PIPERINE: A VALUABLE

1
Department of Biotechnology, Gitam Intit!te of "echnology, Gitam
Plant #cience, #chool of Life #cience, Uni$erity of
Received:
AB#"RA%"
The present scientific peer review describes on novel natural cyclobutane
characterization of this alkaloid showed that it
an efficient bioavailability enhancer for different
anti-cancer, anti-depressant, anti-apoptotic, anti
extraction, quantification and applications of piperine we
substantial knowledge to scientific world to develop
industries.
&ey'or(: Piperine, Alkaloid, Piper nigrum, Piper longum

IN"R)DU%"I)N
Plant derived drugs secured iportance in recent years because of
their unrefuted efficacy as phytoedicines. The active copounds
or principles present in these natural products serve either as
teplates or as interediates for synthetic drug
!"#$%#&'()* is an alkaloid found in the fruits and roots of
nigrum and Piper longum species of Piperaceae faily
This alkaloid is responsible for the pungency
!P.nigrum* and long pepper !P.longum*, along with chavicine !an
isoer of piperine*. This alkaloid was first isolated fro the fruits of
P.nigrum, the source plant of both the black and white pepper grains
+#,. -luckiger and %anbury found that species of .long pepper/
P.longum and P.officinarum also contain this alkaloid
to the above species, this copound is also present in
pepper species +),. The pungency of piperine is caused by the
activation of the heat and acidity sensing Transient receptor
potential vanilloid !T0P1* ion channel T0P1# on nociceptors !pain
sensing nerve cells* +2,.

*ig+ 1: %hemical tr!ct!re of piperine+

Piperine fors white priss, which elt at #34
alost insoluble or slightly soluble in water !25g67
readily soluble in alcohol !#g6#8l* and ether !
very weak base9 fors salts only with ineral acids
dissociated by water. Piperine was first hydrolyzed
+8, into a base and an acid, which were later naed
piperidine and piperic acid respectively +:,.
synthesized by the action of piperoyl chloride on piperidine
genus Piper has ore than #555 species, but the
species are P.nigrum, P.longum and P.betel +4,. (ut
is faous as the spices king due to its pungent quality
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PIPERINE: A VALUABLE AL&AL)ID *R), PIPER #PE%IE#

&+ VA#AVIRA,A-
#
, ,A.E#. UPENDER
3

Department of Biotechnology, Gitam Intit!te of "echnology, Gitam Uni$erity, R!hi/on(a, Via/hapatnam
Plant #cience, #chool of Life #cience, Uni$erity of .y(era0a(, .y(era0a( 1
Email: $aa$i23gmail+com
Received: 21 Feb 2014 Revised and Accepted: 5 March 2014

review describes on novel natural cyclobutane-containing alkaloid piperine isolated fro P
showed that it iparts pungency and edicinal value to Piper species. ;t has been
for different nutrients and trace eleents and exhibits potential anti-icrobial,
apoptotic, anti-pyretic and analgesic activities. ;n this review, origin,
n and applications of piperine were presented. ;ense study of this type of valuable
develop right technologies for its aple production, to eet its
Piper longum, <edicinal value
Plant derived drugs secured iportance in recent years because of
their unrefuted efficacy as phytoedicines. The active copounds
or principles present in these natural products serve either as
teplates or as interediates for synthetic drugs. Piperine
found in the fruits and roots of Piper
species of Piperaceae faily !-igure#*.
the pungency of black pepper
*, along with chavicine !an
This alkaloid was first isolated fro the fruits of
of both the black and white pepper grains
pecies of .long pepper/
this alkaloid +3,. ;n addition
is also present in =est African
The pungency of piperine is caused by the
d acidity sensing Transient receptor
potential vanilloid !T0P1* ion channel T0P1# on nociceptors !pain

%hemical tr!ct!re of piperine+
fors white priss, which elt at #34A>-3#&A>. ;t is
25g67 at #4>"*, but
and ether !#g6#.$l*. ;t is a
fors salts only with ineral acids and these are
hydrolyzed by using alkalis
into a base and an acid, which were later naed as
. This alkaloid was
iperoyl chloride on piperidine +$,. The
but the ost well-known
(ut of these, P.nigrum
is faous as the spices king due to its pungent quality. P.nigrum is a
flowering wine !-igure 3* ostly cultivated for its fruit.
used to produce black, white and green
valued due to the presence of
isoers.

*ig+ 4: Piper nigrum plant 5In(ian 0lac/ pepper6 'ith immat!re
pepper corn+

*ig+ 7: Blac/ an( 'hite peppercorn from

?lack pepper is ground fro dried
white pepper is ground fro dried
layer reoved. People use black and white pepper for stoach
upset, bronchitis, alaria, cholera and cancer.
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491
Re$ie' Article
AL&AL)ID *R), PIPER #PE%IE#
Uni$erity, R!hi/on(a, Via/hapatnam 1 879 9:8,
4
Department of
1 899 9:;
lkaloid piperine isolated fro Piper species. The
has been confired that piperine acts as
icrobial, anti-oxidant, anti-inflaatory,
origin, structure and biological properties9
this type of valuable natural copounds will provide
its deand in food and pharaceutical
ostly cultivated for its fruit. ;ts fruits are
used to produce black, white and green peppers !-igure )* which are
to the presence of an alkaloid piperine along with its

In(ian 0lac/ pepper6 'ith immat!re
pepper corn+

*ig+ 7: Blac/ an( 'hite peppercorn from Piper nigrum.
ro dried whole unripe fruit, where as
dried ripe fruit that has had the outer
People use black and white pepper for stoach
upset, bronchitis, alaria, cholera and cancer. ?ecause of these
International Journal of Pharmacy and Pharmaceutical Sciences
Vol 6, Issue 4, 2014

properties P.nigrum is edicinally iportant +&,
digestive and respiratory disorders +#5-#3,. P.l
is also a flowering cliber !-igure 2* cultivated for its fruit and root
This plant is source of drugs pippali and pippaliula
prepared fro dried ripe fruits !-igure 8* and roots of
well known edicines for respiratory tract disease
bronchitis and cough. The =est African black pepper !
iportant as flavourant and its different parts are used as internal
edicine for curing bronchitis, gastric ulcer, rheuatis and viral
diseases +#),.

*ig+ :: In(ian long pepper plant 'ith immat!re corn+



*ig+ 8: ,at!re (rie( corn of long pepper

@ovindraAan +#2, reported that pungent quality
P.longum is due to piperine content and other copounds
iparting pungent nature is very negligible. ;t is interesting to note
that these two species are iportant coponent
edicine, which is the ancient ;ndian edical
probles. 'early :5B of all traditional Ayurveda
soe special blend of ingredients, which include
blend. ;n addition, P.longum is being used in
forulations and it is one of the ingredients of Tri
is used for bronchitis and astha. -ruits and roots
P.longum contain a nuber of constituents including
alkaloids, isobutyl aides, lignans and esters etc.
piperine is the priary constituent and reported to be
iparting edicinal value for these spices.
%oner$ation an( propagation of Piper pecie
Ceed propagation in spices is cubersoe, uncertain and yields only
a few heterogeneous species due to their short viability and high
sterility in post fertilization stages +#8,. P.nigrum
propagated through cuttings with 3-: nodes for nursery and field
plantations. ?ecause of this, P.nigrum gerplas
seed bank is not pragatic due to heterozygous nature induced
through cuttings +#:,. ;n P.longum also conventional
beset with different probles like poor seed viability, lo
percentage of gerination, scanty delayed rooting of vegetative
cuttings. Therefore, there is a need for alternative propagation
ethods +#$,. The traditional ethods of crop iproveent are not
Vaa$irama et al.
Int Pharm
+&, and is used to cure
longum !long pepper*
cultivated for its fruit and root.
pippali and pippaliula which are
8* and roots of P.longum are
s for respiratory tract diseases like astha,
he =est African black pepper !P.guineese* is
rant and its different parts are used as internal
gastric ulcer, rheuatis and viral

long pepper plant 'ith immat!re corn+
*ig+ 8: ,at!re (rie( corn of long pepper
pungent quality of P.nigrum and
and other copounds role in
;t is interesting to note
iportant coponents in Ayurveda
ancient ;ndian edical syste for different
'early :5B of all traditional Ayurveda edicine contains
ents, which include P.nigrum in the
is being used in )32 Ayurveda
of Trikatuchurna which
and roots of P.nigrum and
constituents including volatile oil,
utyl aides, lignans and esters etc. (ut of these,
ary constituent and reported to be significant in
er pecie
Ceed propagation in spices is cubersoe, uncertain and yields only
heterogeneous species due to their short viability and high
igrum is conventionally
: nodes for nursery and field
gerplas conservation in a
seed bank is not pragatic due to heterozygous nature induced
conventional propagation is
poor seed viability, low
delayed rooting of vegetative
cuttings. Therefore, there is a need for alternative propagation
traditional ethods of crop iproveent are not
suitable to address the proble. Co to circuvent the above crises,
odern ethods of plant propagation and gene transfer are very
uch useful. <aAor weakness responsible for low productivity
Piper species is non-availability
crop losses due to abiotic and biotic stresses
other factors influencing the yield of these species are endogenous
icrobial containation and very slow growth rate of cultures.
Dstablishent of containation free plants fro greenhouse grown
plants was very difficult due to endogenous icrobial containation
as reported in Piper methysticum
Proce(!re for e<traction of piperine
Cince piperine has any applications
it should be extracted in a pure for which is free
solvents to enable its direct use in edicinal
products. (n an industrial scale, pepper is coinuted
ground into coarse powder and then extracted repeatedly with an
organic solvent such as acetone, ethan
hydrocarbons +35,. This longer duration of r
extraction of raw pepper particles
coponents such as gus, polysaccharides
substances. This type of solvent extraction process usually gives
coplex crude products, which
ultistep techniques such as
%igh-pressure stea treatent can also be used to extract piperine
by an osotic shock9 however, this technique is relatively slow and
consues a large aount of stea
extracted piperine efficiently by
that it has treendous potential for
selective extraction of bioactive copounds on a coercial scale
%arapurkar et al. +)3, reported that
has ore extraction efficiency and reduced extraction tie than
soxhlet extraction ethod. The B w6w yield of piperine in
supercritical fluid extract was 4.$: for
P.longum in 5.8 hr tie period, whereas in the case of Coxhlet
extract, the B w6w yield for P.n
2.)3 in 4.5 hr tie period. The yield of piperine was found to be
higher in P.nigrum copared to
=!antification of piperine
-or estiation and quantification
were used i.e E1 spectrophotoetry
+32,, %PT7" +38-3:, and %P7"
the piperine content in fruits of
and 5.:-#.:B by %P7" technique
content of piperine in fruit and root of
5.)#B and in fruit of P.nigrum
al. +)#, showed that the total yield of piperine
was 5.$&B by 0P-%P7" technique
root !5.8 c in dia.* and 5.#2B in the thick root !) c in dia.*9
5.22B in the cortex and 5.3&B
c were deterined. The average conte
batches of pepper roots was in the range of :.:$
%arapurkar et al. +)3, reported
with excellent accuracy with in short tie period through %PT7"
ethod. The accuracy values obtained
to &4.8$B in P.nigrum and &:.85B to &$.85B in
Patent on piperine
The natural extract fro black pepper is arketed under the
tradeark ?ioPerine
F
and has
patents for the efficacy of this unique ingredient. The patents held on
?ioPerine are 8,88):,85:, 8,$22,#:#, 8,&$3,)43 and :,582,
relate to increase the bioavailability of nutritional cop
aking high purity piperine for nutritional use. 1arious studies have
proven the effectiveness of ?ioPerine and soe showed that
absorption levels were increased up
reported that it will aintain a healthy colon and gives
against colon cancer. =attanathorn
anti-depression like activity and
Guar et al.+)8, showed that it ay cont
allergic properties.
Int Pharm Pharm !ci" #$l %" Issue 4" &4'&(
)8
suitable to address the proble. Co to circuvent the above crises,
opagation and gene transfer are very
<aAor weakness responsible for low productivity of
availability of healthy planting aterial and
crop losses due to abiotic and biotic stresses +#4,. ;n addition to this,
yield of these species are endogenous
icrobial containation and very slow growth rate of cultures.
Dstablishent of containation free plants fro greenhouse grown
plants was very difficult due to endogenous icrobial containation
Piper methysticum +#&,.
e<traction of piperine
applications in food and phara industries,
extracted in a pure for which is free fro residual
t use in edicinal forulations and food
rial scale, pepper is coinuted into flakes or
ground into coarse powder and then extracted repeatedly with an
organic solvent such as acetone, ethanol or chlorinated
onger duration of repeated solvent
action of raw pepper particles results in the extraction of other
gus, polysaccharides and non-flavour
substances. This type of solvent extraction process usually gives
which have to be purified further by
ultistep techniques such as chroatography or crystallization.
pressure stea treatent can also be used to extract piperine
by an osotic shock9 however, this technique is relatively slow and
aount of stea +3#,. 0aan and @aiker+33,.
by hydrotropic extraction and showed
potential for cell pereabilization and
selective extraction of bioactive copounds on a coercial scale.
reported that supercritical fluid extraction
has ore extraction efficiency and reduced extraction tie than
soxhlet extraction ethod. The B w6w yield of piperine in
supercritical fluid extract was 4.$: for P.nigrum and 2.&: for
in 5.8 hr tie period, whereas in the case of Coxhlet
nigrum was 4.#) and for P.longum was
he yield of piperine was found to be
copared to P.longum.
and quantification of piperine following ethods
E1 spectrophotoetry +3),, T7"-E1 densitoetry
+3$-34,. <ukherAee +3&, showed that,
piperine content in fruits of P.nigrum and P.longum was )-:B
#.:B by %P7" technique. Cantosh et al.+)5, reported that
content of piperine in fruit and root of P.longum was 5.4$&B and
was 2.8B by 0P-%P7" analysis. %u et
showed that the total yield of piperine in the root of P.nigrum
techniqueH separately, 5.&&B in the thin
root !5.8 c in dia.* and 5.#2B in the thick root !) c in dia.*9
in the cortex and 5.3&B in the stele of a root in dia. of 3
The average content of piperine in three
batches of pepper roots was in the range of :.:$:.$$gIg-#.
reported that this alkaloid can be quantified
excellent accuracy with in short tie period through %PT7"
The accuracy values obtained were in the range of &$.38B
and &:.85B to &$.85B in P.longum.
The natural extract fro black pepper is arketed under the
and has unique distinction of having four
this unique ingredient. The patents held on
?ioPerine are 8,88):,85:, 8,$22,#:#, 8,&$3,)43 and :,582,848. They
bioavailability of nutritional copounds and
aking high purity piperine for nutritional use. 1arious studies have
the effectiveness of ?ioPerine and soe showed that
absorption levels were increased up to :5B. Juessel et al. +)),
aintain a healthy colon and gives protection
on cancer. =attanathorn et al.+)2, showed that it has
depression like activity and cognitive enhancing properties.
it ay contain antibacterial and anti-
Vaa$irama et al.
Int Pharm Pharm !ci" #$l %" Issue 4" &4'&(
):

Application of piperine
Piperine has diverse biological and therapeutic activities. ;t can
draatically increase the absorption of seleniu, vitain ? and K-
carotene as well as other nutrients +):,. ;t can stiulate pancreatic
and intestinal digestive enzyes and also increases biliary bile acid
secretion when orally adinistrated +)$,. ;t prevents and iniizes
diarrhoea produced by various oil and also reduces the intestinal
fluid accuo-latin in ouse intestine +)4,. ;n addition to its
involveent in increasing the absorption of other nutrients in the
body, piperine has other novel applications like helping to fight
against colon cancer. ;t has anti-inflaatory, therogenic, growth
stiulatory, anti-thyroid and cheo preventive activities +)&,. This
also displays antipyretic, analgesic, insecticidal, iuno-
odulatory, antituor, anti-depressant and anti-apoptotic activities
+25-22,.

;t is involved in inhibition of hepatic drug etabolis +28,,
enhancing pentobarbitone induced hypnosis+2:,, bioavailability of
oxyphenyl butazone +2$,, hepatoprotective activity +24,, inhibition
of lipid peroxidation during experiental inflaation +2&,,
antifertility +85, and radio protective effects +8#,. ;t has also been
shown to have analgesic, anti-convulsant, anti-arthritic, anti-ulcer,
antioxidant activities and cytoprotective effects +83-8$,. ;n a recent
study, =attanathorn et al. +)2, deonstrated that piperine also
affects ood and cognitive disorder. Gapoor et al. +84, recently
deonstrated that the protective effect of piperine is ost likely due
to its antioxidant activity. ;t provides protection against seizures in
epilepsy and gained increased attention as a bioavailability enhancer
in the forulations of several drugs +8&-:5,. ?ecause of its
protective effect against radiation, it can also be adinistered to
cancer patients before radiotherapy +:#,. ;t has been found to inhibit
huan "LP)A2, P-glycoprotein and enzyes iportant for
etabolis and transport of xenobiotics and etabolites +:3,.
Darlier anial studies reported that, piperine can inhibit other
enzyes iportant for drug etabolis +:)-:2, and in this way by
inhibiting drug etabolis it ay increase the bioavailability of
various copounds and alter the effectiveness of soe edications
+:),. 'otably, piperine enhanced bioavailability of curcuin by
3555B in huans +:8,. "heo preventive efficacy of curcuin and
piperine has been shown during $,#3-diethylbenz+a, anthracene-
induced haster buccal pouch carcinogenesis +::,. 0ecently, it was
reported that piperine can enhance the pharacokinetic paraeters
of resveratrol by inhibiting its glucuronidation, thereby slowing its
eliination +:$,. Coe researchers discovered that piperine can
stiulate pigentation in the skin, together with the exposure to
E1? light +:4,. Toxicity and syptos of high intake of piperine was
not noticed. Piperine ay be required in ore quantity during ties
of stress.
%oncl!ion an( f!t!re (irection
This review collectively presents source, extraction, significance
along with applications of piperine in different food and
pharaceutical industries. Piperine is an alkaloid present in the
fruits and roots of P.nigrum and P.longum species of Piperaceae
faily, which contributes pungent quality to the. The two species
are valued for the presence of this iportant alkaloid and are used
edicinally to cure digestive and respiratory disorders. Piperine can
be extracted by using an organic solvent like acetone or ethanol and
quantified with excellent accuracy through %PT7" ethod. ;t has
various applications in food and pharaceutical industries. ;t is used
as a bioavailability enhancer to increase the availability of seleniu,
vitain ?, K-carotene and other nutritional copounds. ;n addition,
it possesses anti-inflaatory, therogenic, growth stiulatory,
anti-thyroid activities and also acts as a cheo preventive agent.
This also displays antipyretic, analgesic, insecticidal, iune-
odulatory, antituor, anti-depressant, anti-apoptotic,
anticonvulsant, anti-arthritic, anti-ulcer, antioxidant and
cytoprotective effects. 0ecently it has been shown that, this also
affects ood and cognitive disorder and acts as a bioavailability
enhancer in the forulations of several drugs. <ultiple activities
exhibited by this alkaloid can be attributed to prepare large nuber
of edical forulations in pharaceutical industries. This review
can provide treendous knowledge to conduct research related to
this valuable natural product.
%)N*LI%"# )* IN"ERE#"
The authors do not have any conflict of interest to declare.
A%&N)>LEDGE,EN"#
The authors acknowledge the support of Jepartent of
?iotechnology, @ita ;nstitute of Technology, @ita Eniversity,
1isakhapatna, ;ndia and Jepartent of Plant Cciences, Eniversity
of %yderabad, %yderabad to coplete this review.
ABBREVIA"I)N#
%P7" %igh perforance liquid chroatography
0P-%P7" 0everse phase high perforance liquid chroatography
%PT7" %igh perforance thin layer chroatography
T7"-E1 Thin layer chroatographic- Eltraviolet
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)4

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