PHARMACOLOGICAL EVIDENCE OF HYPOTENSIVE ACTIVITY OF MARRUBIUM VULGARE AND FOENICULUM VULGARE IN SPONTANEOUSLY HYPERTENSIVE RAT

PHARMACOLOGICAL EVIDENCE OFHYPOTENSIVE ACTIVITY OF MARRUBIUMVULGARE AND FOENICULUM VULGARE IN

SPONTANEOUSLY HYPERTENSIVE RAT

Sanae El Bardai1 Badiaa Lyoussi1 Maurice Wibo2 and Nicole Morel2

1UFR Physiologie-Pharmacologie Faculteacute des Sciences Dahar-Elmahraz Fes Maroc

2Laboratoire de Pharmacologie Universiteacute catholique de LouvainUCL-5410 Avenue Hippocrate 54 B-1200 Brussels Belgium

ABSTRACT

The hypotensive effects of the water extract of Marrubium vulgare L andFoeniculum vulgare L were investigated in spontaneously hypertensive rats(SHR) and in normotensive Wistar-Kyoto rats (WKY) Oral administration ofMarrubium or Foeniculum extract lowered the systolic blood pressure of SHRbut not of WKY In SHR Foeniculum but not Marrubium treatment increasedwater sodium and potassium excretion Ex vivo as well as in vitro Marrubiumextract inhibited the contractile responses of rat aorta to noradrenaline and toKCl (100 mM) Inhibition was greater in aorta from SHR compared to WKYand was not affected by the NO synthase inhibitor N-nitro-L-arginine Vascular effects of Foeniculum extract were less pronounced than those ofMarrubium and were blocked by N-nitro-L-arginine These results indicatethat hypotensive activity of Marrubium and Foeniculum extracts seems to bemediated through different pathways Foeniculum appeared to act mainly as adiuretic and a natriuretic while Marrubium displayed vascular relaxant activity

Key Words Foeniculum vulgare Marrubium vulgare Diuresis Hyperten-sion Vasorelaxation SHR WKY

CLIN AND EXPER HYPERTENSION 23(4) 329ndash343 (2001)

Copyright copy 2001 by Marcel Dekker Inc wwwdekkercom

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INTRODUCTION

Marrubium vulgare L (horehound Lamiaceae) and Foeniculum vulgare L(fennel Apiaceae) are two medicinal plants used in folk medicine to cure a varietyof diseases In Moroccan traditional medicine water extract of Foeniculum vul-gare is used in association with Marrubium vulgare for the treatment of hyperten-sion Foeniculum ethanol extract has been reported to exhibit diuretic (1) antimi-crobial choleretic analgesic and antipyretic activities (2) It has also been reportedto lower the blood pressure of anesthetized rats (3) Hydroalcoholic extract of Marrubium vulgare has been shown to have analgesic (4) antispasmodic (5) andantidiabetic effects (6) However experimental evaluation of the hypotensive ac-tivity ascribed to this plant by traditional medicine is lacking

The aim of the present study was to investigate the pharmacological effectsof the aqueous extracts of the aerial parts of Marrubium and of Foeniculum fruit inan hypertensive rat strain (SHR) Our results provide experimental basis for furtherevaluation of these agents in the treatment of hypertension

MATERIALS AND METHODS

Preparation of the Extracts

Aerial parts of Marrubium vulgare L and fruits of Foeniculum vulgare Lwere used Plants were identified and authenticated according to the EuropeanPharmacopoeia They were cleaned and shade dried Water extracts were preparedby boiling 10 g of Foeniculum fruits or 5 g of Marrubium in 100 ml of distilled water for 10 min The water extracts were then filtered and lyophilized yielding ap-proximately 19 (ww) and 16 (ww) of dry extract for Foeniculum and Mar-rubium respectively

Experimental Animals and Schedule of Treatment

Male 9 weeks-old SHR and WKY rats (Iffa Credo lrsquoArbresle France) wereused They were divided at random in one control and two treated groups The Mar-rubium- and Foeniculum-treated rats were given Marrubium extract (80 mg dry ex-tractkg-1) and Foeniculum extract (190 mg dry extractkg-1) respectively once aday by gavage for five days The doses were choosen according to those used intraditional medicine Control rats received the same volume of water by gavageAll rats were fed with laboratory diet and water ad libitum They were kept in thesame environment in metabolic cages Urine was collected daily and stored atndash20degC until analysis The systolic blood pressure (SBP) was measured every dayby the tail-cuff method in conscious animals prewarmed at 37degC in thermostaticcages (Physiograph Narco Houston Tx USA) For each rat SBP was expressedas a percentage of the value before treatment

330 EL BARDAI ET AL

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Measurement of Contractile Response of Isolated Aorta

In order to investigate the effect of treatment on vascular reactivity ex vivoSHR and WKY rats were treated with the extracts for 4 days Rats were sacrificedby decapitation and aorta was rapidly removed and cleaned from the surroundingconnective tissue in cold (4degC) physiological solution

Contractile responses were measured as previously described by Morel et al(7) aortic rings (2 mm wide) were suspended under a resting tension of 20 mN in125 ml organ baths filled with a physiological solution (composition (mM) NaCl122 KCl 59 NaHCO3 15 MgCl2 125 CaCl2 125 glucose 11) bubbled witha gas mixture of 95 O2 5 CO2 and maintained at 37degC After an equilibrationperiod each preparation was contracted either by changing the physiological solu-tion in the bath to a depolarizing 100 mM KCl solution (composition (mM) NaCl27 KCl 100 NaHCO3 15 MgCl2 125 CaCl2 125 glucose 11) or by cumu-latively increasing the concentration of noradrenaline (Nad) in the physiologicalsolution Relaxation to acetylcholine (10-6 M) in Nad-precontracted arteries wasused to check the functional integrity of the endothelium At the end of the exper-iment the tissue was blotted between filter papers and weighed The contractiletension was expressed in mN per mg of wet weight

To investigate the effects of the plant extracts in vitro aortic rings from un-treated SHR and WKY rats were used After a first control contraction arteries wereincubated for 20 min in the presence of extract of Marrubium or Foeniculum beforea second contraction was evoked Isotonic extracts (437 mg dry extractml-1 and 45mg dry extractml-1 for Marrubium and Foeniculum respectively) were used finalconcentrations in the bath were 070 mgml-1 and 072 mgml-1 for Marrubium andFoeniculum respectively The amplitude of the second response was compared tothe response to the first stimulation Responses were corrected for the change in con-traction measured in control rings that were incubated in the absence of plant ex-tract Cumulative Ca2 concentration-effect curves were obtained after incubationof the artery rings in Ca2-free solution In some experiments NO synthase activitywas blocked with nitro-L-arginine (L-NOArg-100 M-30 min preincubation) (8)

Urine Analytical Procedure

Determinations were performed with a Technicon Axon System (Bayer Tar-rytown NY USA) Ions were quantified using ion selective electrode Urea andcreatinine were determined by colorimetric reaction

Statistics

Data are means sem Comparisons between values were performed usingStudentrsquos t-test or ANOVA when more than two groups were involved Differ-ences with a probability level 005 were considered statistically significant

MARRUBIUM AND FOENICULUM IN HYPERTENSION 331

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RESULTS

Effect of the Plant Extracts on SBP

SBP before treatment was 210 5 mm Hg in SHR (n17) and 156 1 mmHg in WKY (n15 P005) The SBP of untreated SHR did not change duringthe treatment period Both Marrubium and Foeniculum extracts significantly de-creased the SBP of SHR The hypotensive effect was detectable from day 2 andwas maximal at day 4 and 5 (Fig 1) At the end of treatment SBP rapidly returnedto its pretreatment value in the Foeniculum-treated rats In the Marrubium-treatedrats SBP remained significantly lower than the pretreatment value for 2 days andthen progressively increased (Fig 1)

In WKY both plant extracts produced a slight decrease in SBP at day 1 andday 2 but after 3 days of treatment the SBP was no longer significantly differentin treated and untreated rats (Fig 1)

332 EL BARDAI ET AL

Figure 1 Effect of the treatment with Marrubium or Foeniculum extract on SHR and WKY sys-tolic blood pressure Rats were treated with water (control SHR n6 WKY n3) with Marrubiumextract (80 mg dry extractkg-1day-1 SHR n5 WKY n3) or with Foeniculum extract (190 mgdry extractkg-1day-1 SHR n5 WKY n3) from day 1 to day 5 The treatment period is indicatedwith dashed lines Data are expressed as percentage of pretreatment value Mean values sem areshown significant difference between control and Marrubium treated rats (P005) dagger significantdifference between control and Foeniculum treated rats (P005)

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Screening for Diuretic Activity

The daily urine output of SHR was half that of WKY (65 03 ml n16rats versus 134 13 ml n9 rats P005) Foeniculum-treatment markedly en-hanced the daily urine output of SHR rats (Fig 2) This effect was maximal at day3 (80 12 of control) and remained stable until the end of treatment The ef-fect of Foeniculum was slowly reversible and the urine volume decreased to its pre-treatment value three days after the end of treatment Foeniculum-treatment induced a significant increase in Na and K renal excretion in SHR but did notaffect the excretion of creatinine and urea (Table 1)

Marrubium-treatment of SHR produced only a small effect on urine volumeat the beginning of the treatment (at day 2 and day 3 Fig 2) which vanished after


Figure 2 Effect of the treatment with Marrubium or Foeniculum extract on urine output in SHRand WKY Rats were treated either with water (control SHR n6 WKY n3) with Marrubiumextract (80 mg of dry extractkg-1day-1 SHR n5 WKY n3) or with Foeniculum extract (190mg of dry extractkg-1day-1 SHR n5 WKY n3) Treatment period is indicated with dashedlines Data are expressed in percentage of pretreatment value Mean values sem are shown sig-nificant difference between control and Marrubium-treated rats (P005) dagger significant differencebetween control and Foeniculum-treated rats (P005)

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3 days Marrubium extract had no effect either on electrolytes or on creatinine andurea excretion (Table 1 a)

Treatment of WKY with the plant extracts did not affect diuresis and elec-trolyte excretion significantly (Fig 2 and Table 1 b)

Ex Vivo Effect of the Plant Extracts on Contractile Responses of theAorta

As shown in Fig 3 the contractile response of aortic rings to 100 mM KClsolution was depressed by 19 34 (n14 P005) after treatment of SHR byMarrubium extract whereas it was not affected after treatment with FoeniculumNo significant ex vivo effect of the plant extract treatment on the contractile re-sponses to KCl was detected in WKY aorta (Fig 3)

Fig 4 shows that the concentration-response curve to Nad was depressed intreated SHR rats compared to control The effect of Foeniculum on the contractionto Nad was significantly smaller than that of Marrubium Plant treatment had no ef-fect on the Nad-evoked contraction of WKY aorta

In Vitro Effects of the Plant Extracts on Aortic Reactivity toVasoconstrictor Agents

Fig 5 shows the effect of the preincubation of aortic rings in the presence ofMarrubium or Foeniculum extract on the contraction evoked by 100 mM KCl-de-polarizing solution At the concentrations used the extracts did not change the os-

334 EL BARDAI ET AL

Table 1 Effect of Treatment with the Plant Extracts on the Renal Function of SpontaneouslyHypertensive Rats (SHR) and of Normotensive Wistar Kyoto Rats (WKY)

Untreated rats Foeniculum-treated Marrubium-treateda SHR (n=10) rats (n=8) rats (n=8)

Na+ (meqdayndash1) 134 plusmn 008 165 plusmn 009 121 plusmn 010K+ (meqdayndash1) 182 plusmn 010 233 plusmn 009 166 plusmn 013Urea (gdayndash1) 038 plusmn 002 041 plusmn 004 032 plusmn 002Creatinine (mgdayndash1) 921 plusmn 078 872 plusmn 068 838 plusmn 046

Untreated Foeniculum-treated Marrubium-treatedb WKY rats (n=12) rats (n=12) rats (n=11)

Na+ (meqdayndash1) 159 plusmn 012 147 plusmn 007 149 plusmn 008K+ (meqdayndash1 193 plusmn 014 181 plusmn 011 182 plusmn 011Urea (gdayndash1) 032 plusmn 002 031 plusmn 002 028 plusmn 002Creatinine (mgdayndash1) 902 plusmn 028 938 plusmn 024 856 plusmn 045

Determinations were performed on the urine of untreated rats and of rats treated with aqueous extractof Foeniculum (190 mgkgndash1dayndash1) or Marrubium (80 mgkgndash1dayndash1) Urine was collected at day 4and 5 of the treatment Plt005 versus untreated rats

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molarity of the solution and did not increase tone Marrubium extract inhibited theKCl-induced contraction of untreated SHR and WKY aorta (Fig 5) while Foenicu-lum did not exhibit a significant effect Higher concentrations of Foeniculum (upto 15 mgml-1) were also tested at these higher concentrations Foeniculum pro-duced a marked transient increase in contractile tension which could be related tothe hypertonicity of the solution but did not affect KCl-evoked contraction (notshown) The inhibition of the KCl-evoked contraction by Marrubium extract wasconcentration-dependent and was slightly greater in aorta from SHR compared toWKY (Fig 6) Maximal inhibition was produced with 07 mgml-1 of Marrubiumextract and reached 87 15 (n5) and 73 37 (n5) of the control con-traction in SHR and in WKY respectively (P005) Concentration producing 50 inhibition of the KCl-evoked contraction was equal to 014 001 mgml-1 and019 002 mgml-1 in SHR and WKY respectively (P005) In SHR the con-traction evoked by the cumulative addition of Ca2 in 100 mM Ca2 free KCl so-lution was also markedly blunted in the presence of Marrubium extract (Fig 7)

Fig 8 shows the effect of the incubation of the aortic rings with the plant ex-tracts on the contraction evoked by Nad Nad concentration-effect curves were de-pressed in aortic rings incubated in the presence of Marrubium extract Maximumcontraction to Nad (3 M) was inhibited by 73 44 (n5) and 37 35 (n5) in SHR and WKY respectively (P005 Fig 8) In the presence ofFoeniculum extract the maximum contraction to Nad was depressed by 19 62 in SHR aorta but was not significantly affected in WKY aorta (Fig 8)


Figure 3 Effect of the gavage with plant extracts on contractions to KCl (100 mM) in SHR andWKY aorta Aortic rings were taken from control rats (n 7) Marrubium-treated rats (80 mg of dryextractkg-1day-1 n7) and Foeniculum-treated rats (190 mg of dry extractkg-1day-1 n7) Dataare mean values sem significant difference between control and Marrubium-treated rats(P005)

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336 EL BARDAI ET AL

Figure 4 Effect of the gavage with plant extracts on noradrenaline induced contractions in SHR (a)and WKY (b) aorta Aortic rings were taken from control rats (n 19) Marrubium-treated rats (80mg of dry extractkg-1day-1 n20) and Foeniculum-treated rats (190 mg of dry extractkg-1day-1n20) significant difference between control and Marrubium-treated rats (P005) dagger significantdifference between control and Foeniculum-treated rats (P005) Dagger significant difference betweenMarubium- and Foeniculum-treated rats (P005)

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Figure 5 In vitro effect of the extracts on contractions to KCl (100 mM) in aortic rings from SHRand WKY For each preparation two runs were performed the first contraction was evoked by KCl100 mM solution in the absence of the extract the second one was obtained after 20 min preincuba-tion without extract (control) with Marrubium extract (07 mgml-1) or Foeniculum extract (072mgml-1) Results are expressed in of the first run Each value is the mean sem of at least 8 mea-surements significant difference between control and Marrubium (P005)

Figure 6 Concentration-inhibition curve of KCl-induced contraction in SHR and WKY aorta byMarrubium extract in vitro After a first contraction was evoked by KCl (100 mM) in the absence ofthe extract a second contraction was obtained after 20 min preincubation with different concentra-tions of Marrubium extract Results are expressed in of the first run Each value is the mean semof at least 5 measurements

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The involvement of the NO synthase pathway in the effect of the plant ex-tracts was tested by incubating the artery in the presence of the NO synthase in-hibitor L-NOArg (100 M) This concentration of L-NOArg completely abolishedthe relaxation evoked by acetylcholine in Nad-contracted artery (not shown) Therelaxation evoked by the addition of Marrubium extract on the plateau of the con-traction evoked by Nad in SHR aorta was not affected by L-NOArg (Fig 9) whilethe relaxation evoked by Foeniculum extract added in the same condition was in-hibited in the presence of L-NOArg (Fig 9)

DISCUSSION

The present results show that the water extracts of Marrubium and Foenicu-lum exhibit potent hypotensive activity when administrated orally to hypertensiverats

The kidney plays a dominant role in the long-term control of blood pressureIndeed hypertension can develop when the ability of the kidney to excrete sodiumand water is impaired Our study shows that in SHR Foeniculum extract likewell-known diuretics promoted water and potassium excretion and restored thedaily rate of renal sodium excretion to a level similar to that observed in WKYSuch an effect has been reported in SHR with some calcium channel blockers and

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Figure 7 Effect of Marrubium extract on contractions evoked by calcium in KCl-depolarizedaorta Preparations were preincubated in calcium-free physiological solution depolarized in calciumfree KCl-rich solution and then incubated with increasing calcium concentration in the absence or inthe presence of Marrubium Responses are expressed in percentage of maximal contraction evokedbefore addition of Marrubium Each point is the average of five measurements sem

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Figure 8 In vitro effect of Marrubium and Foeniculum extracts on cumulative concentration-re-sponse curves to noradrenaline in aortic artery rings from SHR (a) and WKY (b) For each preparation two runs were performed the first contraction was evoked by cumulatively increasingconcentration of noradrenaline in the absence of the extract the second one was obtained after 20 minpreincubation without extract (control) with Marrubium extract (07mgml-1) or with Foeniculum ex-tract (072mgml-1) Results are expressed in of the maximal response of the first run Each pointis the mean of at least 5 determinations sem significant difference between control and Marru-bium (P005) dagger significant difference between control and Foeniculum (P005)

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is related to the selective increase in medullary blood flow (9) Ca2 channel block-ing activity of Foeniculum extract tested by investigating the sensitivity of thecontraction evoked by 100 mM KCl solution was not detected in in vitroexperiments However an important limitation in these experiments was that highconcentrations of the Foeniculum extract caused alterations of the vascular toneNevertheless we have found that the vasodilatation produced by the isosmoticFoeniculum extract in SHR aorta precontracted with Nad was sensitive to the NOsynthase blocker NOArg suggesting that Foeniculum might activate the produc-tion of NO Many studies have indicated that NO plays an important role in the reg-ulation of blood flow in the renal medulla and in sodium excretion (10) The renaleffect of Foeniculum might thus be related to an increased production of NO Wehave also shown that the excretion of creatinine and urea was not altered duringtreatment with Foeniculum suggesting that the extract did not affect the glomeru-lar blood flow or the glomerular filtration rate However further studies are re-

340 EL BARDAI ET AL

Figure 9 Typical records showing the influence of N-nitro-L-arginine (L-NOArg 100 M) on theeffect of Marrubium and Foeniculum extracts on the contraction evoked by noradrenaline in SHRaortic rings Contraction was evoked by noradrenaline (Nad) 1 M (without L-NOArg) or 02 M(with L-NOArg) L-NOArg (100 M) was preincubated for 30 min before the addition of Nad Mar-rubium extract (07 mgml-1) or Foeniculum extract (07 mgml-1) were added as indicated

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quired to determine more precisely the mode of action of Foeniculum extract andthe underlying mechanisms involved At the end of the treatment with Foeniculumthe hypotensive effect disappeared rapidly even though the diuresis was still sig-nificantly increased This finding suggests either that Foeniculum contains at leasttwo active components one long-lasting responsible for the diuretic effect andthe other responsible for the hypotensive effect or that the same component is im-plicated in both actions and acts as a diuretic and an hypotensive agent at highdoses and only as a diuretic at lower doses Such a dissociation between diureticand hypotensive activity was found with Bredemeyera floribunda extract (11)

The treatment of hypertensive rats with Marrubium also produced a potenthypotensive effect This effect was specific for the SHR and apparently did not in-volve changes in renal function but might be related to the vasodilatory effect ex-hibited by the water extract ex vivo as well as in vitro In SHR responses to KCland to Ca2 in a depolarized artery were markedly inhibited by Marrubium extractboth ex vivo and in vitro Nad evoked contraction was also depressed It is wellknown that high-K induced-contraction in smooth muscle is mediated by a cellmembrane depolarization and an increase in Ca2 influx through voltage-gatedCa2 channels (12 13) Inhibition by Marrubium of the KCl-evoked responsessuggests that Marrubium could act as a blocker of voltage-gated calcium channels(14) However the inhibition of the Nad-evoked contraction which is not solelydependent on the entry of extracellular Ca2 through voltage-operated Ca2 chan-nels but which also involves the release of intracellular Ca2 and an increase in thesensitivity to Ca2 of the contractile machinery (15) might indicate that Marrubium extract could have multiple vascular effects Interestingly Marrubiumextract was less effective in aorta from WKY than in aorta from SHR This obser-vation could explain why Marrubium treatment did not produce a significantchange in the SBP of WKY rats while it decreased SBP of SHR The characteris-tics of Marrubium actions are reminiscent of the effect of dihydropyridine Ca2

channel blockers these agents exhibit an increased potency in arteries from hy-pertensive rats compared to normotensive rats (7) a property related to the in-creased activity of voltage-dependent Ca2 channels in hypertensive arteries (7)Dihydropyridine Ca2 channel blockers also selectively depress the SBP of hy-pertensive rats compared to normotensive animals (7 16)

Marrubium is listed by the council of Europe as a natural source of foodflavouring (17) Its chemistry is well documented Expectorant and vasodilatoryproperties have been described for the volatile oil (18) Apigenin (4rsquo57-trihy-droxyflavone) which has been isolated from Apium graveolens but has been reported to be present in Marrubium (19) exhibits blocking activity on both volt-age-and receptor-operated calcium channels (20) and could be responsible forsome of the effects observed in the present study Further studies are being under-taken to identify the active compounds in the extracts

In conclusion the results reported here show that Marrubium and Foenicu-lum water extracts act by different and complementary mechanisms and supportthe use of aqueous decoction of Marrubium vulgare and Foeniculum vulgare as an-tihypertensive treatment in traditional medicine


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ACKNOWLEDGMENTS

This work was supported by grant ARC 9500-188 from the General Direc-tion of Scientific Research of the French Community of Belgium The authorsthank GVandenberg and MCHamaide for their skilful technical assistance and DrMPhilippe for her collaboration

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16 Kazda S and Knorr A Calcium antagonists In Pharmacology of anti-hypertensivetherapeutics Ganten D Mulrow PJ eds Springer-Verlag Berlin 1990 pp 301-75

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17 Newall CA Anderson LA and Phillipson JD Herbal Medicines Aguide forhealth-care professionals The Pharmaceutical Press London 1996

18 Karryev MO Bairyev CB and Ataeva AS Some therapeutic properties andphyto chemistry of common horehound Izv Akad Nauk Turkm SSR Ser BiolNauk 1976 3 86-8

19 Kowalewski Z and Matlawska I Flavonoid compounds in the herb of MarrubiumVulgare L Herba Pol 1978 24 183-186

20 Ko F-N Huang TF and Teng CM Vasodilatory action mechanisms of apigeninisolated from Apium graveolens in rat thoracic aorta Biochim Biophys Acta 19911115 69-74

Submitted August 7 2000Revised September 27 2000Accepted October 2 2000


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INTRODUCTION

Marrubium vulgare L (horehound Lamiaceae) and Foeniculum vulgare L(fennel Apiaceae) are two medicinal plants used in folk medicine to cure a varietyof diseases In Moroccan traditional medicine water extract of Foeniculum vul-gare is used in association with Marrubium vulgare for the treatment of hyperten-sion Foeniculum ethanol extract has been reported to exhibit diuretic (1) antimi-crobial choleretic analgesic and antipyretic activities (2) It has also been reportedto lower the blood pressure of anesthetized rats (3) Hydroalcoholic extract of Marrubium vulgare has been shown to have analgesic (4) antispasmodic (5) andantidiabetic effects (6) However experimental evaluation of the hypotensive ac-tivity ascribed to this plant by traditional medicine is lacking

The aim of the present study was to investigate the pharmacological effectsof the aqueous extracts of the aerial parts of Marrubium and of Foeniculum fruit inan hypertensive rat strain (SHR) Our results provide experimental basis for furtherevaluation of these agents in the treatment of hypertension

MATERIALS AND METHODS

Preparation of the Extracts

Aerial parts of Marrubium vulgare L and fruits of Foeniculum vulgare Lwere used Plants were identified and authenticated according to the EuropeanPharmacopoeia They were cleaned and shade dried Water extracts were preparedby boiling 10 g of Foeniculum fruits or 5 g of Marrubium in 100 ml of distilled water for 10 min The water extracts were then filtered and lyophilized yielding ap-proximately 19 (ww) and 16 (ww) of dry extract for Foeniculum and Mar-rubium respectively

Experimental Animals and Schedule of Treatment

Male 9 weeks-old SHR and WKY rats (Iffa Credo lrsquoArbresle France) wereused They were divided at random in one control and two treated groups The Mar-rubium- and Foeniculum-treated rats were given Marrubium extract (80 mg dry ex-tractkg-1) and Foeniculum extract (190 mg dry extractkg-1) respectively once aday by gavage for five days The doses were choosen according to those used intraditional medicine Control rats received the same volume of water by gavageAll rats were fed with laboratory diet and water ad libitum They were kept in thesame environment in metabolic cages Urine was collected daily and stored atndash20degC until analysis The systolic blood pressure (SBP) was measured every dayby the tail-cuff method in conscious animals prewarmed at 37degC in thermostaticcages (Physiograph Narco Houston Tx USA) For each rat SBP was expressedas a percentage of the value before treatment

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334 EL BARDAI ET AL







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338 EL BARDAI ET AL


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ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

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332 EL BARDAI ET AL


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334 EL BARDAI ET AL







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336 EL BARDAI ET AL


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338 EL BARDAI ET AL


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340 EL BARDAI ET AL


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ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

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332 EL BARDAI ET AL


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334 EL BARDAI ET AL







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336 EL BARDAI ET AL


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338 EL BARDAI ET AL


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342 EL BARDAI ET AL

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334 EL BARDAI ET AL







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336 EL BARDAI ET AL


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338 EL BARDAI ET AL


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340 EL BARDAI ET AL


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ns D

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ns D

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ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

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334 EL BARDAI ET AL







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336 EL BARDAI ET AL


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338 EL BARDAI ET AL


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onl

y

ORDER REPRINTS



Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


340 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS





Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

336 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS




Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


DISCUSSION



338 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS



Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


340 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

336 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS




Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


DISCUSSION



338 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS



Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


340 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS




Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


DISCUSSION



338 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS



Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


340 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


DISCUSSION



338 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS



Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


340 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS



Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


340 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS


340 EL BARDAI ET AL


Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS

ACKNOWLEDGMENTS


REFERENCES

















342 EL BARDAI ET AL

Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

ORDER REPRINTS







Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Order now








Clin

Exp

Hyp

erte

ns D

ownl

oade

d fr

om in

form

ahea

lthca

rec

om b

y U

nive

rsity

of

Gla

sgow

on

092

613

For

pers

onal

use

onl

y

Documents

PHARMACOLOGICAL EVIDENCE OF HYPOTENSIVE ACTIVITY OF MARRUBIUM VULGARE AND FOENICULUM VULGARE IN SPONTANEOUSLY HYPERTENSIVE RAT