ArticlePDF Available

A comparative study on the effectiveness of herbal extracts vs 2.5% benzoyl peroxide in the treatment of mild to moderate acne vulgaris

Authors:

Abstract

Background Although there is a standard guideline for the treatment of acne, it is still a common skin disease, and suboptimal medication adherence is a major reason for treatment failure. Herbal extracts are an interesting alternative medicine because they consist of a variety of active ingredients. Moreover, herbal extracts may have improved therapeutic efficacy because of the combination of various herbs. Objectives To evaluate the effectiveness of herbal extracts for the treatment of mild to moderate acne vulgaris. Methods A total of 77 patients were randomized to receive either an herbal extract or 2.5% benzoyl peroxide, which were applied for a period of 12 weeks. Acne lesion counts, adherence, porphyrin counts, the Dermatology Life Quality Index, satisfaction and side effects were assessed. Result At the 12‐week point, the acne lesion counts decreased, with statistically significant differences from the baseline values in both groups and for all types of acne (P‐value < 0.001). The adherence rate was significantly higher in the patients using the herbal extract than in the patients using 2.5% benzoyl peroxide (P‐value = 0.002). There was no statistically significant difference in terms of porphyrin counts, spot scores, the Dermatology Life Quality Index or satisfaction with efficacy between the groups; however, satisfaction with drug administration was significantly higher in the patients using the herbal extract (P‐value = 0.001). Conclusion Herbal extracts could be beneficial for anti‐acne pharmaceutical preparations and may be used as an alternative medicine for patients with mild to moderate acne vulgaris who do not adhere to benzoyl peroxide treatment.
J Cosmet Dermatol. 2019;1–9. wileyonlinelibrary.com/journal/jocd  
|
 1
© 2019 Wiley Periodicals, Inc.
Received:22October2018 
|
  Revised:23Februa ry2019 
|
  Accepted:22March2019
DOI: 10.1111/jocd.12962
ORIGINAL CONTRIBUTION
A comparative study on the effectiveness of herbal extracts vs
2.5% benzoyl peroxide in the treatment of mild to moderate
acne vulgaris
Patrida Lubtikulthum MD1| Nanticha Kamanamool MD, PhD2|
Montree Udompataikul MD1
1SkinCenter,SrinakharinwirotUniversity,
Bangkok,Thailand
2Depar tmentofPreventiveandSocial
Medicine,SrinakharinwirotUniversity,
Bangkok,Thailand
Correspondence
MontreeUdompataikul,SkinCenter,
SrinakharinwirotUniversity,114Soi
Sukhumvit23,KhlongToeiNuea,Watthana
10110,Thail and .
Email: umontree@gmail.com
Funding information
SrinakharinwirotUniversity;Bangkok
Botani ca Co., Ltd.
Abstract
Background: Althoughthereisastandardguidelineforthetreatmentofacne, it is
stillacommonskindisease,andsuboptimalmedicationadherenceisamajorreason
fortreatmentfailure.Herbalextractsareaninterestingalternativemedicinebecause
theyconsist ofavarietyofactive ingredients.Moreover,herbalextractsmayhave
improvedtherapeuticefficacybecauseofthecombinationofvariousherbs.
Objectives: Toevaluatetheeffectivenessofherbalextractsforthetreatmentofmild
tomoderateacnevulgaris.
Methods: Atotalof77patientswererandomizedtoreceiveeitheranherbalextract
or2.5%benzoylperoxide,whichwereappliedforaperiodof12weeks.Acnelesion
counts, adherence,porphyrincounts,theDermatologyLife QualityIndex,satisfac
tionandsideeffectswereassessed.
Result: At the 12‐week point, the acn e lesion counts decre ased, with stat istically
significantdifferences from thebaselinevalues inbothgroupsandfor alltypesof
acne (P‐value<0.001).The adherencerate wassignificantly higher in the patients
using the herbal extract than in the patients using 2.5% benzoyl peroxide (P
value=0.002).Therewasnostatisticallysignificantdifferenceintermsofporphyrin
counts,spotscores,theDermatologyLifeQualityIndexorsatisfactionwithefficacy
betweenthegroups;however,satisfactionwithdrugadministrationwassignificantly
higherinthepatientsusingtheherbalextract(P‐value = 0.001).
Conclusion: Herbalextractscouldbebeneficialforanti‐acnepharmaceuticalprepa
rationsandmaybeusedasanalternativemedicineforpatientswithmildtomoderate
acnevulgariswhodonotadheretobenzoylperoxidetreatment.
KEYWORDS
acne,benzoylperoxide,herbalextract,mangosteen,niacinamide,teatreeoil
1 | INTRODUCTION
Systemic and topical medications have been widely prescribed
forthe treatmentofacne vulgaris fordecades.Althoughthese
agents,such as retinoic acid, benzoyl peroxide (BP), adapalene,
and clindamycin, generally continue to be the standard treat
ments,acnevulgarisisstillthefifthmostcommondermatologic
disorderowingtotreatmentfailure.1Themainreasonsfortreat
mentfailurearepoorpatientadherencea ndantibioticresis tance.
Adverse e ffect sa nd regimen com plexity ar e two major fac tors
2 
|
   LUBTIKULTHUM eT aL.
associated with medication nonadherence.2 Adherence to BP
treatmentwasfoundtodecreasecontinuouslyovertimeandwas
reducedsubstantiallyinjust6weeks,whilefixed‐dosecombina
tionproducts,suchasadapalene‐benzoylperoxide,mayincrease
patient ad herence but indu ce significantl y more irritati on than
5%BPalone.3‐5
The use of he rbal medicin es in the treat ment of acne vulg aris
is no longer co nsidered old‐fashi oned. Herbal me dicine has been
developed and researched continuously for standardization and
credibilityasanevidence‐basedmedicine.Manystudieshavefound
thatherbalmedicinescan treatdermatitisandacne.6Interestingly,
anherbalextractcancontainvariousactiveingredients.Theuseof
multih erbalex tra ctscanalsoac tiv atemanymechanismsorsy nergi s
ticeffects.7Thisisconvenientbecausepatientsdonotneedtouse
multipletreatments.
Thepresentstudy aimed to explore theseproperties. The ex
perimentaltreatmentwasacombinationofmultipleherbalextracts
and4%niacinamide,whichhasanti‐inflammatoryproperties,inhib
itsmelanosometransfertokeratinocytesandpromotesskinbarrier
function.8‐1 1Thesetwocompoundswereexpectedtosupporteach
otherinacnetreatmentthroughtheiractionsinmanypathophysio
logicalprocesses.Thecomponentsandpropertiesoftheexperimen
taltreatmentareasfollows.
Teatree oilandmangosteenpericarpcontainterpinen‐4‐o and
xanthonecompounds,respectively,astheirmainactiveingredients.
Both of these components have antimicrobial and anti‐inflamma
tory properties andact as a bactericide to Cutibacterium (formerly
Propionibacterium) acnes.12‐14
Additionally, Cutibacterium acnes (C acnes) play an important
roleinthepathogenesisof acne,andskinbarrier function also re
lates to acn e severity.5,14‐16 Aloevera contains many compounds
and properties, such as vitamins and acemannan,which could in
creaseskinhydrationandhasanti‐inflammatoryproperties.A50%
aloe vera gelwith 0.025%tretinoincream couldimprove acnele
sionstoagreaterextentthanusing0.025%tretinoincream alone.
Moreover,thesideeffect sweresignificantlylower.17Aloeveracan
reducefreeradic alsandinflammator ysubstancesfromwhiteblood
cells,increasemoisture,andcurewounds.Allofthesefactorscan
increasetheefficiencyofacnetreatment.17Inadditiontoacneskin
lesions,sequelae, suchas acne scarspostinflammatoryerythema
and hyperpigmentation, alsoaffect the quality of life of patients.
Theextractsfromthebarkandtherootofpapermulberrycontain
kazino lF,whicha ctsasat yro sinaseenz ymein hibitoran daratelim
itingste pofthemelaninproduc tionprocessintheskin.18Thiscom
poundcantreatblackspotssuchasmelasmaandpostinflammator y
hyperpigmentation.19Qu ercetin, whichis found in onion extra ct,
candecreasetheproductionofinterleukin‐6andtheexpressionof
metalloproteinase‐1.All of these componentscan reduce inflam
mationandfibroblastproliferation duringthehealingprocess.20, 21
Draelosetal22reportedthatusing a commercially available onion
extra ct cream formul ation for patient s with seborrhe ic keratosis
aftershavebiopsysignificantlyreducedinflammationandsoftened
thescarsafter4weeks.
2 | MATERIALS AND METHODS
2.1 | Study design
Thiswasanobserver‐blinded,noninferiorityrandomizedcontrolled
study.Patientswhowereolderthan18yearsandwhohadmoderate
acnevulgarisaccording to the Leeds‐revised criteriawereincluded
int hiss tudy.23T heexclusio ncri te riainc ludedpatientswh owereun
abletofollow‐upaccordingtothestudyprotocol;hadotheractive
skin lesi ons on the stud y site; had horm onal disorde rs or drug‐in
duced acn e; were pregnant or b reast‐feeding; wer e allergic to BP
or any of the fol lowing herbal ex tracts: o nion, lavandula , mango
steen,aloevera,papermulberry,andteatree;hadreceivedsystemic
therapyforacne,hormonalcontraceptionordrugsknowntoaffect
endogenoussexhormones6monthspriortothestudy;tookanyof
thefollowingoralsupplementsormedicineswithin6weekspriorto
study:zinc,vitaminC,vitaminE,antibiotics,andcorticosteroids;and
usedtopicaltherapyforacne,includingcorticosteroids,erythromy
cin, clindamycin, BP,retinoid, vitamin C, vitamin E,herbalextracts
andchemicalpeels,within2weekspriortothestudy.
2.2 | Study protocol
Allconsecutivepatientswhofulfilledtheinclusionandexclusioncrite
riawereinvitedtoparticipateinthestudy.Allpatientswererandomized
using preplanned, blocked randomization to apply either a topical
herbalextractformula(HBE)(SCAGELAcneSpot®;BangkokBotanica
CoLtd.)(clearlight yellowgel)twicedailyor 2.5%BP(2.5%Benzac®;
GaldermaCanadaInc) (whitecream) twice dailyfollowedbywashing
thetreatmentoffafter15minutesofapplication.Thetwomedications
weredistributed in thesametypeofplastic tubesusing sealed enve
lopes containing randomized codes, and 1g ofthe topical treatment
wa sap plie dtothe ent iref ace t wiceda ily.T h epr oto colwasa ppr ove dby
theClinicalResearchEthicalCommitteeofSrinakharinwirotUniversity
onDecember20,2016,CertificatenumberSWUEC/E‐330/2559.
2.3 | Outcome measurements
The clinical outcome assessments were noninflammatory (come
dones),inflammatory(papules, pustulesandnodules)andtotal acne
counts. The patients' adherence, satisfaction score (7‐point scale:
−3=extremely dissatisfied, −2=very dissatisfied, −1=dissatisfied,
0=neither satisfied nor dissatisfied, 1=satisfied, 2=very satis
fied, 3=ex tremely sati sfied) and the sc ores from the Thai ve rsion
of the Derm atology Life Qua lity Index (DLQI) wer e evaluated.24, 25
Thepatientswereexamined atbaselineandweek2,4, 6, 8, 10,and
12. Porphyrin counts andspot scorewere obtainedatbaseline and
week12byVISIA®Complexion Analysis System (Canfield Imaging
Systems). VIS IA® has ultraviol et light source wh ich is used to gen
erate a porphyrin image.The overall mean adherence rate for each
studypatientwascalculatedbyaveragingtheadherencerateforthe
applicationofeachmedication.Theadherencerateforeachvisitwas
calculatedasapercent agebydiv id ingt henumberoftimesth ep at ient
appliedthemedicationbythenumberofdosesprescribedduringthe
    
|
 3
LUBTIKULTHUM e T aL.
entireperiod(eg100%adherencerateforthe12weeksoftreatment
was168times).Theadverseeffectswerealsoreportedateachvisit.
2.4 | Cointerventions
Iftherewerelocaladverseeffectssuchasirritationorcontactder
matitis,acreambaseor0.02%triamcinoloneacetatewasprescribed
andtheadverseeffectswererecorded.
2.5 | Statistical analysis
Thesamplesizewascalculatedbytheformulausedtocomparetwo
means in atwo‐sample parallelnoninferiority trialto provide80%
power to establish noninferiority of theprimary endpoint (percent
acnereduction)withanassumedresponseof44%reductionintotal
acnelesioncountsintheBPgroupand38%reductionintotalacne
lesion counts in the HBE group, a noninferiority margin of 15%,
a stand ard deviation of 15% an d a loss to follow‐up of 10% . 26‐31
Finally,77patientswithmoderateacnevulgariswereenrolled. The
studywasconductedattheSkinCenter,SrinakharinwirotUniversity
and was app roved by the Clinic al Research Ethica l Committee of
SrinakharinwirotUniversity,Bangkok,Thailand.
Descriptive statistics were used to describe clinical demo
graphicsthatwererecorded at the baseline visit.An independent
Student'st‐test was used to compare theaverage means between
thetwogroupsforcontinuousdatawithanormal distribution.The
Mann‐WhitneyUtestwasusedfornonparametricdatatocompare
the differences between the two independent groups. Pearson's
chi‐squaredtestwasusedtotestthedifferencesincategoricaldata.
Repeatedmeasuresanalysisofvariance(ANOVA)wasusedtocom
parethemeanchangefromthebaselineatdifferentvisits.Statistical
data analysis was performedusing the IBMstatistical package for
the socialsciences(SPSS) version 19.0.Forthe noninferiority test,
thestatistical analysisrequiredbothper‐protocol and intention‐to‐
treatanalysesforpercentacnereduction.Thenoninferioritymargin
forthedifferenceinpercentacnereductionbetweenthetreatments
(HBE‐BP)waspredefinedas15%,withnoninferioritydemonstrated
byexcluding the15% noninferiority marginwith the upperlimit of
a two‐sid ed 95%c onfidence inter val for the me an differen ce be
tweentreatments.Theper‐protocolanalysisincludedonlypatients
whomettheinclusioncriteria,followedtheprotocolrequirements,
received thestudymedication, completed allfollow‐upvisits (only
datafromvisitswithinspecifiedtimewindowsof1weekwereused)
andhadadherencerates higherthan 80%per12‐weekperiodand
higherthan 75%per2‐weekperiod. The intention‐to‐treat analysis
includeddata from all randomizedpatients, with the last observa
tioncarriedforward(LOCF).Forsecondaryoutcomes,datafromthe
equalitytestacrossthegroupswerereportedasP‐values.
3 | RESULTS
3.1 | Demographic data
Ofthe90eligiblepatients,77patients(30(38.96%)maleand47
(61.04%)female) who mettheinclusioncriteriawereenrolledin
thestudyandrandomizedtofollow‐upvisitsschedule dat2‐week
FIGURE 1 Flowdiagramofsubjectenrollmentandrandomization
4 
|
   LUBTIKULTHUM eT aL.
intervals.Seventy‐fourpatientscompletedthestudy,and51pa
tients wereincludedin the per‐protocol analysis (28 in theHBE
groupand23intheBPgroup)(Figure1).Themissingvalueswere
imported using the LOCF method. The HBE and BPgroups'av
erage ageswere 21.79±2.238and 21.89±2.153years,respec
tively.Thebaselinenoninflammatorylesioncounts,inflammatory
lesion counts, total lesioncounts,porphyrin counts, spotscores
and DLQI scores were reported. However,no significant differ
ences in baseline characteristics were detected between the
groups(Table1).
3.2 | Primary outcomes
3.2.1| Acne lesions
In the inten tion‐to‐treat analysi s, the mean perce nt reductions in
comedone,inflammatory andtotal lesioncountsinthe HBE group
after12weeksoftreatmentwere34.51±31.01%,40.54±44.75%,
and 36.47±30.1%, respectively. In the BP group, the mean per
cent reductions in comedone, inflammatory and total lesion
counts were 39.4±22.18%, 45.3±35.68%, and 40.9±21.67%,
respec tively (Table 2). In th e per‐protocol analysis , the mean per
cent reductions in comedone, inflammatory and total lesion
counts we re 36.68±28.03% , 49.63±5.98%, and 3 9.56±29.20%,
respectively,inthe HBE group.Inthe BP group,themean percent
reductionsincomedone,inflammatoryandtotallesioncountswere
44.65±27.33%, 55.37±4.83%, and 46.41±29.75%, respectively
(Table 2).
The mean differences between the HBE and BP groups in the
percentreductionincomedone,inflammatoryandtotallesionsafter
12weeksoftreatmentwere4.90%(95%CI:7.37,17.16),4.77%(95%
CI:13.64%‐23.17%),and4.43%(95%CI:7.51%‐16.36%),respectively,
intheintention‐to‐treatanalysisand7.97%(95%CI:3.14%‐19.07%),
5.74%(95%CI:14.43%‐25.91%)and6.86%(95%CI:4.21%‐17.92%),
respectively,intheper‐protocolanalysis.Thus,thedataindicatedan
inconclusive result for noninferiority (noninferior margin=15%) in
boththeintention‐to‐treatandper‐protocolanalyses(Table2).
Based on the intention‐to‐treat analysis, in the HBE group,
comedone,inflammatoryandtotal lesioncountsweresignificantly
improved atweeks 2and12comparedwith the valuesat baseline.
At week 2, the comedone, inflammatory and total lesion counts
decreasedfrom 68.05±37.24,10.64±7.257and78.69±38.46to
58.03±37.24 (P‐value<0.001), 8.51±6.20 (P‐value = 0.006) and
66.54±38.01 (P‐value<0.001), respectively.In theBP group, the
resultsalso showedstatisticallysignificant differences, withlesion
countsafter2weeksdecreasingfrom68.63±35.15,10.66±6.201
and 79.29±38.01 to 58 .79±35 (P‐value<0.001), 8.16±7.26 (P
value=0.0 01) and 66.97±38.46 (P‐value<0.001), respectively.
The numbers of acnelesions gradually decreased until the end of
thetreatmentperiod.Atweek12,there werealsostatisticallysig
nificantdifferencesbetweenthecomedone,inflammatoryandtotal
lesion counts compared with those at baseline (P‐value < 0.001:
amongallt ypesofacnelesionsandbet weenbothgroups)(Figure2).
3.3 | Secondary outcomes
3.3.1 | Adherence
In the inten tion‐to‐treat analysis , the median 12‐week adh erence
rate in the H BE group was 92. 86% (25th percent ile=87.5%, 75th
percentile=100%), which was significantly different from the
86.31% (25th percentile=75.3%, 75th percentile=95.24%) ad
herence rateintheBPgroup (P‐value=0.002).Intheper‐protocol
analysis , there were als o statisti cally signif icant dif ferences in th e
median 12‐week adherence rate between the HBE group (97.02%
(25th percentile=92.26%, 75th percentile=100%)) and the BP
group (91.07% (25th percentile=87.5%,75thpercentile=97.62%))
(P‐value=0.016)(Table3).Regardingtheanalysisofthetimeofthe
day when volu nteers forget to u se the medicin e in the intention‐
to‐treat ana lysis, the HBE g roup usually d id not forget to use t he
medicineandthe individualsin the BPgroup usually forgottouse
themedicineinthemorning.
3.3.2 | Porphyrin
Inthewithin‐groupanalysis,after12weeksoftreatment,themean
porphyrin counts decreased significantly from 1511.17±1126.23
TABLE 1 Baselinedemographicandefficacyendpointdataofall
randomizedpatients
Characteristic
HBE BP
(n = 39) (n = 38)
Sex,n(%)
Male 15(38.5) 15(39.5)
Female 24(61.5) 23(60.5)
Age,years
(mean±SD)
21.79±2.238 21.89±2.153
Comedoneacnelesion
counts(mean±SD)
68.05±37.24 68.63±35.15
Inflammatoryacne
lesioncounts
(mean±SD)
10.64±7.257 10.66±6.201
Totalacnelesion
countsa (mean±SD)
78.69±38.46 79.29±38.01
SpotscorebyVISIA
(mean±SD)
108.10±24.31 111.13±23.33
Porphyrincountsby
VISIA(mean±SD)
1511.17±1126.23 1815.73±1313.87
DLQI(interquartile
range)
−9.5(−23,−2) −8(−21,−1)
Note.Dataareexpressedasthemean(SD),median(interquartilerange)
orfrequency(n[%]).
Abbreviations:BP,benzoylperoxide;DLQI,DermatologyLifeQuality
Index;HBE,topicalherbalextractformula;SD,standarddeviation.
aTotalacnelesioncounts=comedonelesion+inflammatorylesion
counts.
    
|
 5
LUBTIKULTHUM e T aL.
to 1204.45±765.73 (P‐value=0 .003) in the H BE group and f rom
1815.73±1313.87to1397.43±916.20(P‐value<0.001) intheBP
group. Regarding themean change in porphyrincounts,therewas
nostatisticallysignificantdifferencebetweenthechangeobserved
inthe HBEgroup (−306.71±600.00) and that observed inthe BP
group(−418.30±619.87)(P‐value=0.425)(Table4).
3.3.3 | DLQI
No significant differences between groups with regard to mean
changeinDLQIscoreswereevident(P‐value=0.344)(Table4).The
medianDLQIscoreincreasedsignificantlyatweek2and12.Inthe
HBEgroup,theDLQIscoreincreasedfrombaselineto−2(25thper
centile=−19,75thpercentile=0,P‐value<0.001)atweek12.Inthe
BPgroup,themedianDLQIscoreroseto−3.5atweek12(25thper
centile=−20,75thpercentile=−0,P‐value < 0.001).
3.3.4 | Satisfaction
Nostatisticallysignificantdifferencebetweenthegroupsinterms
ofsatisfactionwithefficacywasfound(P‐value=0.391).However,
themediansatisfactionwithdrugadministrationintheHBEgroup
(2(25thpercentile=1,75thpercentile=2))washigherthaninthe
BP group (1.5 (25th percentile=0, 75th percentile=2)), which
resulted in a statistically significant difference (P‐value = 0.011)
(Table4).
3.4 | Adverse effects
Nosystemic side effects occurred in either group. Themost com
mon side effect was skin irritation. The highest incidence was re
porte d at week 2, and the i ncidence decr eased dramat ically aft er
week4.Theincidenceandseverityofthecutaneousadverseeffects
weremeasuredintwocategories:glazingwithpeelingandcracking
anderythemawithminimaledemaorminimalpapularresponse.At
week2,glazingwithpeelingandcrackingwaslesscommon among
theHBEpatients,occurringin5(12.82%)patientsintheHBEgroup
vs11(28.95%)patientsintheBPgroup,anderythemawithminimal
edemaorminimalpapularresponseoccurredin0patientintheHBE
groupandin3(7.89%)patientsintheBPgroup(Figure3).Transient
itching of acnelesions andburning sensationswerereported after
theapplicationofHBEandBP.
TABLE 2 Thepercentreductionininflammatory,noninflammatoryandtotalacnecountsfrombaselineto2weeksand12weeksandthe
meandifferenceinpercentreduction(HBE‐BP)intheintention‐to‐treatandper‐protocolanalyses
Acne lesion counts
at baseline
Acne lesion counts
at week 2
Acne lesion counts
at week 12
Mean percent acne
reduction (week
12‐baseline)
Mean difference in
percent reduction
(HBE‐BP 2 .5%)
(mean ± SD) (mean ± SD) (mean ± SD) (mean ± SD) (95% CI)
Intention‐to‐treat
Comedonelesion
HBE(n=39) 68.05±37.24 58.03±37.24 40.33±19.83 −34.51±31.01
BP2.5%(n=38) 68.63±35.15 58.79±35.15 41.58±26.01 −39.4±22.18 4. 9 0 (−7.37, 17. 16)
Inflammatoryacnelesion
HBE(n=39) 10.64±7.257 8.51±6.20 5.67±5.26 −40.54±44.75
BP2.5%(n=38) 10.66±6.201 8.16±7.26 4.87±3.91 −45.3±35.68 4.77(−13.64,23.17)
Totalacnelesiona
HBE(n=39) 78.69±38.46 66.54±38.01 46.08±22.21 −36.47±30.1
BP2.5%(n=38) 79.29±38.01 66.97±38.46 46.45±27.87 −40.9±21.67 4.43(−7.51,16.36)
Per‐protocol
Comedonelesion
HBE(n=28) 68.21±34.43 58.36±26.98 39.93±17.7 −36.68±28.03
BP2.5%(n=23) 67.83±39.21 53.87±29.89 36.17±19.97 −44.65±27.33 7.97(−3.14,19.07)
Inflammatoryacnelesion
HBE(n=28) 9.96±6.98 7.79±6.07 4.29±4.17 −49.63±5.98
BP2.5%(n=23) 10.91±6.10 8.26±4.65 4.48±4.23 −55.37±4.83 5.74(−14.43,25.91)
Totalacnelesiona
HBE(n=28) 78.18±34.85 66.14±28.17 44.32±19.59 −39.56±29.20
BP2.5%(n=23) 78.74±41.80 62.13±32.1 40.65±21.93 −46.41±29.75 6.86(−4.21,17.92)
Note.Dataareexpressedasthemean±SDorthemean(95%CI).
Abbreviations:95%CI,95%confidenceinter val;BP,benzoylperoxide;HBE,topicalherbalextractformula;SD,standarddeviation.
aTotalacnelesioncounts=comedonelesion+inflammatorylesioncounts.
6 
|
   LUBTIKULTHUM eT aL.
The patie nts in the HBE gr oup experie nced fewer adver se ef
fects;however,onesubjectfromtheHBEgroupwithdrewfromthe
studyduetoanincreaseinacnelesions.Furthermore,threepatients
reportedthattheyfeltitchinganddevelopedsmallpinkpapuleson
thetreatmentareas.Noneofthese patientsattendedthe physical
examintheadd‐onfollow‐upperiod.Theseskinsignsandsymptoms
disappeared afterdiscontinuing the useofHBEfor4days without
usingtopicalsteroids,afterwhichthepatientscouldcontinueHBE
anddid not experiencethese adverse effectsforthe remainder of
thetreatment.
4 | DISCUSSION
Inourstudy,theBPgroup,whichwasthecontrolgroup,exhibiteda
reductioninacnelesionsthatwasclosetothereductionsobserved
inthestudiesbySwinyeretal32andHughesetal,33inwhichBP5%
wasused to treatacne for12and 8weeks,and acnelesions were
reduced by34.3% and 50.1%, respectively. In both of thestudies,
acnelesioncountswereperformedatbaseline.Moreover,thisstudy
demonstratedreductionsinacnelesionsclosetothereductionsob
servedin the studiesbyBassettet al29andEnshaiehetal,34which
revealed that a 5%extract of tea treeoil reduced acne lesions by
29.3%after8weeksand43.64%after6weeks.
Itcouldnotbeconcluded whetherHBEisinferior toBPdueto
inconclusiveresults.However,intheHBEgroup,acnelesionswere
reducedcontinuouslyandweresignificantlydifferentfrombaseline.
Moreover,intheHBEgroup,thetrend ofacne reduction,satisfac
tionwiththetreatmentefficiencyandqualityoflifeweresimilarto
thoseobservedintheBPgroup.Bothgroupshadbetterlifequality
after the treatmentthanatthe baseline, and theeffectonthepa
tients'qualityofliferangedfrommoderatetosmall.Thisresultisan
indicatorofthebenefitofthemedicine.
Thisresultmightbesimilartotheeffectofclindamycin,inwhicha
comparisonwithBP32showedthatclindamycinsignificantlyreduced
acnelesionstoa lesserextentthanBP.32However,clindamycin was
beneficialinthetreatmentofacne.31Therewerevariousreasonsthe
analysis wasinconclusive.First,the herbalextract reducedacne le
sions with a h igher stan dard deviatio nt han BP,in dicating th at the
data points are spread out over a wider range of values. This find
ingindicatesthatsomepatientsexperiencednotableimprovements
in their clinical symptoms, while some patients experienced minor
improvements or wor sening of their symptoms. Second, the base
materials inthe BP treatment (2.5%Benzac® containsan acrylates
copolymer/glycerincomplex,carbopol940,docusatesodium(dioctyl
sodium sulfosuccinate), poloxamer 182,propyleneglycol and water)
include an anionic surfactant and an acrylates copoly mer/glycerin
complex,whichbetterenhancethepercutaneouspenetrationofthe
BP treatm ent than that of th e HBE (the HBE cont ained acr ylates/
C10•30alkylacrylatecrosspolymer(carbopol1382),polysorbateand
water).35Third,thel argesta ndarddeviationmightbetheresul tofthe
smallsamplesize.Fourth,theresultsmightbeaffectedbythemethod
ofacnemeasurement,whichwasmeasuredasthepercentacnere
ductioninthedatafromthepatientswithmildacnevulgarisseverity
werehighlyinfluential.Ifthevalueatbaselinewassmall,evenasmall
changeinacnegreatlyaffectedthepercentacnereduction. Further
studiesneedtodevelopcriteriafortheobjectiveassessmentofacne
severitythat canbe supportedbyanoninferioritymarginstudy, or
futurestudiescanincludeonlypatientswithmoderateacne.
For the porphyrin counts, Burkhart CN36 previously noted a
porphyrin reduction associated with BPtreatment, and the current
study re vealed that the h erbal ext ract could al so reduce por phyrin
counts.The likelymechanisms includethepossibilityofthedestruc
tion of porphyrinsbyHBE or thedownregulationofporphyrin syn
thesisbyHBE.36However,theuseofporphyrincountsororange‐red
FIGURE 2 Thepercentreductionin
totalacnelesioncountsfromthebaseline
toweek12betweentheHBEandBP
groupsintheintention‐to‐treatandper‐
protocolanalyses
TABLE 3 Comparisonofthe12‐weekadherencepercentage
betweentheHBEandBPgroups
Median (interquartile
range) P‐value
Intention‐to‐treat
12‐weekadherence
HBE(n=39) 92.86(87.5,100)
BP(n=38) 86.31(75.3,95.24) 0.002*
Per‐protocol
12‐weekadherence
HBE(n=28) 97.02(92.26,100)
BP(n=23) 91. 0 7 (8 7. 5 ,97. 6 2 ) 0.016*
Abbreviations:BP,benzoylperoxide;HBE,topicalherbalextract
formula.
*p‐value < 0.05.
    
|
 7
LUBTIKULTHUM e T aL.
fluorescencetomeasuretheeffectivenessofamedicineremainscon
troversial.36 Alth ough studies have s hown that orange‐ red fluores
cenceresultscorrelatewiththeC acnepopulationandthatorange‐red
flu o r e s c e n c e isare l i a b l e , e a s yscreeningt e c h n i q u e todemonstratet h e
suppressiveeffectoftopical antibacterialagentson C acnes,studies
haveopposedthese findingbystatingthat orange‐red fluorescence
haslowsensitivityandmightnotrelatetotheculturerateofC acnes
butrather totheamount ofsebumandthepHofthesurface ofthe
skin.37, 3 8TheadherenceoftheBPgroupwasreducedby10%‐20%in
thefirst3days,demonstratingthedisadvantagesofBPincludingthat
it was inconve nient to use and ind uced irritati on, especial ly during
thefirstfewweeksofthetreatment.5HBE hadahigheradherence
ratethanBP,whichincreasedit seffectivenessandrevealedthatHBE
couldbeusedinpatientswhocouldnottolerateBP.
Acne treatment by HBE was safe, and adverse effects were
mild,includingsmalleffects onthe qualityoflife.Thedry skin and
irrita tion side effec ts were signific antly less common in t he HBE
group thanintheBP group.Theeffect of irritation resulted in pa
tients usingthe creambase to enhance skin hydration.Itmight be
concludedthatwhenusing 2.5%BP in dailylife,duetotheskin ir
ritationsymptomsthatreducedadherence,patientsmightneedad
ditional productstoincreasethemoistureoftheir skin andreduce
thesesymptoms.39However,patientswouldprobablychooseprod
uctsthatcontainedcomedogeniccomponents,whichwouldreduce
theeffectivenessofthetreatmentandleadtoincreasedtreatment
regimencomplexity.40
5 | CONCLUSION
Thisstudyrevealedthatamultiherbextractcombinedwithniacina
midewaseffective in reducing acnelesions. Moreover,there were
HBE BP
P‐value (n = 39) (n = 38)
Meanchangeinporphyrincounts
atweek12±SD
‒306.71±600.00 ‒418.30±619.87 0.425
Meanchangeinspotscoreatweek
12±SD
‒1.75±13.67 ‒2.66±11.15 0.74 9
MeanchangeinDLQIatweek
12±SD
5.90±5.16 4.58±5.15 0.344
Mediansatisfactionwithefficacy
score(interquar tilerange)
2(1,3) 1.5 (0, 2) 0.391
Mediansatisfactionwithdrug
administrationscore(interquartile
range)
2 (1, 2) 1.5 (0, 2) 0.011*
Numberofpatientsusingthe
creambase
10(25.64%) 26(68.42%) <0.001*
Note.Dataareexpressedasthemean±SD,median(interquartilerange)orfrequency(n[%]).
Abbreviations:BP,benzoylperoxide;DLQI,DermatologyLifeQualityIndex;HBE,topicalherbal
extractformula;SD,standarddeviation.
*p‐value < 0.05.
TABLE 4 Comparisonofthechange
frombaselineto12weeksbetweenthe
HBEandBPgroupsintheintention‐to‐
treatanalysis
FIGURE 3 Percentageofpatients
presentingwithlocaladverseeffects
8 
|
   LUBTIKULTHUM eT aL.
feweradverseeffectsandbettersatisfactionwithdrugadministra
tion, which resulted in better adherence inthe HBEgroup than in
theBPgroup.Thisisveryimportantforpracticaluse.TheHBEmay
be used as an a lternative me dicine inste ad of BP in patient s with
mildtomoderateacnevulgariswhodonotadheretoBPtreatment.
However,toincreasetheeffectivenessoftheHBE,furtheradjust
mentsintheproportionofingredientsandimprovedpenetrationof
theherbalextractsareneeded.
ACKNOWLEDGMENTS
Wewould liketothank the Faculty ofMedicine, Srinakharinwirot
UniversityforprovidingthegranttofundthisresearchandBangkok
Botanic a Co., Ltd. for pr oviding the her bal extra ct (SCAGEL Acne
Spot®).
CONFLICT OF INTEREST
SCAGELAcneSpot®wasprovidedbyBangkokBotanicaCo.,Ltd.
ETHICAL APPROVAL
ThisstudywasapprovedbytheClinicalResearchEthicalCommittee
of Srinak harinwirot Uni versity on De cember 20, 2016, C ertific ate
numberSWUEC/E‐330/2559.
ORCID
Patrida Lubtikulthum https://orcid.org/0000‐0003‐4235‐0124
REFERENCES
 1. Alexis AF, Sergay AB, Taylor SC . Common dermatologic dis
orders in skin of color: a comparative practice survey. Cutis.
2007;80(5):387‐394.
 2. Snyder S, Crandell I, Davis SA, Feldman SR. Medical adher
ence to acne therapy: a systematic review. Am J Clin Dermatol.
2014;15(2):87‐94.
 3. Andres P,PerninC, PoncetM.Adapalene‐benzoylperoxideonce‐
daily,fixed‐dosecombinationgelforthetreatmentofacnevulgaris:
arandomized,bilateral(split‐face),dose‐assessmentstudyofcuta
neoustolerabilityinhealthyparticipants.Cutis.2008;81(3):278‐284.
 4. Gollnick H,DraelosZ, Glenn MJ, et al.Adapalene–benzoylper
oxide, a unique fixed‐dose combination topical gel for the
treatment of acne vulgaris: a transatlantic, randomized, dou
ble‐blind, controlled study in 1670 patients. B r J Dermatol.
2009;161(5):1180 ‐1189.
 5. YentzerBA,Alikhan A,TeuschlerH,et al.Anexploratorystudyof
adherenceto topical benzoyl peroxideinpatientswith acne vul
garis.J Am Acad Dermatol.2009;60(5):879‐880.
 6. ErnstE,PittlerMH,StevinsonC.Complementary/alternativemedi
cine in der matology. Am J Clin Dermatol.20 02;3(5):341‐348.
 7. Kalemba D, Kunicka A . Antibacterial and antifungal proper ties of
essentialoils.Curr Med Chem.20 03;10(10):813‐829.
 8. KaymakY,Önder M.Aninvestigationofefficacyoftopicalniacin
amideforthetreatmentofmildandmoderateacnevulgaris.J Turk
Acad Dermatol.2008;2(4):jtad82402a.
9. Matts PJ, Oblong JE, Bissett DL . A review of the range of ef
fectsof niacinamideinhumanskin.Int Fed Soc Cosmet Chem Mag.
2002;5:285‐289.
10. DraelosZD,Ertel K,Berge C.Niacinamide‐containingfacial mois
turizer im proves skin ba rrier and ben efits subje cts with ro sacea.
Cutis.2005;76(2):135.
11. HakozakiT,MinwallaL,ZhuangJ,etal.Theeffectofniacinamideon
reducingcutaneouspigmentationandsuppressionofmelanosome
transfer.Br J Dermatol.2002;147(1):20‐31.
12. Pazyar N, Yaghoobi R, Bagherani N, Kazerouni A. A review
of applications of tea tree oil in dermatology. Int J Dermatol.
2013;52(7):784‐790.
13. Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan
W. Effect of Garcinia mangostana on inflammation caused by
Propionibacteriumacnes.Fitoterapia.2007;78(6):401‐408.
14. Scholz CF, Kilian M. The natural history of cutaneous propi
onibacteria, and reclassification of selected species within
the genus Propionibacterium to the proposed novel genera
Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and
Pseudopropionibacterium gen. nov. Int J Syst Evolut Microbiol.
2016;66(11):4422‐4432.
15. Del Rosso JQ. T he role of skin c are as an integr al compone nt in
themanagementofacnevulgarispart1:theimportanceofcleanser
and mois turizer ingr edients, d esign, and p roduct sel ection. J Clin
Aesthet Dermatol.2013;6(12):19‐27.
16. SagranskyM,YentzerBA,FeldmanSR.Benzoylperoxide:areview
of its cur rent use in the tre atment of acne v ulgaris. Exp ert Opin
Pharmacother. 2009;10(15):2555‐2562.
17. Hajheydari Z, SaeediM, Morteza‐SemnaniK, Soltani A. Effectof
Aloevera topicalgelcombinedwithtretinoinintreatmentof mild
andmoderateacnevulgaris:arandomized,double‐blind,prospec
tive trial. J Dermatolog Treat.2014;25(2):123‐129.
18. IozumiK,HogansonGE,PennellaR,EverettMA,FullerBB.Roleof
tyrosinase as the determinant ofpigmentation incultured human
melanocytes.J Invest Dermatol.1993;100 (6):806‐811.
19. Ha J, Jo N, Lee H, Kim J,Lee B,Park W. The depigmentation ef
fectofanewmaterialextractedfromPaperMulberryanditscom
parisonbythreecolorimetricinstruments.J Soc Cosmet Sci Korea.
1996; 22(2) :9‐19.
20. Pikula M, Zebrowska ME, TrzonkowskiP,Mysliwski A,Sznitowska
M.Effectsofenoxaparinandonionextractoncy tokineproduction
inskinfibroblasts.Cent Eur J Immunol.2009;34(2):68‐71.
21. Pikula M, Ze browska ME, P oblocka‐ Olech L , Krauze‐B aranowsk a
M, Sznitowska M, Trzonkowski P.Effect of enoxaparinand onion
extractonhumanskinfibroblastcellline–therapeuticimplications
forthetreatmentofkeloids.Pharm Biol.2014;52(2):262‐267.
22. DraelosZD,BaumannL,FleischerAB.Anewproprietaryonionextract
gelimprovestheappearanceofnewscars:arandomized,controlled,
blinded‐investigatorstudy.J Clin Aesthet Dermatol. 2012;5(6):18.
23. O'brienSC,LewisJB, CunliffeWJ.TheLeedsrevisedacnegrading
system.J Dermatolog Treat.1998;9(4):215‐220.
24. KulthananK,JiamtonS,WanitpakdeedechaR,Chantarujikaphong
S. The validity and reliability of dermatology life quality index
(DLQI)inThais.Thai J Dermatol.2004;20(3):113‐123.
25. FinlayAY,KhanGK .Dermatolog yLifeQualityIndex(DLQI)—asim
ple pra ctical measu re for routine clini cal use. Clin Exp Dermatol.
1994;19(3) :210‐216.
26. Chow S‐C, Wang H, Shao J. Sample Size Calculations in Clinical
Research.CRCPress;2007:90‐92.
27. Gerlinger C, Städtler G, Götzelmann R, Graupe K , Endrika
J. A noninferiorit y margin for acne lesion counts. Drug Inf J.
2008;42(6):607‐615.
28. Mills OH, K ligman AM, Po chi P,Co mite H. Comp aring 2.5% , 5%,
and 10% benzoyl peroxide on inflammator y acne vulgaris. Int J
Dermatol.1986;25(10):664‐667.
    
|
 9
LUBTIKULTHUM e T aL.
29. BassettI,Pannowitz D,Barnetson R.A comparativestudy of tea‐
tree oil ve rsus benzoylpe roxide in the tre atment of acne. Med J
Aust.1990;153(8):455‐458.
30. HammerK. Treatment of acnewith teatree oil (melaleuca) prod
ucts:areviewofefficacy,tolerabilityandpotentialmodesofaction.
Int J Antimicrob Agents.2015;45(2):106‐110.
31. SeidlerEM,KimballAB.Meta‐analysis comparing efficacyof ben
zoyl peroxide, clindamycin, benzoyl peroxide with salicylic acid,
andcombinationbenzoylperoxide/clindamycininacne.J Am Acad
Dermatol.2010;63(1):52‐62.
32. Swinyer L,Baker M,Swinyer TA, Mills O. A comparativestudy of
benzoylperoxideandclindamycinphosphatefortreatingacnevul
garis.Br J Dermatol. 1988;119(5):615‐622 .
33. HughesB,NorrisJ,CunliffeW.Adouble‐blindevaluationoftopical
isotretinoin0.05%,benzoylperoxidegel5%andplaceboinpatients
withacne.Clin Exp Dermatol.1992;17(3):165‐168.
34. EnshaiehS,Jooya A,Siadat AH, IrajiF.The efficacyof5%topical
tea tree o il gel in mild to mod erate acne vu lgaris: a ran domized,
double‐blindplacebo‐controlledstudy.Indian J Dermatol Venereol
Leprol.2007;73(1):22.
35. Som I, BhatiaK, Yasir M. Statusofsurfactants as penetrationen
hancersintransdermaldrugdelivery.J Pharm Bioall Sci.2012;4(1):2.
36. Burkhar t CN. Digital fluorescence as a parameter of
Propionibacterium acnes suppression needs assessment. Int J
Dermatol.2001;40(2):101‐103.
37. Richter C, Trojahn C, Dobos G, Blume‐Peytavi U, Kottner J.
Follicularfluorescencequantitytocharacterizeacneseverity:aval
idationstudy.Skin Res Technol.2016;22(4):451‐459.
38. Youn SW, Kim JH, Lee JE , Kim SO, Park KC. T he facial red flu
orescence of ultraviolet photography: is this color due to
Propionibacterium acnes or the unknown content of secreted
sebum?Skin Res Technol.2009;15(2):230‐236.
39. Bowe WP, Kircik LH. The importance of photoprotection and
moisturization in treating acne vulgaris. J Drugs Dermatol.
2014;13(8):s89‐94.
40. Marcum ZA, Gellad WF.Medicationadherence to multidrug regi
mens.Clin Geriatr Med.2012;28(2):287‐300.
How to cite this article:LubtikulthumP,KamanamoolN,
UdompataikulM.Acomparativestudyontheeffectiveness
ofherbalextractsvs2.5%benzoylperoxideinthetreatment
ofmildtomoderateacnevulgaris.J Cosmet Dermatol.
2019;00:1–9. https://doi .org /10.1111/jocd.12962
... In contrast to the above results, in 3 studies, the herbal intervention was less effective in reducing the number of inflammatory lesions than the control [37,46,63]. In the study by Lee et al., the difference between the results achieved by the group that administered the formulation containing Rosa extract and the results obtained in the group that applied adapalene was not statistically significant, although the reduction in the number of lesions was higher in the control group [46]. ...
... In the study by Lee et al., the difference between the results achieved by the group that administered the formulation containing Rosa extract and the results obtained in the group that applied adapalene was not statistically significant, although the reduction in the number of lesions was higher in the control group [46]. In the studies by Bassett et al. and Lubtikulthum et al., benzoyl peroxide, administered as a control in both studies, was superior to tea tree oil and the herbal combination in reducing the number of inflammatory lesions [37,63]. However, only the first study reported that the difference between the two groups was statistically significant [37]. ...
... In vitro studies (n=1) Evidence-Based Complementary and Alternative Medicine 7 [46,47,63]. However, the first two studies reported that the difference between the two groups was not statistically significant [46,47]. ...
Article
Full-text available
Over the past few decades, interest in medicinal plants and phytochemicals for the treatment of skin disorders, including acne vulgaris, has progressively increased. Acne vulgaris is a chronic in ammatory disease of the pilosebaceous unit, which mainly occurs in adolescents and young adults. e treatment focuses on the four main factors involved in its pathogenesis: increased sebum production, hyperkeratinization, overgrowth of Cutibacterium acnes, and in ammation. e treatment includes topical retinoids, benzoyl peroxide, antibiotics, and oral isotretinoin. In this regard, the use of herbal medicine as a complementary and alternative medicine is a promising strategy. e main objective of this study was to systematically evaluate the e cacy and safety of medicinal plants and phytochemicals in the treatment of acne vulgaris. ree scienti c databases (PubMed, Web of Science, and Scopus) were searched from inception to January 2021. Clinical trials comparing herbal therapies with placebo or other medicines for the treatment of acne vulgaris were included and analyzed. Outcome measures of interest comprised acne lesions (in-ammatory and nonin ammatory), sebum production, acne severity, and quality of life. e risk of bias in the included randomized controlled trials (RCTs) was assessed using the Cochrane risk-of-bias tool. A total of 34 clinical trials involving 1753 participants met the inclusion criteria for this systematic review. Most trials showed that herbal medicine signi cantly reduces in ammatory and nonin ammatory acne lesions and has a relevant e ect on acne severity. Some medicinal plants revealed equal or higher e cacy to standard treatments. No signi cant di erence between groups in sebum production and quality of life was observed and no severe adverse events were reported. is systematic review provides evidence that medicinal plants and phytochemicals are promising treatments for mild to moderate acne vulgaris. However, more quality of evidence and standardized methodologies are needed to support their e ectiveness and safety claims.
... Likewise, TTO treatment resulted in a statistically significant reduction of the mean total number of inflammatory and noninflammatory lesions. 17,19 Although TTO was associated with a slower onset of action compared with the control, 17 it was associated with fewer side effects. 17,19 Similarly, GT lotion treatment yielded a statistically significant reduction in the TLC and severity index. ...
... 17,19 Although TTO was associated with a slower onset of action compared with the control, 17 it was associated with fewer side effects. 17,19 Similarly, GT lotion treatment yielded a statistically significant reduction in the TLC and severity index. 5 Lastly, kanuka honey showed little improvement of the investigator's global assessment acne score, and several participants experienced worsening acne with this treatment. ...
Article
Full-text available
Complementary and alternative medicine (CAM) treatments are growing in popularity as alternative treatments for common skin conditions. Objectives: To perform a systematic review and meta-analysis to determine the tolerability and treatment response to CAM treatments in acne, atopic dermatitis (AD), and psoriasis. Methods: PubMed/Medline and Embase databases were searched to identify eligible studies measuring the effects of CAM in acne, AD, and psoriasis. Effect size with 95% confidence interval (CI) was estimated using the random-effect model. Results: The search yielded 417 articles; 40 studies met the inclusion criteria. The quantitative results of CAM treatment showed a standard mean difference (SMD) of 3.78 (95% CI [-0.01, 7.57]) and 0.58 (95% CI [-6.99, 8.15]) in the acne total lesion count, a SMD of -0.70 (95% CI [-1.19, -0.21]) in the eczema area and severity index score and a SMD of 0.94 (95% CI [-0.83, 2.71]) in the scoring of atopic dermatitis score for AD, and a SMD of 3.04 (95% CI [-0.35, 6.43]) and 5.16 (95% CI [-0.52, 10.85]) in the Psoriasis Area Severity Index score for psoriasis. Limitations: Differences between the study designs, sample sizes, outcome measures, and treatment durations limit the generalizability of data. Conclusions: Based on our quantitative findings we conclude that there is insufficient evidence to support the efficacy and the recommendation of CAM for acne, AD, and psoriasis.
... A clinical study in 71 patients with moderate and mild acne compared the application of herbal extracts with BPO gel at 2.5% for 12 weeks. 22 Results were evaluated in terms of acne lesions, adherence to treatment, porphyrin count, and dermatology life quality index (DLQI). In both groups there was a statistically significant reduction in lesions with improvement in DLQI. ...
... However, the rate of adhesion and satisfaction was to a greater extent in the group that used herbal extracts. 22 ...
Article
Full-text available
Acne is a common inflammatory skin disorder affecting the pilosebaceous unit. Patients with mild‐to‐moderate acne can be treated with a combination of topical, systemic and physical therapeutic approaches, with different results depending on patient, disease, and treatment characteristics. Herein we describe and discuss the common and alternative treatment options used for mild‐to‐moderate acne, by comparing three widely distributed guidelines (American Academy of Dermatology (AAD), European Academy of Dermatology and Venereology (EADV) and Italian Society of Dermatology and Venereology (SIDeMaST). This article is protected by copyright. All rights reserved.
... 17 They are often associated with several other side effects, such as contact allergy, local irritation, scaling, pruritis, redness, itching, skin peeling, and photosensitivity, leading to poor medication adherence and treatment failure. 10,18 Therefore, to overcome the underlying issues, products with herbal ingredients that would avoid the side effects of the synthetic ingredients become essential and have been extensively studied as alternative treatments for acne vulgaris. 10,16 Ayurveda uses herbs containing natural phytoconstituents to make the skincare products that protect the skin from external effects without causing any adverse effects. ...
Article
Full-text available
Background Acne vulgaris is a chronic, inflammatory skin condition of pilosebaceous units. The standard treatment involves topical and oral antibiotics, retinoids, benzoyl peroxide, and other synthetic compounds, mostly associated with adverse effects. Hence, herbal skincare products are considered nowadays. Aim To evaluate the safety and efficacy of Purifying Neem Face Wash (PNFW), an herbal skincare product in the prevention and/or reduction of mild-to-moderate acne. Methods An open-label, single-center, single-arm, four-week clinical study was conducted with subjects having either mild-to-moderate acne or oily skin and non-existent acne. The performance of PNFW in the reduction and/or prevention of acne was detected by counting cutaneous inflammatory and non-inflammatory acne lesions in each of the four visits. Sebum level and skin hydration of both cheeks were measured via sebumeter and corneometer, respectively. Self-assessment questionnaires were used to assess the subjects’ responses toward PNFW. Results Out of 120 study subjects, 79% and 72% showed either reduction or no new appearance of inflammatory and non-inflammatory acne lesions, respectively, from baseline to Visits 3 and 4. Skin sebum level and skin hydration showed a statistically significant decrease (p < 0.001) and increase (p < 0.001), respectively, in Visits 3 and 4. Self-assessment surveys showed the satisfaction of the subjects about the product in terms of condition improvement, ease in use, and fragrance. Conclusion The present study indicated the beneficial effect of the herbal ingredients (neem and turmeric) of Himalaya's PNFW in the prevention and reduction of mild-to-moderate acne with no side effects.
... Plenty of literature has revealed that quercetin reduces the production of interleukin-6 and the expression of metalloproteinase-1 and, consequently, reduces inflammation and fibroblast proliferation. 12 Also, as an antioxidant, quercetin scavenges ROS and ultimately repairs damaged cells. Over the past few decades, sustained and efficient drug delivery systems have gained the noteworthy attention of researchers; transdermal drug delivery is one such system that offers productive significance and advantages. ...
Article
Full-text available
Objectives: Nowadays, antioxidants are important for health-related concerns related to acne vulgaris. Acne vulgaris is interrelated with the development of free radicals that interact with cells. Mulberry leaves contain phenolic compounds, including antioxidants such as quercetin. An antioxidant is a scavenger of free radicals. The current study addresses the development of a mulberry leaf extract-based transfersome gel containing quercetin by a thin-layer hydration method for topical antioxidant delivery. The process was optimized by encapsulating the drug in a variety of transfersome formulations. Materials and Methods: Batch optimization was carried out by particle size and zeta analysis, entrapment efficiency (%), polydispersity index, in vitro drug release, and drug content analysis. Results: The optimized batch MF5 provided 86.23% entrapment efficiency of quercetin in the vesicles and 95.79% drug release. It furnished a spherical shaped vesicle with an average diameter of 118.7 nm and zeta potential of -45.11 mV. The MG1 formulation provided superior antioxidant activity, drug content, and entrapment efficiency, ex vivo drug release, spreadability, homogeneity, and stability to MG2. The presence of quercetin in the extract and gel formulation was confirmed by using high performance thin layer chromatography. Conclusion: It is evident from this study that a mulberry leaf extract-based transfersome gel is a promising prolonged delivery system for quercetin and has reasonably good stability characteristics. This research recommends that mulberry leaf extract-based transfersome gel can potentially be used in the treatment of acne vulgaris through a transdermal drug delivery system. Key words: Transfersomes, mulberry leaves, quercetin, antioxidant activity, transfersome gel
... Todavía no muchos, pero potencialmente prometedores son los estudios que han demostrado los efectos antibiofilm de extractos de plantas (13,14), así como también, el uso de extractos de nicotinamida se han presentado como un promisorio agente terapéutico de uso tópico, que en conjunto pueden desempeñar un papel relevante en tratamiento del acné vulgar (13). ...
Article
Full-text available
Acne is one of the most common skin diseases worldwide and carries significant health care costs. However, the pathophysiology of this disorder is not well understood. Host-microbiome interactions that affect both the homeostasis of innate and adaptive immunity appear to be a central factor in this disease, with recent observations suggesting that the composition and activities of the microbiota in acne are disturbed. Staphylococcus epidermidis and Cutibacterium acnes (C. acnes, formerly Propionibacterium acnes) are two main inhabitants of the skin that are believed to contribute to the disease. In this article, we review recent advances in the interactions of skin microbes with host immunity, discussing the contribution of dysbiosis in the immune-biology of acne, the formation of biofilms (biofilms) and their importance in bacterial resistance, thus we will also explore the new possible therapies based on the "microbiome" of the skin for acne.
Article
Full-text available
Acne is one of the most common skin diseases and usually affects almost everyone. Herbal remedies can be given to treat acne and do not cause side effects. The purpose of writing is to see the effectiveness of herbal remedies for healing acne. Methods: Recent literature reviews were conducted using the electronic databases of Pubmed, Wiley Online and Science Direct. The review method uses keyword terms and phrases of Herbal Medicine, Acne, and Facial Treatment. Results: From the results of 9 studies, it was found that there was anti-acne activity of herbal plants and was relatively safe because there were no severe side effects compared to conventional or synthetic treatments. And there is the effectiveness of herbal remedies for healing acne. Conclusion: Herbal plants have antioxidant, anti-inflammatory, antibacterial and anti-inflammatory effects. Some of the recommended plants based on journal reviews for treating acne include: Nigela Sativa L, Amurense Phellodendron, Tea Tree Oil, Mangosteen Fruit Skin, Aloe Vera, Lavandulla, Paper Murbey, Green Tea, Hops, Aloe Ferox, Punica Granatum (Pomegranate).
Article
Full-text available
Herbal extracts have recently received considerable interest in acne therapy owing to their enhanced skin compatibility compared with antibiotics and synthetic agents. In this study, electrospun poly (vinyl alcohol)/chitosan (PVA/CS) fibrous patch incorporating a combination of herbal extracts with complementary mechanisms of action was developed as an alternative acne therapy for patients with resistance to the conventional treatments. The herbal extracts-loaded electrospun fibers displayed uniform and smooth-surfaced nanofibers (dia. 100–300 nm), high drug loading efficiency (89.5–97.7 %) and good water absorbing properties. Results of the in vitro release and antibacterial studies suggest the patches are capable of sustained release of polyphenol-rich extracts, which may, together with the chitosan present in the fiber, endow the patch with potent bacterial inhibition of Propionibacterium acnes. The herbal extracts-loaded patches exhibited pronounced clinical therapeutic efficacy in treating mild-to-moderate facial acne by rapidly reducing inflamed lesions and restoring epidermal barrier. Also, the herbal patches demonstrated improved biocompatibility or tolerability in comparison with the synthetic drug benzoyl peroxide. Overall, the present study has provided a facile approach to develop biocompatible polymers based electrospun fibrous patch for the efficient delivery of herbal extracts for topical skin therapy, opening new perspectives for a new generation of cosmetotextiles.
Article
Full-text available
Background After dermatitis, acne is the second skin disease most contributing to the burden of skin diseases worldwide. Recently, seven core outcome domains have been identified that together form an Acne Core Outcome Set (ACORN project). One of these was satisfaction with acne treatment. Objective Our aim was to identify studies that described the development of patient‐reported outcome measures (PROMS), evaluated one or more measurement properties of a PROM, or evaluated the interpretability of a PROM in patients with acne regarding treatment satisfaction. Methods The COSMIN search strategy for identifying PROMS on acne treatment satisfaction was used. We searched Pubmed, MEDLINE, Embase, LILACS, Web of Science, Cochrane Library, Emcare, PsychINFO and Academic Search premier (June 2020). Study selection, data extraction, and assessment of methodological quality according to COSMIN guidance were carried out independently by two authors. Results Only one study could be included, describing the development of a treatment satisfaction measure in patients with acne. The development was assessed as inadequate, and data on measurement properties were lacking. Additionally, we found 188 studies reporting treatment satisfaction solely as an outcome, using a wide variety of methods, none of them standardised nor validated. Conclusions We could not find a PROM on treatment satisfaction to recommend for a core outcome set in acne. There is an unmet need for a PROM measuring treatment satisfaction in acne that is robustly developed, designed and validated.
Article
Full-text available
Objectives: Nowadays, antioxidants are important for health-related concerns related to acne vulgaris. Acne vulgaris is interrelated with the development of free radicals that interact with cells. Mulberry leaves contain phenolic compounds, including antioxidants such as quercetin. An antioxidant is a scavenger of free radicals. The current study addresses the development of a mulberry leaf extract-based transfersome gel containing quercetin by a thin-layer hydration method for topical antioxidant delivery. The process was optimized by encapsulating the drug in a variety of transfersome formulations. Materials and Methods: Batch optimization was carried out by particle size and zeta analysis, entrapment efficiency (%), polydispersity index, in vitro drug release, and drug content analysis. Results: The optimized batch MF5 provided 86.23% entrapment efficiency of quercetin in the vesicles and 95.79% drug release. It furnished a spherical shaped vesicle with an average diameter of 118.7 nm and zeta potential of -45.11 mV. The MG1 formulation provided superior antioxidant activity, drug content, and entrapment efficiency, ex vivo drug release, spreadability, homogeneity, and stability to MG2. The presence of quercetin in the extract and gel formulation was confirmed by using high performance thin layer chromatography. Conclusion: It is evident from this study that a mulberry leaf extract-based transfersome gel is a promising prolonged delivery system for quercetin and has reasonably good stability characteristics. This research recommends that mulberry leaf extract-based transfersome gel can potentially be used in the treatment of acne vulgaris through a transdermal drug delivery system. Key words: Transfersomes, mulberry leaves, quercetin, antioxidant activity, transfersome gel
Article
The genus Propionibacterium in the family of Propionibacteriaceae constitutes species of various habitats, including mature cheese, cattle rumen and human skin. Traditionally, these species have been grouped as either classical or cutaneous propionibacteria based on characteristic phenotypes and source of isolation. To re-evaluate the taxonomy of the family and to elucidate the interspecies relatedness we compared 162 public whole genome sequences of Propionibacteriaceae strains. We found substantial discrepancies between the phylogenetic signals of 16S rRNA sequence analysis and our high-resolution core-genome analysis. To accommodate these discrepancies, and to address the long-standing issue of the taxonomically problematic Propionibacterium propionicum, we propose three novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov., Pseudopropionibacterium gen. nov. and an amended description of the genus Propionibacterium. Furthermore, our genome-based analyses support the amounting evidence that the subdivision of Propionibacterium freudenreichii into subspecies is not warranted. Our proposals are supported by phylogenetic analyses, G+C content, peptidoglycan composition and an analysis of the genetic losses and acquisitions of the cutaneous propionibacteria during their adaptation to the human host.
Article
Background: Porphyrins are native fluorophores in the follicle openings, visible under ultraviolet-A light. Acne severity might be associated with increased Propionibacterium acnes colonization and porphyrin production. Aim of this study was to investigate whether the parameter fluorescence quantity can be used to measure acne severity. Methods: A validation study was conducted in 24 patients with acne using split-face design. Acne severity was measured using Investigator Static Global Assessment scores and lesion counts. Reliability, construct validity and sensitivity to change in fluorescence quantity were investigated. Results: Mean baseline Investigator Static Global Assessment score was 2.7 (SD 0.1). Mean baseline fluorescence quantities were 24.8 (SD 4.0) on the cheek and 20.3 (SD 4.6) on the chin. On day 25, values ranged from 6.0 (SD 6.0) to 18.1 (SD 18.4) on the cheek and from 2.6 (SD 4.4) to 14.7 (SD 16.2) on the chin. The intraclass correlation coefficients of fluorescence quantity ranged from 0.513 to 0.987. Effect sizes for fluorescence measurements were highest on the chin and cheek ranging from 0.24 to 0.77 and 0.32 to 0.75, respectively. Conclusion: Fluorescence quantity indicates acne severity, especially on the inner cheek and chin areas. Fluorescence quantity is reliable but is not as sensitive as manual lesion counting.
Article
The objective of this article is to provide a brief, but critical, overview of the evidence related to complementary/ alternative medicine (CAM) use, and to offer valid and useful information for dermatologists in clinical practice. Systematic literature searches were conducted on these databases: Medline, EMBASE, The Cochrane Library, CISCOM and AMED (until October 2000). Where appropriate, the evaluation of the published literature was based on systematic reviews and randomized controlled trials. After scanning the literature it was decided to focus on a selection of two conditions (atopic dermatitis and chronic venous insufficiency) and two treatment modalities (aloe vera gel and tea tree oil). Data for the life-time prevalence of CAM use by patients with dermatological disease ranges between 35 to 69%. The most popular modalities include herablism and (other) dietary supplements, while atopic dermatitis is one of the conditions most frequently treated with CAM. For patients with atopic dermatitis the evidence relates to autogenic training, hypnotherapy, diet, herbal medicine, and dietary supplements. Compelling evidence of effectiveness exists for none of these therapies. However, some promising data have been reported for those with a psychological component: autogenic training, biofeedback and hypnotherapy. For chronic venous insufficiency there is relatively convincing evidence for the effectiveness of oral horse chestnut seed extract. The data for aloe vera gel and tea tree oil indicate that for neither is there compelling evidence of effectiveness. The use of CAM treatments is not free of risk; direct and indirect risks associated with CAM must be considered.
Article
Over-the-counter acne treatments containing tea tree oil from the plant Melaleuca alternifolia are widely available, and evidence indicates that they are a common choice amongst those self-treating their acne. The aims of this review were to collate and evaluate the clinical evidence on the use of tea tree oil products for treating acne, to review safety and tolerability and to discuss the underlying modes of therapeutic action. © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Article
Skin care products are recognized by dermatologists as critical adjunctive therapeutic modalities for patients suffering from acne vulgaris (AV). Prescribing an acne medication without reviewing a patient's skin care regimen can lead to poor compliance, intolerable side effects, and resulting patient and physician frustration. Striking that delicate balance between maintaining the skin barrier while controlling oil and shine has always been a challenge when treating this chronic inflammatory condition, and it necessitates a unique set of ingredients and formulation. Cetaphil® DermaControl™ Moisturizer SPF 30 (Galderma Laboratories, L.P., Fort Worth, Texas) is a new generation of skin care specifically designed for acne-prone skin and acne-affected skin. Both Cetaphil® DermaControl™ Foam Wash and Cetaphil DermaControl Moisturizer SPF 30 incorporate pharmacologically tested, state-of-the-art ingredients and technologies that studies have shown impart substantial benefits to AV patients. J Drugs Dermatol . 2014;13(suppl 7):s89-s94.
Article
Acne vulgaris is a very common facial skin disorder accounting for approximately 10 percent of all visits to ambulatory dermatology practices across the United States annually. Over time, greater attention has been directed to the roles of multiple epidermal barrier functions in various dermatological disorders, especially the stratum corneum permeability barrier and antimicrobial barrier. As a result, it has become readily apparent that professional direction of skin care is very important in the overall management of acne vulgaris. This article discusses several reasons that support the importance of incorporating specified skin care recommendations and instructions into the overall management plan for acne vulgaris. In addition, the article reviews formulation characteristics and some of the scientific data on two commercially available products that are recommended for use as a skin care regimen in patients with acne-prone and acne-affected skin, a foam wash and a moisturizer with a sun protection factor 30 broad spectrum photoprotection rating. The rationale for inclusion of specific ingredients are discussed along with an overview of research results including use in patients with acne vulgaris.
Article
Poor adherence of acne patients to treatment may equate to poor clinical efficacy, increased healthcare costs, and unnecessary treatments. Authors have investigated risk factors for poor medical adherence and how to improve this difficult problem in the context of acne. This systematic review aims to describe what methods have been used to measure adherence, what is known about acne patients' adherence to treatment, and the factors affecting adherence. A MEDLINE search was performed for randomized controlled trials published between 1978 and June 2013, focusing on patient adherence to prescribed acne medications. A test for equality of proportions was performed on studies of similar design to collectively analyze adherence to oral versus topical medication. The self-reported adherence data collected from these clinical trials were then compared with adherence data from a pharmacy database study. Studies varied in modalities of data collection, but the majority utilized subjective methods. Topical therapies were more often studied than oral. The overall oral adherence rate, as calculated by a test of equality of proportions, was 76.3 %, while the overall topical adherence rate was 75.8 % (p = 0.927). The occurrence of side effects and young age were cited as the top reasons for poor adherence, followed by forgetfulness. The MEDLINE search resulted in a limited sample of adherence studies. In addition, there is currently no standardized or fully validated method of measurement, allowing for variability in what was considered 'adherent'. Lastly, data collected via subjective methods cannot guarantee reliable results. Overall, the values reflected a population adherent to both topical and oral medications, with no significant difference in adherence between the two. However, the methodologies used by many of the studies were weak, and the findings are not consistent with results of more objective measures of adherence. The leading factors that contribute to poor adherence may be reduced with enhanced patient consultation, reminder systems, and education.
Article
Context: Keloids and hypertrophic scars are hyperproliferative skin disorders resulting in abnormal wound healing. In the prevention and treatment of keloids and hypertrophic scars, ointments containing heparin and onion extract are very popular. Their therapeutic effects, however, are still controversial and the mechanism of action is not fully understood. Objective: The aim of this study was to assess the effect of enoxaparin and dry onion extract on proliferation, apoptosis and β1 integrin expression in human fibroblasts. Materials and methods: Fibroblast human cell lines (46 BR.1 N) were treated for 48 h with various concentrations of enoxaparin sodium (20, 100, 500 µg/mL) and/or onion [Allium cepa L. (Alliaceae)] extract (50, 250, 1000 µg/mL). The cell proliferation was evaluated by [(3)H]-thymidine incorporation assay. Furthermore, the expression of β1 integrin and apoptosis was determined by flow cytometry. Results and discussion: The results demonstrate that enoxaparin and onion extract inhibited the proliferation of human fibroblasts. Almost complete inhibition of cell proliferation was achieved by enoxaparin in 500 µg/mL concentration (91.5% reduction). The onion extract at a concentration of 250 µg/mL also strongly inhibited the proliferation of cells (50.8% reduction). Depending on concentration, enoxaparin and onion extract induced apoptosis (500 and 1000 µg/mL, respectively) and, depending on concentration, downregulated the expression of β1 integrin on human fibroblasts. Conclusion: This work points at possible mechanism of action of enoxaparin and onion extract, when administered in the treatment of patients with keloids and hypertrophic scars.