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Ind ian J Phys io l Pharmaco l 2008 ; 52 (4) : 327–354

DIETARY SPICES IN HEALTH AND DISEASES (II)

K. P . KOCHHAR

Department of Physiology,All India Institute of Medical Sciences,New Delhi – 110 029

( Rece ived on August 18 , 2008 )

Abstract : Dietary spices influence various systems in the body such asgastrointestinal, cardiovascular, reproductive and nervous systems resultingin diverse metabolic and physiologic actions. As inheritors of a long traditionof the use of spices in diet as well as in indigenous medicines we know thatthese a re t r ea tments o f t en honed over cen tu r i e s wi th we l l - e s t ab l i shedreputat ions for eff icacy. A r igorous review of these manifold benef ic ia leffects may provide a fair basis for prescription in many clinical conditionswhere confirmed modern drug treatments do not exist or as adjunct therapyto reduce the dosage or the r isk of s ide effects . This essay at tempts toadjudicate the tradit ional use of dietary spices based on factual researchevidence for their multivalent actions as health promoting dietary additivesas wel l as putat ive therapeut ic agents .

Key words : spices condiments hypoglycaemicgas t ro in tes t ina l card iovascular hypolipidaemican t i hype r t ens ive ant id iabet ic functional foodsnutraceut icals e thnic die ts metabolic syndrome Xp h y t o t h e r a p y phytomolecules phytochemica ls

The history of dietary prescriptions datesback , perhaps to the o r ig in o f the humanrace . P lan t s have been na tura l andtraditional sources of medication in differentd ie ta ry cu l tu res a l l over the wor ld andthe use of seasonings and f lavoring agentshas been the mains tay of ind igenousremedies ac ross the wor ld (1–12) . InInd ia the re fe rences to the cura t ivepropert ies of dietary spices in the Rigvedaand Atharvaveda a rguably seem to be theear l i es t records o f the use o f herbs inmedicine (2–4). Tradition attaches all mannerof benefit to every spice, condiment and herb

and they a re impor tan t ingred ien ts in theprescriptions of Indian systems of medicineinc lud ing Ayurveda , S iddha and Unanisystems (2, 3, 9, 10). In traditional culturesthe medicinal uses are often indistinguishablefrom their culinary uses (11–15).

As has been d i scussed in the p rev iousessay (Par t - I ) d ie ta ry sp ices a re aheterogeneous col lec t ion of a wide var ie tyof vo la t i l e and non-vola t i l e chemica l sobtained from dried aromatic parts of tropicalp lan t s -genera l ly the seeds , be r r ies , roo t s ,pods, and sometimes leaves (1). Though many

3 2 8 K o c h h a r Indian J Physiol Pharmacol 2008; 52(4)

essent ial oi ls of spices are variat ions on acommon theme yet given the wide range ofbotanical species and plant parts from whichsp ices a re der ived , they can con t r ibu tes ign i f ican t var ie ty and complex i ty to thehuman diet and diversity in their therapeuticusage (Table I) (15–21). Spices affect manybody func t ions l ead ing to d iversephys io log ica l e f fec t s on gas t ro in tes t ina l ,metabol ic , ca rd iovascu la r , r eproduc t ive aswel l as per iphera l , au tonomic and cen t ra lnervous systems (2, 11, 22–25). A few decadesback i t was cons idered tha t though dry ,powdered sp ices con ta in s ign i f ican t

concentration of some vitamins and minerals,the normal levels of their use in daily foodmake the i r nu t r i t iona l con t r ibu t ionnegl ig ib le (26–29) (Table I I ) . However ,recently encouraging data have come up toinc lude sp ices as the ‘new nut r ien t s ’ and‘nutraceuticals’ because of manifold bioactiveeffects (29–41).

This review in continuation (Part-II) withthe previous (Part-I) (1) cites salient relevantfac t s regard ing the benef ic ia l sys temicphysiologic and metabolic effects of dietaryspices .

TABLE I : Represen ta t ive vo la t i l e o i l s and sp ices .

N a m e Part used Botanical origin Production areas Important constituents Use

Anise the dried, the annual Spain, 1-3% volatile flavor(aniseed) ripe fruit herb, Pimpinella France , oil containing

anisum (Apiaceae) Egypt 80-90% (E) anethole,10-15% chavicol

C a r a w a y the dried, the biennial herb, Nether lands , 3-6% volatile oil flavorripe fruit Carum carvi Roland, Russia containing 50-58%

(Apiaceae) Northern Africa (+)– carvone,40-50% (+) limonene

Citronella volatile oil the grass, Sri Lanka, 5-55% (+) citronellol, pe r fume ,oil distilled with Cymbopogon Indonesia, China 25-40% geraniol, insect

steam from winterianus and Taiwan, (+)– citronellol repel lantfreshly cut C. nardus Argent ina,or partially (Poaceae) Brazil, Indiadried leaves

Eucalyptus the dried, the tree Eucaly- Australia, Brazil, 70-85% cineole, antiseptic,oil scythe-shaped ptus globules Spain, Portugal 5-15% mild

leaf and other Angola, South α-pinene anesthet ic ,species of Africa, China, st imulatingEucalyptus India expectorant

F e n n e l the dried, the perennial Spain, Russia volatile oil flavor,ripe fruit herb Foeniculum Bulgaria, containing 65-70% carminat ive

vulgare Italy (E)-anethole,(Apiaceae) 10-15% limonene,

6-7% fenchone, 4%Methyl chavicol

Lavender volatile oil the dwarf France , 30-60% (–)-linayl p e r f u m eoil distilled with sh rub , Bulgaria, acetate, (–),

steam from Lavandula Russia, linalool cineole,the fresh angustifolia Austral ia terpinen-4-olflowering

L e m o n volatile oil the small Spain, Italy, 70-80% flavoroil obtained by e v e r g r e e n California, (+) limonene, p e r f u m e

expression evergreen tree Florida, 8-10% β-pinene,without the Citrus limon Argent ina, 8-10% γ-terpinene,aid of heat, (Rutaceae) Cyprus, Brazil, 2-4% citralfrom the Israel, Australia,fresh peel Ivory Coast, Greece]

Contd.....

Ind ian J Phys io l Pharmaco l 2008 ; 52(4 ) Die ta ry Sp ices in Hea l th and Diseases ( I I ) 329

O r a n g e volatile oil the tree, California, 1-2% decanal, flavoroil obtained by Ci t rus Florida, more than

expression sinensis Brazil, Italy, 90% limonenefrom the fresh (Rutaceae) Israelpeel of theripe fruit

P i n e volatile oil the three, S o u t h e a s t e r n 65% α-terpineol, 10% disinfectantoil obtained by Pinus palustrics United States methyl chavicol and deodorant

extraction and and other related phenol ethers,fractionation species of 9% borneol, 8%or by steam Pinus fenchol 4% metholsdistillation of (Pinaceae)the wood

Rose oil volatile oil perennial herbs Bulgaria geranio, (–) citronellol, p e r f u m e(otto) distilled with of shrubs, Rosa S o u t h e r n (–) citronellol, nerol,of rose steam from gallica R. France , 2-phenylethanol

the fresh demascena, R. Turkey ,flowers alba, R. centifolia, Morocco,

and varieties of Rus iathese species(Rosaceae)

Spearmin t volatile oil the perennial Washington 45-60% flavor,oil distilled with herb Mentha Idaho, (–) carvone, carminat ive

steam from spicata or of Wisonsin, (–) limonene,the fresh, M. cardiac Michigan cineoleoverground (Lamiaceae) Indiana,parts of the C h i n aflowering plant

T h y m e the dried an evergreen Spain, volatile oil flavorleaves and herbaceous Italy, containingflowering Shrub, Thymus France , thymol, carvacroltops Vulgaris, T. zygis, G r e e c e ρ-cymene

and its variety α- terpinenegracilis (Lamiaceae) γ - t e rp inene

Turpen t ine volatile oil the tree Pinus S o u t h e a s t e r n 65% α-pinene, counter i -oil distilled from Palustris and United States 30% β-pinene r r i t an t

the oleoresin other species ofPinus (Pinaceae)

Win te rg reen volatile oil the leaves of Eastern United 98% methyl flavor,oil distilled with the shrublike States and salicylates counter i -(gauther ia steam from perennia l C a n a d a r r i t an toil, betula the dried G a u t h e r i a antiinflam-oil, sweet plant material p rocumbens m a t o r ybirch oil) (Ericaceae) or the

bark of the Betulalenta (Betulaceae)

TABLE II : Mic ronu t r i en t s in some common Ind ian sp ices (mg/100 gm food) .

Material Ca lc ium Phosphorous Iron T h i a m i n e Ribof lav in Niac in Vit. A Vit C

Onion 0.3 0.29 Trace 0.42 0.06 0.6 14.7 0.5Garlic 0.1 0.42 0.01 0.68 0.08 0.7 12.0 0.05Ginge r 0.1 0.15 0.01 0.05 0.13 1.9 12.0 0.05Turmer ic 0.2 0.26 0.05 0.09 0.19 4.8 49.8 0.05Dhilly Powder 0.1 0.32 0.01 0.59 1.66 14.2 63.7 1.25Green Chilli 0.03 0.08 1.2 0.19 1.18 0.5 111.0 TraceRed (dried) Chilly 0.16 0.37 2.3 0.93 0.43 9.5 50.1 0.18Mustard seeds 0.3 0.79 0.01 0.65 0.45 8.5 22.1 0.06Tamar ind 0.2 0.11 0.01 nil 0.07 0.7 3.0 0.03Curry leaf 0.8 0.6 0.01 0.08 0.21 2.3 4.0 0.03Dhaniya (coriander Seed) 0.8 0.44 0.01 0.26 0.23 3.2 4.0 3.78Jeera (Cumin seed) 0.9 0.45 0.05 0.73 0.38 2.5 17.0 0.05Adult daily requirement 0.5 0.5 0.024 1.4 1.7 19.0 40.0 0.75


C alanine has also been observed in responseto capsaicin (43, 44).

The s t imula t ion of a f ferent neurons bytopical capsaicin protects the gastric mucosaagainst damage induced by pyloric l igation,e thanol and ac id i f ied aspr ine (67–68) .In t ragas t r ic capsaic in promotes the re leaseof vasodi la tor subs tances l ike n i t r ic oxide(NO) (69, 70). Capsaicin-induced stimulationof afferent neurons within the gastric mucosais associated with release of calcitonin generelated peptide (CGRP) which via formationof NO may cause bo th a p revent ion ofmucosa l in ju ry and modula t ion of gas t ro -intestinal motili ty (73, 81).

Effec t on gas tr ic ac id secre t ion andu l c e r o g e n e s i s

Chill i causes dyspepsia in patients withor wi thout u lce r , and pa t ien t s wi th u lce rare often advised to avoid its use (64, 66).Never the less , ep idemio log ica l and c l in ica ldata suggest that chil l i ingest ion may havea benef ic ia l e f fec t on human pep t ic u lce rd i sease (63–69) . For ins tance ch i l l i has agas t ropro tec t ive e f fec t on asp i r in - inducedgas t r ic mucosal in jury in humans (67–69) .Chilli ingestion has no detrimental effect onthe heal ing rates of pat ients with duodenalu lcer and i t does no t cause macroscopicdamage in humans (82–85) . Ser ia lgas t roscopy had repor ted no de le te r iouseffects of oral intake of 3 g chilli powder perday on u lce r hea l ing in duodena l u lce rpa t ien t s (63–66 , 83 , 86) . Long- te rm ch i l l iintake (360 mg daily for 4 weeks) protectedaga ins t hemorrhag ic shock- induced gas t r i cmucosa l in jury , an e f fec t tha t may bemedia ted by capsa ic in -sens i t ive a f fe ren tneurons (67 , 69) . The pro tec t ive e f fec t of

Gastro intes t ina l e f fec t s

Using the too ls and techniques o fcontemporary phys io logy , researchers a renow e luc ida t ing mechanisms jus t i fy ingthe t rad i t iona l use o f d ie ta ry sp ices asappetite enhancers, digestives, carminatives,an t i f l a tu len t s , sec re tagogues , as wel l asbeneficial in both diarrhoea and constipation(9–10, 12–15). Dietary spices may influencegas t r ic empty ing , gas t ro in tes t ina l mot i l i ty ,secretion of gastric acid as well as intestinalb ica rbona te , b i lopancrea t ic sec re t ions ,absorptive processes and bacterial microflora(44–55) . Loca l e f fec t s on gu t mucosa ,gastrointestinal reflexes and enteric nervousas wel l as sys temic au tonomic responsesinf luence carbohydra te , p ro te in and fa tabsorption in diverse ways (56–61). Changesin mucus bar r ie r , gas t ropro tec t ive e f fec t s ,en te rocy te and v i l lous he igh t change andcytoprotective adaptations all are now knownto occur wi th in take of sp ices o r sp icepr inc ip les (62–73) . The fo l lowing sec t ionhigh l igh ts some of the sa l ien t and provengastrointest inal act ions of dietary spices.

Local ac t ions on gas tro intes t ina l t rac t

Spice in take has been known to beassocia ted wi th many loca l ac t ions on gutin f luenc ing secre t ion , mot i l i ty , absorp t ionand change in microf lo ra (44–55 , 73–80) .Capsaicin the pungent active principle of redchi l l i or papr ika has been shown to causegastr ic mucosal oedema and hyperemia anddecrease in the gastr ic acid output (64–66,81). An analogue of capsaicin as well as drycapsa ic in powder have been found to berespons ib le fo r gus ta to ry swea t ing andincreased salivation (42–43). An increase inthe gastric clearance of aminopyrine and 14


Ginger (Z ing iber o f f i c ina le Roscoe ,Zingiberaceae) also has been suggested forpotential utility in treating peptic ulcerationdue to its action as a thromboxane syntheticinhibitor (90). Synergy is implicated in theantiulcer effect as a result of an experimentwhere the ex t rac t was f rac t iona ted andassayed , and par t i cu la r ly h igh ac t iv i ty(97 .7% inh ib i t ion a t 125 ppm) found tooccur in a fraction containing a-zingiberene,p sesqu iphe l landrene , b i sabo lene andcurcumene (91) .

Aqueous extracts of columbo weed, longpepper , pars ley , ta r ragon, nu tmeg, ye l low-berr ied n ightshade , threads tem carpetweed,sage and cinnamon had bactericidal activitiesaga ins t Hel icobac ter py lor i and those ofturmer ic , borage and pars ley were ab le toinhibit the adhesion of H. pylori strains tothe s tomach sect ion (92) . In another s tudythe in vitro susceptibility of extracts of spiceand food p lan ts f rom Thai t rad i t iona lmedicine inhibi ted the growth of H. pylori(93) . These data indicate that these p lantsmay have chemoprevent ive ac t iv i t i es andthus may par t ly exp la in the reducedincidence of gastric cancer in Asian countries(93).

capsicum could involve vani l lo id receptorsbecause res in i fe ra tox in an u l t rapo ten tana logue of capsa ic in , a l so d i sp laysan t iu lce r ac t iv i ty and bo th capsa ic in andres in i fera toxin ac t on vani l lo id (capsaic in)receptors (7).

Paprika, pepper and cinnamon increasedgastric acid secretion in men and promotedhis tamine induced ulcer formation in dogs,whereas mustard decreased acid output (63,66, 82). Video-endoscopy did not demonstratevisible gastro duodenal damage on intake ofspicy foods (82–85). To study the effect ofspices on gastric acid secretion the stomachof pen tobarb i tone-anes the t ized ra t s wasper fused a t 0 .15 ml /min wi th aqueousextracts (10% w/v) of red pepper (Capsicumannuum) , fenne l (Foenicu lum vu lgare) ,omum/a jwan (Carum copt icum) , cardamom(Elettaria cardamomum), black pepper (Pipern igrum) , cumin (Cuminum cyminum)and cor iander (Cor iandrum sa t ivum) oracetylcholine. All the spices tested increasedacid secret ion. Atropine abol ished the acidsecre t ion induced by ace ty lcho l ine andsignif icant ly reduced acid induct ion by redpepper , omum and cor iander , bu t no t tha tby fennel (85). The spices tested increasedgas t r ic ac id secre t ion , in some by achol inerg ic mechanism but by o thermechanism(s) as well (85–87). Licorice, theroo t and rh izome of d i f fe ren t var ie t i es o fGlycyrrhiza glabra, has been extensively usedin medic ine for i t s ant iu lcer ac t iv i ty (88) .Carbenoxolone der ives f rom the hydrolys isof g lycyr rh iz in ic ac id a f te r i t s ex t rac t ionfrom l icorice root (7) . Several mechanismsof action have been proposed to explain thepharmacolog ica l ac t iv i ty o f ca rbenoxoloneand many sp ices may conce ivab ly ac tsimilarly (Table III).

TABLE I I I : Anti ulcer activity of Licorice: ProposedMechan i sms o f Ac t ion .

1 . S t imula tes gas t r i c mucus p roduc t ion2 . Enhances the ra t e o f incorpora t ion o f va r ious

sugars in to gas t r i c mucosa l g lycopro te ins3 . Promotes mucosa l ce l l p ro l i f e ra t ion4 . Inh ib i t s mucosa l ce l l ex fo l i a t ion5 . Inh ib i t s p ros tag land in degrada t ion6 . Inc reases the re l ease o f PGE 2 and reduces the

fo rmat ion o f th romboxane B 2

7 . Regula tes DNA and pro te in synthes i s in gas t r icm u c o s a


Act ion on enzymes and secre t ions o fgas tro intes t ina l t ract

Dietary curcumin, capsaicin, piperine andginger p rominent ly enhanced in tes t ina ll ipase act ivi ty and also the disaccharidasessucrase and mal tase in ra t s (74) . Die ta rycumin , fenugreek , mus ta rd and asafoe t idabrought about decreases in the l eve l s o fphospha tases and sucrase in in tes t ina lmucosa (74). Platel et al reported that spicemixes con ta in ing cor iander , tu rmer ic , redchilli, black pepper, cumin, ginger and onionenhanced the activities of pancreatic l ipase,chymotryps in and amylase (75) . The sp icemixes customized so as to include spices thata re t rad i t iona l ly cons idered as d iges t ives t imulan ts had the h ighes t s t imula toryinfluence particularly on bile secretion, bileacid output and the act ivi t ies of pancreaticenzymes (75) . The higher secret ion of bi leespecially with an elevated level of bile acidsand a benef ic ia l s t imula t ion of pancrea t icd iges t ive enzymes , par t i cu la r ly o f l ipasecould probably be the two mechanisms bywhich these combinat ions of sp ices a id indigestion (74–75).

Act ion on gas tro intes t ina l mot i l i ty

Chi l l i inges t ion was assoc ia ted wi thgastro esophageal reflux and the magnitudeof the induced reflux seems to be related tothe kind of chilli (94). Cuminum cyminum iswidely used in Ayurvedic medicine for thet rea tment o f dyspeps ia , d ia r rhea andjaundice (99) . Severa l con t ro l led c l in ica lt r i a l s sugges t tha t g inger roo t (Z ing iberof f icinale) can rel ieve symptoms of motionsickness by a mechanism of action that differsfrom that of antihistamines. The responsibleconstituents are believed to be gingerols and

shagaols (100–104) . Ginger cou ld be aneffect ive and cheap ant imemetic adjunct tocancer chemotherapy but one double b l indrandomized con t ro l t r i a l p roved i t sineffectiveness in low doses (100–101). Themechanism of act ion of ginger in reducingnausea and vomi t ing i s unknown but i t i sspeculated that it probably works regionallyon the gastro intestinal tract rather than onthe central nervous system (102–103). It mayincrease gas t r i c mot i l i ty and absorbneutralizing toxins and acids and affectivelyb lock gas t ro in tes t ina l re f lexes andsubsequent nausea feedback with no reporteds ide e f fec t (102–104) . Peppermin t andcardamom oi l exer t the i r an t i spasmodicaction through muscarinic receptor blockage.(97 , 98) . Nine commerc ia l essen t ia l o i l sproduced four d i f fe ren t e f fec t s on the ra tisolated phrenic nerve-diaphragm preparationwhilst only a contracture in guinea-pig ileumprepara t ions (105) . The in tes t ina l t r ans i tt ime of Ind ians i s shor te r and the i r s too lweigh t l a rger than tha t o f the Europeanson a comparab le f ib re in take (106) . Onefac tor which may be respons ib le fo r th i sphenomenon is the presence of several spicesin the Indian diet (2, 106–108). Ingestion ofd ie ta ry sp ices i s assoc ia ted wi th a s lowergas t r ic empty ing bu t a fas te r whole gu ttransit (108). A high chilli diet increases themotility in normal subjects but has no effecton symptoms in patients with irritable bowelsyndrome (109).

Act ions on membrane permeabi l i ty andtransport propert ies

Hot spices may in terac t wi th epi the l ia lcells of the gastrointestinal tract to modulatetheir transport properties (110). Permeabilityfor fluorescein isothiocyanate (FITC)-labeled


dextrans with graded molecular weight, andmorphological al terat ions of t ight junct ionsby immunofluorescence were s tudied us ingan an t i -ZO-1 an t ibody , a marker fo r t igh tjunction integrity (110). Extracts from blackor g reen pepper , bay lea f o r nu tmegincreased the t ransep i the l ia l e lec t r i ca lresis tance and macromolecular permeabil i tyremained low (110) . Capsa ic in t rans ien t lyreduced res i s tance and p iper ine increasedres i s tance , making them candida tes fo rcaus ing the e f fec t s seen wi th c rude sp iceextract (111).

Both b lack and red pepper may induceepigas t r ic pa in by removing the s tomach’shydrophobic l in ing and ac t iva t ingin t ramucosa l pa in recep tors (112) .His topa tho log ica l s tud ies showed lesse rin f i l t ra t ion in to the submucosa , fewerpapillae and lesser changes in the cytoplasmof the cells in the colon in cumin and blackpepper g roups when compared to theDimethyl hydrazine (DMH) and chilli treatedanimals (112) . The mechanism by whichdie ta ry pepper causes dyspeps ia andepigastric pain is poorly understood. Cuminand black pepper may protect the colon bydecreasing the activity of beta-glucuronidaseand mucinase (113) . Both b lack and redpepper rapidly induced a decrease in gastricsur face hydrohobic i ty in a dose dependentfashion (114).

Act ion o f absorpt ion across gas tro intes t ina lt r a c t

Capsaic in decreased g lucose absorpt ionf rom ever ted sacs o f hamste r and ra tintestine (44, 70, 71, 115). Perfusion studiescar r ied ou t us ing je juna l segmentdemons t ra ted revers ib le reduc t ion in the

absorption of water, glucose and alanine inthe presence of capsaicin (70–71, 116). Whenspice active principles were associated withmixed mice l les the i r in v i t ro i n tes t ina labsorption was relatively higher (117). Chilliand tu rmer ic be ing r ich in phenol iccompounds would be expected to bind ironin the intestine and inhibit its absorption inhumans . Desp i te the much h igher amountof phenolics in the turmeric meal, it did nota f fec t i ron absorp t ion (118) . Capsa ic inaffec ted carbohydra te absorpt ive abi l i ty ofduodenal epithelial cells but lipid absorptionwas not affected (79, 80, 119, 120).

Piperine the pungent alkaloid present inPiper n igrum Linn , and P. longum Linnenhanced the b ioava i lab i l i ty o f var iouss t ruc tura l ly and therapeu t ica l ly d iversedrugs (111). It may act as an apolar moleculeforming an apolar complex with drugs andso lu tes and may modula te membranedynamics due to i t s easy par t i t ioning thushelping in eff icient permeabil i ty across thebarriers (111, 121). It was observed that theless weight gain in rats fed with North Indiant rad i t iona l sp ice mix ture garam masa la ascompared to the control group although theanimals were consuming s imi la r quant i t iesof diet could be due to changes in absorption(122). Garam masala when consumed for aper iod of four weeks decreased the lengthand weight of the intestine in weanling ratsbut mucosal enzymes were not studied (122–123).

Poss ib le mechanisms o f ac t ion

Release of se ro ton in f rom mucosa lenterochromaffin cel ls t r iggered by luminalsubstances is one of the key events in theregula t ion of gu t mot i l i ty and secre t ion .


Sero tonin re lease was measured in cu l turesuperna tan ts by a se ro ton in enzymeimmunoassay and amperomet ry (124) .Ca lc ium imaging s tud ies revea led tha todorant l igands of the ident i f ied o l fac toryreceptors cause calcium influx, elevation ofin t race l lu la r f ree ca lc ium leve l s , and ,consequently, serotonin release (124). Spicesand odoran ts p resen t in the lumina lenvi ronment o f the gu t may s t imula tese ro ton in re lease v ia o l fac tory recep torspresent in human enterochromaff in ce l l s .

The capsaicin sensi t ive primary neuronshave been implicated in local regulation ofinflammation, visceral tract motility, trophicef fec t s and immune func t ion v ia the i rvar ious pep t ides (125) . An a t t rac t ivespeculation arises that just like capsaicin andits multipotent action via effects on primarysensory neurons leads to a host of autonomicresponses , the re i s a s t rong poss ib i l i ty o foccur rence of endogenous recep tors andl igands homologous to capsa ic in (125) .Similarly the various other spice principlescould have yet undiscovered homologues orlike-structured stereo chemical ligands whichmay modula te ac t iv i ty (2 , 11 , 21 , 41) .Capsa ic in has been used ex tens ive ly as aprobe to e luc idate the funct ion of sensoryneurons in var ious o rgans and sys tems(including the stomach), because of its abilityto excite and later defunctionalize a subsetof primary afferent neurons (131, 134). Thediverse effects of spices on these networksthus ind ica te the wide rang ing po ten t ia ltherapeu t ic use o f sp ices (2 ) . Thegas t ropro tec t ive (69 , 70 , 73) as wel l asgast ropropuls ive (71, 76, 77, 78) effect ofcapsa ic in as wel l as the cho l inominmet iceffect of certain spices is well known (126,127). Both central autonomic as well as local

effector systems seem to mediate this effect(Fig. 1). Noncholinergic noradrenergic nervesmay also play a part to modulate the f inaloutcome (128). The exact s i te of act ion ofspices sti l l remains to be elucidated thoughhypotheses including action via nitric oxiderelease abound (129, 130).

Fig . 1 : Summary o f pa thways con t ro l l inggas t ro in tes t ina l func t ion and in f luenced byd ie ta ry sp ices .

Effec t on carbohydrate metabol i sm

Spices a re known to exer t severa lbenef ic ia l phys io log ica l e f fec t s inc lud ingthe an t id iabe t ic in f luence v ia shor t t e rmhypoglycemia and long te rm improvedglucose to le rance (F ig . 2 ) (135–139) . Anumber of condiments and spices includingpepper, asafetida, aloes, ocimum and eugenolf rom Jamun have been ascr ibed ahypoglycaemic act ion in normal as well asexper imenta l ly induced d iabe t ic an imalmodels and a l so in humans (140–150) . Arecen t comprehens ive rev iew has c i t edev idence f rom an imal exper imenta t ion aswel l as c l in ica l t r i a l s where sp ices , the i rex t rac t s o r the i r ac t ive p r inc ip les wereexamined for t rea tment o f d iabe tes (139) .


Fenugreek seeds (Trigonella foenumgraecum),garlic (Allium sativum), onion (Allium cepa),and tu rmer ic (Curcuma longd) have beenexper imenta l ly documented to possesspotent ia l to funct ion as ant idiabet ic agents(139) . Cumin seeds (Cuminum cyminum) ,ginger (Z ing iber o f f i c ina le ) , musta rd(Brass ica n igrd) , cur ry l eaves (Murrayakoenigii) and coriander (Coriandrum sativum)have a l so been repor ted to havehypoglycaemic effects (139).

Oral administration of Cumin for 6 weeksto d iabe t ic ra t s resu l ted in s ign i f ican treduction in blood glucose and body weightand an increase in total hemoglobin andglycosylated hemoglobin. It also prevented adecrease in body weigh t . (99) . Cuminsupplementa t ion was found to be moreeffective than glibenclamide in the treatmentof diabetes mel l i tus (99) . Fructose feedinghas been shown to induce insulin resistancein ra t s , a ssoc ia ted wi th hyper insu l inemia ,hyperg lycemia , and hyper t r ig lycer idemia(167). Rajamani et al. investigated the effect

of admin is te r ing food seasoning sp icesmix ture on g lucose , insu l in , and l ip ids incirculation and carbohydrate enzymes in theerythrocytes of high fructose-fed rats (167).High homeostatic model assessment (HOMA)value indicated that adminis t ra t ion of foodseasoning sp ice mix ture improved g lucosemetabol i sm and p lasma l ip id p rof i l e inf ruc tose- fed ra t s and cor rec ted insu l inresistance possibly through improved insulin-sens i t i z ing ac t ions o f the ac t ive sp icecons t i tuen ts (167) . Var ious sp ices d i sp layinsulin-potentiating activity in vitro, and inpart icular , c innamon spice and i ts phenolicex t rac t s (168–170) . Cinnamon inges t ionreduced to ta l p lasma g lucose responses asmeasured by area under the curve (AUC) tooral glucose ingest ion as well as improvedinsu l in sens i t iv i ty (169) . Cinnamonsupplementa t ion may thus be impor tan t toin v ivo g lycaemic con t ro l and insu l insensi t ivi ty in humans, and not only are i tse f fec t s immedia te , they a l so appear to besustained for 12 hour (169). Cinnamon alsos igni f icant ly de layed gas t r ic emptying andprofoundly lowered post prandial glycaemicresponse wi thout any s igni f icant e f fec t onsatiety (170). The hypoglycaemic mechanismof efficacy of sumac (Rhus coriaria L.) andblack cumin (Bunium pers icum Boiss) wasinvestigated and the inhibition of a glycosidehydrolase-a lpha amylase may have in teres tin the t rea tment and preven t ion ofhyperg lycemia and d iabe tes as wel l asdyslipidemia and obesity (171).

Adminis t ra t ion of turmeric or curcuminto Al loxan diabet ic ra ts reduced the bloodsugar , hemoglobin and g lycosy la tedhemoglobin leve l s (172) . Turmer ic andcurcumin supplementat ion a lso reduced theoxida t ive s t ress encounte red by these

Fig . 2 : Die ta ry sp ices may ac t a s pu ta t ivean t imetabo l ic syndrome X presc r ip t ions [ fo rde ta i l s , s ee Kochhar (2 ) ] .


diabet ic ra ts as demonstra ted by the lowerlevels of TBARS (thiobarbituric acid reactivesubstances) which may have been due to thedecreased influx of glucose into the polyolpa thway lead ing to an increased NADPH/NADP ra t io and e leva ted ac t iv i ty o f thepoten t an t iox idan t enzyme GPx (172) .Moreover , the ac t iv i ty o f sorb i to ldehydrogenase which ca ta lyses theconvers ion of sorb i to l to f ruc tose , waslowered s ign i f ican t ly on t rea tment wi thturmeric or curcumin (172).

Both Murraya koen ig i i and Brass icajuncea showed s ign i f ican t hypoglycemicaction in experimental rats (144, 173). Therewas increase in the concentration of hepaticg lycogen and g lycogenes i s , a s ev iden tf rom the decreased ac t iv i ty o f g lycogenphosphorylasse and gluconeogenic enzymes(173, 174). The stimulatory effect of capsaicinon se rum insu l in may be v ia capsa ic ininduced beta adrenergic ac t iv i ty on B cel lreceptors in pancreatic islets (175–177). Manyenzymes of the liver including gluconeogenic,enzymes have been reported to be affectedby spices both in vitro cell culture systemsas well as in vivo in experimental animals(174 , 175–183) . The increased leve l s o fg lucose 6 phospha te dehydrogenase , theability of insulin to activate lipoprotein lipaseactivity and also the effect of long term spiceingestion on these lipotropic effects could beresponsible for the net hypoglycaemic effectsind ica t ing a more e f f ic ien t op t imalutilization of dietary carbohydrate on intakeof spices (2) (164, 184–190).

Effec t on l ip id metabol i sm

Severa l ac t ive ingred ien t s o f sp icesinc lud ing capsa ic in ( red pepper ) p iper ine

(black pepper), curcumin (turmeric), eugenicac id (c love) , f e ru l ic ac id ( tu rmer ic ) andmyr is t i c ac id (mace , amla) have beenrepor ted to in f luence l ip id metabol i smpredominantly by mobilization of fatty acids(120 , 190–195) . Curcumin and capsa ic ina l te red b i le sa l t sec re t ion to make i t l e ssl i thogenic and a l so lowered cho les te ro lleve l s , wi thout any s ign i f ican t e f fec t onfa t absorp t ion (193–194) . Capsa ic in ac tedas a l ipo t rope , p reven t ing t r ig lycer ideaccumula t ion and increas ing pre fe ren t ia lutilization of fats (190–198). It also stimulatedl ip id mobi l i za t ion and lowered per i rena lad ipose t i s sue weigh t and se rumtriglycerides in fat fed rats (197). Curcumin,eugenol and ferulic acid reduced fat ty acidb iosyn thes i s in ra t l ive r and increasedske le ta l musc le l ipopro te in l ipase ac t iv i ty(120) . Sa l imnath and Sa tyanarayana havereported that capsaicin inhibits calcium andca lmodul in dependent phosphodie te raseac t iv i ty in ra t ad ipose t i s sue v ia anadrena l ine re leas ing ac t ion of capsa ic inreported earl ier (189).

Embelic acid and turmeric are potentialhypol ip idemic and hypocholes te ro lemicagents (194–195) . In ra t s renderedhypercholes te ro lemic by main ta in ing themon a cholesterol-enriched diet (0.5%) for 8weeks, inclusion of curcumin (0.2%) capsaicin(0.015%) or garlic powder (2.0%) in the diet,produced the expected hypolipidemic effect(199). Dietary curcumin, capsaicin and garlicwere observed to cause a 10–14% decreasein erythrocyte membrane cholesterol contentand cor rec t the increased f rag i l i ty o fe ry throcy tes (199) . Cloves , mace andcardamom demonstrated significant ability toinhibi t ini t ia t ion as wel l as propagat ion ofl ip id peroxida t ion due to the i r po lyphenol


conten t , s t rong reduc ing power andsuperox ide rad ica l scavenging ac t iv i ty(199).

Modulation of inflammatory responses inobes i ty may be usefu l fo r p revent ing oramel io ra t ing obes i ty - re la ted pa tho log ies(200). Woo et al in an elegant study treatedraw 264 .7 macrophages wi th an ad iposet issue condi t ioned medium with or withoutactive spice-derived components (i .e. diallyld i su l f ide , a l ly l i so th iocyana te , p iper ine ,z ingerone and curcumin and measuredmacrophage migrat ion and act ivat ion (200).Al ly l i so th iocyana te , z ingerone , andcurcumin significantly inhibited the cellularproduc t ion of p ro inf lammatory media torssuch as tumor necros is fac tor -a lpha (TNF-a lpha) and n i t r i c ox ide , and s ign i f ican t lyinh ib i ted the re lease of monocyte chemoat t rac tan t p ro te in MCP-1 f rom ad ipocytes(200).

Laboratory s tudies have shown that theres i s tance of i so la ted LDL-choles te ro l o rl ino le ic ac id to ox ida t ion i s inc reased inincubations with chill i extracts or capsaicin(201) . I t i s unknown i f these in v i t roantioxidative effects also occur in the serumof individuals ea t ing chi l l i regular ly . In arandomized cross-over s tudy, twenty-sevenpar t i c ipan ts a te ‘ f resh ly chopped ch i l l i ’blend and ‘no chilli’ diets for 4 weeks each(201) . Regular consumption of chi l l i for 4weeks increased the res i s tance of se rumlipoproteins to oxidation (201). Capsaicin andcurcumin have a l so been shown to reducethe susceptibil i ty of LDL to oxidation in aconcentration-dependent manner (202). Ahujaet al investigated the effects of (202). A 50%increase in lag time copper-induced oxidation

of se rum l ipopro te ins ( f rom cont ro l ) wasobserved a t d i f fe ren t concen t ra t ions o fcapsa ic in , d ihydrocapsa ic in , and curcumin(202).

Cumin t rea tment improved g lucosetolerance and also resul ted in a s ignif icantreduc t ion in U-assoc ia ted hyper l ip idemiaassessed by p lasma and t i ssue choles tero l ,phosphol ip ids , f ree fa t ty ac ids andt r ig lycer ides and s ign i f ican t ly reduced thefa t ty changes and in f lammatory ce l lin f i l t ra tes in pancreas (99) . The e thanol icex t rac t o f nu tmeg (myr i s t i ca f ragrans)showed platelet anti-aggregatory abil i ty andsignificantly lowered total cholesterol: HDLratio and LDL: HDL ratio in experimentallyinduced hyper l ip idaemia in a lb ino rabb i t s(203). Rats fed M. Koenigii (curry leaf) andB. juncea (mus ta rd) showed decreasedconcent ra t ion of malondia ldehyde whi lehypdroperox ides and con juga ted d ienes aswel l as superox ide d i smutae and ca ta laseactivity were found to be increased in liverand hear t (204) . Glu ta th ione leve l s inl iver , hear t and k idney were loweredand g lu ta th ione reduc tase , g lu ta th ioneperox idase and g lu ta th iones - t ranfe raseac t iv i ty showed a sharp increase in theexperimental groups (173, 204) . Curry leafor mustard seeds resulted in a reduction intotal serum cholesterol and LDL+VLDL, anincrease in the HDL, lower re lease o fl ipopro te ins in to the c i rcu la t ion and anincrease in the LCAT ac t iv i ty (203–205) .Dried f lowers of A. al l iaceum when fed at2% level in diet for 6 weeks to experimentalra t s rendered hypercholes te ro lemicby cho les te ro l - feed ing , exh ib i ted b loodcholesterol lowering effect by l imitat ion inintest inal cholesterol absorption (205).


Act ions on vascu lar endothe l ium

Pro tec t ion of endothe l ia l in tegr i ty byelimation of certain risk factors has provento be effective in maintaining hemostasis andin slowing the progress of the cardiovasculardisease (206–208). Rings of rat aorta with orwi thout an in tac t endothe l ium, weremounted in t i s sue ba ths , con t rac ted wi thphenylephrine, and then exposed to di lutedextracts of herbs and spices (206). Many butno t a l l ex t rac t s exh ib i ted endothe l ium-dependent relaxations that were reversed byNG-monomethyl -L-arg in ine and a l soincreased t i ssue levels of cycl ic GMP, themedia tor of n i t r ic oxide- induced vascularsmooth muscle relaxat ion (206).

Foenicu lum vu lgare , Murraya koen ig i i ,Curcuma aromat ica , Mentha arvens i s andCurcuma longa demons t ra ted po ten t dosedependent scavenging of ni t r ic oxide (NO)(207) . Sp ices might be po ten t and nove ltherapeutic agents for scavenging of NO andthe regu la t ion of pa tho log ica l condi t ionscaused by excessive generat ion NO and i tsoxidation product, peroxynitrite as indicatedby inh ib i t ion of l ipopolysacchar ide andinterferon gamma induced nitri te productionin mouse peritoneal cells by epigallocatechingallate, carnosol, and curcumin (Fig. 3) (208).

Gar l ic and tu rmer ic a re po ten tvasore laxan ts as wel l as reduce theatherogenic proper t ies of choles terol (209–213). Garlic has long been widely used notonly as a flavoring agent but also as a folkmedication (8–9). I ts consumption has beenrepor ted shown to have an t ia therosc lero t icactivity to increase high-density l ipoprotein(HDL) leve l s , which may he lp to removeexcess cho les te ro l f rom ar te r ia l t i s sue in

animal models and human cell cultures (7).It has been reported to have lipid-and bloodpressure - lower ing ac t ion , as wel l a san t ip la te le t , an t iox idan t , and f ib r ino ly t iceffects (7). The sulfur-containing component,allicin, is often considered to be the principalactive ingredient of garlic, but several otherb ioac t ive ingred ien t s , have a l so beenisolated (186).

Some of the beneficial effects of garl ichave been a t t r ibu ted to i t s cons i s ten thypolipidemic and antioxidant properties (7–9) . Long- te rm exposure to gar l i c , wa te r -soluble garlic extracts, or garlic oil resultedin dose dependent decreased serum levels ofcho les te ro l and t r ig lycer ides in ra t s andrabbits fed with high lipid diet (213). Perhapsthe hypolipidemic action is primarily due tothe decrease in hepa t ic cho les te ro lgenes i sin gar l i c - t rea ted ra t s p robab ly by theinh ib i t ion of 3 -OH-3-methyl g lu ta ry l CoAreduc tase (HMG-CoA) , the ra te - l imi t ingenzyme, ea r ly in cho les te ro l syn thes i s ;whereas the triacylglycerol-lowering effect ofgarlic appears to be due to inhibition of fattyacid synthesis (213) . A notable res torat ionof a r te r ia l b lood pressure was seen inanimals on garlic and turmeric supplementeddie t (213) . The vasore laxan t response toadenosine , acetylchol ine , i soproterenol wasenhanced and cont rac t i l e e f fec t o f 5 -hydroxyt ryp tamine was s ign i f ican t lyat tenuated (213) .

Onion o i l has been shown to inh ib i tcyc looxygenase and 12- l ipoxygenase inp la te le t s as wel l a s p la te le t aggrega t ioninduced by epinephrine, ADP, or arachidonicacid (AA) (214). More specifically, “cepaenes”found in onions have been found to be potentinh ib i to rs o f sheep semina l microsomal


cyc looxygenase and porc ine leukocyte 5 -lipoxygenase (7, 191, 214). Both aqueous andorganic gar l ic extracts have been found toinhibit several steps of the incorporation ofAA into platelet phospholipids, directly anda lso by inh ib i t ing deacy la t ion of p la te le tphospho- l ip ids upon s t imula t ion wi th thecalcium ionophore A23187, resulting in lesse icosanoid synthes is (214) . More recent ly ,Al i e t a l . observed noncompet i t ive andirreversible inhibition of cyclooxygenase byaqueous extracts of raw garlic (215).

Wei and Lau (216) determined the effectsof aged gar l i c ex t rac t s (AGE) on thegenera t ion of hydrogen perox ide andsuperox ide an ion (O 2) and the ac t iv i ty o fth ree an t iox idan t enzymes on bovinepulmonary ar te ry endothe l ia l ce l l s (PAEC)(216). Confluent monolayers of PAEC wereincubated with AGE, and oxidative stress wast r iggered by hypoxanth ine and xan th ineoxidase or H 2O 2 (216) . AGE exhib i tedboth concen t ra t ion- and t ime-dependentsuppression of H2O2 and O2 generation, andit also significantly increased the activi t iesof SOD, CAT and GPX. The results suggestthat AGE may be an effective antioxidant inprevent ing or t rea t ing d isorders re la ted toendothel ia l cel l injury associated with freerad ica l s (216) . I t has been sugges ted tha tdue to their eicosanoid-modulating property,spices may serve to provide clues to drugsdirec ted a t a rachidonic ac id (AA) pathwayenzymes as pharmacolog ica l t a rge t s (216-218). Curcumin, inhibited platelet aggrationinduced by a rach idona te , adrena l ine andcol lagen and th romboxane B2 produc t ionf rom exogenous a rach idona te wi th aconcomitant increase in the formation of 12-l ipoxygenase p roduc ts (219) . Moreover , i tinhib i ted the incorpora t ion of amino ac ids

in to p la te le t phosphol ip ids as wel l a sthe deacy la t ion of amino ac id l abe ledphosphol ip ids on s t imula t ion wi th ca lc iumionophore A23187 (220) . Curcumin’s an t i -in f lammatory proper ty may , in par t , beexpla ined by i t s e f fec t s on e icosanoidbiosynthesis (219–220).

Excess n i t r i c ox ide (NO) produced byinduc ib le n i t r i c ox ide syn thase ( iNOS) i simplicated in the development of a numberof diseases including cardiovascular diseasesDue to absence of any na tura l spec i f icenzymat ic defense sys tem in v ivo , theconsumption of certain foods which exhibitselective suppress NO overproduction mightboos t the hos t ’ s p ro tec t ive e f fec t s aga ins tNO-mediated toxicity (222–223). Spices, richin phenol ics , a re specu la ted conce ivab lyto act as potential NO- scavengers or iNOSsuppressors (219) . Severa l medi te r raneanculinary spices including rosemary, tarragon,c innamon, o regano , bas i l , mar joram andallspice with the exception of clove, displayeda ra ther l inear dose-dependent NO-suppress ing effect wi thout any effect uponcell viability (219). Polyphenolic test extractsresu l ted in cons iderab le endothe l ium-dependent re laxa t ion in r ings o f ra t aor taand mesen te r ic vascu la r beds in ra t s tha tappears to be mediated via NO-independentand non-prostanoid mechanisms (222).

Rietz et al. investigated the susceptibilityof ra t Langendor f f hear t p repara t ion toventricular arrhythmias under the conditionsof cardiac i schemia and reperfus ion (223) .The incidence of ventricular fibrillation (VF)during 20-minute occlusion of the descendingbranch of the l e f t coronary a r te ry (LAD)was s ign i f ican t ly reduced in the ra t sfed pu lver ized wi ld gar l i c l eaves (223) .


Ace ty l sa l i cy l ic ac id cou ld no t comple te lypreven t the ca rd iopro tec t ive e f fec t ssugges t ing tha t the p ros tag land in sys temdoes no t p lay a dec i s ive ro le in thecardioprotective action of wild garlic (223).Fur thermore , a modera te ang io tens in-conver t ing enzyme (ACE) inhibi t ing act ionof wild garlic was found in vitro as well asin v ivo tha t cou ld con t r ibu te to i t scardioprotective and blood pressure-loweringaction (223).

Effec t on energy ba lance , metabol i c ra te andresp iratory quot ient

Capsa ic in and p iper ine have beenreported to reduce thermogenesis and causethermal ana lges ia (11 , 226–230) . On theother hand ginger has been repor ted to bethermogenic (134). Spicy food has been shownto lower metabolic rate (228–230). Spicy foodsa l so have been es t imated to be r i ch insalicylates (Table IV) (164, 231) and liberateace ty l cho l ine in v ivo (126 , 127) . Manyreports, quite a few of them preliminary haveemerged but the resultant effect of a spicy‘mix ture ’ on long te rm ef fec t on bodytemperature and sleep activity cycle are stillnebulous (161, 162, 232–237). Possibly thiscould be due to mutual antagonism, cross-reactivity, cross sensitization or competitiveinh ib i t ion of ce r ta in endogenous recep tors i t es fo r these func t ions in f ree l iv inghumans (238–239). There is a great differencein the effects of capsaicin on local ingestionand paren te ra l admin is t ra t ion s ince themetaboli tes of capscaicinoids seem to haveno ex t rahepa t ic metabol i sm and no ac t ivemetabolites were observed after x first pass’in liver (240–241).

Ciapsa ic in in i t i a l ly inc reased oxygenconsumpt ion and resp i ra to ry quot ien t

fo l lowed by a decrease in both before theleve l s re tu rned to normal , r esu l t ing in anoveral l enhancement of energy metabol ism.The effect was direct as well as via adrenalinre lease f rom adrena l medul la (175–176) .Accord ing to E ldershaw crude ex t rac t s o fboth fresh and dry ginger induce the perfusedhind l imb to consume more oxygen inassoc ia t ion wi th increase in per fus ionpressure and lac ta te p roduc t ion (163) .Prev ious s tud ies have shown tha t the ra t s

TABLE IV : Natu ra l ly occur r ing sa l i cy la tes ind ie ta ry sp ices .

T y p e mg/100 g

S p i c e sAllspice Powder , d ry 5 .2A n i s e e d Powder , d ry 2 2 . 8Bay l ea f Leaves , d ry 2 . 5 2Bas i l Powder , d ry 3 .4C a n e l l a Powder , d ry 4 2 . 6C a r d a m o m Powder , d ry 7 .7C a r a w a y Powder , d ry 2 . 8 2C a y e n n e Powder , d ry 1 7 . 6C e l e r y Powder , d ry 1 0 . 1Chi l l i F lakes , d ry 1 . 3 8

Powder , d ry 1 .3C i n n a m o n Powder , d ry 1 5 . 2C l o v e s Whole , d ry 5 . 7 4C o r i a n d e r Leaves , f r e sh 0 .2C u m i n Powder , d ry 4 5 . 0C u r r y Powder , d ry 218 .0Di l l F r e s h 6 .9

Powder , d ry 9 4 . 4F e n n e l Powder , d ry 0 .8F e n u g r e e k Powder , d ry 1 2 . 2Five sp ice Powder , d ry 3 0 . 8Garam masa la Powder , d ry 6 6 . 8G a r l i c Bulbs , f r e sh 0 .1G i n g e r Root , f r e sh 4 .5M a c e Powder , d ry 3 2 . 2M i n t Garden , f r e sh 9 .4Mixed he rbs Leaves , d ry 5 5 . 6M u s t a r d Powder , d ry 2 6 . 0N u t m e g Powder , d ry 2 .4O r e g a n o Powder , d ry 6 6 . 0P a p r i k a Hot powder , d ry 203 .0

Swee t powder , d ry 5 .7P a r s l e y Leaves , f r e sh 0 . 0 8P e p p e r Black powder , d ry 6 .2

Whi te Powder , d ry 1 .1P i m e n t o Powder , d ry 4 .9R o s e m a r y Powder , d ry 6 8 . 0S a g e Leaves , d ry 2 1 . 7T u r m e r i c Powder , d ry 7 6 . 4T h y m e Leaves , d ry 183 .0


consuming a d ie t conta in ing garam masalaspent more t ime in locomot ion , moved agreater distance and had more average speedas compared to control animals (122–123). Asingle bolus of spice may not change thermiceffect of feeding acutely but spices may havea modula tory ro le a f te r cumula t ive in take(190–193). Since liver is the chief organ ofmetabol i sm there may be a change in themetabolic status of animals (190–193).

Long te rm in take of sp ices l eads toalterations in the levels of hepatic enzymesin response to in take of sp ices and a l soinf luences the basa l metabol ic ra te (228) .L iver microsomal cy tochrome p-450dependent a ry l -hydroxlase has been shownto be general ly s t imulated by spices (247).S ingh and Rao have assessed the chemopreventive role of garam masala through itsimpac t on hepa t ic l eve l s o f de tox ica t ionenzymes l ike g lu ta th ione-S- t rans fe rase ,cytochrome b-5 and cytochrome p-450. Theyhave repor ted tha t d ie ta ry doses of garammasala modulate the hepatic levels of theseenzymes (243–244).

Effec t s on autonomic funct ions

Green chi l l ies cause gusta tory sweat ingassocia ted wi th lacr imat ion , sa l iva t ion andflushing of the face and the distribution ofswea t ing i s the same as thermal swea t ing(42). On intake of spicy meal a trend towardsslight lowering of blood pressure soon afterthe mea l in take or even pos t p randia lhypotens ion was observed (245–247) . Pos tprandial meal responses to food have beenshown to be altered by capsaicin analogues(248–249) . Acute haemodynamic effects ofpan masala powdered mixture of areca nut ,slaked lime, catechu and condiments caused

acute increase in pulse and systolic as wellas diastolic blood pressure (225). Capsaicinana logues media te a number o f gas t ro-cardiovascular and pancreatico-cardiovascularre f lexes (240 , 250–255) . Converse ly theautonomic nervous system i tse l f inf luencesd ie ta ry thermogenes i s (256–258) . Thenut r i t iona l s ta tus o f the sub jec t a l soinfluences autonomic function as well as Badrenergic responsiveness (258–259).

On acute administration, both peripherallyand centrally, capsaicin produced hypothermiaand vasodi la ta t ion v ia s t imula t ion ofhypothalamic temperature sensi t ive neuronswhereas chronic or in t ra cerebral in ject ionled to a desensitization, impairment of heatdissipating mechanism and loss of behavioralthermoregulatory responses to high ambienttempera ture (254) . Capsa ic in has po ten thyper tens ive e f fec t s on in t ravenousadmin is t ra t ion and a p ressor response onin t racaro t id in jec t ion (240) . I t sens i t i zesaort ic baroreceptors via vagus nerve (250).Similarities between cardiovascular reponsesto food ingestion and to gastric intra arterialcapsa ic in inges t ion sugges ted tha t thecompound s t imula tes gas t r i c d i s tens ionrecep tors (257) . Sp lanchnic nerve i t se l fconta ins capsaic in sens i t ive neurons whichcan mediate cardiovascular effects (248, 253,256). Piperine (black pepper) and capsaicinshowed posi t ive intoropic and chronotropicef fec t s in i so la ted ra t a t r i a and exh ib i tedcross tachyphylaxis (253). Air way reactivityis ini t ial ly increased by capsaicin fol lowedby desens i t i za t ion (254) . The resp i ra to ryef fec t s o f capsa ic in vary f rom apnoeato tachynoea depending on rou te o fadministration (254). Aloes, garlic, onion andginger are also beneficial in improving thesymptoms of asthma (260, 261).


Donner re r e t a l sugges ted a poss ib lemechanism for the se l f - l imi t ing ef fec ts ongenera l autonomic responsively because ofthe fac t tha t a major i ty o f capsca ic ino idsundergo comple te metabol i sm in the f i r s tpass in the l iver (241, 263). Therefore theeffect of local ly ingested and sys temical lyinges ted sp ice pr inc ip les may be d i f fe ren t(263, 266).

Several Indian spices have been screenedfor cholinominmetic activity (126–127). Thefreeze dr ied aqueous extracts f rom roas tedseeds (analogous to the farm garam masalaused in Ind ian cooking) conf i rmed thepresence of acetylchol ine and a lso chol inein l a rge amounts when sub jec ted to gaschromatography and mass spectrometry (126,127) . Thus the ex t rac t s f rom these sp icess t imulated muscar inic chol inergic receptorsin ‘ ra t b lood pressure ’ and ‘ ra t j e junum’bio log ica l p repara t ion and a l so s t imula tedn ico t in ic recep tors in ‘ f rog rec tus ’ (126) .These e f fec t s were b locked by spec i f icantagonis t s . Roas t ing appears to br ing outthe presence of acetylcholine in the aqueousext rac ts . There does not appear to be anydestroying enzyme like cholinesterase in theaqueous extracts of spices (126, 127, 131).This gives rise to the possibil i ty of certainendogenous neuropept ide ana logues whichare s imi la r o r may even inh ib i t gas t roin tes t ina l and vasoac t ive ac t ions due tostructural similarity (41, 128, 130).

Effec t s on reproduct ive sys tem

Spices a re cons idered as sexua linv igora tors in the Unani Sys tem ofmedic ine . Aniseed has been used as anes t rogenic agen t (7 ) . I t has been repor tedto increase mi lk secre t ion , p romote

mens t rua t ion , fac i l i t a te b i r th , a l l ev ia tesymptoms of the male c l imac te r ic , andincrease libido (7). Ginger root is a putativeagent for preventing ageing dependent penilevascular changes and impotence (267). Theextracts of the nutmeg and clove were foundto s t imula te the mount ing behaviour o fmale mice, and also to significantly increasethe i r mat ing per formance devoid of anyconspicuous general short term toxicity (267).Pimentol from allspice, rosmarinic acid andlu teo l in 7-0 be ta g lucuronide f rom thyme,quercetin 3-0 beta glucuronide from thyme,coriander and rut in from tarragon inhibi tedova lbumin permeat ion th rough Caco-3ce l l monolayers were iden t i f i ed as theactive principles (268). A structure-act ivi tyrelationship study among these spices activeand their active principles indicated that thepresence of ca techol s t ruc ture p layed animportant role in the inhibi tory act ivi ty ofeach compound (268).

Daware et al studied the effect of piperineon estrous cycle, mating behaviour, toxicityto male germ cells, fertilization implantationand growth of pups (269). Piperine interferedwith several crucial reproduct ive events ina mammalian model (269). I t increased theper iod of the dies t rus phase which seemedto resu l t in decreased mat ing per formanceand fert i l i ty. Considerable anti- implantat ionact ivi ty was recorded af ter f ive days post-mating on oral t reatment with piperine andin t rau te r ine in jec t ion of p iper ine causedthe to ta l absence of implan ts in e i ther o fthe u te r ine horns (16 .66%) or one of thehorns (33%) (269) . Glycyrrh iz in decreasesp lasma c lea rance and increases p lasmaconcent ra t ions of predniso lone (270) . Ora lcon t racep t ive use may increase sens i t iv i tyof glycyrrhizin acid; women are reportedly


more sensi t ive than men to adverse effectsof l i cor ice (270) . Many of the commonlyconsumed foods , herbs , and spices conta inphytoestrogens and phytoprogestins that actas agonis t s and antagonis t s in v ivo (271) .Over 150 herbs traditionally used for treatinga variety of heath problems were extractedand tes ted fo r the i r re la t ive capac i ty tocompete wi th es t rad io l and proges te roneb ind ing to in t race l lu la r recep tors fo rproges te rone (PR) and es t rad io l (ER) inintact human breast cancer cells (271). Thes ix h ighes t ER-b ind ing herbs tha t a recommonly consumed were soy, l icorice, redclover , thyme, turmeric , hops and verbena.The six highest PR—binding herbs and spicescommonly consumed were oregano, verbena,tu rmer ic , thyme, red c lover and damiana(271). Acute and chronic oral toxicity studieson the e thanol ic ex t rac t s o f Cinnamomumzeylan icum and Piper longum in miceinduced a significant increase in reproductiveorgan weights, sperm motil i ty, sperm countand failed to illicit any spermatotoxic effect(271).

C o n c l u s i o n

Reports from studies on animals modelsand in vitro system, leads us to direct futureresearch perspectives in this area by targetings tudy of con t ro l led sys temic , p lanned ,b l inded , qua l i ty assured t r i a l s on normalsubjects as wel l as in pat ients of l i fes tylere la ted d i seases l ike d iabe tes mel l i tus ,hyper l ip idemia , obes i ty , a therosc le ros i s ,hyper tens ion , dysau tonomia and metabol icsyndrome X and gas t ro in tes t ina l d i seaseslike acid reflux, peptic ulcer and functionalbowel disorders. The analgesic, antioxidant,an t i in f lammatory as wel l as immunemodula t ing ro les o f sp ices need fur ther

elaboration. The action of spices onreproductive functions as well as their potentialrole as regulators of fertility and/or conceptionalso is an area holding great future promise.

I t i s obv ious ly a l a rge t ask tocomprehensively capture and review at anyone t ime the now ex tens ive l i t e ra tu re onspices and herbs. Over the las t decade thegrea t exc i tement and in te res t in themechanism, epidemiology, and preclinical andclinical effects of dietary spices on variousbody systems cont inues and is ref lected inthe large number of publications on this topicfrom Asian countries and the United States.The potent ia l c l in ica l promise i s temperedby disappointment in the lack of efficacy ofep idemio log ica l ly p red ic ted micronut r ien taddi t ives . Most of the work on spices hasbeen done on animal models for whom spiceintake is novel and not “physiological”. Evenin humans the usual intake is in the form ofgroups or mixtures of spices (2). Synergy andpolyvalent act ion are important concepts inspice physiology and have a pharmacokineticbasis. Components of whole spices which arenot active themselves can act to improve thestabi l i ty , solubi l i ty , bioavai labi l i ty or half-l i fe o f the ac t ive components . Hence aparticular chemical might in pure form haveonly a fraction of the pharmacological activitythat it has in its plant matrix thus suggestingthat measur ing an individual ’s food in takeand assess ing ind iv idua l var ia t ion indisposi t ion, bioavai labi l i ty , and metabolismof micronut r ien t s might a l low for moreaccura te and ind iv idua l ized nu t r i t iona lapproaches for dietary prescript ion. Dietarymodifications will only work if they are inconsonance wi th ind iv idua l p re fe rences ,culture values, and philosophical orientationstoward heal th and disease .


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