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Acta Medica Philippina

Mahogani(Mahogany) The Effectof Swietenia Extract On Indomethacin-InducdGastric Seed Rats. UlcersIn FemaleSprague-Dawley
J.; H.; Motalban' S; Javillo,J; Manzanilla, L;Diaz I; Espina, K; Chavez, Bacsal, A.; Sumpaico C.; Talip, B.; Yap, S. Panganiban, C.; Rodriguez, of Phamacology UPCM, Deparunent

ABSTRACT
Swietenia mahogani (mahogany)has been teatment suchas to have medicinaluses, reported che stpains anaebiasis, n, cancer, hypertensio for and intestinalparasitism. This studyexamined the effect of mahogany seed extacts on tric ulcer s in female thacin-inducedgas indome rats. Fortyfive2-3 nnnthold Spragrc-Dawley ratsweighingI 50-200g wererandomlyassigned into 5 trestment groups, namely: [1] 59o polyvinylpyrrolidone (PVP), [2] misoprostol (144ueIkSBW), [ 3] 0.I ag malaganyse edextractl g seed extract I kg mahogany kg BW, t4l 0.28 g seed extractlkg BW, and tsl 0.57 nahogany BW. After three days of administration of tnethod, the rats were treatncnlsusinggavage graded grossly sacrificed,and their stomachs using Besl's Ulcer Staging Index. H i stopatlw logic gradingwasalsoconducted. At utilizedin this study,nnhoganyseed tlu doses onthe apotential effect to have extraclwasfound that healingof gastric ulcers. It is speculated this effectcan be auributed to theplwspholipid acid content of andlong chainunsatwatedfatty mahogany seeds. Further studies are to verifi these recomnended ftndings.

multinational companieswhich have been in variousindustries, baulingoutfor marketshare indusry. oneof which is thedrug when numberofproblems Filipinosencountera the need !o use drugs arises such as: their and affordability. availability, accessibility, Because of the fierce competitionamong the ofdrugsused various theprices drugcompanies, Thus, haveescalated. illnesses to treatcommon most impoverishedFilipinos have trouble procuringtheseessential drugsthat would meet their healthneeds. Sincemost drug companies are more or less located in the major cities, are people in thePhilippines from far-flungareas theseexpensive leftwithnootherchoicebuttobuy drugs or improvise with the use of herbal medicine.

Our country, blessedwith a vast number of indigenous resources,has turned to herbal medicine as an alternativeto commerciallyproduced andeasier!o drugs. They arecheaper by moreFilipinos. obtain,thus,theycanbeused in herbal In this light, therehasbeenan upsurge medicine researchin order to investigateand useof maximizefully thepotentialtherapeutic plants.Pharmacological andoxicological studias with useof plants will prevent theindiscriminate effects and toxic side uses and both therapeutic INTRODUCTION species. test insurethesafctyandefficacyof these isfaced withcountless challcnges Many of our countrymensuffer from peptic ThePhilippines of which areexcessive the majorcauses in its questfor attaininga Newly Industrialized ulcers, intake, smoking andstres. and/oTNSAID alcohol (NIC) ycar2000. Forthese by thc Countrystatus which act number medicines There a of are our doorsto numerous we haveopened reasons,

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through different mechanismsused for the treatment of ulcers. Investigations arecunently being undertakento discovermedicinal plants with anti-ulcer functions. The discovery of a plant with anti-ulcer properties would be contribuory o the growing list of medicinal plants currently being ,usedin the country, alleviating some of the problems of coat and availability of commercially-produced drugs. Swictenia nwhogani (mahogany)seedshave been reported to have medicinal value for trsatment of hypertension, cancer,amoebiasis, coughs,chestpains and intestinalparasitism. The biologically active ingredienrs, tetranortriterpenoidsand fatty acids are for the.se considered o beresponsible therapeutic vast It is effects. this rangeof usesof mahogany that haspeakedour interestto investigate seeds potential the anti-ulceractivity of S. mahogani seedextract.

SpecificObjectives: To determinetlre size and number of gastric mucosal lessions in femaleSpnague-Dawley ras !o which0.14g/kgbodyweight,0.28/kg body weight and 0.57 gAg body weight mahogany seedexnact wereadministered, as measured by the Ulcer StagingIndex. To compare the scorBs of thegastricmucosae of tteratsineach of thefollowingtreatmentgroups: O.la g,ftgbody weightmahqgnny segd extract; 0.28 gkg body weightmahqgpny seedextract; 0.57 gkg mahogany seedexract; misoprostrol solution;andpolyvinylpynolidone solurion. Significance of the Study This research will makea valuablecontribution !o thedevelopmentof anti-ulcerdrugsttr,at utitze medicinalplants,in orderto moreefficiently and appropriately respondto the healtlrneeds of the ordinaryFilipino. Reviewof RelatedLiterature

ResearchQuestion Amongfemaletwoto threemonth-oldSpragueDawley ras with gasric ulcers inducedusing indomethacinat30mglkg?t4 hoursbefore,how will the daily oral administrationof Swietenia nahogani (mahogany) seedextractsat0.l4 g kg, 0.28 g/kg and 0.57 gftg affect the gastric mucosa,measured by the size and number of ulcersusingtheUlcer Staging Index,compared to those of female sprague-Dawley rats with gastric similarlyinduced ulcers andadministered with misoprostolor polyvinylpyrrolidone solution? Objectives GeneralObjective: A peptic ulcer is a breachin the mucosaof the duodenum andstomach, which extends through the muscularismucos:linto the submucosa or deeper.Ulcersaremone commonlyfound in the duodenum than in the antrumof the stomach. Theyarechronic,mostoftensolitarywhichtend (1). to be lessthan4 cm in diameter Normally,the gastricmucosilis protected by a compacdy ananged epitheliumand thick layer protective of mucus.Othersuggested factors are the regenerative capacityof tle mucosal cells, juiceswhich alkalinityofpancreatic andintestinal neutralize gastric contentsand an adequate vascular supply (2). All these are aimed at preventing digestion of thesomachby pureacid gasric juice.

To determine theeffects of Swietenia mahogani (mahogany)sced extracts on indomethacingastric of the stomach to digestion induced in femalc ulcers Sprague-Dawley However,resistance does fail. The following facors have been rats. postulated to causeulcer.

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Gastric MucosalInjury Peptic ulcers are produced by an imbalance thd gasroduodenal mucosal between defensive forces. Agressive forcesinvolve andagressive (2) peptic activity derived (l) acid secretion; from pepsinogen;(3) Helicobacterpylori infectionof thegastric antrum ; (4)useof NSAIDS (5) impaired inhibition of stimulatory (6) increased mechanisms relcase such asgastrin parietalcell mass,(7) increased sensitivityto secreOry stimuli(8) ircreased basal acidsecretory (l). drive In vitro experiments haveshownthatdigestion of thesaidmucus by thegasnicacids, especially pepsinI, predisposes mucosalbarrierto erosion which eventually resultsin the development of ulcers. (l) However, there are certain mechanismsfactors within the gasrointestinal tract that protects the stomach from these aggressivefactors. These defensiveforces irclude the following l) secretion of surface mucuslayerby epithelialcells. The natureand of the mucous, a adherentcharacteristics glycoprotein getsecreted by surface epithelium wall, is responsible overthegastric in protecting the underlyingcell fiom thedamage caused by forces themechanical of digestion.Likewise,it lubricates themucosa, assisting themovement of foodoverthesurface andretains waterwithin its gelatinous matrix; (2) secretion of bicarbonate producing intothemucus layer, thus apHgradient fromthehighlyacidicgastric lumen to thealmost neutralmucosalsurface(3) protectionagainst diffusion of H+ ions into the mucosaby the apicalsurfaceof thegastricmucosal specialized cells (4) remartableregenerative capacityof mucosal epithelial cellsfor rapidrepair of injuries (5) mucosal elaboration of prostaglandins having activity,possibly cytoprotective by maintaining mucosal adequate bloodflow andby stimulating of mucusand bicarbonate.Possible secretion causesinclude increasedparietal cell mass, increasesensitivity to secretorydrive and impairedinhibitionof stimulatory mechanisms (l). like gastrinrelease

Mucosal Blood flow. A decreased in blood supplyto 0relesser curvature of thestomach has been suggested to playa role in thedevelopment part. Focal ofchroniculceration on theaffected ischemiaand consequent necrosisof certain segments of thegasric wall alsoleadto ulcers. Environmental Factors. Some common exogenous agentssuch as NSAIDS, alcohol, smoking anddietarysalts arethought to damage themucosa. Symptomatology. A symptom complex refened to as"ulcerpain"is fle usual manifestation of an activeulcer. Two factorshavebeenproposed Lo explainulcer pain. Theseare (l) the actionof acidgasricjuice on theraw surface of theulcer, and (2) cause of muscularnatureunconnected with the actionof tlre acidjuice on the mucus. Theinflammatory foci in fte muscularis mucosa give riseto contractions in theneighborhood of pressure theulcerwhichincreases theinragastric fibers,thusproducing andthetension of muscle a sensation of pain. Ulcerpainmayrange from theclassical burning sensation tovaguecomplaints such asasensation of "being hungry". The pain is steady, mild to moderate, well-localized in the epigastrum and often relievedby food, wateror antacid. It is usuallyperiodic. Complications. Complicationsinclude perforations, hemonhage andpyloricobsnucdon. Perforations are usuallylocatedat the anterior wall of the duodenum, less commonlyin the A freeperforation stomach. usuallypresents an acute abdominal emergency. The patient experiences suddenintensesteadypain in the epigastrum. Thepatient usuallyliesstill because any movementexacerbated the pain. The aMomen is tender, the abdominal muscles are rigidandbowelsounds arediminished orabsent. Peritonitis may subsequentlydevelop. Hemonhage is anothercommoncomplication. In casesof massivebleeding,it may lead to hypovolemic shock.

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causes. Pyloricobsfuction maybedueto several It may be due to duodenitisand antral gastritis motility of theantrum impairingthepropulsive It of thepyloric sphincter. andactiverelaxation may also be due to scarring and relief of obsrucdon.(2) Agents Ulcerogenic an indoleaceticacid derivative, Indomethacin, for drugs wasthe productof a laboraory search wirh anti-inflammatoryproperties. It was rheumatoid in 1963 for thetreatmentof introduced arthritisandrelated disorders. hasprominent anti-inflammatory, Indomethacin similar to and antipyrcticproperties analgesic is a potent thoseof salicylates.Indomethacin cyclooxygenase. inhibitor of the prostaglandin Italsoinhibis themotilityof polymorphonuclear Like manyotheraspirin-like drugs, leucocytes. oxidative increases indomethacin phosphorylation in supratherapeutic of thebiosynthesis andexpresses concentrations it increases In addition, mucopolysachharides. of cyclic AMP intracellularconcentations, (3). inhibitingphosphodiesterase

particularis thoughto promotepepticulceration via itsinhibitionofclyclooxygenase tlut isneeded of which in the formation of endoperoxides, prosaglandins @2)is anexample.Theduodenal mucosa produces prostaglandinE2 and for themaintenarrce whichareneeded bicarbonate of is integrity. ulcersin the A studyof indomethacin-induced of indomethacin, mouse showed thattwo doses at 85 mg/kg body administered subcutaneously weight, induced well-definedgastrointestinal ulcers accompaniedby inflammatory and vascularchangesin the stomachand small intestine. Maximal damagewas observed20 hours after the seconddose of indomethacin. in all identifiedchanges Morphometric analysis of thesmallintestine.Therewas compdtments a markedreduction in the length of the small intestinal intestine, dilation,asignificantdecrease in villous height, with the formation of blistersor blebswithin villi, and subepithelial vascular dilatation. There wasno submucosal changein the numberof villi or submucosal musclepresent or in theloial amountof arterioles in thewall of theintestine. has also beenfound to increase Indomethacin gastric acidsecretion dueto thelossofhydrogen mucosal ion-back-diffusion througha damaged barrier, and not due to a direct reductionin parietal cell secretionwhich explains its ulcerogenic action.

from the It is rapidly and completclyabsorbed gastrointestinaltract, with peak plasma attaincdfrom I to 2 hours. The concentations Indomethacin is907o hours. half-lifeisabout4.5 protein-boundand is biotransformedby Boththeparent anddeacylation. demethylation products undergo Anti-UlcerAgents drugandthebiotransformation circulation. Severeside-effects enterohepatic verl.igo, diarrhea and peptic Misoprostol includeheadache, with chronicusc(4). ulceration (Cybtec),a l5-deoxy-15-hydroxyMisoprostol E, has a l6methyl analogue of prostaglandin drugssuchas anti-inflammatory Non-stcroidal weightof 382. It hasbeenprovenby havebeenassociated molecular aspirinandindomcthacin, theories the FDA effective for ttre treatmentof peptic ulcers. Sevcral andduodenal withgastric involves the regarding the mechanisms ulcer disease. The mechanism havebcenproposed maintenance of mucosalintegrity which is drugsact. by which thesc in mucosal bloodflow. facilitated by anincrease in nutdents andoxygen Thisresulsin anincrease that the mucosalinjury It has bcen postulatcd to the cell. At the same that may be delivered produccdby the aforementioned drugs is may be removedmore in time, toxic substances multifactorial. Howcver, indomethacin 130

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efficiently from the tissucs.(5) Specifically, of misoprostol actsby inhibiting thc secretion gastric :rndin response to food, acid,bothbasally histamine,pentagastrin, and coffee, by direct action on parietal cells (6, 7, 8). This propertyof Misoprostolcan be cytoprotective attributedo its ability to stimulateincreased secretion mucoussecretion and bicarbonate by mucosa. In anexperimentcomparing thegastric protective propcrties of MisoprosLol, themucosal in rats,Misoprostol at andSucralfatc Cimetidine two dosesof 100 and 200 ug/kg reducedthe lesions mean number of gastric by 587o and,7$Vo of control, respectively. Gastric ulcers were indomethacin, induced by aspirin, stress, sodium, andethanol.In all 5 experimental taurocholate ulcer models the gastric mucosalprotective activity of misoprostolwas not rclatcd to its effcctsas the dosesuseddid not antisecretory havesignificant antisccrctory activityin therat. providcd It was concludcdftat misoprostol protcction not mucosal bya nlcchanism thatdocs require a reduction of gastric acidsccretion for its protective effcct.(9) Misoprostol is absorbedrapidly after oral administration andis rnetabolizcd to thefreeacid form. Theplasma concentrations of Misoprostol are highestapproximately 30 minutesafter of thedrug. Plasma administrations bindingis not extensive, and plasmadrug concentrations are not substantially affectedby age. Renal excretionis minor, and the dosedocsnot.nrcd in patientswith renal impairment. adjustment (10)

mahogani) Mahogany( Swietenia Swieteniamahogani,otherwiseknown as to mahogany belongs or WestIndianmahogany, (Mahogany family),agrcup thefamilyMeliaceae as of plantsknownto haveinsecticidal activities (12) well asmedicinal uses. This plant is a moreor lessdecidous, erecttree growingup to l0 meters or morein height,with a heavy, darkgreen, dense crown. The trunk is moreor lessbutlressed. The bark is dark gray yieldsa highly prized andridged. S. mahogani reddish is similar to brown wood. This species Mahogany (Swietenia the broad-leaved macrophylla king),but it differsin its smaller leaves, leafles,andfruis. (13) In the Philippines, mahogany is considered as groupof trecsused for oneof themostimportant purposes (14) but it has also been decorative rcportedto have medicinalvalues,namcly, for hypertension, troaLment cancer, amocbiasis, pains parasitism.Related chest and intestinal specieshave been known to be effective (15) antihelminthics andanti-cancer agents.

Isolationof chemicalcomponents from seeds using highsaturated differenttechniques showed and unsaturated fatty acid content. It was also reported to be positive for the presenceof phospholipids, neutml lipidsandglycolipids from ( 16). mahogany seed extracts Phosphatidylcholine is themostabundant. Other studies revealed the presence of (specifically tetranorriFrpenoids swietenoloids (12,14,15) Misoprostol is generaly well tolerated, andit has andswietenines, diacetate resins and nervous (14). Oral administration nomajorcentral system orcardiovascular phenolic compounds effects. The most frequentlyreported adverse of triterpenoid saponinshas been reported to protect rats from developing gastric ulcers eventis diarrheawhich can be so severe as to warrant discontinuation of trcatmcnt.Theother inducedby various experimental models: is increased NSAIDS, (17). important sideeffcctof Misoprostol stress andShayrat method whichcanprovokc contractility uterine abortion. (PVP),thccontrol Misoprostol is contraindicatcd in pregnant Polyvinylpyrrolidone womenand hasbcensoldasan abortifacient in (ll) (PVP), now more Brazil. Polyvinylpyrrolidone commonlyknownas providoneis a mixtureof essentiallylinear syntheticpolymers of

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Philippina ActaMedica manifestas joint pains, hepatesplenomcgaly This is calledthePVP disease. anddyspnea. All authors agee that the storage of high molecularPVP in the liver, lungs, secrelory organs and the granulation tissues has no of the influence on the functioning unfavorable hcal. organsor lhe tendcncyof the tissuesto carcinogcnic PVP hasbcenstudicdfor possible effecs andnonehavebecnnoted. of peptic ulcers,it is In the pathophysiology areimportantin knownthatbothacidandpepsin (l). its occurrence HelicobacterPylori activity has beenimplicatedin Phospholipase by H. pylori-induced caused damage themucosal theorganism ulceration.Accordingto Berstad, or inducesthe hostto release possiblyproduces phospholipases that metabolizettre protective (20). Studiesby layer of phospholipids on H. pylori colonizedthe mucous Yamashiro coveringnormalgastricepithelium; layertlrereby (2) lay atopinegularmicrovilli aswell asamong junctionsof damaged cells;and theintercellular junction zoneand (3) adhered specific firmly by epithelial to thc appendages loselyby filamentous of cells which lacked evidenceof a surfaces (21). laYer prolective mucous

asa it is described vinylpynolidone.Physically odorless colored, finewhiteor veryslightlycream powder. It is hygroscopic,soluble in lvater, alcohol and chloroform but insoluble in ether. As aSVosolutionin water,it hasa pH varying from 3-7 (18). It is mostly neutraland its toxicity is very low, timeit is saidto haveadetoxicant butat thesame effect. It also hasno antigencffcct (19). The rcmporaryaccepabledaily intake sel by the FAQ ilHO in 1983is 25mg/kg.Theacuteoral pigsis abovelOOg/kg. toxicity in ratsandguinea of PVP in Medicine Ljses lhe it serves to increase In extemalapplications, to difficult which are solubility of substances as importance of dissolvein water. It is also agent(up to 57osolution),binding dispersing it is used andlubricant.In opthalmology agent, in eyedroPs. asan admixture PVP can be taken orally. It is used as an admixturein tabletseitherasa binderor ascoat in the (0.5-57osolution). It is not absorbed tract of thegastrointestinal membrances mucous (19). (if so,in negligibleamounts) Effectsof PVP skin fromcontactwith thatdamagc states Wesscl by oral intakco[ PVPhas mcmbrancs or mucous not becn known of sincc,as statcdearlicr, ils canbe ignored.It situations in these absorption that some is only with parcntaladministration effectsare noted.

METHODOLOGY

Study Design. This experimentutilized a randomizedcontrolled parallel design. The behavesreciprocally treatmentgroupswereas follows: orelimination PVPretention as weight of thecompound, molecular with the No. of rats 20,000 and of weighs Group treatment molecular with those partly and delay a aflet aboveare eliminated l0 (PVP solution) A GFontrol for wceksor months. retained of long term After l0 yearsof administration occursin of PVP, accumulation administration system' These sometimes $ereticulo-entothelial

l0 (l44ug/kg) B (+)misoprostol l0 I (0.lag7kg)-dose extrrct mahogany C l0 (0.28glkg)-dose 2 extract D mahogany (0.57 gAg)'dose l0 3 extract E mahogany

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Experimental Animals. Forty-five female 150-200 ratsweighing between sprague-Dawley grams and aged2-3 montts were used in this study. Two rats werekept in every cage. Preparation of the Treatment Solutions (Detailsare shown in Appendicesl and 2)

weighedandrandomly the ratswerenumbered, groups asdescribed o thefive treatrnent assigned above. Indomethacinwas computedbasedon via the weight of erch rat, w.ls administered intragasric gavage.

Administrationof Treatments.After24hours, initial adminisration of thedifferent treatments mahoganyexuact, The three dosesof Mahogany. @VP solution,misoprostolsolution,mahogany dose 3) 2, andmahogany 2gKg, dose dose1,mahogany namely,O.l4Zgftg, 0.2839kg, and 0.57 for day I weredonealsoby intragasric gavage. on the initial findingsof based wer€computed in mice. acuteloxicity experiments 24houn thrice, Thetreatment wereadministered rats were days, the During the reatment aparl all a stock of session, each expcrimental During provided for 24 with food rvith kept in their cages of a concentration seed extract. mahogany prcparcd. hours next schedule. This until tre trealrnent was ml solution, extracU 0.1316 was dissolvedin l5Vo polyvinylpynolidone thesubjects Six hoursafterthettrirdtreatment(3), @VP)solution. were sacrificedby chloroform inhalation in an For eachtestgroup,thevolumeof stocksolution air-tight jar. The stomach,were surgically and removed by cuuing from the esophageal based on to theratswascomputed administered pyloric were opened ends.Theisolatedstomach thatthe the body weightof eachrat. To ensure curvature.Thecontents andcut alongthegreater equallyamong all the volumes areadministered using groups, cleaned, and the stomach anadditional wereremoved, ras in thedifferenttreatmcnt soas normalsaline solution.Carewasexercised wasadded to makeI ml volumeof PVPsolution to keep the mucosalblood vesselsintact. The extractsolution. of mahogany panandthe wasspread stomach overadissecting pinned. Misoprostol (Cytotec). For eachexperiment peripheralborderssecurely 200ug containing of Cytotec twotablets session, OutcomeEvaluation werccrushcd usinga mortarand of misoprostol pestle,and dissolvein l0 ml of NSS. This of 40 ug/ Gross Analysis. Grading of the ulcers was yieldeda solutionwith a concentration whowasunaware observer werc made in order to conducted by thesame ml. Computations givento therats. Thestomachs of thetreatment determine,the amount of solution to be microscope. wereexamined undera dissection on the doseof to eachrat, based administered The diameten of the lesionswere measured l44ugkgbody weight. wasbased on Best'sUlcer using a ruler.G.rading Indexshownbelow(22). four 25g staging Indomethacin. For each scssion, wcrc dissolved in l0 of indomcthacin capsules [.esion Score m l o f N S S , y i e l d i n g a s o l u t i o nw i t h a of solution of IOg/mi.Thcamount concentration 4 givento eachrat wascomputcd Deeplinearulcer> l0 mm long based on thedose Deeplinearulcer< l0 mm long 2 of 30mg/kgbodyweight.(23) I Circularulcer I -3 mm I mm 0.5 Aftcr week Circularulcer< one of Ulcer-induction. 2 Fraction showing of stomach theratsweresubjectcd to a24acclimatization, hemonhage lirst evidence of day of experimentation, hour fast. On the

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HistopathologicAnalysis. After gradingthe fromthegross all theslomachs specimens, ulcers namely: fundus, into three segments, were cut pylorus; then brought to UP and body and Pathology for histopatologic Departmentof criterion analysis.Sincethcreis no established of ulcers, theresults for quantitative evaluation were gradedbasedon the number of ulcers, presence anddegree of infl ammation of necrosis, as evidencedby cellular proliferation. The utilizedin this studyareasfollows: categories l. Numberof ulcers No. Normal/ 0 t-2 3-4 >4 Score 0 I 2 3

infiltration.Acuteinflammatory cells,whichare observedbeneaththe ulcerative lesions,are cellswhile composed of polymorphonuclear alsoin the lymphoidaggregates canbeobserved mucosa extending to the submucosa. Analysis.Since were obtained tlredata Statistical using subjectivemethods,the scoreswere analyzedusing the Kruskal-Wallis one way procedure. analysis of variance, anon-parametric (H) that This is usedto t€stthenull hypothesis (24). populations thesamples arefrom identical = wassetat alpha 0.05. I-evelof significance weredonefor scores obrained analyses Separate from grossexamination and histopathologic grading of ulcers.

"hcalcd" ulcers were Absenceof ulcers and given a score of 0. An ulccr is considercd "healed" if thereis evidenceof capillary and tissue andgranulation fibroblasticproliferation formation. 2. Presence of necrosis

RESI.JLTS (45)female ratswere Forty-five Sprague-Dawley randomly assignedto five treatmentgoups (dose namely: extracts threedoses of Mahogany I = 0.148/kB body weight;dose2 = 0.28 g/kg body weight; dose3=0.5'l gke body weight) (M) andPVP as positiveand with Misoprostol negative control,respectively.Nine rats were group. randomly assigned to eachteatment Priorto thecompletion of thetreatmentregimen, dose ratsdied.PVP,Misoprostol andMahogany hadtwo deaths each, while Mahogany I groups were dose3 incurredone death. Thesedeaths postulated to be causedby gastrointestinal profuse tapeworm diarrhea andsevere bleeding, infection. Analysis of GrossSpecimens

(+)
(-)

o
I

Necrotic tissuesin mild forms of ulcers are areasof the usuallyconfinedat the superficial is gradedpositiveif the ulcer. The specimen necrotic tissue extends tc the submucosa, layersof the stomach. muscular, or decper 3. Degreeof iflammation No cellularinfiltratcs cclls Acuteinflammatory Lymphocytic/ Eosinophil inliltration 0 I 2

is graded according Thedegree of inflammation and type of inflammatorycell to the presence

groupsobtaincd Thc scores of the 5 troatmcnt Indexwerecompared. fromBest'sUlcerStaging groupsare The meanranksof the 5 treatrnent in Tablel. Kruskall Wallisoneway summarized significantresult ANOVA showed a statistically at alpha=0.05.

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groupswere AmongTreatment Differencesamongthe 5 treatment Table1. MeanranksofUlcers found Index o be statistically significantatalpha=O.05). GroupsUsingtllcer Staging TREATMENTCROUP MEANRANK N

DISCUSSION
PVP MISOPROSTOL l DOSE DOSE 2 DOSE 3 32.2r I8.I4 17.14 19.17 12.00

7 7 7 9 8

Kruskall Wallis H = 13.23(Critical value at df4,9.49) Results Histopathologic

The desruction of the gasric mucosalbarrier epithelium andmucous consisting of tlresurface themaincauseof ulcer(l). Thii destruction coatis maybe dueto, among otherfactors, an increase in mucus in gastric acid secretion,decrease productionor decrease in mucosalblood flow.

This studyinvestigated theeffecs of mahogany seed extract on gastric ulcers comparedto effects Misoprostol, a drugwhose ulcer-healing the slides have been extensively studied, and Upon viewingunderthe microscope, the of the rat stomach, containingthe sections polyvinylpyrrolidone,an inert solvent. presence of ulcers, was observedin all of the Mahoganyseedextract was found to have an grcups.However, werepresent effecton the gastricmucosal these Eeatment healingsimilar to in varying degrees. Ulceration reachedthe Meanranksfor Misoprostol thatof Misoprostol. while in majorityof the specimens, submucosa 1,2 and3 for both. andMahogany doses thegross wasinjuredin a few. only the mucosa wereverynear fi ndings each andhistopathologic hadlower meanranksthan other. All thedoses There was also evidenceof necrosis,and misoprostol. Further, Misoprosolandthethree involving inflammatory cellinfi lration basically dosesof Mahogany extract were all found to polymorpho-nuclear cells, particularly, havelower mean rankthanthePVP,thenegative waslikewise tissue neurophils.Earlygranulation indeed has control. This suggest thatmahogany found, indicatingeady stages of regeneration. a potentialeffect. werecomputed Meanranksfor statistical analysis for eachof the treatmentgroups(Table2). How is thishealing Based achieved? on studies, Misoprostolis said to make healingpossible Table 2. Mean Ranks of Ulcers Among gastric mechanisms. It decreases through several Treatment Groups Using Histopathologic secretion (9)withoutdecreasing thebloodsupply Analysis that allows more nutrientsand oxygen to be deliveredto the cells. It also removestoxic MEANBANK n TREATMENTGROUP mucus and substances efficiently;andincreases whichrenders bicarbonate secretion themucosa PVP 31.00 7 lessacidicandprotects it from furtherinjury (5).

MrsoPRosToL DOSE l DOSE 2 DOSE 3

18.93 18.50 16.22 14.50

7 7 9 8

Kruskall Wallis H = 9.97, significant at alpha=0.05

hasyet On theotherhand,research on mahogany is properties have to reachits zenith;therefore not been extensivelystudied. Nevertheless, mechanisms maybepostulated to play a several role in protecting or healingthegastricmucos:r.

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The mucuslaycron tlrc gastriccpitltcliummay protection !o thcmucosa, but thisis render some barricrof surfacenotsufficicnt Anothcrphysical ino the dircctly absorbed active phospholipid hasbccnproposcd. luminalliningof thcstomach is hydrcphobic The finding that intact mucosa (25,26). $is hypothcsis supports is phosphatidylcholine. One suchphospholipid of fully At the molecularlcvel, the dimensions phosphatidylcholine areidealfor close saturated packingto form a barrierbccause of thequality arcaof thc polarandnonof thecross-sectional (27). polar moieties fattyacid to notethatthc packed It is intcresting barrier already cxists in the mucosa,but an monolaycr of phospholipid additionalabsorbcd from acid will alsocoatandprotcctthc mucosa (26\. Mahoganysccd extract is high in lipids, particularlyneutral lipids, glycolipidsand phospholipids, of which is thc most abundant (28). Basedon the phophatidylcholine mcchanism, above, therefore, hypothcsized mahogany secd extraclmayprovidea protective phospholipid such coat on the injurcd mucosa state of ulcerintoa moresevere thatprogression allow healing to andthcrcforc maybe inhibited, proceed. mechanism could involve the Anotherpossible property mahogany seed extracL of anti-bacterial pylori has becn found to play a Helicobacter ulceration majorrole in inducingor aggravating (29). Althoughthcsebactcriado not normally survivein rats,thcy havcbccn found to occur (30). in humans naturally

highamounts of Mahogany sced extractconhins fatty acids, including long chain unsaturated longchain l8:3, l8:2 andl8:l (28). Studieson properties, the fatty acidshavefoundanti-ulcer postulated associated mechanism which is to be of metabolism. withtheinhibition ofgastric bacterial with This anti-bacterialproperty increases (29). increasing on Cl8 saturation hasahighfatty component, Sincemahogany seed it has a potentialanti-bactcrialaction. This H. against theory,if proveneffectiveespecially pylori,wouldprovide tn the addition apromising mcthods. vastarrayof ulcertreatment The threedoses secdextractwere of mahogany control. all foundto be betterthanthe negative activily Evenat thelowcstdosc, some anti-ulcer wasobscrved.Bascd on initial toxicity studies, low toxicity. wasfoundto haveavcry mahogany index for This implies a high therapeutic which is idcal for any drug. Ergo, mahogany, agenl mahogany is a relativelysafetherapcutic

CONCLUSION & RECOMMENDATIONS Mahogany seed extract(doses1,2 and3) were found to havea bettereffect on the healingof gilstric ulcers than the negtive control, PVP. healingeffectis similarto thatof Theobserved misoprostol but this needs to be further investigated. procedure should be A multiple comparisons differ from doneo pinpointwhichof thegroups eachother.

REFERENCES thc ability to dcstroy the H. pylori f,osscsscs phospholipid laycrof thcmucosa attd cpithclial l. activity, it of its sphingomyclinasc becausc neccssary lorccll to cell sphingomyclin dcstroys (12). In additionH. pylori reduces adhcsion inphospholysis rcsulting thcrcby hydrophobicity, layer. of themucus Abd El-DayemAM, El-AgainyMA. Non-wood forest products, physiochemical and characteristics fatty-acid of three seedoils. composition -293. Acta horticulturac 1993:333:287

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3.

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5.

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Acepcion VFB, ct. al. A comparative studyof misoprostol andgrcenbanana on thcir protcctivcandhcalingcffccts gastric againstindomcthacin-induced papcrsubmittcd ulccrsin rats.Rcscarch tothcDcpartmcnt of Pharmacology, UP 14Oct. 1994. Collcge of Mcdicinc, Aguwa-CN and Okunji-CO. Gastrrointcstinal studics of Pyrcnacantha lcafextracts. sraudtii JEthnopharmacol. 1986 Jan;15(l):45:55. Akdamar K, Agrawal N. Ertan A. gastric Inhibitionof noctumal secrction in normal human voluntecrsby prostaglandin misoprostol: a synthctic El methyl estcr analog. Am J Castrocnterol 1982:77:9O2-9M. Al Somal,N. Susceptibility of Hclicobactcr activity honcy. of manuka J.of Rovaf Soc. Of MedJan. 1994;87'912. Asante, MA et al. Casric Mucxosal Hydrophobicity andH. pyloriinfection for pcpticulccr dcnsity: a mcchanism pathogenesis? Gut 1995; l). 36(suppl Ballingr A. Cytoprotection with misoprostol: usc in thc treatmcnt and prevention of ulcers. Dig. Dis 1994 Jan-Feb: l2 (l):37-45. BauerRf, et.al. Comparative mucosal protcctivepropcrticsof misoprostol, cimetidine DigDisSci andsucralfate. 1986; suppl 8ls-85s. BerstadK, et al. Phospholipase A2 activity in gasuicjuice from patients with active and H. pylori+radicated healcd duodenalulcer. AlimentPha.acol-Thcr.1994 Apr; 8(2):175180. BestRB, lrwis DA, Nasser, N. The anti-ulccrogcnic activity of thcunripe plantainbanana (Musa species).BrJ Pharmac 1984; 82:107-l16. Bhalare HA, et al. Lipid Composition of somesecds of centralIndia J Food SciTcch1993; 30:54-55. Buencamino RB ct al. A comparative studyon thecffcctivityof commcrcial

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15.

16.

17.

antacid anddiffcrentconccntrations of in the short-tcrm eggshellsuspension gastric tre:ttmentof ethanol-induccd papcrsubmittcd ulccr. Rcscarch lo the Dcpartment of Physiology, UPCollege 1992. of Mcdicine, ChanKC, TangTS,Toh HT. Isolation of swietcnolidc fromswictenia diacctate macrophylla. Phytochem 197 6; | 5:429 430. Corless, et al. Survivalof Hclicobacter by pylori in animal models. Gut. (suppl l). DaviesGR, et al. 1995;36 Hclicobactcrpylori stimulatesantral rnucosalrcactive oxygen metabolitc production in vivo. Gut 1994;35:179185. Davis GA, FordtranJS, Dajani EZ. gastric Dosc-rcsponsc, mcal-stimutarcd proslaglandin anticcscrctory study of El analog, misoprostal, in man.Dig Dis Sci 1988;33:298-302. HillsBA and LichtcnbergcrlM.Gastric mucosalbarricr: hydrophobicityof strcrchcd stomach lining.AmJ.Physiol. 1985:244:G&3-7. Hills BA, ButlcrBD andLichtcnbcrgcr LM. Gastric mucosal barricr: hydrophobic lining to thc lumenof the stomach. Am J Physiol.1983:7;G-

56r-8.
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Hopkins RJ and Morris JG. Hclicobactcrpylori: link in thcmissing pcrspcctive.Am J Med 1994Sep;97 (3):265-277. lcung FW. Disscociatcd effecs of misoprostol on gastricacid secretion andmucosal bloodflow. Dig Dis Sci; 1986;31 : suppl86s-90s. Mata R. Segura-Correa R. New tetranortriterpenoids from swietcnia humilis. J Nat Prod 1993:56: 1567t574. Rosultact al. Drug theraphy in pcptic ulcer discase. Department of Pharmacology,UP College of Mcdicinc.No date. Salud EC. Extract ivcsof fourphilippine

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1. Benzene-soluble mahogany species APPENDIX 1 . fraction. ForpideDig 1977 ;6:24-27 PREPARATIONOF SOLUTIONS L, et al. Inhibitoryeffectof Thompson polysaturated fatty acidson thegrowth I. Preparation Solution of Mahogany of Helicobacterpylori: a possible Extraction A. Seed explanationof the effect of diet on pepticulceration.Gut 1994;35:1557 The mahoganyseedswere dried and 1561. ground. 1.Otkg of theground coarsely Compilation U. P. Collegeof Forestry plant materialwascovered with 3.0 L pp.62-63. distilled water in a glass vesseland Veldhuyzen van Zanten, S. J. O.; colled to room boiled for 30 minutes, for treatment Sherman ,P.M. Indications and filtered in vacuo temperature pylori infection: a of Helicobacter The plant marc throughcheesecloth. systcmatic overview. CanMed Assoc after filtration of the first extractwas (2): 189-198. J 1994:150 water, in 3.0L distilled thenboiled again for thetreatment WaltR.R. Misoprostrol andfiltered.The thistimefor twohours of pcptic ulcer and antiinflammatory overnight extractwasallowedto stland gastroduodenal drug-induced paper. f,rlter 3.0L of decanted using and ulceration. New EnglandJoumal of was ro0a-vaporized extract thecombined 5-1580. Medicine1992. 327 (22): 157 to equivalent Vo decoction, to yield34.7 Wesscl, W.; School;M; Winkler,E. extracl l32.8gof theconcentrated (PVP), It's Polyvinylpyrrolidone Diagnostic, Thcrapcutic andTechnical B . Storage Thereof. Application and Consequences Arzneim.-Forsch.(Drug Research). The concentratedextract was kept 1468-1482 Wilson D. 1971;21(10): refrigerated in a vial wrpped in Therapeut ic aspects of prostaglandins foil. aluminum in thetreatment of pcpticulcerdisease. Dig Dis.Sci.1986;31: suppl42s-46s. extract fromtheconcentrated Solutions Wood AJJ. Misoprostol for the were madefresh everyday. treatment of peptic ulcer and a n t ii n f l a mm a t o r y - d r u gi-n d u c e d Preparation of PVP gastroduodenal ulceration.NE J Med 1992:321:1575-158 A 5VoPYP l0 solution was usedas Y, etal. Helicobacterpylori Yamashiro 5.0g for themahogany extracts. solvent inchildrenwith gastritis colonization of PVP powder were dissolved and peptic ulcer. II. Ultrastructural in 50 mll- of distilledwater thoroughly changeof the gastric mucosa. Acta More until a clearliquid wasobtained. PaediatrJpn. 1994 Apr; 36(2\:17lo make100 distilledwaterwasadded r75. mL. ThepH of thesolutionwasnoted.

e.

Preparationof Mahogany Stock Solution TwentymL of the0.1316g extracVml stock solution was preparedper day. extractwas 2.362g of the mahogany weighedusingthe analyticalbalance.

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It was dissolvedin l0ml- of distilled water. Moredistilledwaterwasadded to makethesolution20 ml. ThepH of thesolutionwasalsotaken. II. Preparation of Misoprostol Solution Two 200ugtablets of misoprostol were groundfinely and dissolvedin l0mlnormal salinesolution. Theresulting 4Oug/mlsuspension wascontinuously mixed to presentthe particlesfrom settling. Thedoseadministered to the ratswas l44ttglkg' III. Preparation of Indomethacin Solution The resultingl0 mg/ml solutionwas administered to theratsata dose of 30 mg/kgbody weight. APPENDIX 2. COMPUTATIONS Based on the pre-test results of acutetoxicity resultson mahogany seed,the no effect dose (NED) is at 6.4 seed/kg mouse. Dosesfor rats werecomputed usinga log doseintervalof 0.3 srarring airhis NED. Dose1: 0.142g extract/kgrat (equivalent to 1.S9g mouse) seed/kg Conversion of dosage in mouseto rat based on surface arearatios(Conversion Factor=7)

1.599seed x x=0.0318g mouse seedp0g _= _; 10009/kg m 20 mouse g rat 0.03128g1kg x7 =A.22269 seed/200 (0.22269f2Wra0(l0OA0= Ll13gseed/kgrat Conversion of g seed to g extract: g extract/kg 1.113x0.1277=0.142 rat Dose2: 0.283g extract/kg rat (equivalentto 3.17g seed/kg mouse) 3'lTgseed 10009/kg m ^,*=0.*rosseed20/smouse 205

g seed/200 g rat 0.0634x7=0.4438 (0.4438g2$grarx1000gAg=2.2t9gs,eAkgnt 2.219x0.1277--0.292g rat extracr/kg Dose3:0.59g extract/kg (equivalentto 6.4 g mouse) seed/kg 6.49seed x -=-;x=0.l28gseed2Ogmouse 10009/kg m 20s gseedl}00gtat 0.128x7=0'896 (0.896g/200g)(10009/kg)={.48g rat seed/kg gkg rat 4.48x0.127 7=0.59 g extract/mlsolution Stocksolution:0.1316 0'572g extract x = -; 2309rat 1000grat 230e

x=0.13169 extracV

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