IJBCP International Journal of Basic & Clinical Pharmacology

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1 Print ISSN: Online ISSN: IJBCP Interntionl Journl of Bsi & Clinil Phrmology DOI: Reserh Artile Antihypertensive nd ntitherogeni effets of Tnopti trditionl reipe used for the tretment of high lood pressure Amni Komenn Nzire 1 *, Djyh Bernrd Nzire 1, Bog Gogo Luien 1, Koussi Konn 1, Severin Koukou Konn 2, N Guessn Jen Dvid 1 1 Deprtment of Biohemistry, Lortory of Biohemil Phrmodynmy, Félix Houphouët Boigny, University of Aidjn, (225)22 BP 582 Aidjn 22, Côte d Ivoire 2 Deprtment of Biohemistry nd Food Sienes, Gon Peleforo University of Korhogo, (225)22 BP 1328 Korhogo, Côte d Ivoire Reeived: 15 My 216 Aepted: 9 June 216 *Correspondene to: Dr. Amni Komenn Nzire, Emil: nzire.mni@yhoo.fr Copyright: the uthor(s), pulisher nd liensee Medip Ademy. This is n openess rtile distriuted under the terms of the Cretive Commons Attriution Non- Commeril Liense, whih permits unrestrited nonommeril use, distriution, nd reprodution in ny medium, provided the originl work is properly ited. ABSTRACT Bkground: The ojetive of the present study ws to investigte the possile effet of Tnopti on indued hyperholesterolemi in rts nd hypertension in rits. Methods: Twenty wistr rts were divided into 4 groups eh nd then sujeted to different tretments. Hyperholesterolemi ws indued y indued dietry holesterol; the rts re then treted with Tnopti nd Questrn ) Sixteen rits mles, divided in four lots with four rits eh, were used in this study. Hypertension ws indued y drenlin (1 mg/ml for 2 weeks intrmusulrly) in the lots 2 to 4. After indution of hypertension in nimls, they were treted with the extrt of Tnopti. The rdiovsulr prmeters of rits (systoli lood pressure (SBP), distoli lood pressure (DBP) nd hert rte (HR) ws tken with n eletri mnometer. These three rdiovsulr prmeters were then ompred to the witness group. Results: The tretment with the Tnopti nd with Questrn signifintly improved (p <.5) these prmeters y deresing the onentrtions of totl holesterol, triglyeride nd LDL-holesterol ginst n elevtion of HDL holesterol levels. After 8 dys of tretments on rits indued hypertension with Tnopti or with Tenordte, rdiovsulr prmeters deresed signifintly up to their normliztion vlues. Conlusions: The results otined onfirm the ntihypertensive effet of Tnopti nd justify it trditionlly use in tretment of high lood pressure. Keywords: Tnopti, Antihyperholesterolemi, Crdiovsulr index, Adrenline INTRODUCTION Crdiovsulr disese (CVD) is the leding use of mortlity worldwide nd hypertension remins the most ommon rdiovsulr disese nd mjor puli helth issue in oth developed nd developing ountries. 1 Hypertension, ording to the Ntionl High Blood Pressure Edution Progrm (NHBPEP), is defined s systoli lood pressure (SBP) equl or greter thn 14 mmhg nd distoli lood pressure (DBP) s equl or more thn 9 mmhg, tking ntihypertensive medition, or eing told twie y physiin or other professionl tht one hs hypertension. It is lso defined s ondition in whih the rteril lood pressure is hronilly elevted. Hypertension is onsidered n independent, useful nd powerful prognosti inditor for rdiovsulr nd renl disese, wheres it is signifintly ssoited with the inresed moridity nd mortlity from ererovsulr disese, myordil infrtion, ongestive hert filure nd renl insuffiieny. 1 Vrious studies indite tht high levels of serum holesterol re losely linked to theroslerosis nd inresed risk of vrious rdiovsulr diseses. Interntionl Journl of Bsi & Clinil Phrmology Septemer-Otoer 216 Vol 5 Issue 5 Pge 193

2 Nzire AK et l. Int J Bsi Clin Phrmol. 216 Ot;5(5): Crdiovsulr diseses, inluding oronry hert disese, stroke (stroke) nd hypertension hve some mjor helth threts worldwide tody. High plsm lipids (hyperlipidemi nd other norml lood lipid profile) re mong the risk ftors ommonly involved in most rdiovsulr prolems. Under these onditions, lipids nd other relted sustnes umulte on the rteril wll, forming plte whih oludes the lumen nd ostruts lood flow to vitl orgns suh s the hert, rin, liver, or kidneys. Lipids with signifint elevtions re involved in these diseses re holesterol nd triglyerides. They re generlly trnsported in the form of lipid-protein omplexes lled lipoproteins, whih re lssified ording to their density nd their lods. Cholesterol nd high density lipoprotein (HDL-C) trnsports lipid lood ells in the liver, while the low-density lipoprotein holesterol (LDL-C) moilizes lipids in the ells nd lood vessels. The inresed levels of triglyerides, totl holesterol nd LDL-C nd HDL-C redution promote the development of theroslerosis nd relted ererovsulr disorders. The tretment mngement is usully lifelong tretment nd the ost of tretment is not ffordle to the mjority of the developing ountries popultion tht hs reourse to reipe from mediinl plnts. In the lst three dedes, lot of onerted efforts hve een hnneled into reserhing into lol plnts with hypotensive nd ntihypertensive therpeuti vlues, with the therpeuti potentils of some of these mediinl plnts either vlidted or outrightly disproved. However, ttempts y the low-inome group, prtiulrly the rurl dwellers in the developing ountries, to ontrol hypertension nd its ttendnt omplitions in the fe of the sre soioeonomi resoures, hve led more people opting for herl remedy. 2 Identifition of ntihypertensive foods nd herl remedies is urrently interested euse they re expeted to prevent hypertension with lower side-effets thn ntihypertensive drugs. 3 But, these drugs hve vrious side effets tht ould led to the mlfuntioning of the ody funtion e.g. formtion of gll stones, gll ldder diseses, ithing nd dirrhe. Therefore, muh ttention hs een shifted to the use of nturl produts from plnts with very few side effets in the tretment of theroslerosis. 3 The mehnisms of these produts re eliited to ountert the effet of hypertension nd ssoited risk ftors suh s hyperholesterolemi, hypertriglyeridemi, nd oxidtive stress on lood vessel wlls. They inlude diret vsodiltion of the lood vessel, loking of lium hnnels, inhiition of α-drenoreeptor response, indution of negtive ionotropi response of smooth musle, inhiition of pltelet ggregtion, redution of vsulr resistne, nd improvement of pulmonry oxygen utiliztion. 4 Enhned tivity of nitri oxide nd improved hndling of intrellulr lium hs lso een found to ply ritil role in the redution of vsulr resistne nd lood pressure tht re elevted in hypertensive rts nd humns. 5 Mny reserhers re tively looking for ntihypertensive ompounds derived from vrious nturl produts for the use in funtionl foods. Severl studies hve shown tht food ingredients rih in flvonoids nd other polyphenols n lower lood pressure. 6 Ours erlier studies hve demonstrted tht the extrt of Tnopti, polyherl formultion used in tretment of high lood pressure is rih in phenoli ompounds suh s tnnins, flvonoids, leuonthoyns, nthoyns. 7 The im of the present study ws to investigte the possile effet of Tnopti on indued hyperholesterolemi in rts nd hypertension in rits. METHODS Chemils Quesrn, ws otined from phrmeutil ompny in Aidjn (Cote d Ivoire). HDL Cholesterol, Totl Cholesterol nd Triglyeride Kits, Potssium Phosphte uffer nd Cholesterol, were otined from Rohe Dignostis (Frne). Plnt mteril The plnt mteril is reipe otined from the deotion of roots, leves nd rk of ivorin trditionl mediine plnts. These re: Agertum onyzoides, Newouldi levis, Phyllnthus muellerinus, Aloe ver nd Cssi oidentlis. This reipe ws ppointed y the helth Tnopti trditionl heler. Animls Mle s wistr rts weighing 15-2 g proured from the niml house of the fulty of phrmeutil nd iologil sienes, Félix Houphouet-Boigny University of Aidjn. Rits mles of the speies Orytolgus uniulus, ged 1 weeks weighting 18 to 22 g were used. These nimls were rought from poultry frm in Aidjn, were limted for two weeks t the Animl unit of the fulty of phrmeutil nd iologil sienes, Félix Houphouet-Boigny University of Aidjn. All these nimls were housed in plsti ges where they hd free ess to wter nd food, nd kept t temperture of 22±3 C with reltive humidity of 5.15%. The yle of light nd drkness ws 12 h/12 h. All the experimentl proedures were pproved y the Ethil Committee of Helth Sienes, Félix Houphouet- Boigny University of Aidjn. These guidelines were in ordne with the Europen Counil Legisltion 87/67/EEC for the protetion of experimentl nimls. Interntionl Journl of Bsi & Clinil Phrmology Septemer-Otoer 216 Vol 5 Issue 5 Pge 194

3 Nzire AK et l. Int J Bsi Clin Phrmol. 216 Ot;5(5): Preprtion of lyophilized extrt Tnopti This reipe ws provided y M. Adou Tno Alert, n Ivorin trditionl prtitioner. The deotion ws then lyophilized nd stored in the freezer for the study. Evlution of ntitherogeni tivity of lyophilized extrt Tnopti This study ws to indue hyperholesterolemi with dietry holesterol nd to evlute the ntihyperholestérolémi effet of Tnopti using Questrn s referene produt. Experimentl Protool The experiment ws onduted ording to the method of Erukinure et l. 8 Twenty (2) mle lino rts were divided into 4 groups of 5 nimls eh nd then sujeted to different tretments. Group 1 (norml ontrol) hs reeived from orn oil (.3 ml / rt) throughout the experiment. Group 2 (experimentl ontrol) RCU hs only holesterol (4 mg/kg w) for the durtion of the experiment. Group 3 (Tnopti) hs reeived holesterol (4 mg/kg w) then Tnopti Group 4 (Questrn ) hs reeived holesterol (4 mg / kg BW) followed Questrn (26 mg/kg w). The dministrtion of Questrn, Tnopti, nd holesterol were given orlly 5 times week for 6 weeks using n intrgstri tue to the volume of 5 ml/kg w. Corn oil ws used s vehile to Tnopti, Questrn nd holesterol. The dose of the extrt of Tnopti ws lulted from the dosge given y the helth trdiprtitioner. At the end of 6 weeks of tretment, nimls were srified under light nesthesi with ether vpor. The lood olleted in EDTA tues ws entrifuged t 3 revs/min for 1 min nd the superntnt (plsm) ws used for the determintion of totl holesterol, HDL holesterol nd triglyerides. Estimtion of iohemil prmeters of interest Totl holesterol ws ssyed y the method of holesterol oxidse (CHOD)/peroxidse (POD). 9 HDL holesterol ws mesured y the method preipittion. 1 The onentrtion of serum LDL is determined y the differene method of the eqution y Friedewld et l. 11 Triglyerides were ssyed y the method of the oxidse glyerol 3-phosphte (GPO)/peroxidse (POD). 12 The therogeni index ws lulted y the following formul: Effet of Tnopti on lood pressure nd hert rte Chemils nd drugs Adrenlin nd Ténordte were otined from lol offie, Aidjn, Cote d Ivoire, Tnopti ws gifted y n Ivorin trditionl prtitioner, ll regents, solvents nd hemil ompounds used for nlysis met the qulity riteri in ordne with interntionl stndrds Experimentl protool The experiment ws performed y the method desried y Tiekp et l. 13 Sixteen (16) mle rits were divided into 4 lots of 4 rits (Lot1to 4). Lot 1 or witness lot reeived throughout the durtion of the experiment distilled wter; Lot 2-6 or experimentl lots were intrmusulrly injeted with n insulin syringe, drenline dosed t 1 mg/ml to use elevted lood pressure or hypertension, whih ws lter stilized fter 14 dys of tretment. Blood pressure of rits ws tken with n eletri mnometer whih uff ws dpted to the leg of rit. The uff ws wrpped round the left hide leg of the niml nd its infltion guge enled with the on utton. The uff infltes to the mximum to tighten up the leg of the niml nd defltes immeditely. It ppers on the mnometer sreen, systoli pressure, distoli pressure nd the hert rte of rit. These three rdiovsulr prmeters of rits were then ompred to the witness group. After indution of hypertension in nimls, they were treted with the Tnopti nd Ténordte referene ntihypertensive sold in the mrket. Eh lot ws treted s follows: LOT 1: Witness + distilled wter LOT 2: Witness treted with drenline (Adr) LOT 3: Treted with Adrenlin + Ténordte (Atenolol + Nifedipine) (1 mg/kg w) LOT 4: Treted with Adrenlin + Tnopti (1 mg/kg w) Sttistil nlysis The results re expressed s men±sem. The results were nlyzed using one-wy ANOVA followed y Turkey s multiple omprison tests. Dt ws omputed for sttistil nlysis y using grph pd prism 5 Softwre. P vlues.5 were onsidered s signifint. RESULTS Effet of the extrt of Tnopti on indued hyperholesterolemi in rts The results show tht plsm onentrtions of totl holesterol, triglyeride nd LDL holesterol were signifintly higher (p <.5) in the group ddited to Interntionl Journl of Bsi & Clinil Phrmology Septemer-Otoer 216 Vol 5 Issue 5 Pge 195

4 onentrtion de triglyérides(mg/dl) onentrtion de holestérol totl(mg/dl) Nzire AK et l. Int J Bsi Clin Phrmol. 216 Ot;5(5): dietry holesterol, while HDL holesterol rte is lower thn the norml group ontrol. The tretment with the Questrn nd Tnopti signifintly improved (p <.5) these prmeters y deresing the onentrtions of totl holesterol, triglyeride nd LDL-holesterol ginst n elevtion of HDL-holesterol levels ompred to rts of hyperholesterolemi group. Furthermore we see tht there's signifint differene (p >.5) results etween the group treted with Tnopti nd the other treted with Questrn regrding the onentrtions of totl holesterol nd LDL holesterol, ut no signifint differene (p >.5) results in terms of triglyeride nd HDL for oth groups. The link etween dyslipidemi rdiovsulr diseses is prtiulrly well estlished. The elevtion of Totl Cholesterol nd LDL Cholesterol is ssoited with n inresed rdiovsulr risk. A low onentrtion of HDL n e regrded s n dditionl risk ftor, then high onentrtion of the HDL is protetive ftor. Beuse of this inverse reltionship etween rdiovsulr risk nd LDL one hnd, the other hnd HDL, it hs een proposed tht the rtio [totl holesterol/hdlc] or therogeni index s preher rdiovsulr risk. Prtiulrly rdiovsulr risk inreses when this rtio exeeds 5. Figure 36 shows the estimted rdiovsulr risk of different groups. The results indite tht rdiovsulr risk is very High signifintly (p <.5) in the group of rts ddited to holesterol ompred to tht of nimls of norml ontrol groups. Tretment with Tnopti nd Qestrn extrt signifintly deresed (p <.5) this risk with vlues elow norml for Tnopti. Effet of Tnopti on lood pressure nd hert rte in rits (BP nd HR) Tle 1 shows the vlues of rdiovsulr prmeters systoli lood pressure (SBP), distoli lood pressure (DBP) nd hert rte (HR) of nimls of the ontrol lots, sik not treted nd treted with Tnopti nd Tenordte (tenolol+nifedipine). Crdiovsulr prmeters vlues for nimls in witness lot, SBP, DBP nd HR were respetively 123.4±.2 mmhg for SBP; 81.1±3 mmhg for DBP nd 23.8±5.7 et/min for HR. These vlues inresed signifintly (p <.5) fter the indution of hypertension in rits respetively to 178.5±.5 mmhg for SBP, ±1.33 mmhg for DBP nd 329; 97±2.3 et/min for HR tht is perentges inrese of 44, 65.43%, 44.79%, 42,96% respetively. These prmeters (SBP, DBP nd HR) deresed signifintly (p <.5) up to their normliztion with the tretment of Tenordte (1 mg/kg w) nd Tnopti, t doses of 1 mg/kg w. The SBP vlues hnge from 178.5±.5 mmhg to 12.7±1.6 mmhg for SBP, ±1.33 mmhg to 83±1.3 mmhg for DBP nd 329; 97±2.3 mmhg to 231±1; 21 mmhg for fter 14 dys of tretment with Tnopti. With Tenordte (1 mg/kg.w), the vlues otined re ±.7 mmhg, 79.61±2.1 mmhg nd 223±4.5 mmhg for SBP, DBP nd HR respetively. Tle 1: Vlues of SBP, DBP, nd HR in rits treted nd not treted with drenline, the Tenordte nd Tnopti fter 14 dys of tretment. Tretments Crdiovsulr prmeters SBP DBP HR Distilled wter 123.4± ± ± 5.7 Adrénline 178.5± ± ± 2.3 Adrénline+ 12.7± 83± ± 1.21 Tnopti 1.6 Adrénline+ Ténordte 117.8± ± ± 4.5 Vlues re mens±sem for 4 rits. nd re row vlues with different supersripts re signifintly different (p.5). SBP: systoli lood pressure, DBP: distoli lood pressure, HR hert rte ontrôle norml d Reg Hyperhol questrn tnopti Figure 1: Effet of the extrt of Tnopti on totl holesterol ontrôle norml ontrôle expérimentl Figure 2: Effet of the extrt of Tnopti on triglyerides. questrn tnopti Interntionl Journl of Bsi & Clinil Phrmology Septemer-Otoer 216 Vol 5 Issue 5 Pge 196

5 Index thérogenique onentrtion de HDL(mg/dl) onentrtion de LDL(mg/dl) Nzire AK et l. Int J Bsi Clin Phrmol. 216 Ot;5(5): ontrôle norml ontrôle expérimentl questrn tnopti Figure 3: Effet of the extrt of Tnopti on LDL nd LDL holesterol nd derese HDL holesterol. In those irumstnes, the lipids umulte on the rteril wll, therey forming plte whih oludes the lumen nd redues lood flow to vitl orgns suh s the hert, rin, liver, or kidney. This nrrowing of the vsulr lumen would result in the elevtion of lood pressure. The inrese in the level of triglyerides, totl holesterol nd LDL holesterol nd redued HDL holesterol thus promote the development of theroslerosis nd hypertension. 14 Our results indite tht the extrt of Tnopti, dministered t the doses of 1 mg/kg w uses derese of the onentrtions of triglyerides, totl holesterol nd rendered LDL serum holesterol in rts hyperholesterolemi y onsumption of dietry holesterol. The underlying mehnism y whih the extrt Tnopti exerised its hypoholesterolemi effet my e derese in intestinl sorption of holesterol y inding with the ile ids in the intestine nd inresed iliry exretion ontrôle norml ontrôle expérimentl questrn tnopti Tnopti ould lso t y reduing holesterol iosynthesis speifilly y deresing the tivity of hydroxymethylglutryl-oeenzyme A (HMG-CoA) redutse. 16 In ddition, the Tnopti ould lower the onentrtion of serum holesterol y modifying the lipoprotein metolism, enhning the sorption of LDL y the LDL reeptors inrese nd/or inresing the tivity of leithin yl trnsferse-holesterol (LCAT). 17 Figure 4: Effet of the extrt of Tnopti on HDL ontrôle norml Figure 5: Effet of the extrt of Tnopti on therogeni index. DISCUSSION ontrôle expérimentl questrn tnopti The results show tht dietry holesterol intke five times week for six weeks in rts uses hyperholesterolemi resulted in n inrese in totl holesterol, triglyerides The link etween dyslipidemi nd rdiovsulr diseses is prtiulrly well estlished. The elevtion of Totl Cholesterol nd LDL Cholesterol is ssoited with n inresed rdiovsulr risk. A low onentrtion of HDL-C n e regrded s n dditionl risk ftor, nd then high onentrtion of HDL-C is protetive ftor. Beuse of this inverse reltionship etween rdiovsulr risk nd LDL one hnd, the other hnd HDL, it hs een proposed to use the rtio [totl holesterol/hdl-c or therogeni index s rdiovsulr risk preditor. The rdiovsulr risk inreses prtiulrly when this rtio exeeds 5 ording to the Frminghm study. Our results indite rtio of 6.7 in rts mde hyperholestérmiques, mening exposure to high risk of rdiovsulr disese. However, the tretment with the Tnopti signifintly redued this index in hyperholesterolemi nimls y pssing 6.7±4.2 to 1.5. This ould still justify ntihyperholestérolémique effet of the extrt of Tnopti. Aording to Nwnkp et l, Phyllnthus sp hs protetive role ginst rdiovsulr disese y signifintly reduing the serum totl holesterol, LDL, triylglyerides nd therogeni index whih is preditor of risk ftor, nd y the signifint inrese in HDL. 18 The presene of Phyllnthus sp, Tnopti in the reipe so to justify the low therogeni index nd ntihyperholestérolémique effet oserved. Interntionl Journl of Bsi & Clinil Phrmology Septemer-Otoer 216 Vol 5 Issue 5 Pge 197

6 Nzire AK et l. Int J Bsi Clin Phrmol. 216 Ot;5(5): Furthermore, the phytohemil sreening extrt Tnopti indited tht it ontins flvonoids, tnnins nd sponin glyosides. Flvonoids nd tnnins ply n importnt role in lipid metolism. Flvonoids lok speifi enzymes. For exmple, flvonoids lok onverting enzyme (ACE), whih inreses lood pressure, ylooxygense (COX) nd prostglndinendoperoxide synthse (PTGS), tlyze the formtion of prostglndins from rhidoni id. 19 Flvonoids lso protet the vsulr system nd strengthen pillries tht rry oxygen nd vitl nutrients to ll ells. 19 As tnnins, they form omplexes with proteins nd mke them unville for the ells. 2 The signifint inrese in serum onentrtion of triglyerides oserved my e due to the ility of tnnins extrt Tnopti to form omplexes with the HMG CoA redutse inhiitor nd ylooxygense. These tnnins nd prevent norml metolism enzymes leding to lipid umultion in the serum. Extrt Tnopti thus improves the lipid profile in rts nd redues therogeni risk. Hypertension ws indued in rits fter 14 dys of dily tretment with drenlin. This hypertension would settle ording to vrious moleulr mehnisms. I) At the hert, the link oupled with the G protein (Gs) to β1 reeptors leds to tivte denylyl ylse (AC ), whih onverts ATP into AMP. The AMP tivte protein kinse A (PK-A) whih in the turn llows phosphoryltion of the li hnnels thus involving the inrese the flow of the lium from endoplsmi retiulum. It follows from there n inrese in the fore (positive inotropi effet) nd the frequeny (positive hronotropi effet) of the hert. This inrese in fore nd frequeny of the hert then use elevtion of lood pressure. 21 (ii) The drenline in the lood vessels diretly tivtes ntriureti peptide nd vsopressin whih tivte the lium hnnels in the endothelium using the relese of lium nd inresed lium flow s result of vsoonstrition leds to the elevtion of lood pressure. 22 (iii) The drenline inds to the β- drenergi reeptor present on the juxtglomerulr kidney unit to tivte denylyl ylse (AC), whih onverts ATP into AMP. The MPA tivtes protein kinse A whih involves the relese of renin. Renin onverts ngiotensin I to ngiotensin II, leding to vsoonstrition nd thus high lood pressure. 23 In this study, the results show tht the extrt of Tnopti normlizes in eight dys rdiovsulr prmeters nmely systoli lood pressure (SBP), distoli lood pressure (DBP) nd hert rte (HR) of hypertensive nimls. The phytohemil sreening showed tht the extrt Tnopti is rih in polyphenol, while ording to Lorenz et l. 24 polyphenols t y rpid dose-dependent nd sustined tivtion of the PI3K/PKB (phosphtidylinositol 3-kinse/protein kinse B) pthwy whih phosphoryltes the endothelil nitri oxide synthse (enos). This phosphoryltion ours on serine 1197 independently of the intrellulr C 2+ nd tivtion of enos in response to the inrese in intrellulr C 2+ vi the C 2+ omplex-cam (liumlmodulin). 24 The prodution of NOS would thus involve vsodiltion nd onsequently normliztion of rdiovsulr prmeters. The vsodiltor nd vsuloprotetive effet of polyphenols is potentited y mplifition of the effetiveness of endogenous ntioxidnts, like tlse, inhiition of the pro-oxidnt enzymes (NADPH oxidse) nd the dismuttion of the surrounding ROS. We used Ténordte s n ntihypertensor of referene euse Ténordte is n ssoition of tenolol nd nifedipine. Our results show tht the extrt of Tnopti hs the sme effets s Ténordte, it ould thus t y its mehnism. Indeed, Nifedipine is lium ntgonist nd tenolol, β loker. Ténordte ts y inhiiting the lium hnnel, preventing the entry of lium into the ontrtile strutures, thus using the derese in rdiovsulr prmeters or y inding to drenergi β reeptors, onsequently preventing the relese of lium into the intrellulr environment. This results in vsodiltion nd derese in systoli lood pressure, distoli lood pressure nd hert rte. 25 The extrt of Tnopti ould therefore ontin ntgonist ompounds of lium nd/or β lokers. ACKNOWLEDGEMENTS The uthors re grteful to M. Alert Tno ADOU n Ivorin trditionl prtitioner for providing the reipe Tnopti. Funding: No funding soures Conflit of interest: None delred Ethil pprovl: The study ws pproved y the Institutionl Ethis Committee REFERENCES 1. Tlh J, Priynk M, Aknksh A. Hypertension nd herl plnt. Interntionl Reserh Journl of Phrmy. 211;2(8): Chen Z, Peng C, Jio R, Wong YM, Yng N, Hung Y. Anti-hypertensive nutreutils nd funtionl foods. Journl of Agriulturl nd Food Chemistry 29;57(11): Grssi D, Lippi C, Neozione S, Desideri G, Ferri C. Short-term dministrtion of drk hoolte is followed y signifint inrese in insulin sensitivity nd derese in lood pressure in helthy persons. The Amerin Journl of Clinil Nutrition 25;81(3): O Kne PD, Queen LR, Ji Y, Reeye V, Strtton P, Jkson G, et l. Aspirin modifies nitri oxide synthse tivity in pltelets: effets of ute versus hroni spirin tretment. Crdiovsulr Reserh. 2;59(1): Interntionl Journl of Bsi & Clinil Phrmology Septemer-Otoer 216 Vol 5 Issue 5 Pge 198

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