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keg|stered off|ce 2S L|nco|n C|ose, 1ewkesbury, GL20 S1

1 November 2013
A paper from the Luropean nerba| and 1rad|t|ona| Med|c|ne ract|t|oners Assoc|at|on -
(2,98S words |nc|ud|ng attached tab|e)
1he Ln1A |s an umbre||a body wh|ch represents profess|ona| assoc|at|ons of
herba|]trad|t|ona| med|c|ne pract|t|oners offer|ng var|ous|y western herba| med|c|ne,
Ch|nese herba| med|c|ne, Ayurveda and trad|t|ona| 1|betan med|c|ne. 1he Ln1A |s
ded|cated to the deve|opment of herba|]trad|t|ona| med|c|ne, preserv|ng and enhanc|ng
the |ega| bas|s of pract|ce across LU Members States and promot|ng best pract|ce
throughout the trad|t|ons. Contact v|a the Cha|r, M|chae| McIntyre,
ehpaQg|oba|net.co.uk.
nerbs to combat the threat of m|crob|a| res|stance to ant|b|ot|cs
Lxecut|ve Summary
In ||ght of grow|ng concerns re|at|ng to m|crob|a| res|stance to ant|b|ot|cs |ncreas|ng
attent|on |s be|ng g|ven to the ro|e that herba| med|c|nes may p|ay as autonomous ant|-
bacter|a| agents or as ad[uvant treatments used to potent|ate convent|ona| drugs. 1h|s
paper se|ect|ve|y rev|ews the ev|dence for herba| med|c|ne as a va|uab|e resource to
combat bacter|a| res|stance to ant|b|ot|cs and suggests that further research |s warranted.
1. Synergy ls an lmporLanL characLerlsLlc deLermlnlng Lhe medlclnal acLlon of many
herbal medlclnes occurrlng aL pharmacodynamlc and pharmacoklneLlc level
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and a
number of papers have been publlshed lnvesLlgaLlng poLenLlal beneflLs conferred by
Lhe synerglsm of phyLoconsLlLuenLs.
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ln parLlcular, researchers have
demonsLraLed LhaL comblnlng anLlbloLlcs wlLh planL medlclnes can enhance Lhe
acLlon of anLlbloLlcs Lhereby overcomlng anLlbloLlc reslsLance.
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2. 1hls ls achleved ln Lhree maln ways: flrsLly by means of a comblned phyLochemlcal
and anLlbloLlc aLLack on Lhe bacLerlal cell wall - eplgallocaLechln gallaLe (LCCC) as
found ln green Lea and carob powder ls effecLlve ln Lhls regard. Secondly, anLlbloLlc
reslsLance can be overcome by lnhlblLlon of enzymes LhaL are generaLed by bacLerla
for Lhe deacLlvaLlon of anLlbloLlcs (agaln LCCC ls acLlve here) or by Lhlrdly by
dlsabllng an efflux pumplng sysLem developed by several bacLerla ln order Lo prevenL
poLenLlally desLrucLlve compounds such as anLlbloLlcs from peneLraLlng lnLo Lhe
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bacLerla, or Lo expel Lhe anLlbloLlcs ouL of Lhe bacLerla cell once Lhey have lnvaded
lL.
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3. 1hymol and carvacrol, Lwo compounds ln Lhe essenLlal oll of Lhyme (!"#$%&
(%)*+,-&) acL as so-called 'membrane permeablllzers' enabllng anLlbloLlcs Lo
peneLraLe lnLo Cram-negaLlve bacLerla.
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1hyme also conLalns balcaleln also presenL
ln Lhe ScuLellarla specles and balcaleln has shown slgnlflcanL ablllLy Lo reverse M8SA
reslsLance Lo Lhe anLlbloLlc clprofloxacln by lnhlblLlng Lhe bacLerla's defenslve efflux
pump.
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4. MosL research Lo flnd agenLs Lo supporL anLlbloLlcs becomlng lneffecLlve agalnsL
common bacLerla has been lab-based raLher Lhan on human populaLlons. A recenL
revlew provlded evldence of 34 dlfferenL herbs conLalnlng consLlLuenLs known Lo
lnhlblL Lhe bacLerlal efflux pumps .
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lor example, ./ 01)- ls currenLly demonsLraLlng
reslsLance Lo several anLlbloLlcs buL, comblned wlLh exLracLs of 213"1,+
+)1340%,1-54&6 lsolaLes of Lhe bacLerla were found suscepLlble Lo clprooxacln.
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Similarly, Klan!nik et al. (2013) found that extracLs of
71&$+,-8%& 199-0-8+)-& lnhlblLed drug reslsLanL sLralns of :+$3#)1;+0<4,.
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LxLracLs
from several oLher planLs ln Lhls sLudy, have shown slmllar lnhlblLory effecLs on
:+$3#)1;+0<4, as have exLracLs of green Lea.
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3. AnoLher ma[or concern ls Lhe drug reslsLanL bacLerlum, MeLhlclllln-reslsLanL
2<+3"#)10100%& +%,4%& (M8SA). Lxposure Lo berberlne, a compound found ln many
medlclnal planLs (e.g. :13<-& 0"-848&-& and ="4))15485,18 +$%,48&> LogeLher wlLh
anLlbloLlcs such as levofloxacln and azlLhromycln
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, recenLly proved lneffecLlve
agalnsL M8SA, resulLed ln Lhe reacLlvaLlon of Lhe efflcacy of Lhe anLlbloLlc drugs.
Slmllar resulLs were found employlng 20%<4))+,-+ ;+-0+)48&-& agalnsL 2<+3#)10100%&
+%,4%& Lo resLore Lhe anLlbacLerlal acLlons of clprofloxacln vla slmllar mechanlsms of
efflux pump lnhlblLlon.
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lndlrubln, exLracLed from Lhe leaves of ?,-*"<-+ <-80<1,-+6
used ln Ayurvedlc medlclne, has also been found Lo have an lnhlblLory effecL on
2<+3#)10100%& +%,4%&.
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nlneLeen herbs commonly used ln Chlnese medlclne have
lnhlblLory effecLs of whlch @485,1;48<"+$-+ 0+3-<+<+, .)&"1)<A-+ ,%*%)1&+6 .)&"1)<A-+
;)+85+6 B4,+8-%$ &<,-0<-34&6 =1)#*18%$ $%)<-9)1,%$ offer promlslng anLl-M8SA
posslblllLles.
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Zuo eL al. lnvesLlgaLed Lhe anLlmlcroblal effecLs of 30 planLs
LradlLlonally used Lo LreaL skln lnfecLlon focuslng on Lhelr poLenLlal Lo lnhlblL
2<+3#)10100%& +%,4%&/ Cf Lhese, 21 exLracLs were found Lo have anLl-M8SA effecLs
wlLh C/ #%88+848&-& and 2/ +,;1,4&048& belng Lhe mosL acLlve.
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6. 8elow we provlde a Lable revlewlng some promlslng evldenced-based research on
herbal medlclnes Lo help combaL Lhe growlng LhreaL of anLlbloLlc reslsLance. 1hls
presenLaLlon ls a selecLlve revlew lllusLraLlng Lhe way ln whlch herbal medlclnes
mlghL make a useful conLrlbuLlon, lL ls noL a comprehenslve and sysLemaLlc
evaluaLlon of Lhe evldence. 1o produce Lhls revlew searches were performed ln
CcLober 2013 ln AlLPealLhWaLch, AMLu, Lmbase, LsLar, Clnahl, Lhe Cochrane
Llbrary and ubMed.
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7. 1o provlde a pracLlcal evaluaLlon of Lhe evldence presenLed ln Lhls revlew we have
adapLed a verslon of Lhe wldely used C8AuL approach (Crades of 8ecommendaLlon,
AssessmenL, uevelopmenL and LvaluaLlon).
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1hls allows for 4 levels of raLlng of Lhe
research evldence - Plgh, ModeraLe, Low and very Low. lor slmpllclLy, we have
amalgamaLed Low and very Low grades lnLo a slngle caLegory of rellmlnary
evldence. 1hls selecLlve revlew hlghllghLs poLenLlally frulLful areas for fuLure
research.
8. Perbal medlclnes can help Lo resolve Lhe problem of anLlbloLlc reslsLance more
dlrecLly. uocLors faced wlLh relaLlvely mlnor, ofLen self llmlLlng, buL common
lnfecLlons eg pharynglLls, larynglLls and LonsllllLls or mlld urlnary LracL lnfecLlons
(u1ls) have llLLle Lo offer excepL advlce on how Lo manage Lhe condlLlon or oLherwlse
prescrlbe an anLlbloLlc whlch may noL be approprlaLe.
9. Perbal medlclnes can flll Lhls LherapeuLlc gap, provldlng effecLlve LreaLmenL LhaL
reduces anLlbloLlc prescrlblng and does noL conLrlbuLe Lo mlcroblal reslsLance. lor
example, a number of herbal medlclnes are LradlLlonally used Lo LreaL sore LhroaL
such as sage D2+)(-+ 199-0-8+)-&>
EF

EE
, dyers woad DG&+<-& <-80<1,-+)
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, echlnacea
(.0"-8+04+ 3%,3%,4+ or +8*%&<-91)-+)
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and burdock (H,0<-%$ )+33+>/
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Perbal
medlclne can also help Lo ease u1ls employlng remedles such as H,0<1&<+3"#)1& %(+
%,&-
EK
and L4+ $+#&/
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10. CLher common mlnor lnfecLlons may also be successfully LreaLed wlLh herbal
medlclnes sparlng use of more poLenL anLlbloLlcs. 1h|s |s a potent|a||y r|ch terr|tory
worth exp|or|ng as a pract|ca| way of combat|ng m|crob|a| res|stance to
convent|ona| ant|b|ot|cs. Perbal medlclnes have been used as anLlbloLlcs for
Lhousands of years, yeL remaln effecLlve, suggesLlng LhaL bacLerla have a reduced
ablllLy Lo adapL Lo a planL derlved anLlbacLerlal reglmen.