, urticarial, and inflammations5 mm22/2 daysWound contraction was calculated as percentage of the reduction in wounded area12 days

Kim et al., 2013 [31]KoreaHairless mice102 mo?25?Matrigel solutionPanax ginseng (Araliaceae)?LGinsenoside Rd10 mLStrengthening immune system and atherosclerosis activities?3/3 days?9 days

Chaudhari et al., 2006 [32]IndiaWistar
rats
30♂♀?180–250 g56?Soft paraffin (85%), cetostearyl alcohol (5%), hard paraffin (5%), and wool fat (5%)Terminalia arjuna (Combretaceae)NSb Fraction I hydroalcohol Fraction II phytoconstituents extraction of tannins Fraction III consisted of saponins 0.5 g Diuretic, cooling, aphrodisiac, expectorant, antidysenteric, urinary astringent, antioxidant, and antibacterial activities 4 cm22/2 days?16 days

Swamy et al., 2006 [33]IndiaWistar
rats
24♂♀?150–200 g46?Framycetin ointmentEmbelia ribes (Myrsinaceae)?LEmbelin4 mg/mL of 0.2% sodium alginate gelAnti-inflammatory to relieve rheumatism and fever activities500 mm24/4 days?16 days

Hernandes et al., 2010 [34]BrazilWistar
rats
15?180–200 g351Ointment baseStryphnodendron adstringens (Fabaceae)?SbEtOAc fraction?Antioxidant, cicatrizant, and anti-inflammatory activities7 mm24, 7, and 10 days?10 days

Sidhu et al., 1999 [35]USA and IndiaSprague Dawley rats??250–300 g4?1Vehicle PBSArnebia nobilis (Boraginaceae)N?Arnebin-1 (5,8-dihydroxy-2-(19-b,b-dimethylaryoxy-49- methylpent-3-enyl)-1,4-naphthoquinone??8 mm2Daily?11 days

Paramesha et al., 2015 [36]IndiaWistar
rats
18??150–200 g36?Sodium alginate Carthamus tinctorius (Asteraceae)NLDehydroabietylamine of C. tinctorius L., var. Annigeri-2 50 g to get 0.2% (w/w) ointment gelLaxative, appetizer, and diuretic also useful in urorrhea and ophthalmopathy activities?4/4 days?16 days

Nagappan et al., 2012 [37]MalaysiaSprague Dawley rats84?200–250 g7121Not treatedMurraya koenigii (Rutaceae)NLCarbazole alkaloids mahanine () (0.40%) (C23H25NO2), mahanimbicine () (0.24%) (C23H25NO), and mahanimbine () (0.66%) Mahanine () (0.40%), () (0.24%), and () (0.66%) (w/w) Stimulants, tonics, treating influenza, fever, and bronchial asthma activities 8 mm2Daily % of wound contraction = Ø of wound area −  Ø of unhealed w.a./diameter of w.a. (wound area) × 100% 18 days

Qu et al., 2013 [38]ChinaSprague Dawley rats54?200–220 g961VaselineAmorpha fruticosa (Fabaceae)NFr6a,12a–dehydroamorphin, D–3–O–methyl–chiro–inositol, Kaempferol-3-gluco- 7-rhamnoside,7,2′,4′,5′-tetrom–ethoxyoflavone, dehydrosermundone, tephrosin, 7,4′-dimethoxyisoflavone??500 mm22/2 daysPercent wound contraction = (original wound area − unhealed area)/original wound area × 100%22 days

(b)

References Country Animal strain Animal number Sex Age Weight Experimental groups Animal number per group Numbers of animals per box Treatment control group Plant species Native/exotic Used parts Isolated Dose Popular indication Wound area Measurement interval Wound area calculation Treatment time

Ghosh et al., 2012 [39]IndiaWistar rats/Swiss albino mice36?150–180 g/20–25 g66?Ointment basePedilanthus tithymaloides (Euphorbiaceae) NL2-(3,4-Dihydroxy-phenyl)-5,7-dihydroxy-chromen-4-one, 1, 2-tetradecanediol, and 1-(hydrogen sulfate)50 mgAntiviral, antibacterial, antihemorrhagic, antitumor, abortive, and anti-inflammatory activities500 mm23/3 days(%) wound contraction 1/4 (initial × final wound area) × 10021 days

Mukherjee et al., 2013 [40]IndiaSwiss albino mice/Wistar rats???18–20 g/150–180 g10??Ointment base and povidone iodineShorea robusta (Dipterocarpaceae)NLCompound I: bioactive bergenin and compound II: triterpene
ursolic acid
0.025 g of isolated compounds 1 and 2 mixed with 10 g ointment base Wounds and burn healing6 cm 3/3 days Two-day interval/(wound area on day 0 × wound area on day )/wound area on day 0 × 100?

Melo et al., 2011 [41] BrazilSwiss mice3012 wk45.0 ± 2.0 g4?1NaClCratylia mollis (Leguminoceae)NSCramoll
1,4 lectin
100 g/mL?0.5 cm 2, 7, and 12 days12 days

Pieters et al., 1995 [20]BelgiumWistar rats40?250–300 g2021Not treatedCroton spp. (Euphorbiaceae)ELx3′,4-0-Dimethylcedrusin, taspine hydrochloride0,5 mL/2x dayWound healing activities3 cm Daily?18 days

Ahamed et al., 2008 [42]IndiaWistar
rats
24♂♀?240–250 g466Tween 80Grewia tiliaefolia (Tiliaceae)NSbGulonic acid γ-lactone (GAGL)50 mg/1x dayBurns, skin diseases, inflammation, diarrhea and pruritus, chronic wounds, and gastric ulcers?4/4 days?16 days

Zyuz’kov et al., 2012 [43]Russian?/mice1362 mo22–24 g6??WaterAconitum baikalensis (Ranunculaceae)??Songorine, napelline, hypaconitine, 12-epinapelline N-oxide, and mesaconitine30 mL?10 × 10 mmDaily?16 days

Singh et al., 2005 [44]IndiaWistar
rats
20♂♀?150–200 g56?TragacanthElephantopus scaber (Asteraceae)NLDeoxyelephantopin50 mgDysuria, diarrhea, dysentery, stomach pain; eczema and ulcers, and wound healing500 mm24/4 days?14 days

Sharath et al., 2010 [45]IndiaWistar
rats
?♂♀?200–250 g25?NitrofurazoneBacopa monnieri (Scrophulariaceae)N?Bacoside-A200 mg Laxative, ulcers, anemia, leucoderma, and scabies500 mm24/4 days?16 days

Vidya et al., 2012 [46]IndiaWistar
rats
30??160–200 g46?NitrofurazoneEntada pursaetha (Mimosaceae)NSEntadamide, phaseoloidin, and entagenic acid ?Cancer, dropsy, eye diseases, wounds, snake bite, respiratory problems, and antibacterial 500 mm24/4 days?16 days

Ad: adults; wk: week; mo: month; d: days; ♂: male; ♀: female; N: native; E: exotic; L: leaves; F: flowers; Sb: stem bark; S: seed; Wp: whole plant; Fr: fruits; Lx: latex; ?: not related.