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“Ammi Visnaga In Treatment Of Urolithiasis And Hypertiglyceridemia" Running title: Ammi Visnaga urolithiasis and hypertriglyceridemia

DOI:10.4103/0974-8490.167894
Authors:
Akshaya Srikanth Bhagavathula at University of Arkansas
Akshaya Srikanth Bhagavathula
Ahed Jumal Mahmoud Al-Khatib
Ahed Jumal Mahmoud Al-Khatib
Ahed Jumal Mahmoud Al-Khatib
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Asim Ahmed Elnour at Al Ain University
Asim Ahmed Elnour
Naama MS Al Kalbani
Naama MS Al Kalbani
Naama MS Al Kalbani
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Abstract

Ammi visnaga is a widely distributed Ancient Egyptian medicinal plant used for treatment of several diseases including urolithiassis (kidney stones). The active chemical constituents khellin and visnagin obtained from the Ammi visnaga seeds have activity of antilithiogenic and pleiotropic. However, little is known about its activity on hypertriglyceridemia. The main aim of this review is to to explore the use of Ammi visnaga in urolethisis and to present a case of relevancy. We highlighted a case of a patient who has recurrent urethral stones and hypertriglyceridemia. The patient was treated with Ammi visnaga seeds, has recovered completely from ureteral stones and his High Density Lipoprotein (HDL)-Cholesterol low levels retained to normal after using of Ammi visnaga seeds for 10 days. The present case of Ammi visnaga seeds being local medicinal plant has shown effect in treating urolithiasis with extended effect on raising HDL-cholesterol. These results may provide insights for in vitro studies for isolation of these biologically active compounds for potential in raising HDL-cholesterol. Whether or not the later effect can have clinical utility remains to be explored.
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2/2/2017 Amm iVisnagaintreatmentofurolithiasisandhypertriglyceridemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660521/?report=printable 1/6
PharmacognosyRes.2015OctDec;7(4):397–400.
doi:10.4103/09748490.167894
PMCID:PMC4660521
AmmiVisnagaintreatmentofurolithiasisandhypertriglyceridemia
AkshayaSrikanthBhagavathula,AhedJumahMahmoudAlKhatib, AsimAhmedElnour, NaamaM.S.AlKalbani,
andAbdullaShehab
DepartmentofClinicalPharmacy,UniversityofGondarCollegeofMedicineandHealthSciences,Gondar,Ethiopia
DepartmentofNeurosciences,FacultyofMedicine,JordanUniversityofScienceandTechnology,Irbid,Jordan
DepartmentofPharmacology,CollegeofMedicineandHealthSciences,UAEUniversity,AlAin,UAE
DepartmentofPharmacy,TawamHospital,AbuDhabi,UAE
DepartmentofInternalMedicine,CollegeofMedicineandHealthSciences,UAEUniversity,AlAin,UAE
Addressforcorrespondence:Dr.AbdullaShehab,DepartmentofInternalMedicine,CollegeofMedicineandHealthSciences,UAE
University,AlAin,UAE.Email:a.shehab@uaeu.ac.ae
Received2014Nov7;Revised2014Nov22;Accepted2015Oct21.
Copyright:©PharmacognosyResearch
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNonCommercialShareAlike3.0License,which
allowsotherstoremix,tweak,andbuildupontheworknoncommercially,aslongastheauthoriscreditedandthenewcreationsarelicensed
undertheidenticalterms.
Abstract
AmmivisnagaisawidelydistributedAncientEgyptianmedicinalplantusedfortreatmentofseveraldiseases
includingurolithiasis(kidneystones).Theactivechemicalconstituents’khellinandvisnaginobtainedfrom
theA.visnagaseedshaveactivityofantilithiogenicandpleiotropic.However,littleisknownaboutits
activityonhypertriglyceridemia.ThemainaimofthisreviewistoexploretheuseofA.visnagain
urolithiasisandtopresentacaseofrelevancy.Wehighlightedacaseofapatientwhohasrecurrenturethral
stonesandhypertriglyceridemia.ThepatientwastreatedwithA.visnagaseeds,hasrecoveredcompletely
fromureteralstonesandhishighdensitylipoprotein(HDL)cholesterollowlevelsretainedtonormalafter
usingofA.visnagaseedsfor10days.ThepresentcaseofA.visnagaseedsbeinglocalmedicinalplanthas
showntheeffectintreatingurolithiasiswithextendedeffectonraisingHDLcholesterol.Theseresultsmay
provideinsightsforinvitrostudiesforisolationofthesebiologicallyactivecompoundsforpotentialin
raisingHDLcholesterol.Whetherornotthelatereffectcanhaveclinicalutilityremainstobeexplored.
Keywords:Ammivisnaga,highdensitylipoprotein,khellin,ureteralstones,urolithiasis,visnagin
INTRODUCTION
AmmivisnagawithsynonymsAmmidaucoidesandDaucusvisnagaisoffamily,Apiaceae/Umbelliferae.A.
visnaga(Khella)isanannualherbaceousfolkplantwithbiortripinatisectlinearsegmentedleavesandlarge
compoundumbelsofwhiteflowersgrowswildinMediterraneanregionespeciallyinEgypt,Moroccoand
IslamicrepublicofIran.[1,2]Theseedsofovate,oblongfruit(2–2.5cm)constitutesfuranochromones
havingactivityofhyperbilirubinemia,[3]ripefruitconstitutesantilithiogenicactivityandpleiotropiceffecton
urolithiasis,dieresis,[4]antispasmodic[5]andactivecomponent(60μg/ml)havingvariouscardiovascular
beneficialeffects.[6]Duetotheseversatileeffects,AncientEgyptianstraditionallyusedA.visnagaasatea
preparationforthetreatmentofurolithiasisandforanalgesia.[7]Furthermore,severalstudieshadreported
theimportanceofA.visnagaforthetreatmentofseveraldiseasesincludingpsoriasis,[8]asthma,[9]recovery
ofvitiligo,[10]hypoglycemia[11]andpoisonousbites.[12]Furthermore,preliminaryevidencewasobserved
1 2 3
4
1
2
3
4
2/2/2017 Amm iVisnagaintreatmentofurolithiasisandhypertriglyceridemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660521/?report=printable 2/6
Mechanismofaction
Dosingandadministration
Safetyprofile
Possibleadverseeffects
thatkhellinmightalsoincreasehighdensitylipoprotein(HDL)cholesterollevelwithouteffectingtotal
cholesterolortriglyceridesconcentrations.[13]
Therearemanyconventionaldrugsincludingamiodarone,nifedipine,andcromolyn,havebeendeveloped
fromkhella.Khellaissometimesconfusedwithitslessusedrelative,bishop'sweed(Ammimajus).Thetwo
specieshavesomecommonchemicalconstituentsandpharmacologicaleffects,butkhellaismorecommonly
usedforcardiacandpulmonaryconditions,andbishop'sweedismorecommonlyusedfordermatological
conditions.Isolatedkhellin,aconstituentofkhellaandbishop'sweed,isusedforanginapectoris;asthma;
andinconjunctionwithphototherapyforvitiligo,psoriasis,andalopeciaareata.
Pharmacologicalprofile
Theusedpartsofkhellaarethedried,ripefruits.Khellahasseveralconstituentswith
knownpharmacologicalactivity,includingvisnadin,visnagin,andkhellin.Alloftheseconstituentsmay
havecardiovasculareffectsattributedtocalciumchannelblockingactions.Visnadinisthemostactive.Itcan
inhibitvascularsmoothmusclecontractionandmaydilateperipheralandcoronaryvesselsandincrease
coronarycirculation.Visnaginalsohasnegativechronotropicandinotropiceffectsandreducesperipheral
vascularresistance.Thekhellinconstituentalsoactsasavasodilatorandhasbronchodilatoryactivity.There
issomepreliminaryevidencethatkhellinmightalsoincreaseHDLcholesterollevelswithoutaffectingtotal
cholesterolortriglycerideconcentrations.[13]
Akhellaextractseemstohavesomeantimicrobialactivity.Thismightbeattributabletoboththekhellinand
visnaginconstituents,whichbothseemtohaveantifungal,antibacterial,andantiviralactivity.Researchers
areinterestedinkhellaforuseinpsoriasis.Thekhellinconstituentisstructurallysimilartothepsoralen
nucleusandmightbeusefulasaphotosensitizerinpatientswithpsoriasis.[6]
Ammivisnagauses
Orally,khellaisusedasantispasmodicforcolicandabdominalcramps,kidneystones,menstrualpain,and
premenstrualsyndrome.[14]Khellaisalsousedforrespiratoryconditionsincludingasthma,bronchitis,
cough,andwhoopingcough.Itisalsousedforcardiovasculardisordersincludinghypertension,cardiac
arrhythmias,congestiveheartfailure,angina,atherosclerosis,andhypercholesterolemia.Itisalsousedfor
liverandgallbladderdisorders,diabetes,andasadiuretic.Topically,khellaisusedontheskinforvitiligo,
psoriasis,patchyhairloss(alopeciaareata),woundhealing,inflammationconditions,andpoisonousbites.
[15]
Orallykhellaistypicallygivenasanextractstandardizedbasedonkhellin
content.Extractsareusuallystandardizedto12%khellin.Atypicaldoseofkhellaisanamountthatprovides
20mgofthekhellinconstituentperday.Forangina,khellainanamountprovidingdosesof30–300mgof
thekhellinconstituenthasalsobeenused.Khellaissometimesusedasatea.Theteaisusuallypreparedby
pouringboilingwateroverpowderedfruit,steeping10–15min,andstraining.[16]
Ammivisnagaispossiblyunsafewhenusedorallyinhighdoses.Highdosesofkhellacan
causeincreasesinliverenzymesandpossibleliverdamage.Itisunlikelysafewhenusedorallyinpregnancy.
Theactiveconstituent,khellin,hasuterinestimulantactivity;thereforeiscontraindicatedinpregnancy.[17]In
lactationinsufficientreliableinformationisavailable,however,itisadvisedtoavoidusing.
Orally,prolongeduseoruseofhighdosesofkhellacancausenausea,dizziness,
constipation,lackofappetite,headache,itching,andinsomnia.Insomepatients,khellacancauseelevated
livertransaminase(enzymesaspartatetransaminaseandalaninetransaminase)andgamma
glutamyltransferaselevels(alkalinephosphatase),[6]probablyduetothekhellinconstituent;whichisknown
toaffectliverenzymes.Liverdysfunctionandjaundicearetypicallyreversiblewhenkhellaisdiscontinued.
Thereisalsosomeconcernthatkhellamightcausephotosensitivitybecauseoftheconstituentskhellinand
2/2/2017 Amm iVisnagaintreatmentofurolithiasisandhypertriglyceridemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660521/?report=printable 3/6
Urolithiasis
thefurocoumarin.Prolongeduseoroverdosemaycausenausea,vertigo,constipation,lackofappetite,
headache,andsleeplessness.[18]
Urolithiasisisaurologicalclinicalconditioncommonlycalledaskidneystonediseasewithan
averagelifetimeriskofstoneformationin5%–10%ofthepopulation.[19]Severalfactorscanpromotethe
formationofkidneystonessuchasdehydration,consumptionoffoodscontaininghighamountofcalcium,
uricacid,andsomeinfectiousdiseases.[20]Althoughpatientswithurolithiasismightbeasymptomatic,many
havepainandthuscommonlypresenttotheemergencydepartment(ED).[21]Khellin,achemicalobtained
fromA.visnaga,wasusedasasmoothmusclerelaxantandhasbeenthoughttohavepleiotropiceffectson
urolithiasis(smoothmusclerelaxation,diuresisandtheeffectsonurinarycitrate).[4]
Themainconstituentofkidneystones(80%)iscalciumoxalate(CaOx).However,ifthestoneenlargesit
causesureteralobstruction(stones>5mmunlikelytopassspont)andproducessymptomsofflankpain,
burningmicturitionandhematuriarequiresemergencymedicalandsurgicalmanagement.Although,medical
andsurgicaltreatmentsarewidelyusedtherewereseveraldisadvantagesincludingreoccurrenceofkidney
stonesandpotentialrenaldamage.Khellinmayinterferewiththecitratemetabolism.SinceCaOxurinary
stonesarethemostcommontypeofurinarystone(upto80%)andcitrateisawellknowninhibitorofCaOx
crystallization[22]Khanetal.reportedthaturinarycitrateplaysanimportantroleinreducingrecurrencesof
CaOxstones.[11]
Therefore,traditionalandalternativemedicationswereotheroptionstoinvestigate.Inthisregard,we
presentedhereacaseofurolithiasisandhypertriglyceridemiatreatedwithseedsofA.visnaga.
CASEREPORT
A50yearoldmanwasreferredtoEDatKingAbdullahUniversityHospitalinJordanfromprimaryhealth
centerwithchiefcomplaintsofflankpainwithdysuriafor3hbeforeadmission.Indetailedhistory,patient
wasknownhypertensivesince10yearsusingonlyantihypertensivemedication.Hehasahistoryof
urolithiasisforthepast3yearsandunderwentregularmedicaltreatmentpreviouslybutnotwellbenefitted.
AtthetimeofadmissiontotheED,physicalexaminationrevealedtendernessoncostovertebralangelwas
observedonbothsidesandburningmicturitionwhilepassingtheurine.Hehadabodytemperatureof
37.5°Candelectrocardiogramremainsnormal.Theclinicalandlaboratoryfindingsweredescribedin
Table1.Further,hishematologicalandelectrolyticexaminationsshowednormal.Onultrasound
examination,itwasobservedtwostonesobservedonrighturethra(3–5mmdiameter)andoneontheleft
kidney(3mmdiameter).PainreliefwasprovidedintheEDandadvisedtohavesurgicalremovalofthree
stones.
Duetopreviousexperiencewithsurgeriesandtherapeutictreatmentfailures,preferredtosearchforother
therapeuticoptions.Insearchofotheralternatives,phytotherapeuticoptionA.visnagawasconsideredand
advisedforthepatienttouseitsseedsthroughboilingateaspoonsize(10g)in200mlofwaterfor10days
twicedaily.Duringfollowup,2daysafterinitiationoftheA.visnagaseedthepatientwasrelievedfrom
painandnohematuriawasobserved.Onday5,thestoneinkidneypassedoutthroughurine,furtheronday
7and8theothertwostonesintheureterwerealsopassedout.Onday10ofultrasoundexamination,no
renalstoneswereobservedandfurtherthepatient'slipidprofilehasshowedimprovementofHDL
cholesterollevelfrom32to56mg/dL.Therewasnomuchimprovementobservedinotherlipidparameters
ascholesterolandlowdensitylipoprotein(LDL)cholesterolandallotherlaboratoryinvestigationswere
normal.
DISCUSSIONS
ThecasepresentedconfirmedtheimportanceofA.visnagaintreatmentofurolithiasiswithabeneficial
effectinimprovingHDLlevelswithouteffectingthetriglyceridesandLDLlevels.Inourcase,theuseofA.
visnagawasabletorelievethepainandproveneffectivetreatmenttowardurolithiasisbyremovingstones
2/2/2017 Amm iVisnagaintreatmentofurolithiasisandhypertriglyceridemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660521/?report=printable 4/6
fromkidneyandurethras.Similarresultswerereportedinotherstudies.[12,14,15]Thedetailedmechanism
ofactionofA.visnagaseedswasnotyetelucidated.However,itmaybeduetothemaincompoundskhellin
andvisnaginthatcanpreventcelldamagecausedbyCaOxcrystalsinrenalepithelialcells.[13]Further,
morethanonemechanismhasbeenproposedbyvariousresearchers.Hashimetal.[19]describedtheaction
ofA.visnagatobeattributedtoitsvasodilatinganddiureticproperties.OtherresearchersasKilicaslanand
Coskun[20]explaineditmaybeduetokhellininterferewiththecitratemetabolismininhibitingtheCaOx
crystallization.Charafietal.[23]foundthatA.visnagaseedswereefficientininhibitingthecrystallizationof
CaOx.Furthermore,Khanetal.[11]reportedthaturinarycitratesarecrucialinreducingrecurrencesofCa
Oxstones.
Someofthemedicaltherapieshavebeenreportedtoeaseurolithiasisandstudieshighlightedtheactive
metabolitesofαantagonistsandcalciumchannelblockersbenefittoenhancestonepassage.[21]Inourcase,
thepatientisusingamlodipine5mgoncedailyformanagementofhypertensionsince5yearsandwas
sufferingwithrecurrenturolithiasisfrom3years.Inthepresentcase,thecalciumchannelblockerhasnot
shownanypositiveeffectinpreventingrenalcalculipassage.Inaddition,thechemicalcompositionoftheA.
visnagafruitattributestohavefuranochromonesderivativesaskhellinandvisnaginwhichreportedtohave
antiinflammatoryandanalgesicactivity.[24,25]
Inourcase,althoughthepatienthasurolithiasis,butlaboratoryinvestigationsshowedelevatedlevelsoflipid
profileoftriglyceridesandafterusingA.visnagafor9daysthepatienthasshowedincreaseinHDL
cholesterollevels,butalsoloweringeffectontriglycerides.InHarvengtandDesager,[13]placebocontrolled
study,oraladministrationof50mgofkhellin(A.visnagacompound)fourtimesdailyfor4weeksshowed
significantincreasedlevelsofHDLcholesterolconcentrationwithoutaffectingtotalcholesterolor
triglyceridesconcentration.ThissupportsthatthekhellincompoundinA.visnagacanalsobeofvalueto
raiseHDLcholesterol.
CONCLUSIONS
ThepresentcaseofA.visnagaseedsbeinglocalmedicinalplanthasshowntheeffectintreatingurolithiasis
withextendedeffectonraisingHDLcholesterol.Theseresultsmayprovideinsightsforinvitrostudiesfor
isolationofthesebiologicallyactivecompoundsforpotentialinraisingHDLcholesterol.Whetherornotthe
latereffectcanhaveclinicalutilityremainstobeexplored.
Footnotes
SourceofSupport:Nil
ConflictsofInterest:Nonedeclared.
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22.ByerK,KhanSR.Citrateprovidesprotectionagainstoxalateandcalciumoxalatecrystalinduced
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FiguresandTables
2/2/2017 Amm iVisnagaintreatmentofurolithiasisandhypertriglyceridemia
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660521/?report=printable 6/6
FiguresandTables
Table1
Patientclinicalandlaboratorydatabeforeinitiationof“Ammivisnaga”
ArticlesfromPharmacognosyResearchareprovidedherecourtesyofMedknowPublications
... Ammi visnaga L. (Daucus visnaga L., Visnaga daucoides Gaertn.), a member of the Apiaceae, commonly known as Toothpick weed in England, or Khella in Arab countries, has only recently been reviewed for its numerous curative properties, out of which the antioxidant ones have been approached by very few studies [17]. A Northern hemisphere widespread biennial or annual herbaceous plant [17,18], A. visnaga L. presents an erect, cylindrical, and highly branched stem reaching 130 cm in height, covered with greyish green foliage. Its white flowers are grouped into umbels of 6-10 cm in diameter and the fruits are tiny, ovoid, and smooth formed of two partial mericarps, each 2 mm long greyish brown in color when the plant is dry [17]. ...
... Its white flowers are grouped into umbels of 6-10 cm in diameter and the fruits are tiny, ovoid, and smooth formed of two partial mericarps, each 2 mm long greyish brown in color when the plant is dry [17]. In the popular pharmacopoeia, the plant is used as dried powder or boiled in water to treat renal colic, mild angina symptoms, asthma, spastic bronchitis, abdominal cramps, urinary calculi, vitiligo and psoriasis, vertigo, diabetes, and kidney stones [18]. In the pharmaceutical industry, various prescription drugs, such as amiodarone (ventricular arrhythmias), nifedipine (treatment of stable, variant, and unstable angina, mild to severe hypertension, and Raynaud's phenomenon), and cromolyn (mastocytosis) are derived from A. visnaga L. [18]. ...
... In the popular pharmacopoeia, the plant is used as dried powder or boiled in water to treat renal colic, mild angina symptoms, asthma, spastic bronchitis, abdominal cramps, urinary calculi, vitiligo and psoriasis, vertigo, diabetes, and kidney stones [18]. In the pharmaceutical industry, various prescription drugs, such as amiodarone (ventricular arrhythmias), nifedipine (treatment of stable, variant, and unstable angina, mild to severe hypertension, and Raynaud's phenomenon), and cromolyn (mastocytosis) are derived from A. visnaga L. [18]. ...
Chemical Composition and Antioxidant Activity of Ammi visnaga L. Essential Oil
Article
Full-text available
  • Feb 2022
The present study evaluated the chemical composition and the in vitro and in vivo antioxidant potential of Ammi visnaga L. essential oil to provide a scientific basis for the use of this plant in the traditional pharmacopoeia. Gas chromatography-mass spectrometry was used to identify the volatile constituents present of the oil. The in vitro antioxidant capacity was evaluated by the DPPH and the reducing power assays. For the in vivo tests, oral administration of Ammi visnaga L. oil (600 and 1200 mg/kg body weight) was performed in Swiss albino mice treated with acetaminophen (400 mg/kg). The toxic effect of acetaminophen and the action of the essential oil were measured by determining the levels of lipid peroxidation and antioxidant enzymes in liver and kidneys homogenates. The major components identified were butanoic acid, 2-methyl-, pentyl ester, (Z)-�-ocimene, D-limonene, linalool, pulegone and lavandulyl-butyrate. The in vitro DPPH and reducing power assays showed moderate to low free radical scavenging activity and the antioxidant power was positively correlated with the polyphenols’ concentration. In vivo, the Ammi visnaga L. essential oil showed a high antioxidant capacity at both concentrations (600 and 1200 mg/kg), effectively increasing the levels of reduced glutathione, superoxide dismutase, and catalase and significantly reducing the lipid peroxidation. The results obtained from this study suggest that Ammi visnaga L. could represent a source of molecules with antioxidant potential in the prevention of free radical-related diseases.
... Ammi visnaga L. (Daucus visnaga L., Visnaga daucoides Gaertn.), a member of the Apiaceae, commonly known as Toothpick weed in England, or Khella in Arab countries, has only recently been reviewed for its numerous curative properties, out of which the antioxidant ones have been approached by very few studies [17]. A Northern hemisphere widespread biennial or annual herbaceous plant [17,18], A. visnaga L. presents an erect, cylindrical, and highly branched stem reaching 130 cm in height, covered with greyish green foliage. Its white flowers are grouped into umbels of 6-10 cm in diameter and the fruits are tiny, ovoid, and smooth formed of two partial mericarps, each 2 mm long greyish brown in color when the plant is dry [17]. ...
... Its white flowers are grouped into umbels of 6-10 cm in diameter and the fruits are tiny, ovoid, and smooth formed of two partial mericarps, each 2 mm long greyish brown in color when the plant is dry [17]. In the popular pharmacopoeia, the plant is used as dried powder or boiled in water to treat renal colic, mild angina symptoms, asthma, spastic bronchitis, abdominal cramps, urinary calculi, vitiligo and psoriasis, vertigo, diabetes, and kidney stones [18]. In the pharmaceutical industry, various prescription drugs, such as amiodarone (ventricular arrhythmias), nifedipine (treatment of stable, variant, and unstable angina, mild to severe hypertension, and Raynaud's phenomenon), and cromolyn (mastocytosis) are derived from A. visnaga L. [18]. ...
... In the popular pharmacopoeia, the plant is used as dried powder or boiled in water to treat renal colic, mild angina symptoms, asthma, spastic bronchitis, abdominal cramps, urinary calculi, vitiligo and psoriasis, vertigo, diabetes, and kidney stones [18]. In the pharmaceutical industry, various prescription drugs, such as amiodarone (ventricular arrhythmias), nifedipine (treatment of stable, variant, and unstable angina, mild to severe hypertension, and Raynaud's phenomenon), and cromolyn (mastocytosis) are derived from A. visnaga L. [18]. ...
Chemical Composition and Antioxidant Activity of Ammi visnaga L. Essential Oil
Article
Full-text available
  • Feb 2022
The present study evaluated the chemical composition and the in vitro and in vivo antioxidant potential of Ammi visnaga L. essential oil to provide a scientific basis for the use of this plant in the traditional pharmacopoeia. Gas chromatography-mass spectrometry was used to identify the volatile constituents present of the oil. The in vitro antioxidant capacity was evaluated by the DPPH and the reducing power assays. For the in vivo tests, oral administration of Ammi visnaga L. oil (600 and 1200 mg/kg body weight) was performed in Swiss albino mice treated with acetaminophen (400 mg/kg). The toxic effect of acetaminophen and the action of the essential oil were measured by determining the levels of lipid peroxidation and antioxidant enzymes in liver and kidneys homogenates. The major components identified were butanoic acid, 2-methyl-, pentyl ester, (Z)-β-ocimene, D-limonene, linalool, pulegone and lavandulyl-butyrate. The in vitro DPPH and reducing power assays showed moderate to low free radical scavenging activity and the antioxidant power was positively correlated with the polyphenols’ concentration. In vivo, the Ammi visnaga L. essential oil showed a high antioxidant capacity at both concentrations (600 and 1200 mg/kg), effectively increasing the levels of reduced glutathione, superoxide dismutase, and catalase and significantly reducing the lipid peroxidation. The results obtained from this study suggest that Ammi visnaga L. could represent a source of molecules with antioxidant potential in the prevention of free radical-related diseases.
... Previous studies have shown that furochromone compounds have broad biological activities [1,2]. Furochromone derivatives have been widely used in modern medicine to treat many ailments such as vitiligo and hair loss [2], urolithiasis and hypertriglyceridemia [3], spasms and kidney stones [4], and pain associated with renal colic [5]. They are also known to have antioxidant, antidiabetic, antispasmodic, antimutagenic, herbicidal, larvicidal, insecticidal, immunostimulatory, cardiovascular, antigastric, antineoplastic, anti-anaphylactic, anti-atherosclerotic [3], cytotoxic [6], analgesic and anti-inflammatory [7,8], antimicrobial [9,10], antiviral [11], and anticancer activity [12,13]. ...
... Furochromone derivatives have been widely used in modern medicine to treat many ailments such as vitiligo and hair loss [2], urolithiasis and hypertriglyceridemia [3], spasms and kidney stones [4], and pain associated with renal colic [5]. They are also known to have antioxidant, antidiabetic, antispasmodic, antimutagenic, herbicidal, larvicidal, insecticidal, immunostimulatory, cardiovascular, antigastric, antineoplastic, anti-anaphylactic, anti-atherosclerotic [3], cytotoxic [6], analgesic and anti-inflammatory [7,8], antimicrobial [9,10], antiviral [11], and anticancer activity [12,13]. In addition, they have the ability to bind to DNA [14] and act as coronary vasodilators [15]. ...
The Synthesis, Antimicrobial Activity, and Molecular Docking of New 1, 2, 4-Triazole, 1, 2, 4-Triazepine, Quinoline, and Pyrimidine Scaffolds Condensed to Naturally Occurring Furochromones
Article
Full-text available
  • Oct 2022
This study aims to synthesize a new series of furochromone derivatives, evaluate their antimicrobial properties, and improve the permeability of potent compounds to inhibit different types of bacteria and fungi. Hence, Substituted furo[3,2-g]chromene-6-carbonitrile (3a,b) readily form 7-amino-5-methyl-furo [3,2-g]chromene-6-carbonitrile (4a,b) via reduction using sodium borohydride in methanol. The same compounds of (4a,b) were used as starting materials for the synthesis of new furochromone derivatives such as furochromeno [2,3-d]pyrimidines, N- (6-cyano-5-methyl-furochromene) acetamide, N-(6-cyano-5-methyl-furo chromene)-2-phenyl acetamide, N-(6-cyano-5-methyl-furochromene) formimidate, furochromeno[1,2,4]triazepin-5-amine, furochromene-6-carboxamide, furochromeno[1,2,4]triazolopyrimidines, and furochromeno[2,3-b]quinolin-6-amine. The structures of the new compounds were determined using spectroscopy: Nuclear Magnetic Resonance (1H, 13C), Mass spectra, Infrared, and elemental analysis. Molecular docking studies were conducted to investigate the binding patterns of the prepared compounds against DNA-gyrase (PDB 1HNJ). The results displayed that compounds furochromenotriazolopyrimidine (20a,b), furochromenoquinolin-6-amine (21a,b), furochromenotriazepin-amine (9a,b), and furochromenopyrimidine-amine (19a,b) were excellent antimicrobials.
... Ammi visnaga is a short biennial medicinal herb native of Africa, Europe, and Asia [18] used to treat ailments such psoriasis, asthma, vitiligo, analagesia, urolithiasis, hypoglycemia, hypercholesterolemia, and atherosclerosis [19][20][21]. Visnagin, a furanochrome derivative one of the major components present in Ammi visnaga and previous investigations revealed that the visnagin has the anti-pancreatitis activity [22], neuroprotective activity [23], and cardioprotective activity [24]. Based on these biological activities of visnagin, here we planned to conduct the study to unveil the anti-ischemic stroke activity of visnagin. ...
Neuroprotective, Anti-inflammatory Effect of Furanochrome, Visnagin Against Middle Cerebral Ischemia-Induced Rat Model
Article
Full-text available
In recent years, the medical field had significantly progressed to a greater extent which was evidenced with increased life expectancy and decreased mortality rate. Due to the growth of medical field, numerous communicable diseases are prevented and eradicated, whereas the non-communicable disease incidence has been increased globally. One such non-communicable disease which threatens the global population is stroke. Stroke tends to be the second leading cause of death and disability in older population. In lower- and middle-income countries, increased incidence rate of stroke was also evidenced in younger population which is alarming. Lifestyle changes, poor physical activity, stress, consumption of alcohol, oral contraception, and smoking tend to be the causative agents of stroke. Since thrombus formation is the major pathology of stroke, drugs were targeted to thrombolysis. Currently thrombolytic, antiplatelet, and anticoagulant therapies were given for the stroke patients. But the recovery rate of stroke patients with available drugs is very slow. Hence, it is a need of today to discover a drug with increased recovery rate and decreased or nil side effects. Phytochemicals are the best options to treat such non-communicable chronic diseases. Visnagin is one such compound which is used to regulate blood pressure, treat kidney stones, tumors of bile duct, renal colic, and whooping cough. It possesses anti-inflammatory, neuroprotective, and cardioprotective properties; it was also proven to treat epileptic seizures. In this study, the anti-ischemic effect of a furanochrome visnagin was assessed in in vivo rat model. Middle cerebral ischemic/reperfusion was induced in healthy male Sprague Dawley rats and treated with different concentrations of visnagin. The neuroprotective effect of visnagin against cerebral ischemia-induced rats was assessed by analyzing the neurological score, brain edema, infract volume, and Evans blue leakage. The anti-inflammatory property of visnagin was assessed by quantifying proinflammatory cytokines in serum and brain tissues of cerebral ischemia-induced rats. Prostaglandin E-2, COX-2, and NFκ-β were estimated to assess the anti-ischemic effect of visnagin. Histopathological analysis with H&E staining was performed to confirm the neuroprotective effect of visnagin against cerebral ischemia. Our results authentically confirm that visnagin has prevented the inflammation in brain region of cerebral ischemia-induced rats. The neurological scoring and the quantification of PGE-2, COX-2, and NFκ-β prove the anti-ischemic effect of visnagin. Furthermore, the histopathological analysis of hippocampal region provides evidence to the neuroprotective effect of visnagin against cerebral ischemia. Overall, our study confirms visnagin as a potent alternative drug to treat stroke.
... It is known for its content of furanochromones mainly khellin and visnagin, flavonoids and essential oil 2 . Khellin, the major metabolite of A. visnaga, is used for the treatment of vitiligo [3][4][5] , urolithiasis 6 and angina pectoris 7 . In addition, both khellin and visnagin are reported as environmentally safe bioherbicides 8 . ...
... Therefore, barley, halfa bar, lemon rind, camel grass, and khella have dual mechanisms of their action in ameliorating the symptoms of urolithiasis, including the anti-aggregation and the antispasmodic mechanisms. It is worth noting that some of these herbs are known for their antispasmodic activity due to the established identity of bioactive compounds, such as khellin and visnagin (khella) (Bhagavathula et al. 2014) ...
In-Vitro Evaluation of Some Traditional Medicinal Plants on Calcium Oxalate Urolithiasis
Article
Full-text available
  • Nov 2021
The prevalence of urolithiasis in Middle East countries is predominantly high. Traditional medicinal plants play a role in the prevention and management of urolithiasis. The effect of Petroselinum crispum, rind of Citrus sinensis L., rind of Citrus limon L., Ammi visnaga (L.) LAM., Tamarindus indica L., Nigella sativa L., Cymbopogon proximus Hochst. ex A. Rich., Hibiscus sabdariffa L., Hordeum vulgare L., and Cymbopogon schoenanthus (L.) Spreng. on calcium oxalate crystallization was investigated in-vitro. The antispasmodic activity on acetylcholine-induced contraction in rat ileum was also screened ex-vivo. A significant reduction in the mean diagonal of calcium oxalate crystals was observed for P. crispum, C. proximus, N. sativa, and C. limon (4.41, 4.71, 5.44, and 5.67 μm, respectively) compared to the negative control (12.19 μm). H. sabdariffa exhibited antinucleation effect however, P. crispum showed a marked inhibition of calcium oxalate aggregation at 10 mg/mL after 60 min compared to the negative control. A remarkable ex-vivo antispasmodic activity was observed for C. proximus, C. schoenanthus, and A. visnaga extracts. Our results provide scientific evidence for the traditional use of the studied plant-derived products as potential therapies for calcium oxalate urolithiasis.
... 14 The second mechanism is through decreasing lipid levels such as cholesterol and triglycerides as reported in other studies. 15 Using rat model, we previously found that molecular defects in the brain white matter were beyond the events involved in the development of diabetes. 16 We also found similar effects on liver induced by anti-oxidants. ...
The use of Ammi visnaga in the treatment of prediabetes and weight loss: the antioxidant impacts in diabetes treatment as a new medical hypothesis
Article
  • Nov 2020
Introduction: Prediabetes status is considered as an important feature in either controlling the development or progression of diabetes. It may pass unnoticed because the symptoms of diabetes are usually not well established. Study objectives: The main objectives of the present study were to explore the efficacy of using Ammi visnagain treating pre-diabetic cases and weight losing. Methods and subjects: A prospective study was conducted to investigate the impact of using Ammi visnaga treatment of pre-diabetes and weight control. The study included 5 patients with pre-diabetes (glucose level was 128±32mg/dl). The age of patients was 42±18.5years. The study included 3 males and 2 females. In general, patients were overweight according to body mass index level was 28±7.8kg/m2. The patients used the aqueous extract of Ammi visnaga for two months (200 ml daily). Results: At the end of the experiment, the glucose level was significantly reduced (p<0.05)to the level of 88±12.5mg/dl. There was also a significant reduction in the level of BMI from 28±7.8kg/m2 to 22±6.4kg/m2(p<0.05). Conclusion: The results of the present study showed that Ammi visnaga has the therapeutic potential to control the progression of complete episodes of diabetes by controlling the pre-diabetic status
Ammi-visnaga extract; a novel phyto-antiviral agent against bovine rotavirus
Article
  • Jan 2023
The spread of bovine rotavirus has a great impact on animal productivity, milk products, and human public health. Thus, this study aimed to develop a novel, effective and accessible Phyto-antiviral treatment made from methanolic Ammi-visnaga seed extract against rotavirus infection. Rotaviruses were isolated from raw milk and cottage cheese samples randomly collected from Cairo and Qalubia governorates. They were all identified serologically, however, only three of them were both biologically and molecularly confirmed. The methanolic extract derived from Khella seeds (MKSE) was chemically analyzed with mass chromatography. The cellular toxicity of MKSE was tested on Caco-2 cells and its antiviral activity against one of the isolated bovine rotaviruses (BRVM1) was tested by both the cytopathic inhibition assay and the plaque reduction assay. Our results showed that 17.3% of the total collected 150 dairy samples were bovine rotavirus antigen positive. Three representatives of them were phylogenetically identified to be included in group A based on a 379 bp coat protein gene. Visnagin, Benzopyran, Khellin, and Benzenepropanoic acid were the major active components found in the MKSE. The maximum non-toxic concentration of MKSE was 5 µg/mL and the CC50 value was 417 µg/mL. The MKSE exhibited in-vitro antiviral activity against BRVM1 indicated by inhibition of the viral cytopathic effect (SI = 204.5, IP = 98%), causing a 1.5 log decrease in BVRM1 TCID50 and reducing the viral plaques count by the percentage of 93.14% at MNTC (5 ug/ml). In conclusion, our study showed that bovine rotavirus represents a severe health problem that needs attention in Egypt, and it supports using MKSE as a potential natural anti-rotavirus agent.
Therapeutic potential of medicinal plants for the management of renal stones: A review
Article
Full-text available
  • Jun 2022
Kidney stones are among the oldest and most widespread urinary tract ailments, impacting people all over the globe with a high recurrence rate. The mechanism of kidney stone formation includes events such as urine supersaturation, aggregation, retention, nucleation, and growth of crystals in the cells of the renal tubular epithelium. Kidney stones may cause extreme pain and blockage of urine flow. They are usually treated with synthetic drugs and extracorporeal shock wave lithotripsy (ESWL) as well as a variety of medications that may cause several adverse effects. The remaining stone fragments and the risk of infection following ESWL are severe problems in the treatment of kidney stones. Recently, despite the emergence of synthetic drugs, medicinal plants have been recognized and utilized in many nations due to their safety profile, efficiency, cultural acceptance, and fewer side effects than synthetic drugs. Medicinal plants are used in different cultures as a reliable source of natural remedies. The aim of this review is to provide comprehensive information about traditionally used antiurolithiatic plants as well as their scientifically proven pharmacological activities, their primary chemical ingredients, and potential mechanisms of action, such as analgesic, astringent, demulcent, diuretic activity, antioxidant activity, inhibition of the inflammatory process, nucleation inhibition, crystallization inhibition, inhibition of crystal aggregation, reducing hyperoxaluria, reducing stone size, and reducing urine supersaturation.
study of ammi visnaga lam on oxalocalcic crystallization
Article
Full-text available
  • Sep 2012
The aim of this study is to test scientifically vitro inhibitory effect of Ammi visnaga Lam extract (AVL) including the aqueous extract of whole plant extract and its seeds on the oxalocalcic crystallization in human urine oxalate supersaturated calcium Method: The turbidimetric kinetics were measured using a spectrometry , in the program, set at 620 nm wavelength with model developed in our laboratory The frequency, nature and crystal morphology of calcium oxalate in urine natural supersaturated calcium oxalate in the absence and presence of test substances were monitored by OLYMPUS microscopy with polarized light. The results demonstrate the effectiveness of extracts of the seeds of AVL in inhibiting the crystallization of calcium oxalate. These extracts reduce oxalate calcium crystallization and specially monohydrate oxalate calcium (MOC).
A review: Herbal plants used in the treatment of Urolithiasis
Article
Full-text available
  • Nov 2010
Kidney stone formation is a complex that results from a succession of several physicochemical events including supersaturation, nucleation, growth, aggregation and retention within the kidneys. Urinary stones affect 10-12 % of the population in industrialized countries. There are only a few geographical areas in which stone disease is rare e.g. Germany and in the coastal areas of Japan. So in the present review aims to give data highlighting the present trends in research of medicinal plants accredited with antiurolithiatic activity. This article may help investigators to identify lead compounds or herbal products responsible for urolithiatic activity. INTRODUCTION: Urinary stone disease continues to occupy an important place in everyday urological practice. The average life time risk of stone formation has been reported in the range of 5-10 %. A predominance of men over women can be observed with an incidence peak between the fourth and fifth decade of life.
Spontaneous stone passage: Is it Ammi visnaga effect?
Article
Full-text available
Ammi visnaga was used in Ancient Egypt as an herbal remedy for renal colic. "Khellin", a chemical obtained from Ammi visnaga, was used as a smooth muscle relaxant and has been thought to have pleiotropic effects on urolithiasis. We report a case with multiple ureteral stone passages possibly as a result of medication with an herb preparation, Khellin.
Synthesis of New Visnagen and Khellin Furochromone Pyrimidine Derivatives and Their Anti-Inflammatory and Analgesic Activity
Article
Full-text available
6-[(4-Methoxy/4,9-dimethoxy)-7-methylfurochromen-5-ylideneamino]-2-thioxo-2,3-dihydropyrimidin-4-ones 1a,b were prepared by reaction of 6-amino-2-thiouracil with visnagen or khellin, respectively. Reaction of 1a,b with methyl iodide afforded furochromenylideneaminomethylsulfanylpyrimidin-4-ones 2a,b. Compounds 2a,b were reacted with secondary aliphatic amines to give the corresponding furochromen-ylideneamino-2-substituted pyrimidin-4-ones 3a-d. Reaction of 3a-d with phosphorus oxychloride yielded 6-chlorofurochromenylidenepyrimidinamines 4a-d, which were reacted with secondary amines to afford furochromenylideneamino-2,6-disubstituted pyrimidin-4-ones 5a-d. In addition, reaction of 5a-d with 3-chloropentane-2,4-dione gave 3-chloro-furochromenylpyrimidopyrimidines 6a-d. The latter were reacted with piperazine and morpholine to give 1-(furochromenyl)-pyrimidopyrimidine-3,6,8-triylpiperazines or -3,6,8-triylmorpholines 7a-d. The chemical structures of the newly synthesized compound ware characterized by IR, ¹H-NMR, ¹³C-NMR and mass spectral analysis. These compounds were also screened for their analgesic and anti-inflammatory activities. Some of them, particularly 3-7, exhibited promising activities.
Phytochemistry and medicinal properties of Ammi visnaga (Apiacae)
Article
Ammi visnaga (bisnaga, toothpick weed or khella) belongs to the family Apiaceae and it is a herbaceous medicinal plant. It is found mainly in the Mediterranean regions and also distributed abundantly throughout the world as introduced species. Many times, A. visnaga is weed as well as used in many countries as herbal medicine for different purposes. Ancient records reveal various medicinal properties of A. visnaga as a popular source to cure variety of different ailments. The plant is used directly as a herb or as a component for production of a number of herbal medicines used in the cure of renal colic, ureteric stones, angina pectoris, the coronary vessels, cardiovascular disorders and asthma. Also it is used as a folk medicine for vitiligo and psoriasis. This review highlights the commonly recognized medicinal uses of A. visnaga, its chemistry and ethnobotanical uses and will also serve as ready reference for future research.
Drugs Originating from the Screening of Dyes
Chapter
  • Jan 2006
Written by a leading authority with an excellent reputation and ability for writing a good narrative, Drug Discovery: A History is a far cry from simply a list of chemical structures. This lively new text considers the origins, development and history of medicines that generate high media interest and have a huge social and economic impact on society. Set within a wide historical, social and cultural context, it provides expanded coverage of pre-twentieth century drugs, the huge advances made in the twentieth century and the latest developments in drug research. Hallmark features: Up-to-the-minute information in drug research. Vignettes of special and unusual information, and anecdotes. Discusses drug prototypes from all sources. More comprehensive than other volumes on history of drug discovery. From the reviews: "...an excellent bibliographic resource for those interested in the background papers that serve as the foundation for discovery of specific drug entities." JOURNAL OF MEDICAL CHEMISTRY, June 2006. "...a very comprehensive overview of drug development. It should be on the shelf on any aspiring pharmacist, medicinal chemist, or person interested in the history of therapeutic agents." JOURNAL OF CHEMICAL EDUCATION, February 2006.
Anti-inflammatory and analgesic activity of different extracts of Commiphora myrrha
Article
  • Dec 2010
This present study was carried out to evaluate the anti-inflammatory and analgesic effects of 85% ethanol extract (EE) of Commiphora myrrha and its different fractions partitioned with petroleum ether extract (EPE), ethyl acetate extract (EEA), n-butanol extract (EBu), and the water extract (ECY). Moreover, the chemical constituents in EPE were analyzed and identified by UPLC-QTOF/MS/MS. The anti-inflammatory activities were investigated by utilizing the paw edema mice induced by formalin. In addition, we determined the levels of PGE(2) in the edema paw. While the analgesic activity was examined against thermally and chemically induced nociceptive pain in mice, using the acetic acid and hot-plate test methods. The effects of the administration of dolantin or indomethacin were also studied for references. The components in EPE were analyzed by the ultra-performance liquid chromatography coupled with mass spectrum. In the anti-inflammatory test, EE inhibited the development of paw swelling induced by formalin significantly. The pharmacological activities of the petroleum ether fraction (EPE) were stronger than the EE extract and other fractions at the dose of 100mg/kg, and furthermore significantly decreased the levels of inflammatory factor PGE(2) in the edema paw tissue at the fourth hour after formalin injection. It has been also shown that the ethanol extract (EE) significantly reduced acetic acid-induced writhing response in mice at the dose of 200mg/kg, and 100mg/kg. The petroleum ether fraction (EPE) showed significant analgesic activity in the model at the dose of 100mg/kg (p<0.01), and the ethyl acetate fraction (EEA) exhibited less analgesic activity (p<0.05). All test samples showed no significant analgesic activity on the hot plate pain threshold in mice. The UPLC-MS/MS chromatogram analysis of EPE stated that EPE contains the ingredients of sesquiterpenes, diterpenes, and diterpenic acids. Moreover, seven main compounds were identified. These data demonstrated that the EE and EPE posses analgesic and anti-inflammatory activities and may support the fact the traditional application of this herb in treating various diseases associated with inflammatory pain.
An aqueous extract of Ammi visnaga fruits and its constituents khellin and visnagin prevent cell damage caused by oxalate in renal epithelial cells
Article
  • Jul 2010
Teas prepared from the fruits of Ammi visnaga L. (syn. "Khella") have been traditionally used in Egypt as a remedy to treat kidney stones. It was the aim of our study to evaluate the effect of a Khella extract (KE) as well as the two major constituents khellin and visnagin on renal epithelial injury using LLC-PK1 and Madin-Darby-canine kidney (MDCK) cells. Both cell lines provide suitable model systems to study cellular processes that are possibly involved in the development of a renal stone. LLC-PK1 and MDCK cell lines were exposed to 300 microM oxalate (Ox) or 133 microg/cm(2) calcium oxalate monohydrate (COM) in presence or absence of 10, 50, 100 or 200 microg/mL KE. To evaluate cell damage, cell viability was assessed by determining the release of lactate dehydrogenase (LDH). KE (e.g. 100 microg/ml) significantly decreased LDH release from LLC-PK1 (Ox: 8.46+0.76%; Ox + 100 microg/ml KE: 5.41+0.94%, p<0.001) as well as MDCK cells (Ox: 30.9+6.58%; Ox+100 microg/ml KE: 17.5+2.50%, p<0.001), which indicated a prevention of cell damage. Similar effects for KE were observed in both cell lines when COM crystals were added. In LLC-PK1 cells khellin and visnagin both decreased the % LDH release significantly in cells that were pretreated with Ox or COM crystals. However, khellin and visnagin exhibited different responses in MDCK cells. Whereas khellin slightly reduced the % LDH release after exposure of the cells to Ox and COM crystals, visnagin significantly decreased % LDH release only after COM crystal exposure. Overall both compounds were more active in LLC-PK1 than in MDCK cells. In summary, exposure of renal epithelial cells to Ox or COM crystals was associated with a significant release of LDH indicating cell injury. Our data demonstrate that KE as well as khellin and visnagin could prevent renal epithelial cell damage caused by Ox and COM and could therefore play a potential role in the prevention of stone formation associated with hyperoxaluria.
Preliminary Report on the Therapeutic Effect of Khellin in Psoriasis
Article
A double-blind study has been performed to search for the possible effect of khellin in psoriasis. 10 patients were treated orally with khellin and subsequently exposed to sunlight for 4 months; a total of 8 cases responded positively with variable degrees of clearance. None of 10 controls had any response. A relapse-free duration of 3 years was recorded for 6 out of the 8 responders. This study would introduce the nonpsoralen compound khellin as a possible agent for the therapy of psoriasis.
HDL-cholesterol increase in normolipaemic subjects on khellin: A pilot study
Article
An evaluation has been made of the action of khellin, a furochromone derivative from Ammi visnaga, at the dose of 50 mg q.i.d. during four weeks, on the plasma lipids of 20 non-obese normolipaemic male subjects after a placebo period of two weeks. The plasma lipids were measured each week and one week after discontinuation of treatment; 14 subjects were evaluable. Plasma total cholesterol and triglycerides concentrations remained unchanged throughout the study, whereas HDL-cholesterol levels were significantly increased from the first week until one week post-medication. A lowering of the LDL-C/HDL-C ratio was shown during the same period. No specific effect on plasma LCAT activity was obtained. Compliance, checked by the plasma khellin determination, was good. Some untoward effects were observed. Nausea and vomiting were responsible for the withdrawal of four volunteers, and elevation of SGOT and SGPT for that of two others. It can be concluded that khellin at this dosage induces an important shift of cholesterol to the HDL fraction which is maintained until one week post-medication.