Contributors
YusufAbubakar DepartmentofBiochemistry, NaturalProductResearchLaboratory, BauchiStateUniversity,Gadau,BauchiState, Nigeria
A.A.Adam BiomedicinalResearchCentre, ForestryResearchInstituteofNigeria,Ibadan, Nigeria
CharlesOluwaseunAdetunji Departmentof Microbiology,AppliedMicrobiology, BiotechnologyandNanotechnology Laboratory,EdoUniversityIyamho,Iyamho, EdoState,Nigeria
JulianaBunmiAdetunji Departmentof Biochemistry,NutritionandToxicology ResearchLaboratory,OsunStateUniversity, Osogbo,Osun,Nigeria
KhalilAhmad InstituteofHomeandFood Sciences,FacultyofLifeSciences,Government CollegeUniversityFaisalabad,Faisalabad, Pakistan
MuhammadAkram DepartmentofEastern Medicine,GovernmentCollegeUniversity Faisalabad,Faisalabad,Pakistan
AmanjotAnnu DepartmentofPharmacology, FacultyofMedicine,MbararaUniversityof ScienceandTechnology,Mbarara,Uganda
ShabnamAnsari DepartmentofBiotechnology, FacultyofNaturalSciences,JamiaMillia Islamia,NewDelhi,India
GodwinAnywar DepartmentofPlantSciences, Microbiology&Biotechnology,Collegeof NaturalSciences,MakerereUniversity, Kampala,Uganda
Asha DepartmentofBotany,HNBGarhwal University,Srinagar,Uttarakhand,India
TamiratBekeleBeressa Pharmbiotechnology andTraditionalMedicineCenterofExcellence, MbararaUniversityofScienceandTechnology, Mbarara,Uganda;DepartmentofPharmacy,
CollegeofMedicineandHealthScience,Ambo University,Ambo,Ethiopia
JaspalChauhan DepartmentofHimalayan AquaticBiodiversity,H.N.B.Garhwal University,Srinagar,Uttarakhand,India
PriyankaDhar DepartmentofBiotechnology, TechnoIndiaUniversity,SaltLakeCity, Kolkata,WestBengal,India
AdomDickson DepartmentofEducational InnovationsinScienceandTechnology, KwameNkrumahUniversityofScienceand Technology,Kumasi-Accra,Ghana
ChukwuebukaEgbuna Departmentof Biochemistry,FacultyofNaturalSciences, ChukwuemekaOdumegwuOjukwu University,Uli,AnambraState;Nutritional BiochemistryandToxicologyUnit,WorldBank AfricaCentreofExcellence,Centrefor PublicHealthandToxicologicalResearch (ACE-PUTOR),UniversityofPort Harcourt,PortHarcourt,RiversState, Nigeria
ChiomaBerthaEhis-Eriakha Environmental andMolecularBiologyLaboratory,Edo UniversityIyamho,Iyamho,EdoState,Nigeria
ChikaPreciousEkwuabu Departmentof ClinicalPharmacyandPharmacyPractice, UniversityofBenin,BeninCity,EdoState, Nigeria
MahitabH.ElBishbishy Departmentof Pharmacognosy,FacultyofPharmacy,October UniversityforModernSciencesandArts (MSA),6thofOctober,Egypt
DinaM.ElKersh Departmentof Pharmacognosy,FacultyofPharmacy,British UniversityinEgypt,ElSherouk,Egypt
AbeerM.ElSayed Departmentof Pharmacognosy,FacultyofPharmacy,Cairo University,Cairo,Egypt
BensonChukwunweikeEphraim-Emmanuel DepartmentofDentalHealthSciences,Bayelsa StateCollegeofHealthTechnology,Otuogidi, OgbiaTown;EnvironmentalHealthUnit, WorldBankAfricaCentreofExcellence,Centre forPublicHealthandToxicologicalResearch (ACE-PUTOR),UniversityofPortHarcourt, PortHarcourt,RiversState,Nigeria
NebechiJaneEzeofor DepartmentofFood Technology,SchoolofAppliedScienceand Technology,FederalPolytechnic,Oko, AnambraState,Nigeria
DevarajEzhilarasan Departmentof Pharmacology,SaveethaDentalCollege, SaveethaInstituteofMedicalandTechnical Sciences,Chennai,TamilNadu,India
ShahiraM.Ezzat Departmentof Pharmacognosy,FacultyofPharmacy,Cairo University,Cairo;Departmentof Pharmacognosy,FacultyofPharmacy,October UniversityforModernSciencesandArts (MSA),6thofOctober,Egypt
MuhammadAdilFarooq SchoolofFood ScienceandEngineering,GuangdongProvince KeyLaboratoryforGreenProcessingof NaturalProductsandProductSafety,South ChinaUniversityofTechnology,Guangzhou, China
ReenaGangwar DepartmentofBotanyand Microbiology,H.N.B.GarhwalUniversity, Srinagar,Garhwal,Uttarakhand,India
AjayKumarGautam DepartmentofPlant Sciences;DepartmentofBiochemistryand MicrobialSciences,SchoolofBasicandApplied Sciences,CentralUniversityofPunjab, Bathinda,Punjab,India
LaurenceJohnFrancisJ.Gido ResearchCenter oftheCollegeofMedicine,DavaoMedical SchoolFoundation,Inc.,DavaoCity, Philippines
AshutoshGupta DepartmentofBiochemistry, UniversityofAllahabad,Allahabad,Uttar Pradesh,India
EnaGupta DepartmentofHomeScience, UniversityofAllahabad,Allahabad,India
RakeshKumarGupta Environmental BiotechnologyandGenomicsDivision,CSIRNationalEnvironmentalEngineeringResearch Institute(NEERI),Nagpur,Maharashtra,India
PoonamGusain UttarakhandStateCouncilfor Science&Technology,Dehradun, Uttarakhand,India
SadiaHassan InstituteofHomeandFood Sciences,FacultyofLifeSciences,Government CollegeUniversityFaisalabad,Faisalabad, Pakistan;FoodProcessingCentre,Department ofFoodScienceandTechnology,Universityof Nebraska-Lincoln,Lincoln,NE,UnitedStates
MuhammadBilalHussain InstituteofHome andFoodSciences,GovernmentCollege UniversityFaisalabad,Faisalabad,Pakistan
MuhammadImran UniversityInstituteofDiet andNutritionalSciences,FacultyofAllied HealthSciences,TheUniversityofLahore, Lahore,Pakistan
FarhatJabeen DepartmentofZoology, GovernmentCollegeUniversityFaisalabad, Faisalabad,Pakistan
JaisonJeevanandam DepartmentofChemical Engineering,FacultyofEngineeringand Science,CurtinUniversity,Miri,Sarawak, Malaysia
RajappaJoga ICARResearchComplexNEH Region,Umiam(Barapani),Meghalaya,India
AbolanleA.A.Kayode Phytomedicine Research,DrugDiscoveryandDevelopment Laboratory,DepartmentofBiochemistry, BabcockUniversity,Ilishan-Remo,OgunState, Nigeria
ShyamSundarKesh DepartmentofVeterinary ClinicalComplex(VeterinaryBiochemistry), FacultyofVeterinaryandAnimalSciences, WestBengalUniversityofAnimalandFishery Sciences,Kolkata,WestBengal,India
MerveKeskin VocationalSchoolofHealth Services,Bilecik ŞeyhEdebaliUniversity, Bilecik,Turkey
ŞabanKeskin VocationalSchoolofHealth Services,Bilecik ŞeyhEdebaliUniversity, Bilecik,Turkey
FahadSaidKhan DepartmentofEastern Medicine,GovernmentCollegeUniversity Faisalabad,Faisalabad,Pakistan
MuhammadKamranKhan InstituteofHome andFoodSciences,FacultyofLifeSciences, GovernmentCollegeUniversityFaisalabad, Faisalabad,Pakistan
MuhammadUsmanKhan Departmentof EnergySystemsEngineering,Universityof Agriculture,Faisalabad,Pakistan;Bioproduct SciencesandEngineeringLaboratory,BSEL, WashingtonStateUniversity,Richland,WA, UnitedStates
SevgiKolaylı DepartmentofChemistry, FacultyofScience,KaradenizTechnical University,Trabzon,Turkey
ShambhuKumar ForestPathology Department,KSCSTE-KeralaForestResearch Institute,Thrissur,Kerala,India
ShashankKumar DepartmentofBiochemistry andMicrobialSciences,SchoolofBasicand AppliedSciences,CentralUniversityofPunjab, Bathinda,Punjab,India
JayaVikasKurhekar Departmentof Microbiology,BharatiVidyapeeth’sDr. PatangraoKadamMahavidyalaya,Sangli, Maharashtra,India
PremPrakashKushwaha Departmentof BiochemistryandMicrobialSciences, SchoolofBasicandAppliedSciences, CentralUniversityofPunjab,Bathinda, Punjab,India
UmmeLaila DepartmentofEasternMedicine, GovernmentCollegeUniversityFaisalabad, Faisalabad,Pakistan
FanuelLampiao AfricaCenterofExcellencein PublicHealthandHerbalMedicine,Collegeof Medicine,UniversityofMalawi,Blantyre, Malawi
I.O.Lawal BiomedicinalResearchCentre, ForestryResearchInstituteofNigeria,Ibadan, Nigeria
MuhammadFaisalManzoor SchoolofFood ScienceandEngineering,SouthChina UniversityofTechnology,Guangzhou,China
AnandPrakashMaurya Instituteof MicrobiologyandInfection,Schoolof Biosciences,CollegeofLifeandEnvironmental Sciences,UniversityofBirmingham, Birmingham,UnitedKingdom
VineetKumarMaurya DepartmentofBotany andMicrobiology,H.N.B.GarhwalUniversity, Srinagar,Garhwal,Uttarakhand,India
MohammadMehdizadeh Departmentof AgronomyandPlantBreeding,Universityof MohagheghArdabili,Ardabil,Iran
AbhayPrakashMishra AcademicResearcher, DepartmentofPharmaceuticalChemistry, HemvatiNandanBahugunaGarhwal University,Srinagar,Uttarakhand,India
NehaMishra SamHigginbottomUniversityof Agriculture,TechnologyandSciences, Allahabad,India
GhulamMohiudin DepartmentofEastern Medicine,GovernmentCollegeUniversity Faisalabad,Faisalabad,Pakistan
AndrewG.Mtewa DivisionofBiological ChemistryandDrugDiscovery,SchoolofLife Sciences,UniversityofDundee,Dundee, Scotland,UnitedKingdom;Chemistry Department,MalawiInstituteofTechnology, MalawiUniversityofScienceandTechnology, Thyolo,Malawi;Pharmbiotechnologyand TraditionalMedicineCenterofExcellence, MbararaUniversityofScienceandTechnology, Mbarara,Uganda
PatriciaA.Nalumansi DepartmentofSciencein EnvironmentalManagement,Facultyof ScienceandTechnology,International UniversityofEastAfrica,Kampala,Uganda
AbhaNegi DepartmentofBotanyand Microbiology,H.N.B.GarhwalUniversity, Srinagar,Garhwal,Uttarakhand,India
KennedyJ.Ngwira InstituteofMolecular Science,SchoolofChemistry,Universityofthe Witwatersrand,Johannesburg,SouthAfrica
ManishaNigam DepartmentofBiochemistry, SchoolofLifeSciences,HemvatiNandan BahugunaGarhwalUniversity,Srinagar, Uttarakhand,India
GodswillNtsomboh-Ntsefong Departmentof PlantBiology,FacultyofScience,Universityof YaoundeI;InstituteofAgriculturalResearch forDevelopment(IRAD),Yaounde,Cameroon AlloysiusChibuikeOgodo Departmentof Microbiology,FacultyofPureandApplied Sciences,FederalUniversityWukari,Wukari, TarabaState,Nigeria
PatrickE.Ogwang Pharmbiotechnologyand TraditionalMedicineCenterofExcellence, MbararaUniversityofScienceandTechnology, Mbarara,Uganda
ChinenyenwaOhia Departmentof EnvironmentalHealthSciences,Facultyof PublicHealth,CollegeofMedicine,University ofIbadan,Ibadan,Nigeria
KelechiJustinOkere DepartmentofChemical Sciences,FacultyofNaturalandApplied Sciences,HezekiahUniversity,Umudi,Imo State,Nigeria
EleonoraOkushanova ShakarimState UniversityofSemey,Semey,Kazakhstan
AhmedOlatunde DepartmentofBiochemistry, AbubakarTafawaBalewaUniversity,Bauchi, Nigeria
T.O.Omogbene BiomedicinalResearchCentre, ForestryResearchInstituteofNigeria,Ibadan, Nigeria
PeculiarFeennaOnyekere Departmentof Pharmacognosy&EnvironmentalMedicine, FacultyofPharmaceuticalSciences,University ofNigeria,Nsukka,EnuguState,Nigeria
TemitopeA.Oyedepo Departmentof Biochemistry,AdelekeUniversity,Ede,Nigeria
SantwanaPalai DepartmentofVeterinary PharmacologyandToxicology,Collegeof VeterinaryScienceandAnimalHusbandry, OUAT,Bhubaneswar,Odisha,India
SunilPareek DepartmentofAgricultureand EnvironmentalSciences,NationalInstituteof FoodTechnologyEntrepreneurshipand Management,Kundli,Sonepat,Haryana,India
ChiomaObianujuPeculiar-Onyekere DepartmentofPharmaceuticalMicrobiology& Biotechnology,UniversityofNigeria,Nsukka, EnuguState,Nigeria
RanuPrasad SamHigginbottomUniversityof Agriculture,TechnologyandSciences, Allahabad,India
AlinaAbdulRahim InstituteofHalalResearch andManagement,UniversitiSainsIslam Malaysia,Nilai,Malaysia
MuhammadRiaz DepartmentofAlliedHealth Professional,UniversityofSargodha, Sargodha,Pakistan
TahreemRiaz DepartmentofEasternMedicine, GovernmentCollegeUniversityFaisalabad, Faisalabad,Pakistan
NarashansAlokSagar Departmentof AgricultureandEnvironmentalSciences, NationalInstituteofFoodTechnology EntrepreneurshipandManagement,Kundli, Sonepat,Haryana,India
MahaM.Salama Departmentof Pharmacognosy,FacultyofPharmacy,Cairo University,Cairo;Departmentof Pharmacognosy,FacultyofPharmacy, BritishUniversityinEgypt,ElSherouk, Egypt
MohamedA.Salem Departmentof Pharmacognosy,FacultyofPharmacy, MenoufiaUniversity,ShibinElkom,Egypt
M.S.SandeepVedaNarayana Departmentof BiotechnologyandBioinformatics,Schoolof LifeSciences,UniversityofHyderabad, Hyderabad,Telangana,India
BarbaraSawicka DepartmentofPlant ProductionTechnologyandCommodities Sciences,FacultyofAgrobioengineering, UniversityofLifeSciencesinLublin,Lublin, Poland
MohammadAliShariati Laboratoryof BiocontrolandAntimicrobialResistance,Orel StateUniversityNamedAfterI.S.Turgenev, Oryol,Russia;KazakhResearchInstituteof ProcessingandFoodIndustry(SemeyBranch), Semey,Kazakhstan
NadiaSharif WomenUniversity,Mardan, Pakistan
SinghP.Shivakumar DepartmentofBotany, PalamuruUniversity,Mahabubnagar, Telangana, India
AtulKumarSingh DepartmentofBiochemistry andMicrobialSciences,SchoolofBasicand AppliedSciences,CentralUniversityofPunjab, Bathinda,Punjab,India
P.ShivakumarSingh DepartmentofBotany, PalamuruUniversity,Mahabubnagar, India
PriyankaSingh CentreofFoodTechnology, UniversityofAllahabad,Allahabad,India
DominikaSkiba DepartmentofPlant ProductionTechnologyandCommodities Sciences,FacultyofAgrobioengineering, UniversityofLifeSciencesinLublin,Lublin, Poland
A.Stephen DepartmentofBotany,St.Joseph’s College(Autonomous),Bengaluru,India
RamLalThakur DepartmentofMicrobiology, SardarBhagwanSinghPostGraduateInstitute ofBio-MedicalSciencesandResearch, Dehradun,India
HabibuTijjani DepartmentofBiochemistry, NaturalProductResearchLaboratory, BauchiStateUniversity,Gadau,BauchiState, Nigeria
CasimU.Tolo Pharmbiotechnologyand TraditionalMedicineCenterofExcellence, MbararaUniversityofScienceandTechnology, Mbarara,Uganda
GenevieveD.Tupas Departmentof Pharmacology,CollegeofMedicine,Davao MedicalSchoolFoundation,Inc.,DavaoCity, Philippines
KrishnanUmachandran NelcastLtd.,Chennai, India
D.P.Uniyal UttarakhandStateCouncilfor Science&Technology,Dehradun, Uttarakhand,India
LisbethVallecilla-Yepez Departmentof BiologicalSystemEngineering,University ofNebraska-Lincoln,Lincoln,NE,United States
P.SeshuVardhan SchoolofBiotechnology, JawaharlalNehruTechnologicalUniversity, Kakinada,AndhraPradesh,India
G.M.Vidyasagar MedicinalPlantsand MicrobiologyResearchLaboratory, DepartmentofPost-GraduateStudiesand ResearchinBotany,GulbargaUniversity, Kalaburagi,Karnataka,India
AbdulWahab InstituteofHomeandFood Sciences,FacultyofLifeSciences,Government CollegeUniversityFaisalabad,Faisalabad, Pakistan
AngeloMarkP.Walag CenterforAdvanced PlantScienceandPhytotechnologies; DepartmentofScienceEducation,Universityof ScienceandTechnologyofSouthern Philippines,CagayandeOroCity,Philippines
AnkeWeisheit Pharmbiotechnologyand TraditionalMedicineCenterofExcellence, MbararaUniversityofScienceandTechnology, Mbarara,Uganda
DineshKumarYadav Departmentof Chemistry,MohanlalSukhadiaUniversity, Udaipur,Rajasthan,India
SauravYadav DepartmentofBiotechnology, HNBGarhwalUniversity,Srinagar, Uttarakhand,India
RidaZainab DepartmentofEasternMedicine, GovernmentCollegeUniversityFaisalabad, Faisalabad,Pakistan
AhmedZayed DepartmentofPharmacognosy, CollegeofPharmacy,TantaUniversity,Tanta, Egypt
Generalprincipleofprimaryand secondaryplantmetabolites: Biogenesis,metabolism,andextraction
CharlesOluwaseunAdetunjia,SantwanaPalaib,Chika PreciousEkwuabuc,ChukwuebukaEgbunad,e,JulianaBunmi Adetunjif,ChiomaBerthaEhis-Eriakha g,ShyamSundarKeshh, andAndrewG.Mtewai,j,k
aDepartmentofMicrobiology,AppliedMicrobiology,BiotechnologyandNanotechnology Laboratory,EdoUniversityIyamho,Iyamho,EdoState,Nigeria bDepartmentofVeterinary PharmacologyandToxicology,CollegeofVeterinaryScienceandAnimalHusbandry,OUAT, Bhubaneswar,Odisha,India cDepartmentofClinicalPharmacyandPharmacyPractice,University ofBenin,BeninCity,EdoState,Nigeria dDepartmentofBiochemistry,FacultyofNatural Sciences,ChukwuemekaOdumegwuOjukwuUniversity,Uli,AnambraState,Nigeria eNutritionalBiochemistryandToxicologyUnit,WorldBankAfricaCentreofExcellence,Centre forPublicHealthandToxicologicalResearch(ACE-PUTOR),UniversityofPortHarcourt,Port Harcourt,RiversState,Nigeria fDepartmentofBiochemistry,NutritionandToxicologyResearch Laboratory,OsunStateUniversity,Osogbo,Osun,Nigeria gEnvironmentalandMolecularBiology Laboratory,EdoUniversityIyamho,Iyamho,EdoState,Nigeria hDepartmentofVeterinary ClinicalComplex(VeterinaryBiochemistry),FacultyofVeterinaryandAnimalSciences,West BengalUniversityofAnimalandFisherySciences,Kolkata,WestBengal,India iDivisionof BiologicalChemistryandDrugDiscovery,SchoolofLifeSciences,UniversityofDundee,Dundee, Scotland,UnitedKingdom jChemistryDepartment,MalawiInstituteofTechnology,Malawi UniversityofScienceandTechnology,Thyolo,Malawi kPharmbiotechnologyandTraditional MedicineCenterofExcellence,MbararaUniversityofScienceandTechnology, Mbarara,Uganda
1.1Introduction
Sincethebeginningoflife,manhasutilizedplantsfordifferentpurposes.Theearlyman intensifiedeffortinsearchoffoodtocope,whichledhimtodistinguishbetweenplantsthat serveasfoodfromthosethathavemedicinalvalue [1].Eversince,manhasdependedonplants fortheirdailyneedsforfood,medicine,andotherthingsincludingshelter,clothing,and fertilizers.
Plantssynthesizehundredsofthousandsofmetabolites.Metabolitesareproductsand intermediatesofmetabolismwithnumerousfunctionsincludingsignaling,inhibitoryeffects onenzymes,defense,cofactortoenzyme,andprotectionoftheplantagainstseveralpathogens anddiseases.Variousplantsofdifferentspeciesandgenerahavebeenrecognizedtoproduce bothprimaryandsecondarymetabolitesofdifferenttypes.Theadvancesintheapplicationof metabolomicshavehelpedintheprofilingofnumeroustypesofmetabolites.Metabolomics ineffectentailsthecomprehensiveanalysisofvariousmetabolitespresentinanybiologicalsystem.Also,ithelpsgiveabetterknowledgeoftheorganizationandprincipleofcellularpurposes atseverallevelsincludinganinsightofbiologicalprocessesinanintegralsystem [2–8].
1.2Plantmetabolites
Biochemicalreactionsthatoccurinorganismsarecollectivelyreferredtoas metabolism. Theproductsofthesereactions,aswellastheirintermediates,whichareusuallysmall molecules,arecalled metabolites.Asearliermentioned,theyareclassifiedaseither primary orsecondary,basedontheirintrinsicfunctionswithintheorganism.
1.2.1Primarymetabolites
Primarymetabolitesaredifferenttypesoforganiccompoundssecretedbyplantsthatare involvedinthevariousdevelopmentandgrowth,synthesisofhormoneandprotein,photosynthesis,andrespiration.Primarymetabolitesarepresentinalmosteverypartoftheplantspecieswithinextensivephylogeneticclusters,whicharesynthesizedusingthesameoralmost biochemicalpathways.Examplesofprimarymetabolitesincludecarbohydrates,thatis,glucose, fructose,sucrose,raffinose,stachyose,mannitol,xylitol,andsorbitol;thenonstarchincludes lignin;aminoacids,thatis,arginine,histidine,isoleucine,leucine,lysine,methionine,phenylalanine,tryptophan,andvaline;vitaminBcomplex,thatis,thiamine,riboflavin,niacin, pantothenicacid,pyridoxine,andfolicacid;organicacids;ascorbicacid;oxalicacid;aconitic acid;andunsaturatedfattyacids,thatis,monounsaturatedandpolyunsaturated [9].
1.2.2Secondarymetabolites
Plantssecretesomeusefulbiologicallyactivechemicalsubstancesthatarenotinvolvedin thedevelopmentandgrowthofplants.Thesesubstancesarecalledsecondarymetabolites andareoftendifferentiallycirculatedamongtaxonomicsetswithintheplantkingdom. Althoughthefunctionofmanyoftheplantsecondarymetabolitesstillremainsunknown,
therearefourmajorgroupsofsecondarymetabolitesthatincludethesulfur-containing compoundsandalkaloids,whicharealmostabout12,000compounds;phenolicandpolyphenoliccompounds,whichareabout8000compounds;andtheterpenoids,whichareabout 25,000compounds.Moreoverthefunctionofthesesecondarymetabolitesmainlyistopreventthebodyfromdiseases.Examplesofsecondarymetabolitesincludesflavonoids,that is,quercetin,apigenin,luteolin,myricetin,andcyanidin;phenolicacids,thatis,chlorogenic acid,caffeicacid,ferulicacid, p-coumaricacid,vanillicacid,sinapicacid,andprotocatechuic acid;lignans,thatis,lariciresinol,pinoresinol,secoisolariciresinol,andmatairesinol;carotenoids, α-carotene, β-carotene, β-cryptoxanthin,zeaxanthin,andlycopene;tocopherols andtocotrienols,thatis, α-tocopherol, β-tocopherol, γ-tocopherol, α-T3,and γ-T3;quinones, thatis,phylloquinone;sterols,thatis,campesterol,campestanol,stigmasterol, β-sitosterol, β-sitostanol;alkaloids,thatis, α-tomatine,dehydrotomatine, α-solanine, α-chaconine, lactucin,andlactucopicrin;glucosinolates,thatis,glucoiberin;andglucosinolates,thatis, glucoraphanin,glucoalyssin,sinigrin,gluconapin,progoitrin,andgluconasturtiin [10].
Thesebioactivesarecapableofelicitingpharmacological/toxicologicalresponseinhumans (Table1.1)whileincreasinghealthynutritionasthemajorcomponentofnutraceuticalsand dietarysupplements.Theyalsohelpincreaseagriculturalyieldsasgrowthenhancersofplants andanimalsaswellasbeingusedasdyes,fragrances,flavors,andcosmetics [23]
Traditionally,secondarymetabolitesareobtainedfromplantpartsbyextractionmethods suchassteam,solvent(organic/inorganic),andsupercriticalextraction.Othermodern methodsexist [24].However,thishasencounteredalotofchallenges,whichthescientificcommunityhasconstantlybeenworkingtoovercome.Planttissueandcellcultureisamethodin metabolicengineeringthathasbeenfoundasaworthyalternativetomitigatingthelimitations associatedwiththeconventionalmethodsofextraction.Thisinvolvestheisolationofadvantageouscellsandculturingthemunderspecialorganizedenvironments.Themetabolites obtainedarefreefromcontaminants;themetabolicprocesscanberationallycontrolled,labor costisdecreased,increasedyieldofhigh-valuemetabolitesisachieved,andcellsarecultured undercontrolledconditionfreefromclimaticvariations/soiltypes [23].Improvedmethodsof biotechnologyhavebeenappliedinplantcellandtissueculturetofurtherincreaseyieldofmetabolitesforcommercialandindustrialpurposes.Asseenin Table1.1,themostprominentand bioactiveprinciplesofmedicinalandtoxicologicalsignificanceareasfollows:
1.Alkaloids:Thesearegroupofnitrogenousheterocyclicbasesobtainedfromvariousparts oftheplant.Alkaloidsarebitterintaste.Theyarewasteproductofplantmetabolism,and theirnamesusuallyendwith“ine.”Alkaloidsarealkalinesecondarymetaboliteswith pharmacologicalactivity.
2.Flavonoids:Thesearepigmentsfoundinplantmorespecificallyinthecoloredareasofthe plant,likepetalsofflowerorleafitself.
3.Anthocyanins:Theseareantioxidantsmadeupofaromaticringsofthecyanidinwith substituentssuchashydroxyl,methyl,orglycosylgroups.Theyexhibitantioxidantand antiviralproperties.
4.Saponins:Thesearegroupofcompoundswithsugarmoietiesboundtoasapogeninsteroidalkaloids,steroids,ortriterpeneresultingtostructuralvarietiesofsaponins.They reducethedigestionofproteinduetoformationoflesssolublesaponin-proteincomplexes andstoptheabsorptionofmicronutrients.Theyexhibitantioxidantproperties.
TABLE1.1 Medicinalimportanceofsecondaryplantmetabolites.
S/no.PhytochemicalsExamples
1.AlkaloidsMorphine,caffeine,berberin, codeine,piperidine,camptothecin, vinblastine,vincristine,serpentine, aceclidine,rutaecarpine,quinine, artemisinin
2.FlavonoidsQuercetin,reservaratrol kaempferol,caffeicacid,flavones, rutin,naringin,hesperidintannic acid,gallicacid,ellagicacid
3.Anthocyanins3Caffeoylquinicacid, 5caffeoylquinicacid,polymeric procyanidins,5caffeoylquinic acid,procyanidins
4.SaponinsDiosgeninandhecogenin α hederinandhederasaponinC
5.Tannins Procyanidins,prodelphinidins, epicatechin,epigallocatechin procyanidin,orprodelphinidin
6.Phenolsand phenolicacids
p Hydroxybenzoicacids, protocatechuicacids,vanillicacid, syringicacid
Medicinaluses References
Diuretic,localanesthetic, bactericidal,anticancerous, antihypertensive, cholinomimeticsspasmolytics, antiasthmatics,antimalarials [11]
Hyperlipidemia,hyperglycemia, anticancerous,antioxidative, antiartherosclerotic [12,13]
Antioxidative,antiinfluenza, antiviral [14,15]
Nutraceuticals,functionalfoods, naturalfood,preservatives [16,17]
Hyperglycemia,hyperlipidemia [18]
Antioxidant,antiulcer, antidiabetic,cardioprotective, anticancerous,antiinflamatory, neuroprotective, hepatotprotective,antiaging, antimicrobialactivity [19]
7.GlycosidesAmygdalin,gentiopicrin, rographolide,polygalin,cinnamyl acetate,anthraquinone
8.TerpenoidsIsopreniodsmonoand sesquiterpenes,saponins, sapogenins,sesquiterpene lactones,tetraterpenecarotenoids, β sitosterol,artemisinin
9.CoumarinsUmbelliferone,aesculetin, herniarin,psoralen,imperatorin
Antifungal,antibacterial, antioxidant,antidiabetic,fluid andelectrolyteloss, hepatoprotective, cardioprotective [20]
Antimicrobial,antifungal, antiviral,antihyperglycemic, antiinflammatory,antioxidants, antiparasitic,immune modulatory,skinpermeation enhancer [21]
Antidiabetic,hepatoprotective, antithrombotic,antifungal, antiviral,analgesic, anticarcinogenic [22]
5.Tannins:Thesearebitterastringents,condensed,orhydrolyzable,water-soluble polyphenols.Theybindtoproteinandprecipitateitaswellastoothervariousorganic compoundsincludingaminoacidsandalkaloids.Duetoitsastringentaction,itproducesa tangysensationinmouth.Condensedtanninsofpolyphenoliccompoundsexhibit powerfulantioxidantactivity.
6.Phenols:Phenolsareassociatedwithligninasestergroups.Theyareextractedasalcoholsolublefractionboundtosimpleglycosidesandinsolublefractions.
7.Glycosides:Glycosidesarefoundinallplantswithlargerangeoftherapeuticvalue.They haveglycosylatedprinciplesofmedicinalandtoxicologicalvalue.Cardiacglycosides derivativesofdigitalisandstrophanthussuchasouabainarenotableinhibitorof Na+/K+-ATPaseactivityofbiomembranes.
8.Terpenoids:Terpenoidscombineinmanycombinationstogetawiderangeof isoprenoids.Thesearepresentasglycosides.
9.Coumarins:Thecoumarinsexistindifferentforms,forexample,asbenzopyrene derivativesinmanyplants.Theyarefoundasaromapresentinessentialoil [25].
1.3Biogenesisofprimaryandsecondaryplantmetabolites
Biogenesisisatermthatreferstotheprocessesinvolvedinthesynthesisoforganicsubstancesfromintermediatecompounds.Cellmetabolismincludestwodistinctprocesses: anabolism,whichinvolvesproductionofcomplexcompoundsusingenergyandreducing power,andcatabolism,whichinvolvesthedegradationofcomplexmoleculestoproduce energyandreducingpower.Theseprocessesenabletheplantcelltoutilizeabsorbednutrientsandstayalive.Plantcellmetabolisminvolvesacomplexcascadeofchemicalreactions calledmetabolicpathways.Asearlierstated,samebiochemicalpathwaymayproduceboth primaryandsecondarymetaboliteswithcommonintermediates,whichfurthercomplicates theprocess.
Plantsundergophotosynthesisandrespiration,whichusescarbondioxide(asthesole sourceofcarbon),water,sunlightenergy,andammoniaasstartingmaterialstoproduceprimarymetabolitessuchasglucose,aminoacids,lipids,andnucleicacids.Majormetabolic pathwaysinvolvedinplantmetabolismincludephotosynthesis,Calvin’scycle,glycolysis, citricacid(Kreb’s)cycle,pentosephosphatepathway,oxidativephosphorylation,fattyacid oxidation,andrespiration(anaerobic).
1.3.1Biogenesisofcarbohydrates
Plantsarecapableofsynthesizingcarbohydratefromcarbondioxide(CO2)andwater (H2O)inthepresenceofsunlight(energy)viaphotosynthesis [26].Theassimilationofcarbon fromCO2 toproducecarbohydrateisacyclicprocessthatinvolvesvariousintermediatesand enzymaticcatalystsandisreferredtoastheCalvin’scycle.Thelightenergyfromsunlightis capturedandconvertedtochemicalenergy,adenosinetriphosphate(ATP)andnicotinamide dehydrogenase(NADH)viaATPsynthase,toinitiatesubsequentreactions.Anotherenzyme, ribulose-1,5-diphosphatecarboxylaseoxygenase(RuBisCO),thencatalyzesthereductionof CO2 anditssubsequentcovalentbondingtoa5-carboncompound,ribulose1,5bisphosphateto formanunstable6-carboncompound,whichsplitsintotwomoleculesof3-phosphoglycerate. Then,3-phosphoglyceratekinasecatalyzestheintroductionofaphosphorylgrouptoyield 1,3-bisphosphoglycerate,whichisacteduponbyglyceraldehyde3-phosphatedehydrogenase toformglyceraldehyde3-phosphate.Next,triosephosphateisomerasecatalyzestheconversionofglyceraldehyde3-phosphatetodihydroxyacetonephosphate,mostofwhichisused
toreproduceribulose1,5bisphosphate(asstartingmaterialtocontinuethecycle),andtherest carbohydrate.Twomoleculesofdihydroxyacetonephosphatecombinetoproducefructose 1,6-bisphosphate,whichisfurtherconvertedbyfructose1,6-bisphosphatasetofructose 6-phosphateandcomplexcarbohydrateslikestarch.
1.3.2Biogenesisoflipids
FattyacidsarebiosynthesizedinseedplastidsfromacetylCoA,producedfrompyruvate, theendproductofglycolysis [27],andthentransferredtotheERforlipidstorage.Enzymesact onglucoseinglycolysispathwaytoproducelittleamountofATPandNADH,aswellasintermediates(glyceratesandpyruvates),withthemostimportantbeingpyruvate.Pyruvate isinfusedintoKreb’scycle(alsocalledcitricacidortricarboxyliccycle)andundergoesoxidationtoproducegreateramountofenergy(ATP)andseveralbiosyntheticintermediates,oneof whichbeingacetylCoA,theprecursoroffattyacids.Plantstudieshaveshownthatplantlipids aremadeupofatriacylglycerol(TAG)core,surroundedbyproteins [28],whicheventuallybud offaslipidbodies.Thisisformedatspecificsitesintheendoplasmicreticulum [29,30],where substantialamountsoflipidsarestoredinplantseedsasTAG,althoughnotexclusively,as lipidshavealsobeenfoundinothertypesofcellswithintheplant [28].Ithasbeenproventhat lipidbiogenesisinplantsisoneofthevariousfunctionsthatoccurswithintheendoplasmic reticulum [31–33].CertainregionsintheERstoresdiacylglycerolacyltransferase(DGAT), whichistheprecursorenzymeforTAGbiosynthesis,andproteinssuchasoleosin,whichis themajorstructuralproteinoflipidbodiesformedinseeds [28,34–38],othersbeingcaleosin andsteroleosin.Thereisapossibilitythatthemechanismoflipidformationdiffersinothercell types(nonseed)orvaryingspeciesandmaybespecifictothem [39,40].
1.3.3Biogenesisofvolatileoils
Volatileoils(alsoknownasessentialoils)areodoriferousliquidsproducedbydiverse (severalhundreds)odor-activechemicalsinplants.Characteristically,theyevaporatequickly whenexposedandareproducedinvariousplantparts.Theyareproductsofmetabolism, withprimarymetabolitesasthebuildingblocks,andassuchareyieldsofthebasicprocesses suchasglycolysis,Kreb’scycle,fattyacidoxidation,andpentosephosphatepathway.Precursorsincludefattyacids,aminoacids,terpenoids,phenolics,glucosinolates [41],andcarbohydrates [27].Theymaybeclassifiedasprimaryorsecondarymetabolitesdependingon thepointofformationinthemetabolicpathway [42].
1.3.3.1Volatileoilderivationbycarbohydratepathway
Carbohydrate-derivedessentialoilsareuncommon,andtwotypeshavebeenreported:terpenoidcompoundsandfluranones [42].Terpenesrepresentagroupoforganiccompounds synthesizedfromactiveisopreneC5 unitsdimethylallyldiphosphate(DMPP)andisopentenyl diphosphate(IPP).Theyareclassifiedashemiterpenes,monoterpenes,sesquiterpenes, diterpenes,andtriterpeneshaving1,2,3,4,and6isopreneunitsrespectively;however,monoterpenesandsesquiterpenesmakeupmostterpenoidvolatileoils [42].Terpenesaregenerated frommevalonicacid(MVA)oranalternativemethylerythritolphosphate(MEP)pathway.
Theyexistmajorlyashydrocarbonsandtheiroxidizedformsasaldehydes,ketones,phenols, alcohols,oxides,peroxides,andester.BothMVAandMEPpathwayshaveacetyl-CoAand pyruvate,respectively,asthestartingmaterialtoproduceisopreneunits,whichcombines inhead-to-tailfashiontoproduceterpenes.Multiplereactionsincludinghydrolysis,ionization,isomerization,cyclisation,andoxidoreductionoccur,andlargegroupofenzymes,generallyreferredtoas“terpenesynthases,”actonthepathways,toyieldthedifferentclassesof terpenes.AccordingtoReineccius [43],oxygenatedmonoterpenesaccountforthevolatileoils inmanycitrusfruitspecies.Themostprominentexamplesoffuranonegroupare 4-hydroxy2,5-dimethyl-3(2H)-furanone,HDMFknownasfuraneol,and2,5dimethyl-4-methoxy-3(2H)-furanone,DMMFknownasmethoxyfuraneol.Theyareconsideredkeyodorantsintheplantswheretheyoccursuchaspineappleandstrawberryfruits. Thefuranonesaregeneratedviamultiplepathways. D-fructose6-diphosphatehasbeenidentifiedasthebiosyntheticprecursor,whichundergoesasequenceofreactionsandenzymatic actiontoyieldtheintermediate4-hydroxy-5-methyl-2-methylene-3(2H)-furanone(HMMF), andthentheproduct,furaneolandmethoxyfuraneol.Furaneolisalsogeneratedinheated foodsduringMillardreactionasisobservedtogiveanattractivelook [27,42].
1.3.3.2Volatileoilderivationbyfattyacidpathway
FattyacidsthatarederivedfromacetylCoA,producedfrompyruvate,theendproductof glycolysis,actasnonvolatileprecursorsinthebiosynthesisofsomevolatileoils.Fattyacids arestoredinplantERasTAGandreleasedbylipasestoproducevolatilessuchasalcohols, lactones,esters,aldehydes,ketones,andacidsthroughthreemajorpathways,namely, alpha-oxidation,beta-oxidation,andlipoxygenase(LOX)pathway.TheLOXpathwayoccurs majorlyindisruptedplantcellsassociatedwithwoundingordamageasoxygenisintroduced.Alpha-andbeta-oxidationoccursinintactplants.Theycausethedegradationoffatty acidstoproduceshort-tomedium-chainfattyacids,whichundergoseriesofenzymaticreactionstoyielddiverseodoriferouscompounds [27,42].
1.3.3.3Volatileoilderivationbyaminoacidpathway
Volatileoilscanalsobeformeddirectlyfromtheaminoacidpathway [27],andthisdependsontheavailabilityoffreeaminoacids,whichinturndependsondegreeofripeness andenvironmentalconditionsduringgrowth [43,44].Severalaminoacidssuchasmethionine,cysteine,alanine,phenylalanine,leucine,isoleucine,andasparticacidareinvolved asprecursors.Importantly,branched-chainaminoacidsproducebranched-chainvolatileoils suchasmethyl2-methylbutanoateinpricklypear,isoamylacetateinbanana,and2-methyl butylacetateinapples [27].Thebiosynthesisofthesevolatilesproceedsfromaminoacid pathwaythroughdiversereactionsandenzymeaction.Initially,aminoacidundergoesdeaminationbyaminotransferasetoyieldalpha-ketoacid,whichlosesonecarbonatombydecarboxylaseenzymetoformanaldehyde.Seriesofsubsequentreactionsfollowstoproduce correspondingvolatileoils [42]
1.3.3.4Glucosinolate-derivedflavors
Glucosinolatesarenaturallyoccurringcompoundsfoundmajorlyamongplantsofthe Brassicaceaefamilylikecabbage,broccoli,mustard,andhorseradish,majorlyforthepurpose ofrepellinginsects,anditisalsoresponsibleforthesulfuryorsharpflavorcharacteristicto
theseplants [27,42].Inhumansthehydrolyzedproductsofglucosinolatehavebeenreported topossessanticancerproperties [45,46].Inintactplants,glucosinolateandthioglucosinolate (alsoknownasmyrosinase)existinthevacuolesandcytoplasm,respectively,andarethus separatedphysically.Oncecellsdisrupt(damage),myrosinaseactstohydrolyze glucosinolatetoyieldthecorrespondingnitriles,thiocyanates,andisothiocyanatesand by-productsofglucoseandsulfates [42].
1.3.4Biogenesisofresins
Plantresinsaresecondarymetabolitesofcomplexmixtures,whichincludevolatileand nonvolatileterpenoidand/orphenoliccompounds.Theyoftenexistincombinationwithessentialoils(oleoresins),gums(gumresins),oilandgum(oleo-gumresins)sugars(asglycosides),andbenzoic/cinnamicacid(balsams).Theynotonlyareformedandstoredin specifiedstructuresinternallyorexternallyonthetreesurfacebutalsomaybefoundinother plantcellsandcanbeproducedspontaneouslyatthesiteofinjurytotheplant.Theyoccur mainlyasexudatesfromthetreetrunkandaregenerallyinsolubleinwaterbutsolublein alcohol,oil,chloroform,andether.Terpenoidsandphenolicresinshavebeenidentifiedwith theformerconsistingmajorlyoftheinternallyformedresinswhilethelatterlargelyconstitute resinsformedonthesurface.Terpenesasmentionedinthemetabolismofvolatileoilsare madeupofisopreneC5 unitbuildingblocksandareclassifiedaccordingtothenumberof isopreneunitstheycontain.Unlikevolatileoils,mostresinsconsistofdi-andtriterpenes, rarelyboth;however,theyoccurincoexistencewithotherclassesofterpenessuchas mono-andsesquiterpenes(volatileoils)andtetra-andpolyterpenes(gums,rubber,and gutta-percha).Phenolicresinmetabolisminvolvesmultiplepathways.Theshikimicacid pathwayyieldsthearomaticaminoacid,phenylalanine,whichisconvertedtocinnamicacid (phenylpropane)byphenylalanineammonia-lyase(PAL).CinnamicacidisaC9 compound occurringasabenzeneringwithC3 sidechain.Itservesasthesubstratefromwhichother phenoliccompoundsarederivedviacleavageofthesidechainorsubstitution.Malonylacid pathwayfromacetylCoAalsoproducesaromaticbenzeneringthatcombineswiththebenzeneringandC3 sidechainfromtheshikimicacidpathway,toyieldflavonoid,components ofphenolicresins.Manyplantresinshavebeenobservedtoelicitpharmacologicaleffects; hence,theyfindapplicationinmedicineandpharmacy.
1.4Medicinalpotentialsofplantsecondarymetabolites
1.4.1Anticancereffects
Manyplantmetabolitesincludingisothiocyanate [45–47],luteolin [48],resveratrol [49], genistein [50],vitaminAderivatives [51],curcumin [52],greenteaextract [53],soybean extract [54],andlycopene [55] havebeeninvestigatedandfoundtopossessantitumorproperties.Nutraceuticalshavegainedincreasinginterestduetominimalsideeffectsandgeneral acceptanceandhencehavebeenappliedaspreferredalternativeinthepreventionofcancer. Mostplantextractshavebeenstudiedforpreventionratherthantreatmentofcancerresulting inminimalefficacyandadoptioninpractice.Aninvestigationcarriedoutshowedthat
combinationofanticancerplantextracts,producedamoreeffectiveresultwhencompared withtheefficacyofindividualcompounds.
1.4.2Antiinflammatoryactivity
Inflammationisanaturalphysiologicalresponsetocellinjury,disease,orotherformsof disturbanceinanimals.Whileitmaybeprotectiveincertaincases,itcantriggeracascadeof eventsresultinginacontinuumofdisorders,acuteandchronicpain/diseasessuchasrheumatoidarthritis,allergies,hyperventriculardystrophy,atherosclerosis,osteoarthritis,inflammatoryboweldisease,cancer,andcoronaryheartfailure.Inflammationisassociatedwith redness,heat,swelling,pain,andlossoffunction.Duringtheprocessthevesselsaredilated, whichallowsincreasedbloodflowandmobilizationofplasmaproteins,leucocytes,andfluid totheaffectedsite.Inflammationistheresultofanumberofbiologicalpathwaysincluding thesynthesisofplasmaproteins,whichactaschemicalmediatorsforinflammationsuchas prostaglandins,cytokines,leukotrienes,vasoactiveamines,andnitricoxide [56].Attheonset, cyclooxygenaseandlipoxygenasetogetherwiththeirby-products,prostaglandin(PGE2and PGH2),leukotrienes(LTC4andLTB4),andcytokines(IL-1andTNF-a)areproducedbyenzymaticactioninresponsetoatrigger(cellinjury,disease,allergen,andsoon).These by-productsarereferredtoasproinflammatorymediatorsandmakeuptheprincipalmediatorsofinflammation.Currently,antiinflammatorychemicalagentssuchasaspirinandnonsteroidalantiinflammatorydrugs(NSAIDs)existbutarehoweverknowntocausesideeffects suchassuppressionoftheimmunesystemandgastrointestinalbleeding [57].Forthisreason, alternativetherapyisbeingsought.Severalplantshavebeeninvestigatedanddiscoveredto havecapacitytointerrupttheinflammatoryprocessatvariouspointsandhencepossesssubstantialantiinflammatoryproperties(Table1.2),someofwhichhavebeenappliedintherapy.
1.4.3Antimicrobialeffectofcompoundpresentinplantmetabolites
Changetal. [107] investigatedtheantimicrobialactivityofessentialoilsobtainedfrom Cinnamomumosmophloeum inaninvitrotrial.Theresultobtainedshowsthatthetestedessentialoilexhibitedanantimicrobialeffectagainstmethicillinresistant Staphylococcusaureus, Enterococcusfaecalis, Vibrioparahaemolyticus,and Escherichiacoli.Thehighantibacterialactivity mightbelinkedtothepresenceofcinnamaldehydeastheactiveagentintheessentialoil of Cinnamomumosmophloeum. Moreover,someotheressentialoilwithhighantimicrobialactivityincludesoreganooil,whichinhibit Escherichiacoli O157:H7 [108],peppermintand spearmintoilagainstpathogenicbacterial [109],essentialoilfromherbsmostespeciallyfrom LamiaceaeandCompositaefamily [110],essentialoilagainst Helicobacterpylori [109];andessentialoilagainstoralpathogens [111]
Thecompositionandtherichnatureofplantextracthaveinfluencedandenhancedtheir antimicrobialactivityagainstpathogenicmicroorganisms.Someofthefactorresponsiblefor theirantimicrobialactivitymightbelinkedtothepresenceofvariouscompoundswithlow molecularweight [112].Thenatureofchemicalstructure,theposition,andnumberofsubstitutions,forexample,inthebenzeneringofphenolicacidsandsaturatedsidechainlength arefactorstoconsider.Ithasbeenobservedthatsomeofthesecompoundshavethecapability
TABLE1.2 Plantswithantiinflammatoryproperties.
Plantspecies Familyname References
Annonasquamosa Annonaceae [58]
Clerodendrumphlomidis Lamiaceae [59]
Erycibeobtusifolia Benth Convulvulaceae [60]
Garciniamangostana Clusiaceae [61]
Gaultheriayunnanensis Ericaceae [62]
Glycyrrhizauralensis Fabaceae [63]
Gymnasterkoraiensis Apiaceae [64]
Magnoliaofficinalis Magnoliaceae [65]
Malusdomestica Rosaceae [66]
Saussureaheteromalla Asteraceae [67]
Stephanotismucronata Apocynaceae [68]
Terminaliachebula Combretaceae [64]
Withaniasomnifera Solanaceae [69]
Aquilariaagallocha Thymelaeaceae [70]
Arachishypogaea Fabaceae [71]
Chromolaenaodorata Asteraceae [72]
Citrusunshiu Rutaceae [73]
Curcumalonga L. Zingiberaceae [74]
Mangiferaindica Anacardiaceae [75]
Panaxginseng Araliaceae [76]
Punicagranatum L. Punicaceae [77]
Juniperuscedrus Cupressaceae [78]
Vitisvinifera L. Vitaceae [79]
Zanthoxylumpiperitum Rutaceae [80]
Andrographispaniculata Acanthaceae [81]
Belamcandachinensis Iridaceae [82]
Cimicifugaracemosa L. Ranunculaceae [83]
Forsythiakoreana Oleaceae [84]
Salviamiltiorrhiza Lamiaceae [8587]
Schisandrachinensis Schisandraceae [88]
Schisandrasphenanthera Schisandraceae [89]
TABLE1.2 Plantswithantiinflammatorypropertiescont’d
Plantspecies Familyname References
Eriobotryajaponica
Everniaprunastri
Lonicerajaponica
Psoraleacorylifolia
Sarcandraglabra
Scutellariabaicalensis
Vitexrotundifolia
Artemisiaargyi
Caesalpiniasappan
Chloranthushenryi
Cratoxylumformosum
Ligusticumchuanxiong
Oleaeuropaea
Amorphophalluskonjac
Commiphoramukul
Commiphoraincisa
Dumortierahirsuta Nees
Rosaceae [90]
Parmeliaceae [91]
Caprifoliacea [92]
Fabaceae [93]
Chloranthaceae [94]
Lamiaceae [95]
Lamiaceae [88]
Asteraceae [96]
Fabaceae [97,98]
Chloranthaceae [99]
Hypericaceae [100]
Umbelliferae [101]
Oleaceae [102]
Araceae [103]
Burseraceae [104]
Burseraceae [105]
Marchantiaceae [106]
todestroytheprotonmotiveforce,cytoplasmicmembrane,andtheactivetransportavailable inthesepathogenicmicroorganisms [113,114].
Also,someothercompoundspresentinplantmetabolitesareorganicacid,whichform partofplantextract.Ithasbeenobservedthatinthenondissociatednature,theyhavethe potentialtomigratethroughthebacterialcellwallandmoveintothecellwheretheydissociateandbringdownthecytoplasmicpHanddestabilizethenormalphysiologyof pH-sensitivebacteria.Moreover,becausetheorganicacidsarepresentinanionicform,they cannotpenetratethecellmembrane,andthereforetheyaccumulatewithinthecellsurface, whichlaterincreasethelevelofosmoticpressureandinterruptsomeofthemetabolicprocess.
Volatileoilhasbeenobservedtopossessantimicrobialaction [115,116].Ithasbeen reportedthatforplantextracttobeeffectiveagainsttheirtargetmicroorganism,theyhave tobeincontactwiththecell,butessentialoilaremorevolatile.Itshouldbenotedthathydrophiliccompoundsarelessvolatile,butthereisaneedfortheequilibriumachievedbetweenvolatilecompoundsavailableintheheadspace [117].Moreoverthepresenceof lipophilicmoleculesintheessentialoilpresentinthelipidbilayercanaffectthelipid-protein interaction [118] andenhancetheincreaseintherateofmembranepermeability,whichlater leadstofunctionalandstructuralimpairmentofthetargetedmicrobialcells.Thismightalso
leadtoseepageofintracellularcomponentsanddamageofmicrobialenzymesystems,which couldresulttoautolysisoftheaffectedmicrobialcell [112,119].Onthewhole,lipophiliccompoundshavethepotentialtointerreactwiththehydrophobicpartsofcellproteins [120].This mightenhancedthehydrophobicitynatureoftheessentialorvolatileoiltoovercomethe compoundaccumulation,whichmightledtodestructionofcellmembrane [117,121].
1.5Processing,extraction,andisolationofplantmetabolites
Theprocessesinvolvedintheextraction,isolation,andidentificationofplantsecondary metabolitesweresummarized.
1.5.1Selectionofspecificspeciesofplant
Fortheinvestigationofplantsformedicinaleffects,acommonmethodologyisundertaken. Wholeplantoritspartsarerandomlycollectedandtakenforinvestigationinwhichacommon chemicaltestiscarriedouttoidentifythephytochemicalspresent.Theselectionofplantisdone onthebasisofbeingtraditionallyused,andtheapproachistermed ethnobotanical bioprospectingapproach .Theplantsusedtraditionallyhavegenerallygotbiologicallyactive compoundswithmedicinalproperties.Theselectionofplantscanalsobedoneonthebasisof chemotaxonomicalapproachwheretaxonomicallyrelatedplantisestablishedwithstructurallysimilarbiomolecules.Plantsarealsoselectedonthebasisoflocalfieldobservationwith immunityagainstbacteria,fungi,orvirusastheysynthesizedefensivenaturalproductswith bactericidal,fungicidal,orvirucidaleffects.Plantselectionalsoutilizesacombinationofthese three,thatis, ethnopharmacological,taxonomic,andrandomapproaches withadatabaseof relevantinformationofaparticularplant.Thedatabaseprioritizestheplantspeciesforextractionandscreeningofmedicinalactivity.Thisistheacceptedapproachbypharmacological companies.
1.5.2Collectionofplantmaterialanditsidentification
Eitherwholeorpartsofaplantarecollected.Theportionswheremetabolitesarestoredin theplantareselected.Itisbettertoselectabovegroundpartslikeleaf,stem,flower,fruit,seed, andbarkandundergroundpartsliketuber,bulb,androotseparately.Variousfactorslikeage oftheplant,environmentalconditionoflight,rainfall,andhumidityshouldalsobetakeninto considerationforperfectselectionofactiveplantmaterial. Accurateidentificationoftheplantfor isolationofactiveprinciplesisamust.Theplantmustbeauthenticatedbyabotanistoraplanttaxonomist.Theplantname,portionoftheplantcollected,place,anddateofcollectionshouldbenotedand bedepositedintheherbariumforfuturereference.
1.5.3Dryingandgrindingofplantmaterial
Aftercollectingtheplant,itisusuallydriedontraysatroomtemperaturewithproperventilation.Ideally,dryconditionspreventthegrowthofmicrobialorganisms,whichleadto
fermentationordeteriorationofmetabolitesoftheplant.Theplantmaterialsshouldbe groundintofinepowdertogiveauniformsamplewithincreasedsurfacearea.Theplantmaterialcanbecutintomoresmallpiecesforeasygrinding.Mechanicalgrindingcanbedone withthehelpofgrinders,mixture,hammer,orcuttingmills.However,sometimestheprocess resultsincloggingofsieveduetofatandvolatileoilspresentinplant.Plantscanbecutinto smallpiecestofacilitateuniformandfasterdrying.Plantsshouldnotbedriedindirectsunlighttominimizeformationofartifactsbyunwantedreactions.Simpleairdrying,microwave drying,ovendrying,andfreeze-dryingofplantssamplesarethepreferredmethodsof drying.
Airdryingusuallytakeslongsay3–7daystomonthsdependingonthetypesofsample.As hightemperatureisnotinvolved,heat-sensitivecompoundisnotaffected.Theonlydrawbackisthelongertimeandcontamination.Microwavedryingutilizeselectromagneticradiationwithelectricalandmagneticfields.Themethodwilldecreasethedryingtimebutwill alsoleadtodeteriorationofthephytochemicals.Ovendryingistheeasiestmethodusing rapidheatenergytodecreasethemoisturecontentalongwithpreservingphytochemicals. Thismethodnowadaysiscommonbecauseitisfasterandminimizesthechemicalreactions intheplantmaterial.Afterdryingthesamples,theyaretobekeptincoolanddryplace.Longtimestorageofsamplesisnotadvisableasitleadstodegradationofplantmetabolites.In freeze-drying,thesampleisfrozenovernightat 80°Cto 20°Cbeforelyophilizationto avoidthefrozenliquidinthesamplefrommelting.Itisacomplexandexpensive method [122]
1.5.4Extractionprotocol
Extractionistheprocessbywhichweseparatethebioactiveprinciplefromtheplantusing solventslikediethylacetate,ethanol,chloroform,acetone,andsoonthroughstandardized procedurestogettheactiveingredient,whichcanprovidemedicinaleffect.Thesolventis chosenbasedonthesolubilityandpolarityofthebioactiveprincipletobeextracted.Themost commonsolventsofusearewater,organicandinorganicsolvents.Theextractionprocedure ischosenbasedonthenatureofthesourceofplantmaterialandthebioactivecompoundtobe isolated.Thesolubleextractisseparatedfrominsolubleresidue.Themostcommonextraction techniquesusedbyresearchersinthefieldofphytopharmacologyareasfollows:
Maceration:Bythistechnique,theplantmaterialissoakedinclosedcontainercontaininga solventfor4–5daysatroomtemperaturewithintermittentagitations.Thisprocesssoftens andbreakstheplantcellwallleadingtoreleaseofthephytochemicals.Aftertheintended days,themixtureisfiltered.Thetypeofcompoundextractedisdeterminedbythe solventused.
Infusionanddecoction:Infusionanddecoctionhavethesameprincipleasmaceration. Thesampleisboiledforshorttimetoextractvolatileingredientsininfusionandtoget mineralsalts,bittersamplesfromhardmaterialslikeroot,bark,wood,andseedin decoction.
Percolation:Percolationisslowlypassingaliquidthroughfilter.Theequipment percolatorisusedforpercolationwhereboilingwaterandacidareaddedwithshakingtill extractionisdone.
Soxhletextraction/hotcontinuousextraction:Thesampleisfinelygroundedandplaced inthimbleoraporousbagmadeupoffilterpaperintheSoxhletapparatus.Thesolventis heatedbyheatingmantleinthesolventchamber,whichvaporizesinthimbleandthen condensesinthecondenseranddripsbacktothesolventchamber.Ithasthedrawbacksof exposuretoflammablesolvents,toxicity,costly,andnonenvironmentalfriendly.
Microwave-assistedextraction:Here,microwaveenergyisutilizedfortheseparationof bioactiveprinciplesfromthesampletothesolvent.Thismethodfavorspolarsolventswith highdielectricconstantmorethannonpolarsolvents.Thismethodneedslesstimeand volumeofsolvent.Thedrawbackisthermaldegradation.
Ultrasound-assistedextractionorsonicationextraction:Ultrasound-assistedextraction (UAE)usesultrasoundof20–2000kHz.Theultrasoundenhancesthecontactsurfaceof solventsandsamples.Itincreasesthepermeabilityanddisruptsplantcellwall,thus facilitatingextraction.Theprocedurehasadvantagesofbeingsimpleandoflowcostly. Acceleratedsolventextraction:Acceleratedsolventextraction(ASE)isanefficientmethod thatusesminimalamountofsolvent.Theplantsampleispackedwithaninertmaterialin theextractioncell.Thishelpstopreventsampleaggregationleadingtofurtherblockingof system.Themethodhasadvantagesoftemperatureandpressurecontrolandrequires lesstime.
Supercriticalfluidextraction:Supercriticalfluidordensegasisasubstancethathas characteristicsofbothgasandliquidatitscriticalpoint,forexample,CO2 thatbecomes supercriticalfluidatabove31.1°Cand7380kPa.Itisabettersolventfornonpolaranalytes. Theadditionofethanolormethanolmakesitasolventforpolarcompoundstoo.The advantagesarelowcostandhavelowtoxicityofCO2.Alsothestrengthiseasilyalterable bychangeoftemperatureandpressure.
Themethodsemployingsolventforextractionarehighlyinfluencedbythetypeofsolvent used.However,theamountofsolventusedforextractioncausesnodifferenceineffect.All theprocessesdoneforextractionorpreextractionsareverymuchimportantinstudyingthe medicinaleffectofthoseplants.Thestepslikesamplepreparationbygrindinganddrying alsoaffectthelevelofphytochemicalsinfinalextractions.Allthemethodshavetheirown benefitsanddrawbacks [123].
1.5.5Identificationandcharacterizationofbioactiveprinciples
Plantsamplesusuallycontainvariousbioactiveprincipleswhoseisolation,identification, andcharacterizationneedrecentanalyticalprotocolandinstruments.Mostly,thin-layerchromatography(TLC),columnchromatography,flashchromatography,Sephadexchromatography,andhigh-performanceliquidchromatography(HPLC)areusedforisolation.Also, nonchromatographictechniqueslikeimmunoassayusingmonoclonalantibodies(MAbs) andphytochemicalscreeningassayarealsoremarkable.Thebioactivefractionsseparated canbefurtheridentifiedorcharacterizedbyFouriertransforminfraredspectroscopy (FTIR)andgaschromatography-massspectrometry(GC-MS).
HyphenatedtechniqueslikeLC/UV,LC/MS,andLC/NMRcanbeusedtodifferentiate betweennewandalreadyestablishedbioactiveprinciplesfrommedicinalplants.Also,spectroscopictechniqueslikeUV/VISandIRspectrophotometry,carbonandprotonNMR,MS,
andX-raydiffractionarehelpfulforstructuralelucidationofbioactiveprinciples.Furthermore,chemicalreactionsinvolvinghydrolysisandhydrationreactionaredonetoconfirm structuralorfunctionalrelationships.
1.6Qualityandsafety
Purecompoundsisolatedfrommedicinalplantsareusuallyvettedinthelaboratories throughstandardprotocols.Toestablishtheeffectsofmedicinalplants,theethnobotanical claimsandpharmacological,observational,andclinicalstudiesaretakenintoaccount.The doseofbioactivecompoundvaries.Thechangescomingtothesecompoundsovertime mayalsobeadrawbackofitsefficacy.Sobasedonthis,theUnitedStatesandEuropesaw theneedtoregulatethemarketandlicensetheseproducts.Aminimumlevelofquality phytoingredientsisneededintheproductforappropriateresponse.Standardsforactiveingredientsofmedicinalproductsmaybefoundinmonographsand/orpharmacopeias.Standardizedproductsprovideabettersenseofsecurityforusingherbaldrugs.Atthe internationallevel,WHOdevelopedastrategytoreviewtraditionalmedicinesbydeveloping monographsforherbalingredients.Chemicalcompoundsinherbshavepropertiesthatadd tothepharmacologicalactivityoftheextract [124–130].However,adulterationofherbal productscanbeintentionalandsometimesaccidental.Insomecases,herbalremedieshave beenfoundtocontainheavymetalresidues,whichcanleadtoharmfuleffectswhenconsumed.Also,microbialcontaminationisofgreatconcern.Soitisneedfulthatallherbalproductsgothroughsomequalitycontrolprocessesbeforebeingallowedtobereleasedintothe market.
1.7Conclusion
Thischapterprovidesdetailedinformationonthedifferenttypesofprimaryandsecondarymetabolitesandtheirapplicationforthetreatmentofdiseases.Theadvancesinplant metabolomicshavefacilitatedthedetectionofsomeothernewmetabolitesthatmightbeusefulintheproductionofusefuldrugsforthemanagementofdiseases.However,thereisneed tointensifyeffortsontheapplicationofplantmetabolomicsinsynergywithotherfunctional genomics,proteomics,andbioinformaticsforbetterresults.
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