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The medical uses of pepper

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1
THE MEDICINAL USES OF PEPPER
Dr. Majeed and Prakash, L.
The Medicinal Uses of Pepper. International Pepper News.
Vol XXV, No. 1 Jan-Mar 2000. 23-31.
The history of the Pepper family
Members of the botanical family Piperaceae were
among the first cultivated plants1. Black pepper (Piper
nigrum) and long pepper (Piper longum) are the best
known species in this family and are probably among
the most recognized spices in the world. Black pepper
alone accounts for about 35% of the world’s total spice
trade. In addition, black pepper and long pepper have
been used medicinally for centuries In recent years,
extensive research data on the phytochemistry and
unique pharmacological actions of these plants have
also become available.
The Materia Medica of Ayurveda, which dates back to
6,000 B.C., has many references advocating the use of
pepper in a variety of ailments, particularly those
pertaining to the gastro-intestinal tract.2,3,4,5,6,7,8,9
The earliest travelers from Europe who visited India described pepper
cultivation on the Malabar coast.10 Theophrastus mentions two kinds of pepper
in the fourth century B.C., (most likely these were black pepper and long
pepper).10 Discorides in the first century A.D. mentions black pepper and long
pepper as well as white pepper, which is simply black pepper seed with its peel
or pericarp removed. Black pepper and long pepper were among the spices from
India on which the Romans levied import duty at Alexandria, around A.D. 176.11
Pepper is mentioned by Roman writers in the fifth century A.D. It is said that
Attila the Hun demanded, among other items, 3,000 lbs. of pepper as ransom for
the city of Rome.l1
Centuries later, the high cost of pepper led the Portuguese10 to seek their own sea
passage to India. The Portuguese were successful in this mission and
monopolized the spice trade until the 18th century.l In January 1793, an
agreement was made between the Rajah of Travancore and the Crown of
England. The Rajah was to supply large quantities of pepper to the Bombay
Government in return for arms, ammunition and European goods. This is
known historically as the “Pepper Contract”.
Bl
ack pepper
2
From the 16th to the 18th centuries, the struggle for control of the Far Eastern spice
producing regions became so intense that wars were fought between Portugal,
Holland, and England. By the end of the 18th century, the United States entered
the world trade for spices, bartering its salmon, flour, and soap for tea, coffee and
spices.
One reason spices in general, and pepper in particular, became so important in
international trade was their popular culinary role. In those times, tough,
heavily salted long-stored meat was standard fare, and spice additives made
these meats more palatable, while simultaneously masking off-flavors.
The Chemical Constituents of Pepper
Piperine is the active principle of black pepper (Piper nigrum L.) and long pepper
(Piper longum L.). This is also the principal alkaloid of these plants. The piperine
content is 3-9% and 3-5% (on dry weight basis) in P. nigrum and P. longum
respectively.
Structure of piperine
Chemical names:
1- piperoyl piperidine
(E,E) 1-[5-(1,3-Benzodioxol-5-yl)-1-oxo-2, 4-pentadienyl]piperidine
Molecular weight: 285.33
Percentage composition:
C= 71.55% H=6.71% N=4.91% O=16.82%
Molecular structure:
O
O
O
N
Method of extraction48
Piperine can be isolated from the oleoresin of P. nigrum or P. longum. The
powdered fruits of the plant are extracted with dichloromethane at room
temperature with stirring for 12 hours. The extract is filtered, concentrated in
vacuum, and then the residue is purified on an alumina column. Pure piperine
can also be obtained by crystallization from ethanol, which may be required for
food and/or medicinal usages. Piperine is obtained directly from the crude
3
residue in lesser amounts by extraction in alcohol, filtration and successive
crystallization.
Pepper: One of the most common herbs in Ayurveda
Piper species have been used in traditional medicine for intermittent fevers and
to promote the secretion of bile. They are also recommended for neurological,
broncho-pulmonary and gastrointestinal disorders, (including dyspepsia,
flatulence, constipation and hemorrhoids).2,3,4,5,6,7,8,9 In Ayurveda, black pepper,
long pepper and ginger are often used together in equal proportions in a
preparation known as “trikatu”, a Sanskrit word meaning “three acrids”.8 Out of
370 compound formulations listed in the Handbook of Domestic Medicines and
Common Ayurvedic Remedies, 210 contain either trikatu or its individual
ingredients.8 According to Ayurveda, the three acrids collectively act as “kapha-
vatta-pitta-haratwam” which means “correctors of the three humors (doshas) of
the human organism”.
Pepper in the treatment of fever and malaria
The advantage of utilizing black pepper (as opposed to the standard quinine) in
the treatment of refractory intermittent fevers, which are symptomatic of
malarial infections, was reported by Dr. C. S. Taylor in The British Medical
Journal, September 1886.10 At a 1983 symposium in Bombay, India entitled
“Therapeutic Approaches to Malaria” sponsored by Ciba Geigy, Ltd., long
pepper was discussed as a possible treatment for chronic malaria.l2 It was
reported that long pepper was used for patients with chronic malaria with
splenomegaly (enlarged spleen). Long pepper fruits were given in an increasing
dose from 3 to 30, starting with 3 and increasing daily by 3 fruits. Subsequently
the dose was decreased from 30 to 3 fruits, by reducing 3 fruits daily. Long
pepper was boiled in milk and water and drank once a day in the early morning.
Drinking this decoction reportedly caused cessation of malarial parasite
multiplication and regression of splenomegaly.
In traditional Chinese medicine, black pepper has been used for the treatment of
epilepsy.l3 Based on this traditional application, a new antiepileptic drug called
Antiepilepserine has recently been synthesized by Chinese researchers.l3
Antiepilepserine is a chemical relative of piperine, the main alkaloid
phytochemical found in plants of the family Piperaceae. In traditional Middle
Eastern medicine, black pepper has been used as a nerve tonic. Recently, the
analeptic (nervous system stimulant) properties of piperine have been studied.
Based on this research, piperine has been used successfully to counteract
morphine-induced respiratory depression in experimental animals.14
The application of pepper in respiratory diseases
Long pepper, and to a lesser extent trikatu, have been used in the treatment of
asthma and chronic bronchitis in Ayurveda and Unani medicine.l0 In a study
4
involving 240 children of different age groups suffering from frequent asthma
attacks, long-term administration of long pepper fruits significantly reduced the
frequency and severity of the attacks.l5 Twenty-five patients in the study group
showed no recurrence of asthma attacks, 161 showed clinical improvement, 47
did not benefit from the treatment, and 7 patients deteriorated. In another study,
20 pediatric patients with asthma received long pepper in doses ranging from
9.35 to 15.75 gm daily for several weeks. As a result of this treatment all patients
showed clinical improvement.16
Bioavailability enhancement : a significant application of pepper
The use of black pepper, long pepper, or trikatu is traditionally well-known in
the treatment of a variety of gastrointestinal disorders, and all three act to
improve digestion. In the 1920’s Bose, an acknowledged author of
“Pharmacographia Indica”, reported an enhanced antiasthmatic effect of an
Ayurvedic formula containing vasaka (Adhatoda vasica) when administered with
long pepper.l7 In his “Pharmacopoeia lndica”, Bose describes examples of his
preparation which consists of juice from the vasaka leaves boiled with sugar, long
pepper and butter; then this mixture was added to honey and given as a
treatment for asthma.
Through sustained experimentation and observation, ancient practitioners
discovered herbal agents, such as pepper, which could increase the digestibility
and efficacy of both nutrients and herbal drugs. The main purpose of trikatu’s
incorporation into numerous Ayurvedic formulations was most probably to
enhance the efficacy of pharmacologically active ingredients. Several groups of
investigators now attribute this bioavailability enhancing property of pepper to
its main alkaloid, piperine. Piperine is an alkaloid with the molecular formula
C17Hl9O3N, which on hydrolysis with alkali gives piperic acid and piperidine.l8
The piperine content of pepper is directly proportional to its pungency.
The biological properties of piperine have been extensively studied only in recent
years.l9,20 The proposed mechanism for the increased bioavailability of drugs co-
administered with piperine is attributed to the interaction of piperine with
enzymes that participate in drug metabolism, such as mixed function oxidases
found in the liver and intestinal cells. Interaction with the synthesis of drug
chelating molecules in the body such as glucuronic acid has also been proposed.
Piperine may also interact with the process of oxidative phosphorylation, or the
process of activation/deactivation of certain metabolic pathways, slowing down
the metabolism and biodegradation of drugs. This action of piperine results in
higher plasma levels of drugs, rendering them more available for
pharmacological action.
One of the first scientific experiments to confirm that pepper could enhance the
bioavailability of drugs was performed in the late 1970’s by Atal and coworkers
at the Regional Research Laboratory, Jammu-Tawi in India.l9 These experiments
5
revealed that Piper longum co-administered to rats orally with the drugs vasicine
and sparteine increased the blood levels of vasicine by 232% and sparteine by
more than 100% as compared to control animals who did not receive P. longum.
In subsequent experiments, piperine has been proven to enhance the
bioavailability of a number of drugs including rifampicin, phenytoin,
propranolol and theophylline.2l,22,23 A patent based on the drug bioretentive
property of piperine (Indian Patent No. 1232/DEL/89) recommends the use of
piperine in combination with drugs to improve their effectiveness.24
This successful use of piperine to increase bioavailability of certain drugs has
created interest in the area of nutrient and food absorption, since nutritional
deficiencies due to poor gastrointestinal absorption are an increasing problem in
developing countries as well as in Western nations. In developing countries,
overall gross malnutrition may be the culprit. However, in Western nations,
poor gastrointestinal absorption is increasing due to a larger percentage of
elderly people in the population, as well as an increasing incidence of “junk food
diets”, allergies, gastric ulcers, and chronic yeast infections (Candidiasis).
Beta-carotene absorption has been shown to be variable among humans, with
some individuals consistently absorbing it well while others do not. Recently, an
original bioavailability study showed that a standardized extract of black pepper
(Bioperine®), increases gastrointestinal absorption of beta-carotene in humans.25
Bioperine is 98% pure piperine obtained through a proprietary extraction
process, from pepper.25 A small amount of Bioperine® (5 mg) combined with a
formula containing 15 mg of beta-carotene, given as a food supplement once a
day, increased almost twofold the blood levels of beta carotene in human
volunteers (Fig. 1). These results indicate that Bioperine possesses the potential
to increase the bioavailability of nutrients as well.
Bioperine was effective in increasing nutrient absorption with a dose several
times lower than that commonly used to bioenhance blood levels of a drug.
Incidentally, the dose of piperine which increased the bioavailability of beta -
carotene was several times lower than the estimated amount of piperine
consumed daily in the diet by an average individual in the USA.26 Similar
bioavailability enhancement was observed on co-administration of other
nutrients including Coenzyme Q1027, L(+)_Selenomethionine, Vitami B6, Vitamin
C (with propranolol hydrochloride) and herbal extracts such as Curcumin with
Bioperine28.
6
FIGURE 1: BIOAVAILABILITY ENHANCEMENT OF BETA-
CAROTENE BY BIOPERINE: PERCENTAGE COMPARISON OF
AUC (AREA UNDER THE CURVE) FOLLOWING
SUPPLEMENTATION
Pepper’s “hot” taste, “hot” feel, and its thermogenic effect
Almost everyone recognizes that the black pepper sprinkled on their food makes
it taste spicy or “hot”. The hot flavor is even stronger when the pepper is used
fresh. Pepper’s heat is no accidentit is a manifestation of the biological activity
of some of the phytochemicals found in pepper, most notably piperine.
Black and long peppers stimulate the skin as well as the tongue, thus they are
also useful for topical application. They have broad antimicrobial, anti-parasitic
and insecticidal properties. Peppers have been traditionally used as local
anesthetics, but the mechanism of this analgesic (pain-relieving) action has only
been recently described.29 Piperine is thought to be the main phytochemical
responsible for the analgesic action of pepper. It is believed that piperine acts in
a similar (but not identical) way to another well-known pungent phytochemical,
capsaicin, the principal pungent principle found in cayenne peppers (Capsicum
annuum). Black and various red peppers, including cayenne, chilli, and paprika,
are all spicy but are not related botanically. According to one concept, piperine
may deplete sensory nerves of the neurotransmitter called “Substance P”29. This
action may cause local desensitization to pain stimuli. It has been proposed that
Bioperine acts through thermoreceptors, both locally in the skin nerve endings,
and systemically, throughout the nervous system. This, in turn, interferes with
pain stimulus transmission and causes desensitization of pain receptors.25
The proposed mechanism through thermoreceptors, which are sensors of heat
energy in the body, may shed light on the thermogenic (heat-generating) action
of pepper and piperine. The thermogenic effect of piperine and other
100%
160%
0
20
40
60
80
100
120
140
160
180
Carotene +
placebo
Carotene +
Bioperine
AUC Comparison (%)
7
components of spices such as capsaicin, gingerol and shogaol is now broadly
discussed as a new application of spices traditionally known for their body
temperature regulating properties. Thermogenesis is now scientifically linked to
body metabolism and the metabolic rate. The higher the metabolic rate, the more
heat energy is being produced by the body. Could it be that thermoregulation by
piperine is a mechanism through which metabolism can be regulated, including
the metabolization of nutrients and drugs? Considering the profound effects of
piperine on nutrient absorption when given orally in a dose as small as a few
milligrams, piperine deserves to be called a “supernutrient” and based on its
possible thermogenic effect on the body, it might also be dubbed a
“thermonutrient”.30
Although the concept of thermogenesis was not recognized in Ayurvedic
medicine, there existed an empirical use of certain combinations of herbs and
minerals specifically targeted to improve the digestibility of food. Traditionally,
black pepper and its close relative long pepper are used in combination with
ginger in trikatu (three acrids), a remedy used for a broad range of
gastrointestinal disorders31,32. The sharp tasting principles in trikatu are used to
increase the protective gastrointestinal mucous secretion, a long-standing
Ayurvedic treatment which has proven successful for both acute and chronic
gastrointestinal conditions.
Indeed, recent experimental evidence shows that piperine has anti-inflammatory
and antioxidant properties33. Piperine may facilitate nutrient absorption by
alleviating inflammatory conditions at the site of absorption. The mechanisms
behind the beneficial action of piperine as one of the principal ingredients of
numerous digestive formulas employed by Ayurveda needs to be further
investigated. Particular emphasis needs to be placed on the traditional sense of
restoring gastrointestinal function as means of preventing disease and improving
overall nutrition. Black pepper and long pepper are thus potentially useful herbs
in the management of a variety of respiratory and gastrointestinal problems.
Future research on pepper may well retrace the origin and evolution of the
properties which attracted attention to pepper in ancient times. Pliny
commented some 2,000 years ago: “it is quite surprising that the use of pepper
has come so much in fashion, its only desirable quality being a certain pungency;
and yet it is for this that we import it all the way from India!”10
This pungency of pepper is now understood to be a byproduct of the biological
properties of piperine, which can apparently regulate neurohormones, thereby
increasing thermogenesis, or the production of heat by the body. Scientific
research has now revealed that the “hot” pepper taste is due to the production of
heat energy. The biological mechanism of piperine is strongly linked to its hot
taste, further validating its representation as a nutraceutical or “functional food”.
8
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respiratory depression and analgesia. J.Res.Ind.Med. 8(4); 21-26.
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Pediatric Conference in New Delhi, India.
16. Dahanukar, S.A. et al. (1984, June) Efficacy of Piper longum in childhood asthma. Indian
Drugs. 384-386.
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... As a food ingredient, pepper was used for seasoning and obscuring the flavor of preserved meat [3]. In traditional medicine, peppers are utilized for intermittent fevers and gastrointestinal disorders [4], treatment of epilepsy [3], alleviation of pain, muscular pain and influenza [1]. Nowadays, it has been known that the bioactive compound of pepper is piperine, which has therapeutic properties such as antioxidant activity [1], [5], anti-inflammatory activity [6], bio-enhancing ability [7], [8], antiemetic and antipyretic effects [9]. ...
... It was also found that Bangka's white pepper is contaminated with mold in the range of 1.5´10 3 to 2´10 4 cfu/g, and no contamination of yeast, E. Coli, and Salmonella. Irradiation with a dose of 2, 4, 6, 8 and 10 kGy resulted in the reduction of total bacterial content to 4 3.5´10 1 , 2.5´10 1 , less than 10, less than 10 and 1.5´10 1 cfu/g, respectively. Meanwhile, the total mold was reduced to less than 10 cfu/g for all the irradiation dose and no contamination from yeast, E. Coli, and Salmonella was found. ...
... Pipperin and essential oil are bioactive components of pepper. Piperine, a naturally occurring alkaloid, has numerous health effects and beneficial therapeutic properties such as antioxidant, antiinflammatory activity, bio-enhancing ability, [1] [3], [4], [5], [7]. It stimulates the circulatory system, possesses a broad-spectrum antimicrobial activity, analgesic, antipyretic action [7], It has a beneficial influence on lipid metabolism efficacy , as antidiabetic and reduces painful swelling caused by tissue injury [7]. ...
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... In traditional medicine, black pepper has been used to treat epilepsy in China. Also, fruits from piper nigrum (black pepper) have been used as a brain tonic in traditional Middle Eastern medicine (Majeed and Prakash, 2000). As far as we know, there are no scientific studies that show the possible neuropharmacological effects of EOs from fruits from piper nigrum. ...
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... Piper nigrum (Piperaceae) is an important medicinal plant grown in many tropical regions like China and Southeast Asia. It is considered "The King of spices" among the other medicinal plant spices, and this is one of the most traditionally used medicines for malaria in India and epilepsy in China (Majeed and Prakash, 2000). It has a known significant economic importance due to its valuable edible spicy taste worldwide. ...
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A new composition and method for the improvement of gastrointestinal absorption and systemic utilization of nutrients and nutritional supplements, wherein the composition comprises an extract from the fruit of Piper containing a minimum of 98% of pure alkaloid piperine. The method comprises oral, topical, or parenteral administration of the composition of the invention. A new process for the extraction and purification of piperine is also disclosed.
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Thesis (Ph. D.)--Drexel University, 1984. Vita. Includes bibliographical references (leaves 131-152).
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