Table Of ContentMEDICINAL FOODS AS POTENTIAL
THERAPIES FOR TYPE-2 DIABETES AND
ASSOCIATED DISEASES
MEDICINAL FOODS
AS POTENTIAL
THERAPIES FOR
TYPE-2 DIABETES
AND ASSOCIATED
DISEASES
The Chemical and Pharmacological
Basis of their Action
S H
OLOMON ABTEMARIAM
PharmacognosyResearchLaboratories&HerbalAnalysisServicesUK,UniversityofGreenwich,
London,UnitedKingdom
AcademicPressisanimprintofElsevier
125LondonWall,LondonEC2Y5AS,UnitedKingdom
525BStreet,Suite1650,SanDiego,CA92101,UnitedStates
50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates
TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom
©2019ElsevierLtd.Allrightsreserved.
Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronicormechanical,
includingphotocopying,recording,oranyinformationstorageandretrievalsystem,withoutpermissioninwritingfromthe
publisher.Detailsonhowtoseekpermission,furtherinformationaboutthePublisher’spermissionspoliciesandour
arrangementswithorganizationssuchastheCopyrightClearanceCenterandtheCopyrightLicensingAgency,canbefoundat
ourwebsite:www.elsevier.com/permissions.
ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher(otherthanasmaybe
notedherein).
Notices
Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperiencebroadenourunderstanding,
changesinresearchmethods,professionalpractices,ormedicaltreatmentmaybecomenecessary.
Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluatingandusinganyinformation,
methods,compounds,orexperimentsdescribedherein.Inusingsuchinformationormethodstheyshouldbemindfulof
theirownsafetyandthesafetyofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility.
Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assumeanyliabilityforany
injuryand/ordamagetopersonsorpropertyasamatterofproductsliability,negligenceorotherwise,orfromanyuseor
operationofanymethods,products,instructions,orideascontainedinthematerialherein.
LibraryofCongressCataloging-in-PublicationData
AcatalogrecordforthisbookisavailablefromtheLibraryofCongress
BritishLibraryCataloguing-in-PublicationData
AcataloguerecordforthisbookisavailablefromtheBritishLibrary
ISBN978-0-08-102922-0
ForinformationonallAcademicPresspublicationsvisitour
websiteathttps://www.elsevier.com/books-and-journals
Publisher:AndreGerhardWolff
AcquisitionEditor:ErinHill-Parks
EditorialProjectManager:MeganAshdown
ProductionProjectManager:StalinViswanathan
CoverDesigner:ChristianJ.Bilbow
TypesetbySPiGlobal,India
About the Author
Dr Solomon Habtemariam is a Founder/ Dr Habtemariam has been a leader of taught
Owner of Herbal Analysis Services UK & programmes and researches on bioassays &
Leader of the Pharmacognosy Research natural products-based drug development.
LaboratoriesattheUniversityofGreenwich, Thevariousresearchesthathehasundertaken
Chatham-Maritime, UK. Dr Habtemariam includetheidentificationofnovelcompounds
received his BSc degree in Biology (minor: ofnatural-originwithpotentialantimicrobial,
Chemistry) from the University of Addis anticancer, anti-inflammatory, antidiabetic
Ababa and his Master’s degree (combined- and antiobesity applications among others.
studies)inPharmacologyandPhytochemistry He has published more than 171 scientific
from the University of Strathclyde, Glasgow, publications in peer reviewed journals and
UK. He stayed on at Strathclyde to study at filed over three family of patents. He is also
doctoral level, studying on drug discovery the author of a book entitled “The African
researches and obtained his PhD in this area and Arabian Moringa Species: Chemistry
ofresearch.Afteranumberofyearsinteaching Bioactivity and Therapeutic Applications”.
and post-doctoral research at the Strathclyde Detailsofhisresearchactivitiesand publica-
Institute for Drug Research and Strathclyde tions are available via his URL: http://
University, he joined the School of Science, www.herbalanalysis.co.uk/.
University of Greenwich in September 1998.
xiii
Preface
Plants provide by far the most essential intervention from disease prevention to
nutrientsofthehumandietsuchascarbohy- management as well as public education is
drates,fats,proteins,vitaminsandminerals. necessary.MeasuresofT2Dmanagementin-
Collectivelycalledplantfoods,theyarecon- cludelifestylechangessuchasdietaryinter-
sumed togenerateenergyandmaintainour vention, exercise, and weight loss where
normalbodyphysiologyorhomeostasis.Be- necessary, and drug interventions. At the
yondthesevitalnutrients,plantsdoalsosyn- forefront of dietary intervention measures
thesize a variety of compounds that are arethebalancingactofcalorieintakeandex-
called ‘secondary metabolites’ with func- penditure and promoting what are consid-
tions often associated with defense against ered as good diets orhealthy foods.
pathogens, herbivores or for allelochemical Perhaps the most important therapeutic
interactions. The exploitation of these valu- breakthrough in diabetes pharmacotherapy
ablechemicalcompoundsbymankindhave is associated with the discovery of insulin
been evident from prehistoric period of and its application that is dated back to the
herbalmedicinesutilizationtothesignificant 1920s. Since then, numerous classes of com-
proportion of today’s modern medicine pounds of biological/protein/peptide and
whichtracetheiroriginbacktonaturalprod- small molecular weight compounds both
ucts. The use of plants for flavoring and from synthetic and natural product sources
spices as well as exploitation for dyes, cos- (ornaturalproducts-inspiredsynthesis)have
metics, agrochemical and other industries been introduced. The requirement of long-
alsoserveasgoodexamplesofplantsecond- term or life-time treatment coupled with the
ary metabolites applications for human use. numerousside-effectsofthesedrugsstillpush
Whileadvanceindrugdiscoveryandde- us, however, to desperately search for new
velopment in the last two centuries have therapies of T2D. In addition to insulin, the
made it possible to control/manage various incretinanaloguessuchasglucagon-likepep-
diseases, or to improve the quality of life, tidemimicsorexendin-4fromthesalivaofthe
there have also been continued challenges venomous Gila monster, which served as a
from emerging or the modern-era diseases synthesis framework for novel antidiabetic
that are not yet met by effective drug thera- agents, underpins nature as a source of
pies. The classical example is the complex protein/peptide-based antidiabetic drugs.
metabolic disease of type 2 diabetes (T2D). Onthesmall-molecularweightside,ourfirst
The epidemic proportion of recent increase line pharmacotherapy for T2D is still with
in the incidence of this disease along with metformin which is the biguanides class of
itsmajorriskfactor,obesity,broughtsignifi- compounds discovered form research based
cant burdens to our societies, governments on the medicinal application of the plant
and healthcare services. In the absence of Galegaofficinalisasantidiabeticagent.Thera-
drug of cure, a coordinated system of tional for identifying novel drugs ofnatural-
xv
xvi
PREFACE
origin for T2D is thus as good as it has ever extensivelypresented.Inadditiontothenor-
beenandplantsthathavealreadybeenused mal physiological regulations of carbohy-
bymankindforcenturiesandconsideredsafe drate/lipid metabolism from digestion in
have even more added value if they are theguttoabsorption,storageandutilization;
proventobeefficacious. pathological dysregulations and the major
At the junction between what constitute molecular/biochemicaltargetsfordrugther-
food and medicine are the medicinal foods. apy are outlined. One chapter is also dedi-
These include plant food ingredients which cated in this section for pathological
are known to contain a range of secondary features of diabetes complication at macro-
metabolitesthatactthrough-druglikeeffects and microvascular and/or cellular levels.
when they are consumed in sufficient In Section-C, an overview of the current
amount. The various flavoring and spice therapeutic agents for T2D along with their
plantssuchasginger,garlic,turmeric,clove, mechanismofactionareillustrated.Thebio-
fenugreek,etc.maybeincludedintothiscat- synthesis machinery of plants secondary
egory.Whilesomeplantfoodsareregularly metabolites and whatclasses of compounds
consumedinsomeregions,theymayberare are expected from natural sources are also
or considered medicinal in other regions of discussedinthissection.Assuch,theprinci-
theworld.Forexample,wehaveplantslike ples of drug action applicable to potential
Moringa which are eaten as staple food therapy of T2D by plant secondary metabo-
in East Africa and India while they are lites are outlined.
primarily used as herbal medicines in other The choices of plants as medicinal foods
parts of the world. While fruits like figs was based on extensive review of the scien-
andolivesareconsumedasfood,otherplant tificliteratureand theprofile ofplant-based
parts oftheseplantssuchastheirleavesare products in the market relevant to the food,
either routinely employed in herbal medi- nutraceutical and plant-based therapies. On
cine applications or as herbal teas and infu- these basis, three sections (Sections D–F)
sions with some therapeutic implications. are dedicated to exhaustively appraise the
The vast arraysof herbal medicines arealso chemistry and pharmacology of the chosen
recently repurposed as food supplements plants. With over 2270 chemical entries
and are widely available in health shops as backed up with 4258 citations, this book is
over-the-counter medicinal/nutraceutical intended to provide readers with the most
products. Hence, the distinction between comprehensive and up-to-date information
what we consider as food and medicine is on the chemical and biological domains of
evennowbecomingmoreandmoreblurred. these medicinal plants and/or foods. On
This book is intended to provide a com- the pharmacological side, all available re-
prehensive resource on T2D and associated sourcesfrominvitro,theplethoraofanimal
diseases from pathology to intervention by studies and human trials are systematically
natural products that come under plant scrutinized. Mechanistic approach from in-
foods of medicinal importance. Section-A sulinsignalingandinsulinresistancetogen-
providesbasicfactsonT2Dfromsignificance eral mechanisms of actions such as
as a global burden and prevalence (along antioxidant and anti-inflammatory effects
withobesity)toitsdefinitions,classifications are extensively discussed. These include
and diagnostic criteria. In Section-B, the data from the chemical-, diet- and
basic carbohydrate and lipid metabolism as genetically-induced cellular and animal
well as pathological hallmarks of T2D are models of obesity and/or T2D. Along with
xvii
PREFACE
obesity, theT2Dassociated diseases such as this section, one chapter is dedicated to in-
hypertension, diabetes retinopathy, neurop- clude medicinal foods that are emerging to
athy, nephropathy and wound complica- gain interest both scientifically and in the
tions are all used to show pharmacological public domain as T2D modulating agents
andclinicalefficaciesforthecrudemedicinal and include, cocoa (Theobroma cacao), coco-
plant/food preparations as well as their ac- nut (Cocos nucifera), figs (Ficus carica),
tive principles. Under each chapter, the his- Moringa(MoringaoleiferaandM.stenopetala),
torical perspectives of the plants as food soybean(Glycinemax),sweetpotato(Ipomoea
and medicine, their botanical description batatas),andwalnuts(Juglansregia).Thelast
and taxonomic significance are presented chapter is dedicated to the large volume of
alongwiththerelevantchemistryandphar- information on herbal medicines that are
macology. Beyond the detailed pharmaco- now repurposed as food supplements. The
logical effects at in vitro, in vivo and merits of these products as dietary supple-
clinical conditions, their pharmacokinetic ments with intention to modulate T2D
andtoxicologicalprofilesarealsodiscussed. and/or metabolic syndrome are scrutinized
Section-D exhibits fruits that have been with the following key examples: Aloe vera
shown to modulate T2D and the various (L.)Burm.F.,Andrographispaniculata(Burm.
componentsofmetabolicsyndrome.Thisin- F.), Wall. Ex Nees, banaba (Lagerstroemia
cludechaptersonbilberriesandblueberries, speciose (L.) Pers), Cassia or Senna species (in-
bitter melon (Momordica charantia L.), guava cludingSennaauriculata(L.)RoxbandS.alata
(Psidium guajava L.), okra (Abelmoschus (L.) Roxb.), Ginkgo biloba L., ginseng (Panax.
esculentus (L.) Moench), papaya (Carica pa- ginseng C.A. Mey, P. quinquefolius L. and P.
paya L.), pomegranate (Punica grantum L.), notoginseng), gymnema (Gymnema sylvestre
prickly pear cactus (Opuntia species) and the (Retz.)R.Br.exSm.),Jamun(Syzygiumcumini
various pumpkins (Cucurbita species). In ad- (L.) Skeels), olive leaf extract (Olea europaea
dition to the fruits of these plants, discus- (L.)), scutellaria (Scutellaria baicalesis Georgi)
sions on other plant parts as emerging andStJohn’swort(HypericumperforatumL.).
potential therapeutic agents are also in- Finally,thisbookisnotintendedtoadvo-
cluded. Section-E is devoted to the flavour catethemedicinalfoodscitedhereintoserve
and spices groups that have shown to have as a replacement therapy to insulin, metfor-
significant health benefits in recent years min or other antidiabetic pharmacotherapy
and include chapters on cinnamon inusetoday.Itisaratherbalancedappraisal
(Cinnamomum species), cloves (Syzygium ofalltheavailabledataathandwithallneg-
aromaticum (L.) Merr. & L.M. Perry), fenu- ativeandpositiveoutcomesofpharmacolog-
greek (Trigonella foenum-graecum L.), ginger icalandclinicalefficaciespresentedwiththe
(Zingiber officinale Roscoe), garlic (Allium sourceofdatavariabilities,whereappropri-
sativum L.), and turmeric (Curcuma longa ate,identifiedandscrutinized.Infact,theau-
L.). Of the beverages included in Section-F thor, acknowledges that pharmacological
are those known to modulate the diabetes datadiscrepanciesforplantpreparations,es-
pathology,butmostimportantlyinreducing pecially under clinical trial studies, reflects
thediabetesprevalence/riskbasedonepide- thechallengesandfrustrationsofusingme-
miological and clinical data, are coffee, tea dicinal foods or their products as medicine.
(Camellia sinensis (L.) Kuntze), rooibos Hence, the sources of controversies in effi-
(Aspalathus linearis (Burm. F.), and yerba cacy and chemical composition variability
(cid:1)
mate (Ilex paraguariensis A. St.-Hil.). In the for medicinal foods based on genetic and
xviii
PREFACE
environmentalfactorsthatgovernplantsec- researches, professionals in healthcare ser-
ondary metabolites; harvesting, processing, vices, and those with interest in the herbal,
andmanufacturingconditions;experimental food and pharmaceutical industries. Stu-
modelsanddesignsincludingdosage,inter- dentsandscientistsinmedical,pharmaceuti-
ventiontimeandassessmentcriteria,etc.are cal and food science disciplines are other
all taken into consideration. The author be- beneficiaries ofthe book.
lieves that the book would be an invaluable
Solomon Habtemariam
resource to scientist in drug discovery
Acknowledgements
Iwouldliketothankanumber ofpeople Kerala (India) has also been generous in in-
who kindly gave me images of some plants troducingmetothemedicinalfoodsofrele-
usedinthisbook,particularlyDrHelenPick- vance in Asia. Images of a number of food
ering of the Kew Botanical Garden, UK; ingredients and medicinal/nutraceutical
Dr Jianhua Xie (State Key Laboratory of productshavebeentakenfromhealthshops
Food Science and Technology, Nanchang particularly Holland and Barret with the
University,Nanchang,China);andProfessor kind assistance of staff to whom I am grate-
Susana Casal (REQUIMTE/Laboratory ful. I did extensively use the Kew Botanical
of Bromatology and Hydrology, Faculty of Garden (London, UK) resources and this
Pharmacy, Porto University, Rua Jorge included acquiring images of the numerous
ViterboFerreira,Porto,Portugal).DrGeorge medicinal plants in the garden and their
Varghese of Kerala, my very good friend, excellent library services as well as online
who also supported me during my trip to databases.
xix
