A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices

Abstract

Medicinal plants are very popular in different traditional systems of medicines due to their diverse
pharmacological potentials and lesser side effects in biological systems. Piper nigrum L. (Family Piperaceae)
is a well known spice considered as ‘‘The King of spices’’ among various spices. It contains a pungent alkaloid
‘‘piperine’’ which is known to possess many pharmacological actions. Piperine increases bioavailability of
many drugs and nutrients by inhibiting various metabolising enzymes. Piper nigrum L and its active constituent
‘’Piperine’’exhibits diverse pharmacological activities like antihypertensive, antiplatelet, antioxidant, antitumor,
anti-asthmatics, analgesic, anti-inflammatory, anti-diarrheal, antispasmodic, antidepressants, immunomodulatory, anticonvulsant, anti-thyroids, antibacterial, antifungal, hepato-protective, insecticidal and larvicidal activities etc. The current review article is aimed to provide an updated literature review on recent advancement of pharmacognosy, chemistry and pharmacological activities of Piper nigrum L.

Full text

Research Article Open Access
Volume 3 • Issue 3 • 1000161
Med Aromat Plants
ISSN: 2167-0412 MAP, an open access journal
Open Access
Review Article
Medicinal & Aromatic Plants
Damanhouri and Ahmad, Med Aromat Plants 2014, 3:3
http://dx.doi.org/10.4172/2167-0412.1000161
*Corresponding author: Zoheir A Damanhouri, Department of Pharmacology,
Faculty of Medicine, King Abdulaziz University, P.O.Box 80205, Jeddah 21589,
Saudi Arabia. Tel: +966507770848; E-mail: zdamanhouri@kau.edu.sa
Received May 02, 2014; Accepted July 30, 2014; Published August 04, 2014
Citation: Damanhouri ZA, Ahmad A (2014) A Review on Therapeutic Potential of
Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat Plants 3: 161. doi:
10.4172/2167-0412.1000161
Copyright: © 2014 Damanhouri ZA, et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided
the original author and source are credited.
A Review on Therapeutic Potential of
Piper nigrum
L. (Black Pepper): The
King of Spices
Zoheir A Damanhouri1* and Aftab Ahmad2
1Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
2Health Information Technology Department, Jeddah Community College, King Abdulaziz University, Jeddah-21589, Kingdom of Saudi Arabia
Keywords: Piper nigrum; Black pepper; Piperaceae; Piperine;
Bioavailability; Antioxidant
Introduction
Piper nigrum (family Piperaceae) is a valuable medicinal plant. It is
one of the most commonly used spices and considered as ’’e King of
spices’’ among various spices. Black pepper is grown in many tropical
regions like Brazil, Indonesia and India. Piper nigrum is commonly
known as Kali Mirch in Urdu and Hindi, Pippali in Sanskrit, Milagu
in Tamil and Peppercorn, White pepper, Green pepper, Black pepper,
Madagascar pepper in English. Hot and pungent peppercorns are
obtained from Black pepper which is the most famous and one of the
commonly used spices throughout the world. Black pepper is used as
medicinal agent, a preservative, and in perfumery. Whole Peppercorn of
Piper nigrum or its active components are being used in dierent types
of foods and as medicine. Pepper is used worldwide in dierent types of
sauces and dishes like meat dishes. It contains major pungent alkaloid
Piperine (1-peperoyl piperidine, Figure 1) which is known to possess
many interesting pharmacological actions. It is widely used in dierent
traditional systems of medicine like Ayurvedic and Unani System of
medicines [1, 2]. Piperine exhibits diverse pharmacological activities like
antihypertensive and antiplatelets [3], antioxidant, antitumor[4], anti-
asthmatics [5], antipyretic, analgesic, anti-inammatory, anti-diarrheal,
antispasmodic, anxiolytic, antidepressants [6], hepato-protective[7],
immuno-modulatory, antibacterial, antifungal, anti-thyroids, anti-
apoptotic, anti-metastatic, antimutagenic, anti-spermatogenic, anti-
Colon toxin, insecticidal and larvicidal activities etc. Piperine has been
found to enhance the therapeutic ecacy of many drugs, vaccines
and nutrients by increasing oral bioavailability by inhibiting various
metabolising enzymes [8]. It is also known to enhance cognitive action
and Fertility [9]. Piperine also found to stimulate the pancreatic and
intestinal enzymes which aid to digestion. Many therapeutic activities
of this spice are attributed to the presence of piperine apart from other
chemical constituents. e fruits of Piper nigrum are used to produce
white and green peppers. Piper nigrum is also used as a avoring agent [1].
In recent pasts, dierent therapeutic potentials of Piper nigrum,
its extracts, or its important active chemical constituent ‘’piperine’’
have been published in dierent international research journals.
e current review is aimed to provide an updated literature review
on recent research advancement of pharmacognosy, chemistry and
pharmacological activities of Piper nigrum L. We have compiled a
review on therapeutic potential of Piper nigrum by collecting updated
scientic research informations from internet using Google search
engine and Pubmed.
Pharmacognosy of the Piper nigrum
Taxonomical Classication of Piper nigrum:
Kingdom: Plantae
Class: Equisetopsida
Sub class: Magnoliidae
Super order: Magnolianae
Order: Piperales
Family: Piperaceae
Genus: Piper
Species: nigrum
Pharmacognostical Characteristics
Piper nigrum (Black pepper) plant is a owering woody perennial
climbing vine that belongs to Piperaceae family. Pepper plants
easily grow in the shade on supporting trees, trellises or poles up to
maximum height of 13 feets or 4 meters and roots may come out from
leaf nodes if vine touch to the ground. e plants have heart shape
Abstract
Medicinal plants are very popular in different traditional systems of medicines due to their diverse
pharmacological potentials and lesser side effects in biological systems. Piper nigrum L. (Family Piperaceae)
is a well known spice considered as ‘‘The King of spices’’ among various spices. It contains a pungent alkaloid
‘‘piperine’’ which is known to possess many pharmacological actions. Piperine increases bioavailability of
many drugs and nutrients by inhibiting various metabolising enzymes. Piper nigrum L and its active constituent
‘’Piperine’’exhibits diverse pharmacological activities like antihypertensive, antiplatelet, antioxidant, antitumor,
anti-asthmatics, analgesic, anti-inammatory, anti-diarrheal, antispasmodic, antidepressants, immunomodulatory,
anticonvulsant, anti-thyroids, antibacterial, antifungal, hepato-protective, insecticidal and larvicidal activities
etc. The current review article is aimed to provide an updated literature review on recent advancement of
pharmacognosy, chemistry and pharmacological activities of Piper nigrum L.

Citation: Damanhouri ZA, Ahmad A (2014) A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat
Plants 3: 161. doi: 10.4172/2167-0412.1000161
Page 2 of 6
Volume 3 • Issue 3 • 1000161
Med Aromat Plants
ISSN: 2167-0412 MAP, an open access journal
alternate leaves with typically large size of 5-10 cm in length and
3-6 cm across, with 5 to 7 prominent palmate veins. e owers are
small, monoecious with separate male and female owers but may be
polygamous which contain both male and female owers. e small
owers are borne on pendulous spikes at the leaf nodes that are nearly
as long as the leaves. e length of spikes goes up to 7-15 cm. e black
pepper’s fruits are small (3 to 4 mm in diameter) called a drupe and
the dried unripe fruits of Piper nigrum are known as a peppercorn. e
fully mature fruits are dark red in color and approximately 5 mm in
diameter. A fruit contains a single seed. e plants bear fruits from 4th
or 5th year, and continue to bear fruits up to seven years. A single stem
contains 20-30 spikes of fruits. e collected spikes are sun dried to
separate the peppercorns from the spikes. e fresh harvested unripe
green fruits may freeze-dry to make green pepper. e fresh harvested
unripe green fruits may sun-dried to make black pepper. e red skin
of the ripen fruits is removed and the stony seeds are sun-dried to
make white pepper [10].
Chemical Composition of Piper nigrum
e phytochemical investigations of P. nigrum revealed
that it contains variety of phytochemicals. Piperine was the rst
pharmacologically active compound isolated from dierent members
of Piperaceae family. Many investigators isolated dierent types of
compounds viz Phenolics, avonoids, alkaloids, amides and steroids,
lignans, neolignans, terpenes, chalcones etc and many other compounds.
Some of the compounds are Brachyamide B, Dihydro-pipericide,
(2E,4E)-N-Eicosadienoyl-pereridine, N-trans-Feruloyltryamine,
N-Formylpiperidine, Guineensine, pentadienoyl as piperidine, (2E,4E)-
Nisobuty- ldecadienamid, isobutyl-eicosadienamide, Tricholein,
Trichostachine, isobutyl-eicosatrienamide, Isobutyl-octadienamide,
Piperamide, Piperamine, Piperettine, Pipericide, Piperine, Piperolein
B, Sarmentine, Sarmentosine, Retrofractamide A Figure 1. e
dierent pharmacological activities were reported due to the presence
of these phytochemicals. Piperine reported to have four isomers viz;
Piperine, Isopiperine, Chavicine and Isochavicine. Among all isolated
compounds isolated from P. nigrum. Piperine, pipene, piperamide and
piperamine were found to possess diverse pharmacological activities
[1,11].
Evidence Based Pharmacological Activities
An attempt has been made to collect updated research information
on Piper nigrum from the internet using Google search engine and
PubMed. Many researchers carried out their researches on Piper nigrum
& its active constituent ‘’piperine’’ using latest sophisticated scientic
technologies and Important Pharmacological activities of Piper nigrum
and piperine are summarized in Table 1. Some of the pharmacological
O
O
N
O
4
3-Piperamide
O
O
R
O
2-Piperamine
n
O
O
N
H
O
4
4-Pipericide
O
O
1-Piperine
R
O
O
2
5-Sarmentosine
N
O
N
O
4
O
O
7-Trichosta
N
O
n
6-Sarmentine
Figure 1: Important chemical constituents of P. nigrum.
S. No. Activities References
1 Antihypertensive activity 3
2 Anti-asthmatic activity 5
3 Cognitive action and Fertility activity 9
4 Antimicrobial activity 12, 13
5 Antioxidant activity 14, 16, 17, 18, 25
6Anti-cancer activity 4, 15,16,19,20, 21,26
7Anti-inammatory activity 22
8 Hepatoprotective activity 7, 23
9 Anti-diarrheal activity 24
10 Digestive activity 25,26,27,28, 29
11 Antidepressant activity 6, 30
12 Immunomodulatory activity 31,32
13 Anticonvulsant activity 33, 34
14 Analgesic activity 34
15 Effect of piperine on metabolism 2, 8
Table 1:Pharmacological activities of Piper nigrum L (Black Pepper)

Citation: Damanhouri ZA, Ahmad A (2014) A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat
Plants 3: 161. doi: 10.4172/2167-0412.1000161
Page 3 of 6
Volume 3 • Issue 3 • 1000161
Med Aromat Plants
ISSN: 2167-0412 MAP, an open access journal
activities of Piper nigrum are discussed below.
Antimicrobial activity of black pepper
Khan and Siddiqui in 2007 evaluated the antibacterial potential
of aqueous decoction of Piper nigrum L. (black pepper), Laurus
nobilis L. (bay leaf), Pimpinella anisum L. (aniseed), and Coriandum
sativum L. (coriander) against dierent bacterial isolates from oral
cavity of two hundred individual volunteers. Black pepper (aqueous
decoction) showed strongest antibacterial activity comparable to
aqueous decoction of Laurus nobilis and Pimpinella anisum at the
concentration of 10μL/disc [12]. In a recent study, the silver nano-
particles from leaf and stem extract of Piper nigrum were synthesized
and then antibacterial activity of the synthesized silver nanoparticles of
Piper nigrum was evaluated against agricultural plant pathogens. ese
silver nano-particles showed the excellent antibacterial activity against
plant pathogens. Authors concluded that the antibacterial activity of
silver nano-particles is a benecial application in crop improvement
and protection in agricultural nanotechnology [13].
Antioxidant activity of black pepper
Free radicals cause many diseases. Dierent free radicals attack on
membranes causing oxidation of lipids, loss of dierent enzyme activities
and may cause cancer. Antioxidants completely stop or delay the
process of oxidation. Antioxidant protection system includes enzymes
like Ascorbate, Catalase, Peroxidase and Superoxide dismutase which
scavenge both radicals and related non radical oxygen species. Plants
are important source of antioxidants. Some in vitro studies revealed that
Piperine inhibited free radicals and reactive oxygen species, therefore
known to possess protective eects against oxidative damage. Piper
nigrum or piperine also found to decrease lipid peroxidation in vivo.
Piper nigrum reported to possess antioxidant activity that might be due
to the presence of avonoids and phenolic contents. Piper nigrum was
found to prevent the oxidative stress by inhibiting lipid peroxidation,
human lipoxygenase and arresting hydroxyl and superoxide free
radicals, decrease lung carcinogenesis in animal studies. e memory-
enhancing and antioxidant proprieties of the methanolic extract of Piper
nigrum L. fruits at a doses of 50 and 100 mg/kg, orally, for 21 days in
amyloid beta (1-42) were investigated in Alzheimer’s disease model in
rats [14-16]. e memory-enhancing eects of the extract were studied
by means of in vivo (Y-maze and radial arm-maze tasks) approaches.
While, the antioxidant activity was evaluated by measuring activities
of glutathione peroxidase, catalase, superoxide dismutase, and by
measuring the total content of reduced glutathione, malondialdehyde,
and protein carbonyl levels in the hippocampus. e amyloid beta
(1-42)-treated rats showed the diminishing of spontaneous starvariation
percentage within Y- maze task and enhancement of work memory and
reference memory errors within radial arm-maze task. Administration
of the methanolic extract of Piper nigrum signicantly improved
memory performance and exhibited antioxidant potential. ese studies
suggest that methanolic extract of Piper nigrum ameliorates amyloid
beta (1-42)-induced spatial memory deterioration by depletion of the
oxidative stress in the hippocampus of rats [17]. e antioxidant eect
of three Piper species viz P. nigrum, P. guineense and P. umbellatum was
evaluated for the protection of renal, cardiac, and hepatic antioxidant
status in atherogenic diet fed hamsters. Animals were fed atherogenic
diet addition with dierent doses of Piper species viz P. nigrum, P.
guineense and P. umbellatum at a dose of 1 g/kg and 0.25 g/kg for 12
weeks. Piper species signicantly inhibited the atherogenic diet induced
increased lipid prole and alteration in antioxidant enzymes activities.
is study showed an antioxidant protective role of the extracts of Piper
species against atherogenic diet induced oxidative stress in renal, cardiac
and hepatic tissues [18].
Anti-cancer activity of black pepper:
Piper nigrum had been reported to inhibit tumors formation in
dierent experimental models. Many studied revealed the antitumor
activity of P. nigrum or Piperine by the oral administration. e
alcoholic extract of peppercorn and piperine exhibited eective
immunomodulatory and antitumor activities. Piperine is also reported
to reduce the lung cancer by altering lipid peroxidation and by
antioxidative protection enzymes activation [1,15-16]. Piperine has
distinct pharmacological activities along with Anti-cancer activity.
Piperine was reported to inhibit G1/S transition and the proliferation
of human umbilical vein endothelial cells (HUVECs), migration of
HUVECs and in vitro formation of tubule and angiogenesis induced by
collagen and breast cancer cell in chick embryos. Piperine also inhibits
the phosphorylation of r 308 residues of Akt of protein kinase B as
well as Ser 473. Since phosphorylation of these is an essential controller
of angiogenesis and function of endothelial cells. erefore, Piperine
may beused as an inhibitor of the angiogenesis for the treatment of
cancer as angiogenesis plays a key role in the progression of tumor [19].
Docetaxel (a cytotoxic chemotherapeutic agent) is a FDA approved
drug for the treatment for castration-resistant prostate cancer. e
metabolism of docetaxel occurs in the liver by hepaticCYP3A4, and
piperine is reported to inhibit the hepatic CYP3A4 enzymatic activity.
erefore, the administration of docetaxel in combination with
piperine was investigated for both in vitro and in vivo pharmacokinetic
activity of docetaxel. It was also reported that nutritional use of piperine
increased the ecacy of docetaxel in a xenogra model devoid of any
side eects on the mice [20].
e anticancer activity of piperine against many cancer cell lines
has been reported earlier. erefore, the mechanisms of anticancer
activity of piperine against both androgen independent and dependent
cells of prostate cancer were investigated. e proliferation of LNCaP,
22RV1, PC-3, and DU-145 prostate cancer cells was found to be dose
dependently inhibited by piperine. Piperine treatment was also found
to induce apoptosis, by the activation of caspase-3 and by the cleavage
of PARP-1 proteins in dierent prostate cancer cells like PC-3, DU-145
& LNCaP prostate cancer cells. Treatment with piperine also found to
disrupt the androgen receptor expression in LNCaP prostate cancer
cells and cause signicant diminutionin the level of Prostate Specic
Antigen in LNCaP cells. e expression of phosphorylated STAT-3 and
Nuclear factor-κB transcription factors were reduced in LNCaP, PC-3
and DU-145 prostate cancer cells aer treatment of with piperine. ese
results suggested that there was a signicant reduction in the androgen
dependent and independent growth of tumor in naked mice model of
xeno-transplanted with prostate cancer cells aer treatment of piperine
[21]. Piperine is non-genotoxic and found to possess anti-mutagenic
and anti-tumor inuences.
Anti-inammatory activity of black pepper:
e piperine was evaluated for the anti-inammatory, analgesic,
and anti-arthritic activities. e in vitro anti-inammatory activities
were evaluated on interleukin 1β stimulated broblast like synoviocytes
obtained from rheumatoid arthritis, while anti-arthritic including
analgesic activities were evaluated on carrageen an induced acute
paw model of pain and arthritis in rats. e prostaglandin E2,
cyclooxygenase 2, interleukin 6 and matrix metallo-proteinase levels
were evaluated by ELISA and RT-PCR methods of analysis. Piperine
treated groups were found to reduce the synthesis of prostaglandin E2 in

Citation: Damanhouri ZA, Ahmad A (2014) A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat
Plants 3: 161. doi: 10.4172/2167-0412.1000161
Page 4 of 6
Volume 3 • Issue 3 • 1000161
Med Aromat Plants
ISSN: 2167-0412 MAP, an open access journal
a dose dependant comportment at the concentrations of 10-100 μg/mL.
It signicantly inhibited the synthesis of prostaglandin E2 even at 10 μg/
mL. e expression of interleukin 6 and matrix metallo-proteinase 13
were also inhibited. e migration of activator protein1into the nucleus
in interleukin 1β treated synoviocytes was inhibited by piperine while
migration of nuclear factor κB was not aected by piperine. e pain
and arthritic symptoms in rats were signicantly reduced by piperine. It
was concluded that piperine showed anti-inammatory, analgesics and
anti-arthritic activities in arthritis model of rats [22].
Hepatoprotective activity of black pepper:
It was found that piperine inhibited the increased level of serum
GPT and GOT in dose-dependent manner in a hepato-toxicity model
of mice caused by D-galactosamine. e hepatoprotective activity of
methanolic extract of Piper nigrum fruits was evaluated in ethanol-
CCl4 induced hepatic damage in Wistar rats. Ethanol-CCl4was used
to induce hepatotoxicity in the rats. Prophylactic treatment with
methanolic extract of Piper nigrum at a dose of 100 and 200 mg/kg
body weight, p.o. and pre-treatment with piperine at a dose of 50 mg/kg
body weight, p.o. for 15 days with Ethanol-CCl4 treatment rats showed
signicant liver protection as evidenced from the triglycerides levels,
Alanine transaminase, Aspartate transaminase, alkaline phosphatase,
bilirubin and superoxide dismutase, Catalase, Glutathione reductase
and Lipid peroxidation levels to assess the liver functions. In this
study, administration of Ethanol-CCl4 exhibited signicant boost in
triglycerides, Alanine transaminase, Aspartate transaminase, alkaline
phosphatase, and bilirubin levels while there was signicant decrease
in the superoxide dismutase, catalase, and glutathione reductase levels
which were restored to normal level aer pre-treatment of methanolic
extract of Piper nigrum and Piperine. Lipid peroxidations were also
signicantly decreased aer pretreatment with methanolic extract of
Piper nigrum and Piperine at given doses. e results were similar to
that of reference standard-Liv52 at a dose of 1 mL/kg, p.o. for 15 days.
e Morphological and histopathological studies of liver were also
supportive of the biochemical parameters. us it is concluded that
Piper nigrum possesses potential hepato-protective activity due to the
presence of piperine alkaloids and have great therapeutic potential in
treatment of liver ailments [23].
Anti-diarrheal activity of black pepper:
Aqueous back pepper extract (ABPE) at a dose of 75, 150, 300 mg/
kg, po was evaluated for anti-diarrheal, anti-motility and anti-secretory
activity in mice. e castor oil and magnesium sulphate were used
to induce diarrhea for the evaluation of anti-diarrheal activity and
gastrointestinal motility was assessed by charcoal meal, while castor oil
was used for the evaluation of anti-motility and anti-secretory activities.
ABPE showed a signicant and dose dependent anti-diarrheal, anti-
motility and anti-secretary eect. Anti-motility and anti-secretory
activities of Piper nigrum might be due to the presence of carbohydrates
and alkaloids, and anti-diarrheal activity of ABPE may be due to its
anti-motility and anti-secretory activities [24].
Digestive activity of black pepper
Many spices are known for their digestive stimulant action. Dietary
piperine enhances digestion by stimulation of the pancreatic enzymes
and considerably decreases the food transit time of gastrointestinal
tract. Piperine have been reported to increases the saliva production
and gastric secretions, and increases the production and activation of
salivary amylase. e orally administration of piperine or P. nigrum
stimulate the liver to the secrete bile acids which in turn play key role
in the absorption and digestion of fats. e oral administration of
active compounds like piperine, pipene, piperamines and piperamides
signicantly increases the activities of enzymes like pancreatic amylase
activity, protease activity, lipase activity and chymotrypsin activation
[25,26]. An inuence on digestive enzymes of intestinal mucosa
were examined in experimental rats by Platel K and Srinivasan. e
animals were fed with piperine (20 mg%) which signicantly increased
the activity of intestinal lipase, disaccharidases sucrase and maltase
enzymes [27]. In another study, Platel K and Srinivasan evaluated the
inuence of piperine (20 mg%) on digestive enzymes of pancreas in
experimental rats. Dietary piperine (20 mg%) signicantly stimulated
the activities of pancreatic lipase, amylase, trypsin and chymotrypsin
[28]. e inuence of some spices included in the diet, on food transit
time was examine in adult female Wistar rats. Animals were maintained
for 6 weeks on diets containing piperine (0.02 g%). e ferric oxide
(0.5%) was included in the diet as an un-absorbable marker to monitor
the food transit time. Time of excretion of colored stool was noted
to follow the time of consumption of the diet with the marker. e
piperine (0.02 g%) signicantly shortened the food transit time [29].
Antidepressant activity of black pepper
e antidepressant-like eect of piperine and its possible
mechanisms was evaluated in corticosterone-induced model of
depression in mice. Depression-like behavior in mice was developed
aer 3 weeks corticosterone injections. e depression was revealed
by the signicant reduction in sucrose utilization and augmentation in
immobility time in the forced swim test and tail suspension test. Further,
the brain-derived neurotrophic factor protein and mRNA levels in the
hippocampus were also signicantly decreased in corticosterone-treated
mice. Corticosterone induced the behavioral and biochemical changes
were signicantly diminished aer treatment to animals with Piperine.
ese results showed that piperine produces an antidepressant-like
eect in corticosterone-induced model of depression in mice [30].
Immuno-modulatory activity of black pepper
Immuno-modulatory and antitumor activity of piperine was
evaluated. Piperine (250 µg/mL)was reported to be cytotoxic to Ehrlich
ascites carcinoma cells and Dalton’s lymphoma ascites. Piperine at
a concentration of 50 µg/mL showed cytotoxicity to L929 cells in
culture. Piperine administration also causes an increase in the total
WBC counts in Bal b/c mice. Administrations of piperine were also
increase the bone marrow cellularity and alpha-esterase positive cells
[31]. In vitro immunomodulatory activity of piperine was evaluated to
enhance the ecacy of rifampicin in a murine model of Mycobacterium
tuberculosis infection. Mouse splenocytes were used to evaluate in-vitro
immunomodulation of piperine for cytokine production, macrophage
activation and lymphocyte proliferation. Piperine treated mouse
splenocytes demonstrated an increase in the secretion of -1 cytokines
(IFN-γ and IL-2), increased macrophage activation and proliferation of
T and B cell. Protective ecacy of piperine and rifampicin (1 mg/kg)
combination against Mycobacterium tuberculosis was reported due to
immuno-modulatory activity [32].
Anticonvulsant activity of black pepper
e Anticonvulsant activity of piperine in maximal electroshock
(MES) and pentylenetetrazol (PTZ) models of convulsions in
mice was examined and further participation of transient receptor
potential cation channel subfamily V member 1 (TRPV1) receptor
was acknowledged in the inhibition of convulsion caused by
pentylenetetrazol and maximal electroshock models. A signicant

Citation: Damanhouri ZA, Ahmad A (2014) A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat
Plants 3: 161. doi: 10.4172/2167-0412.1000161
Page 5 of 6
Volume 3 • Issue 3 • 1000161
Med Aromat Plants
ISSN: 2167-0412 MAP, an open access journal
delay in the onset of myoclonic jerks and generalized clonic seizures
was observed aer administration of Piperine at doses of 40 and 80
mg/kg and Piperine also diminish the seizure stage and mortality as
compare to the animals treated with vehicle. A signicant reduction
was also observed in the incidence of MES-induced tonic hind limb
extension (THE) and PTZ-induced Fos immune reactivity in the
dentate gyrus aer of piperine administration. Capsazepine (TRPV1-
selective antagonist) blocked the anti-seizure eects of piperine. ese
data reveals the anti-convulsant activity of piperine [33]. In another
study, in vivo anticonvulsant activity of piperine was evaluated in
pentylenetetrazole (PTZ) and picrotoxin (PIC)-induced seizures
models of epilepsy in mice. A signicant (P<0.01) delayedin the onset
of PTZ-and PIC-induced seizures was observed aer intra-peritonial
injection of piperine at a dose of 30, 50 and 70 mg/kg (i.p.), valproic
acid at a dose of 200 mg/kg, Carbamazepine at a dose of 30 mg/kg
and diazepam at a dose of 1 mg/kg in mice. ese results revealed the
anticonvulsant eects of piperine which possibly mediated via GABA-
ergic pathways [34].
Analgesic activity of black pepper
In vivo analgesic activity of piperine in mice was evaluated. e
acetic acid-induced writhing and tail ick assay models in mice
were used to evaluate the analgesic activity of piperine. ere was
a signicant (P<0.01) inhibition in the acetic acid-induced writhing
in mice aer intra-peritoneal (i.p.) administration of piperine at a
dose of 30, 50 and 70 mg/kg as compared with in domethacin at a
dose of 20 mg/kg (i.p.). Intra-peritoneal injection of piperine at dose
of 30 and 50 mg/kg and intra-peritoneal injection of morphine at
dose of 5 mg/kg signicantly (P<0.01) increase in the reaction time
of mice in the tail ick assay. e analgesic activities of both piperine
and morphine in the tail ick assay were reversed on pre-treatment
of animals with naloxone at dose of 5 mg/kg (i.p.). ese results
revealed the analgesic activity of piperine which possibly mediated
via opioid pathway [34].
Eect of Piperine on metabolism: a bioavailability enhancer
Piperine has shown bioavailability enhancing eects on many
therapeutically important drugs and nutrients. Piperine increases the
absorption of many drugs and nutrients from the gastrointestinal tract
by various mechanisms. It alters the membrane dynamics and increases
permeability at site of absorption. Piperine increases the serum half
lives of some substances like beta-carotene and coenzyme Q10 and
decreases metabolism of many drugs by inhibiting various metabolizing
enzymes like cytochrome BS, CYP3A4, NADPH cytochrome, UDP-
glucuronyl transferase, UDP-glucose dehydrogenase (UDP-GDH),
and aryl hydrocarbon hydroxylase (AAH). ese enzymatic inhibition
by piperine resulted in increased bioavailability of many drugs and
nutrients e.g. amoxicillin, ampicillin, acefotaxime, carbamazepine,
ciprooxacin, noroxacin, metronidazole, oxytetracyclin, nimesulide,
pentobarbitone, phenytoin, resveratrol, beta-carotene, curcumin,
gallic acid, tiferron, nevirapine, and sparteine by dierent types of
mechanisms. erefore, piperine is known as bioavailability enhancer
and a potent drug’s metabolism inhibitor [2].
Other pharmacological activities
Piper nigrum (Black Pepper) or pure compound ‘‘Piperine’’
exhibits many more Pharmacological activities like antihypertensive,
antiplatelets, antipyretic, antispasmodic, antifungal, anti-apoptotic,
anti-metastatic, antimutagenic, anti-spermatogenic, anti-Colon toxin,
anti-asthmatics, anti-anxiety, antithyroids, antifungal, insecticidal and
larvicidal activities etc [1-5].
Conclusion
Many original research articles on the pharmacological potential
of Piper nigrum (Black Pepper) or ‘‘Piperine’’ had been published so
far. It was revealed from these articles that Black Pepper possesses
signicant in vitro and in vivo pharmacological potential for the
treatment of dierent ailments and diseases and found to be safe.
Piperine has also been found to increase the absorption of many
drugs and shown bioavailability enhancing activity of many drugs and
nutrients. is important property of piperine may be very helpful to
enhance the therapeutic ecacy of many therapeutically important
drugs. It is therefore concluded that Black pepper and its bioactive
compound Piperine exhibited wide spectrum therapeutic potential
and also emerged as an excellent adjuvant to enhance the therapeutic
ecacy of the concurrently administered drugs and nutrients. Further
detailed research studies are needed to obtain more scientic data on
this miraculous King of spices.
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Citation: Damanhouri ZA, Ahmad A (2014) A Review on Therapeutic Potential of Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat
Plants 3: 161. doi: 10.4172/2167-0412.1000161
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Volume 3 • Issue 3 • 1000161
Med Aromat Plants
ISSN: 2167-0412 MAP, an open access journal
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Citation: Damanhouri ZA, Ahmad A (2014) A Review on Therapeutic Potential
of Piper nigrum L. (Black Pepper): The King of Spices. Med Aromat Plants 3:
161. doi: 10.4172/2167-0412.1000161