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Reassessing the Restorative Prospectives of the King of Spices Black Pepper

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Since ages, spices have been a crucial portion of human diets and trade. The bioactive principles in attendance are of noteworthy merit due to their advantageous probable against an array of disorders. Black pepper, amid piperine as its foremost element, holds affluent phytochemistry and also incorporates a number other important compounds like alkaloids, volatile oils and oleoresins. Piper nigrum is an imperative welfare spice owed to its anti-carcinogenic, antimicrobial, antioxidant apparent and gastro-defensive workings. Piperine also show evidence of speckled pharmacological characteristics like antidepressant, anti-inflammative, immunomodulatory, anticonvulsant, antihypertensive, antitumor, anti-tussive, pain reducing, antidiarrheal, antispasmodic, and cholesterol worsening . Piperine augments bioavailability of quite a few drugs and nutrients by restraining a variety of metabolising enzymes. This review is aimed to provide restructured information in recent progression of pharmacognosy, chemistry and pharmacological behavior of this miraculous King of Spices. Keywords: Black Pepper, Piperine, Antioxidant, Bioavailability, King of Spices
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Goswami et al Journal of Drug Delivery & Therapeutics. 2020; 10(3):312-321
ISSN: 2250-1177 [312] CODEN (USA): JDDTAO
Available online on 15.05.2020 at http://jddtonline.info
Journal of Drug Delivery and Therapeutics
Open Access to Pharmaceutical and Medical Research
© 2011-18, publisher and licensee JDDT, This is an Open Access article which permits
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Open Access Review Article
Reassessing the Restorative Prospectives of the King of Spices Black Pepper
Anindya Goswami1*, Neelesh Malviya 2
1 Department of Pharmacy, Mandsaur University, Mandsaur (M.P.), India
2 Smriti College of Pharmaceutical Education, Indore (M.P.), India
ABSTRACT
Since ages, spices have been a crucial portion of human diets and trade. The bioactive principles in attendance are of noteworthy merit due to
their advantageous probable against an array of disorders. Black pepper, amid piperine as its foremost element, holds affluent phytochemistry
and also incorporates a number other important compounds like alkaloids, volatile oils and oleoresins. Piper nigrum is an imperative welfare
spice owed to its anti-carcinogenic, antimicrobial, antioxidant apparent and gastro-defensive workings. Piperine also show evidence of speckled
pharmacological characteristics like antidepressant, anti-inflammatory, immunomodulatory, anticonvulsant, antihypertensive, antitumor, anti-
tussive, pain reducing, antidiarrheal, antispasmodic, and cholesterol worsening . Piperine augments bioavailability of quite a few drugs and
nutrients by restraining a variety of metabolising enzymes. This review is aimed to provide restructured information in recent progression of
pharmacognosy, chemistry and pharmacological behavior of this miraculous King of Spices.
Keywords: Black Pepper, Piperine, Antioxidant, Bioavailability, King of Spices
Article Info: Received 19 March 2020; Review Completed 02 May 2020; Accepted 09 May 2020; Available online 15 May 2020
Cite this article as:
Goswami A, Malviya N, Reassessing the Restorative Prospectives of the King of Spices Black Pepper, Journal of Drug
Delivery and Therapeutics. 2020; 10(3):312-321 http://dx.doi.org/10.22270/jddt.v10i3.4111
*Address for Correspondence:
Anindya Goswami, Research Scholar, Department of Pharmacy, Mandsaur University, Mandsaur
INTRODUCTION
Black Pepper is one of the most recurrently used spices and
nominated as the King of Spices’’ in the midst of an
assortment of spices. This spice has been a connected part of
human diets. Black pepper is used as restorative agent, an
additive, and in perfumery. Complete Peppercorn of Piper
nigrum or its vigorous components are being used in
different types of foods and as medicine. Black pepper is
omnipresent in many tropical regions like Vietnam,
Indonesia, Brazil and India. Black pepper is
a blossoming trailing plant included in the family Piperaceae,
cultivated for its fruit, which is characteristically dehydrated
by drying and utilized as a zest and seasoning, renowned as a
peppercorn. Black Pepper has conventionally been used in
Ayurvedic and Unani System of medications.1 Black pepper is
used not only in human dietaries but also for a variety of
other functions such as remedial, as a stabilizer, and in
cosmetics. Many profitable pharmacological scope of black
pepper and its foremost vibrant principle piperine have been
put forward in modern decades. When used with foods,
piperine, constructively stimulates the digestive enzymes of
pancreas, augments the digestive competence and drastically
diminishes the gastrointestinal food transit instance.
Piperine has been verified in different in vitro researches to
safeguard against oxidative damage by slaking free radicals
and reactive oxygen groups. Piperine treatment has also
been indicated to lesser lipid peroxidation in vivo and
helpfully manipulates cellular thiol status, antioxidant
molecules and enzymes in a number of investigational
environments of oxidative strain. Piperine's bioavailability
improving property is also to a degree ascribed to amplified
absorption as an conclusion of its produce on the
ultrastructure of intestinal brush boundary.2 Piperine, the
most important alkaloid present in Piper nigrum, is
responsible for the black pepper’s discrete sharp quality.
Piperine has loads of pharmacological possessions and
several wellbeing advantages, particularly against chronic
syndromes, such as lessening of insulin-resistance, anti-
inflammatory potential, and improvement of hepatic
steatosis. 3 Black pepper, with piperine as an dynamic
component, embraces affluent phytochemistry that also
comprises volatile oil, oleoresins, and alkaloids. More lately,
cell-culture experiments and animal modeling forecasted the
character of black pepper against number of maladies. The
free-radical forage exploit of black pepper and its dynamic
ingredients might be accommodating in chemical preclusion
and conniving succession of tumor enlargement.
Furthermore, piperine assists in cognitive brain
implementation, boost up nutrient's absorption and perk up
gastrointestinal functionality.4 Black pepper has an extensive
Goswami et al Journal of Drug Delivery & Therapeutics. 2020; 10(3):312-321
ISSN: 2250-1177 [313] CODEN (USA): JDDTAO
assortment of relevance. It is used as medicine, as an additive
and is also used in fragrances. 5
Many exceptional exploratory editorials and writings on the
pharmacological prospective of Piper nigrum (Black Pepper)
or piperine had been in print to date. It has been open to the
elements that black pepper possesses noteworthy in
vitro and in vivo pharmacological prospective for the
supervision of assorted ailments and syndromes and is found
to be undisruptive.
PHARMACOGNISTIC CONSIDERATIONS OF BLACK
PEPPER
Piper nigrum is an affiliate of family Piperaceae and is firstly
inhabitant to India. The plant is well known for its healing
properties. It is the most recurrently used seasoning, thus
also called “the King of Spices”. Different types of black
peppers are obtainable having dissimilar colors. The
majority regularly known peppers are black and white
peppers.6
Piper nigrum desires warm and humid spaces for growth.
The plant exists in a wide range of sundry environment
varying from tall elevations to assorted soil and climatic
setting. It is abundant in all the tropics as well as subtropics
of the planet. The geographic allotment of black pepper is
prejudiced by the bare minimum temperature of the wintry
month and the wettest month’s rainfall. The physiological
actions in the wettest periods are at their utmost. During the
rainfall episodes, the blossoming occurs, fills grains and
matures. Black pepper requires a plenty sum of rainfall and
dampness. The ideal setting for the expansion and gardening
are the warm and clammy ambiences. Black pepper
productively breeds amid 20 degrees north and south
latitudes. The temperature flanked by 10C to 40C is most
advantageous for its growth.7 The taxonomical classification
8 of black pepper is being depicted in Table 1.
Table 1: Taxonomical Classification of Piper nigrum
(Black Pepper)
Kingdom
Plantae
Division
Manoliophyta
Class
Magnoliopsida
Order
Piperales
Family
Piperaceae
Genus
Piper
Species
nigrum
The plant can accomplish up to 5060 cm in elevation and is
characterized by its simple, alternating leaves, with a few
atypical cases of reverse or verticillate leaves. It is a
perpetual creeping plant and climber that requires
sustaining trellises to grow similar to as escalation
uniqueness as that of beetle plant. The pepper plant initiates
producing tiny round berries subsequent to about three to
four years of planting. Precisely, the pepper berry is a drupe,
measuring about 5-6 mm in diameter, enfolding a sole huge
seed at its interior. The most regularly utilized fraction of the
plant is the scented fruit. Fascinatingly, white, green, and
black peppers are harvest of the black pepper fruits at
dissimilar full-grown phases. Black pepper carries a mightier
essence in contrasting to white pepper whereas green
pepper is characterized by its unsullied and verdant scent.
The piperine alkaloid is accountable for the sharp savor of
black pepper.9 Black pepper is the dried up green berries
and it provides peppercorn. Peppercorn is desiccated fruit
which has not reached full ripening step and it is main part
which is communicated and exploited as spice and
seasoning. In general lingo peppercorn is referred as black
pepper. Peppercorn is the principally consumable section of
pepper plant. Black pepper is just about full-grown absolute
berry that is desiccated up and alienated from their stalks. It
is an angiosperms and a climbing type flowering vine.8 The
Western Ghats woodlands of India are believed as a crucial
center for gardening of black pepper.10 The Malabar coast is
the foundation of black pepper harvest in India. It is
supposed that black pepper was primarily reclaimed in this
region many centuries previously. The farming of pepper
was the next introduced to other countries in Asia and south
eastern Asia. India is the leader in the annual production of
black pepper in terms of tonnage
CHEMICAL CONSTITUENTS
A combination of many compounds is particularly
responsible for the tint, scent and odor of black pepper It
contains lignans, alkaloids, flavonoids, aromatic compounds
and amides. 11 It also includes essential oil up to 3.5% and
this oil composes of sabinene, pinene, phellandrene, linalool
and limonene. Additionally it consists of piperine which is a
weak basic substance with chavicine which is an isomer of
piperine. Piperine and chavicine are not entirely
onscientious for the aroma of the black pepper but piperine
communicates strong flavor to the black pepper. Piper
nigrum contains a biologically dynamic phyto
element, piperine that illustrate signs of many physiological
and pharmacological characteristics including antioxidant,
anti-inflammatory, anti-obesity, antitumor, anti-apoptotic,
antipyretic, antifungal, anti-depressant, anti-infective and
carminative behaviors. Piperine also augments the
bioavailability of different natural compounds as well as
drugs. Piperine stalls free radicals and reactive oxygen
species with restrain of lipid peroxidation thanks to
their flavonoids and phenolic contents. 12, 13
The chemical arrangement of piperine has the structural
formula of C17H19NO3 and the IUPAC name 1-(5-[1, 3-
benzodioxol5-yl]-1-oxo-2, 4-pentadienyl). It is also
acknowledged as piperoylpiperidine. This has been
established to be a very weak base that hydrolyzes to
piperidine and piperic acid. 14, 15 1- Piperoylpiperidine
survives as 4 isomeric structures: piperine (transtrans
isomer), isochavicine (transcis isomer), chavicine (ciscis
isomer), and isopiperine (cistrans isomer). Nevertheless,
the three geometric isomers of piperine incorporate about
no sharpness.16Because piperine represents about 98% of
the entire alkaloids in black pepper; it is well thought-out as
the main provider of strong flavor and a compute of total
pungency of black pepper.17, 18 Piperine is somewhat soluble
in water (40 mg/L at 18 °C) 19and this little solubility of
piperine in water and its reduced dissolution is the rate-
controlling step in the absorption progression of piperine.
The pharmaceutical proceedings of piperine are is somewhat
restricted due to its lesser aqueous solubility and because
use of it at very high concentrations can be noxious for
reproductive and central nervous systems.20 Further
explorations have confirmed the incidence of additional
alkaloids, including piperanine, piperettine, piperylin A,
piperolein B, and pipericine, every one of acquiring some
scale of spiciness in the pepper extract. Yet, the whole
involvement of these alkaloids to pungency of pepper has
been quite skimpy.21
The depth analysis of the nutritional value of black pepper
shows the presence of a number of vitamin, minerals,
Goswami et al Journal of Drug Delivery & Therapeutics. 2020; 10(3):312-321
ISSN: 2250-1177 [314] CODEN (USA): JDDTAO
electrolytes and dietary fibres. The nutritional value per per
100 g of piper nigrum has been summarized in Table 2.
Table 2: Nutritional value per per 100 g of piper nigrum
(Source: USDA National Nutrient data base) 22
Principle
Nutritional Value
Energy
255 Kcal
Carbohydrates
64.81 g
Protein
10.95 g
Total Fat
3.26 g
Cholesterol
0 mg
Dietary Fiber
26.5 g
Vitamins
Choline
11.3 mg
Folic acid
10 μg
Niacin
1.142 mg
Pyridoxine
0.340 mg
Riboflavin
0.240 mg
Thiamin
0.109 mg
Vitamin A
299 IU
Vitamin C
21 mg
Vitamin E
4.56 mg
Vitamin K
163.7 mcg
Electrolytes
Sodium
44 mg
Potassium
1259 mg
Minerals
Calcium
437 mg
Copper
1.127 mg
Iron
28.86 mg
Magnesium
194 mg
Manganese
5.625 mg
Phosphorus
173 mg
Zinc
1.42 mg
Plant Based Nutrients
Carotene-ß
156 μg
Carotene-α
0 μg
Crypto-xanthin-ß
48 mcg
utein-zeaxanthin
205 mcg
Lycopene
6 mcg
Peppercorns enclose a striking list of plant derived chemical
compounds that are known to have disease averting and
health supporting characteristics. The valuable essential oil
of black pepper also hold numerous monoterpenous
hydrocarbons namely sabinene, pinene, terpenene,
limonene, mercene, etc., other than piperine, which
altogether furnish aromatic possessions to the pepper. Black
peppercorns embrace a superior sum of minerals like
potassium, zinc, manganese, iron, magnesium and calcium.
These are also an excellent resource of countless imperative
B-complex groups of vitamins such as Pyridoxine, riboflavin,
thiamin and niacin. Peppercorns possess superior supply of
scores of anti-oxidant vitamins such as vitamin C and vitamin
A. Moreover, peppers are affluent in flavonoid polyphenolic
anti-oxidants like lycopene, cryptoxanthin carotenes, and
zea-xanthin. These composites help the body remove
harmful free radicals and helps protect from quite a lot of
maladies. 23
THERAPEUTIC POTENTIALS OF BLACK PEPPER
Traditional Uses
Years ago, traders measured black pepper the King of Spices.
Designated as ‘black gold’; it was one of the very initial object
of business between India and Europe. Piper nigrum has
found recognition in primordial traditional medicines all
over the universe for thousands of years owing to its high
concentration of compelling, favorable plant compounds. 4,5
In traditional Ayurvedic system, pepper has been claimed to
cure discontinuous fevers, to support the secretion of bile
and has been recommended for neurological, dyspepsia,
flatulence, constipation and hemorrhoids. The pepper plant
has been widely used in traditional Chinese medication to
treat epilepsy and in incidences of treating respiratory and
gastric melanomas. It has also been used as anti-emetic
tranquilizing, in food poisoning as well as beneficial in curing
cholera, dysentery and diarrhea. In conventional Middle
Eastern medicine system, black pepper has been recognized
as a nerve stimulant. The folk remedies of Thailand has used
the root of the plant to take care of chills, headache, adenitis,
abdominal tumors, abdominal fullness, cancer, cholera, colic,
kidney stone, asthma and many other symptoms. Moreover
Ayurvedic also recognizes black pepper helpful in treatment
of rheumatic pain, as expectorant in cough and colds and
bronchitis, in different forms of intestinal and venereal
diseases. The essential oils of black pepper has been widely
recommended in Ayurveda in conditions of skin
inflammations, toothache, congestion inside the nose,
sinusitis. In western medicines black pepper has been
recognized as beneficial in incidences poor digestion and
winds and in a group of symptoms including upper
abdominal pain. Conventionally black pepper and its prime
alkaloid piperine has been utilized in the relief of a number
of diverse symptoms like strep throats, migraine pains,
analgesic, antipyretic, loss of appetite and also as diuretic,
antiseptics and in reduction of blood sugar level. Ayurveda,
Yunani, Siddha and almost all traditional forms of remedies
in India has accredited pepper and piperine containing
dosage forms for the management of aches and sickness of
gullet. Later on it has been published that this can also be
used as an anti-periodic in malarial fever. There have been
instances where black pepper powder when applied
externally has shown redness on skin proving to be a
rubefacient in skin ailments and in hair loss. 21, 24-28
Black pepper is such a condiment which has been providing
innate nutritional and medicinal profit apart from its
culinary relevance since years. As scientific pharmacognostic
screening has evolved, the utility of peeper in
pharmaceutical arena, cosmetics, and food industries as well
as scientific research has been escalating.
Anti-Cancer prospects of Black Pepper
Researchers have hypothesized that piperine, the most
dynamic compound in black pepper, comprise cancer-
battling properties.29, 30Black pepper counteracts cancer
development unswervingly. Pepper averts chemical
carcinogenesis by stimulating the xenobiotic
biotransformation enzymes. Piperine hampers some of the
inflammatory prone cytokines that are created by tumor
cells. In doing so it interferes with the signaling mechanisms
between cancer cells, thereby reducing the chances of tumor
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ISSN: 2250-1177 [315] CODEN (USA): JDDTAO
progression. Animal researches revealed that piperine halts
the replication of colon and prostate cancer cells and has
even encouraged cancer cell demise. Piperine from black
pepper has been showing effective in enhancing the
usefulness of traditional treatment for triple-negative breast
malignancy as well. 31-34, 30The antioxidant actions of piperine
and associated unsaturated amides cooperate a preventive
role in carcinogenesis. Piperine slows up the angiogenic
progression which is a trait in cancer evolution in vitro and
ex vivo and also has been exposed to exhibit inhibition of
breast cancer cell-induced in vivo angiogenesis.35 Black
Pepper and its significant constituents has also shown
promising results in repealing multidrug resistance in
sarcoma cells which impedes with cancer managements
mostly. 36, 37 Piperine is non-genotoxic and establish to
acquire anti-mutagenic and anti-tumor influences.5Abundant
studies have accounted for discerning cytotoxic action of
piperine on cancerous cells in contrast with healthy cells and
these preclinical datas are at present being utilized in intend
of clinical trials with piperine.
Black Pepper and its antioxidant property
Studies have confirmed that Black pepper can be used as an
easily handy source of natural antioxidants. Piperine in
attendance in black pepper is a provider of effectual
antioxidants.38 Rodent studies have experienced that black
pepper and piperine accompaniments may perhaps trim
down free radical spoil.39 Diet soaring in antioxidants may
help avoid the detrimental effects of free radicals, which has
been correlated with cancer, heart ailments, impulsive aging
and a number of different disorders.4 Piperine has been
proved to minimize oxidative stress caused by can reduce
high-fat diet induced oxidative stress to the cells.40 Black
pepper fundamentally sustains and boosts the levels and
worth of important antioxidant compounds. It encloses quite
a lot of powerful antioxidants and is accordingly one of the
major imperative spices for avoiding and restraining
oxidative anxiety. In addition to their through antioxidant
actions, several of these compounds work obliquely by
enhancing the achievement of other antioxidants.8 Piperine
holds back reactive oxygen species as well as lipid
peroxidation owing to their phenolic and flavonoids content.
The antioxidant capability of black pepper was projected
through the determination of superoxide dismutase,
gluthathione peroxidase, catalase, together with
quantification of reduced glutathione volume and the
amount of protein carbonyl and malondialdehyde limits in
the hippocampus.12
Antioxidants are also extensively utilized to postpone
worsening of oxidizable goods such as food, cosmetics and
pharmaceuticals as a natural antioxidant preservative.
Oxidation is the primary basis for quality worsening during
dispensation and storage of these goods, particularly foods.
The essential oil in Black Pepper is the abode of antioxidant
and antimicrobial terpenoids like limonene, α and β-pinene,
δ3-carene and α-terpinene-4-ol, p-cymene along with most
important alkaloid like piperine and its derivatives. Many
studies have talked about the beneficiary effects of black
pepper in food preservation purposes Some researchers
have even postulated that pepper oil had more or less the
same antioxidant activity throughout the experiment as
compared with marketed synthetic antioxidants like
Butylated Hydroxy Anisole and Butylated Hydroxy Toluene.
41-45
Anti-inflammatory potential of Black Pepper
Inflammation is multifaceted usual rejoinder of vascular
tissues to detrimental stimuli, such as pathogens, dented
cells, or irritations. Inflammation can be considered as a
defense machinery of living creatures to various stimuli
involving toxic compounds, and many environmental stress
factors as well. Chronic inflammation may be a fundamental
factor in many conditions, such as arthritis, heart disease,
diabetes, and cancer. Several laboratory studies suggest that
piperine; the key active composite in black pepper may
efficiently brawl inflammation. Treatment with piperine in
animals has shown results in less joint swelling and fewer
blood markers with inflammation due to arthritis. Piperine
has been shown restraining inflammation in the airways
caused by asthma and recurring allergies. Piperine has
illustrated a noteworthy prohibition of increase in edema
intensity in a carragenin provoked test and has acted
extensively on before time sharp changes in inflammatory
development.46-52
Immunomodulatory Potentials of Black Pepper
Black pepper exhibits immunity intonation effect on human
body. It is competent of boosting and sustaining the quantity
and the effectiveness of white cells and lends a hand to raise
a powerful resistance against invading microbes and
sarcoma cells within the body. In an important study, Black
pepper aqueous extracts appreciably improved splenocyte
propagation in a measured quantity-dependent, synergistic
manner. Enzyme-linked immunosorbent assay researches
have revealed that black pepper significantly augment and
repress correspondingly, T helper (Th) 1 cytokine discharge
by splenocytes. The nitric oxide production by macrophages
is significantly amplified by black pepper hence notifying
itself as a natural agent that can promote the maintenance of
a healthy immune system as nitric oxide being an
intercellular envoy that has been renowned as one of the
most resourceful players in the immune system. In vitro
studies with piperine have concluded that it reduces
proliferative response encouraged by lipopolysaccharide and
immunoglobulin IgM antibody. Piperine can even account for
inhibition of IgM antibody discharge and diminished
expression of cluster of differentiation. 53-55
Black Pepper is a colon-gracious spice, which also defends
the intestinal tract against bacterial growth. Piperine helps to
kindle the body into transferring nutrients from the
gastrointestinal tract and into the bloodstream, means
pepper enables us to process more goodness from the food
that we eat. Thus Black Pepper possesses anti-inflammatory,
antioxidant and antibacterial actions, but also immune
system-enhancing benefits.
Black Pepper as Bioavailability Improver
Piperine in pepper increases the availability of valuable
phyto-chemicals present in food items in biological systems
and can enhance the action of biochemically energetic
compounds enclosed in it. It encourages the speedy
absorption of certain chemicals from the gastrointestinal
tract, defending them from being wrecked down by
compounds in the intestinal lumen and by enzymes that
happen in the cells lining of intestines. Once the composites
have got intoed the blood torrent, piperine affords
fortification against oxidative scratch with the assist of liver
enzymes. In this way black pepper enables us to gather most
advantageous benefits from the natural medicinal
compounds found in other dietetic spices. Black pepper’s
bioavailability augmenting characters makes it as one of the
most essential spices.
Research on piperine from Black pepper given as oral
supplementation has shown increase in plasma levels of
coenzyme Q10.56Serum level of β-Carotene has been found to
be increased by piperine, thus to overcome vitamin
deficiency piperine enhanced β-Carotene uptake can be
Goswami et al Journal of Drug Delivery & Therapeutics. 2020; 10(3):312-321
ISSN: 2250-1177 [316] CODEN (USA): JDDTAO
beneficial for maintenance of health.57Also, the serum
concentration, absorption, bioavailability of another
important anticancer phyto compound curcumin have been
found to be influenced by piperine. 58 Piper nigrum promotes
the gastrointestinal absorption and liver metabolism of
vasicine and sparteine causing an increase in their
bioaviailibility.59 Black pepper is expanding bigger
consideration as a bioavailability enhancer in the
formulations of several drugs. The pharmacokinetic profile
of a number of synthetic drugs like omeprazole, propranolol,
ampicllin, norfloxacin ciprofloxacin, amoxicillin, isoniazid,
theophylline and phenytoin has been influenced or improved
by piperine.56, 60, 65Promising results have also been evident
in plentiful other other pharmaceutically active chemicals
like nevirapine, diclofenac, midazolam, tamoxifen,
carbamazepine to name a few.66-68 Piperine has also found to
affect enzyme commotion and biotransformation. It has
been reported to hinder enzymes significant for drug
metabolism and in this fashion holding backing drug
metabolism it may possibly augment the bioavailability of
various compounds and hence amend the value of some
useful therapeutics. 69 Piperine is blessed to have a speedy
absorption rate through the intestinal barricade. Several
findings have suggested that the alkaloid has a submissive
diffusion system, a high evident permeability coefficient, and
diminutive clearance duration.70 Owing to its non-polar
character, piperine is capable of controlling the membrane
characteristics by intermingling with lipids and hydro
anxious parts of the protein, which amend enzyme
conformation owed to a decline in the property of membrane
lipids to function as steric restrictions to enzyme proteins.
Piperine causes an increase the penetration all the way
through the epithelial barrier as it is able to persuade
changes in membrane dynamics and permeation features,
along with orientation in the permutation of proteins related
to the cytoskeletal purpose which boosts the absorptive
surface of the small intestine.71 There are research datas
showing black pepper and its key alkaloid vividly increasing
the absorption of selenium, vitamin B as well.72 Piperine has
been performing the part of a bio-enhancer in the of some
important chemotherapeutic agents like acyclovir,
gatifloxacin, docetaxel. A number of patents have been
related to the increase the bioavailability of nutritional
compounds making high purity piperine for nutritional
use.73-76
Black Pepper and its cholesterol lowering potential
Obesity and high blood cholesterol is a universal peril
associated with an amplified risk of heart disease, which is
one of the foremost reasons of casualty globally.77Black
pepper extract has been considered in animals for its
probable to trim down cholesterol levels.26, 78 It has been
concluded that piperine can reduce cholesterol uptake by
internalizing the cholesterol transporter proteins in high-fat
diet-induced obesity in rats.79Black pepper does not contain
cholesterol as one of its active chemical compound. It
improves digestion procedure by facilitating quicker split
down of bigger fat molecules into effortlessly digestible
uncomplicated molecules and averts the buildup of fat in
body.8 Furthermore; piperine is alleged to heighten the
absorption of dietary supplements that have potential
cholesterol-lowering properties.80 Genome-wide
examination by means of microarray has also holds up the
compelling task of piperine in gene regulation coupled with
lipid metabolism.81Supplementing piperine with elevated fat
diet has shown to be significantly reducing body weight,
entire cholesterol, triglyceride, low and very low density
lipoproteins and fat cluster with an augment in the degree of
high density lipoprotein with no amend in dietary intake.82
Thus it can be postulated that black pepper possesses
impending lipid diminishing and fat sinking effects, not
including any alteration in the desire for food. Some
researchers have commented that the dietary ingestion of
black pepper diminishes the threat of arthrosclerosis via
hypolipidemic and antiatherogenic reactions.40 In another
finding, it has been pointed out that piperine decreases
cholesterol uptake and improves translocation of cholesterol
hauler proteins.83Further studies are being conducted to
prove whether black pepper itself has noteworthy anti-
obesity potentials in humans. 84, 85
Antimicrobial potency of Black Pepper
Loads of literatures confirm the antimicrobial potential of
black pepper. There have been reports of inhibitory
antimicrobial potential against different strains of
Pseudomonas aeruginosa, Candida albicans, Staphylococcus
albus, S. typhi, E. coli, B. megaterium. Antimicrobial activity of
some synthetic piperine derivatives were confirmed against
A. fumigatus , Bacillus subtilis, Streptobacillus species,
Staphylococcus aureus, E. coli, Salmonella typhi, Aspergillus
Niger and A. flavus. Piperine has indications of increasing the
antimicrobial exploit of ciprofloxacin against E. coli and
Bacillus subtilis. When tested against the fungal strain of
Fusarium oxysporum piperine has scored maximum anti-
fungal activity amongst some other microbial groups.
Another research reports the leishmanicidal activity of
ethanoilic and hexane extract of Black pepper against
leishmanicidial activity against Leishmania donovani
promastigoates and amastigoates through apoptosis. Some
derivatives of piperine have also been active against
Leishmania amazonensis and Trypanosoma cruzi amastigotes.
These significant antimicrobial effects in extensive
assortment of micro-organism imply piper nigrum as a
authoritative natural antimicrobial agent. Moreover the
antimicrobial potential of Black pepper makes it a choice
able agent against food spoilage. Researchers have confirmed
the usefulness of black pepper in microbiological
preservation against Listeria monocytogenes in as well as
against a general microbial load in food samples.86-95
Antidiarrheal effects with Black pepper
Black pepper is also effective against some bacteria which
are responsible for causing diarrhea. Research denotes the
enormous potency of this condiment in managing diarrhea
which is still a cause of high infant mortality rate in some
parts of the globe. The incidence of carbohydrates and
alkaloids in black pepper has been cited as the rationale of
noteworthy dose-dependent anti-diarrheal effects. Piperine
has inhibited gastric emptying of solids and liquids in rats
and gastrointestinal transit in mice in a dose and time reliant
behavior.96, 97 An important finding has concluded that
piperine show evidence of antidiarrheal and antispasmodic
behavior, intervened possibly through calcium channel
barricade coupled with some additional mechanisms.
Piperine has been found equally beneficial in controlling
castor-oil stimulated diarrhea like loperamide, a well-
recognized antidiarrheal drug which also constitutes
piperidine ring in its moiety just like piperine. 98, 99
Black Pepper and its gastro-protective properties
Piperine can perk up digestion and kindle the secretion from
the taste buds and this stimulus is a feedback loop for
digestion progression. It transmits impulses to the stomach
to amplify digestive Hydrochloric acid secretion. These juices
fracture down the protein in the stomach, making better
capability for auxiliary digestion in the duodenum. Black
pepper constituents encourage bile acid production which is
extremely crucial for fat absorption and digestion by the
Goswami et al Journal of Drug Delivery & Therapeutics. 2020; 10(3):312-321
ISSN: 2250-1177 [317] CODEN (USA): JDDTAO
liver and its secretion into bile.100 It has already been
established previously that piperine can boost absorption of
selenium, vitamin B, beta-carotene and curcumin in the body.
57, 72 Piperine also has been reported to promote sweating
(diaphoretic) and urination process (diuretic). This
astonishing condiment supports the healthiness of the
digestive tract and helps to obtain the most assistance from
food matters. Different findings illustrate the
hepatoprotective effect of Black pepper in both animals and
humans.6A study has reported the methanolic extract of
Black pepper to be beneficial in ethanol-CCl4 persuaded
hepatotoxicity in rat models. Black pepper has been found to
decline the hepatic biomarker intensity of some of the
important chemicals including bilirubin which gets amplified
in hepatotoxic conditions.101 In calculated doses, piperine
has reported to restrain enhancement in SGPT and SGPT
levels in liver and suggested that this effect depended on
hepatocytes diminished sensitivity headed for tumour
necrosis.102 Enhanced intestinal lipase activity has been cited
as one of the reasons of piperine’s role in improving
digestion as it is already known that lipase is an enzyme
promoting breaking down of fats in food to facilitate their
intestinal absorption.103 Significant increase in gastric cell
exfoliation, pepsin discharge with potassium loss has been
observed in a study on human models with intragastrical
administration of 1.5gm per meal feed of piperine.104Piperine
has also been postulated to activate salivary amylase with
enhanced production of the saliva, and promote gastric
secretion, more over decrease gastrointestinal transport
time.2 Eating black pepper regularly in calculated quantities
may awaken the discharge of enzymes in pancreas and
intestines that help digest fat and carbohydrates.103 Owing to
such positive effects on stomach function, black pepper may
play a constructive role for those with pitiable digestion.
Dehydrated fruits of Piper nigrum have been recurrently
used in gastrointestinal problems since ages.105, 106
Beneficial effects of Black pepper in central nervous
system
The nitrogen bearing sharp alkaloid piperine is one of the
major functionally active constituents responsible from
neuropharmacological activities of Piper nigrum.
Antidepressant, antianxiety, neuroprotective and antineuro-
inflammatory properties of Black pepper extracts have been
examined in multiple animal studies.107A study performed
with methanolic extract of black pepper seeds suggested that
it may have potent anti-neuroinflammatory effects and may
be hopeful in the management of Alzimers disease.108
Piperine has appreciably demonstrated antidepressant and
anxiolytic effects by attenuation of oxidative stress in
different animal models. 109 It has been reported piperine
generates antidepressant-mimic effects through the
hinderance of enzymatic activity of monoamine oxidase and
escalating the intensity of monoamine neurotransmitters in
animal models of behavioral depression and encouraging
reports have been noticed in swim and tail suspension tests
in animals with piperine treatment.110Piperine
administration in corticosteroid induced depression animals
has resulted in marked reduction of unhappy behaviours and
the probable mechanism has been attributed to inflection of
brain-derived neurotrophic feature signalling.111 Diverse
researches have concluded that piperine owns intense
effects on neurodegenerative turmoils of the central nervous
system like Parkinsonism and Alzheimer's disease.107
Presently, quite a variety of piperine-loaded nanosystems
like nanocapsules, solid-lipid nanoparticles; emulsions etc.
are being designed for facilitated delivery of piperine to the
brain for the treatment of neurodegenerative diseases like
Alzheimer's, dementia and epilepsy in animal models.112-114
In cetain preclinical findings, piperine has shown evidence of
anticonvulsant effects probably intervened via GABA-ergic
pathways. It has also been revealed that piperine
demonstrates analgesic behaviour perhaps mediated
through the opioid pathway.115The accurate dynamics and
brain pharmacokinetics with piperine in addition to its
dealings with other central nervous system medicines are
still unexplored completely. The CNS beneficial effects of
piperine have been expansively considered in preclinical
models together with the advantageous exchanges between
piperine and other allied therapeutic compounds. Human
study confirmation on its central nervous system relevance
is scarcely available. 116
Other remedial actions of Black Pepper
The anti-arthritic prospective of piperine has been revealed
in arthritis model of rat together with its analgesic and
inflammation reduction performance.117Traditionally, black
pepper has been utilized as an anti-periodic in malaria fever
and hence it is alleged having antipyretic and anti-pain
properties. Piperine has shown good fever reducing effect on
typhoid vaccinated rabbits and other experimental animals
as well.118 Investigation in rodents recommend that the
piperine in black pepper may well be innate pain alleviator.
Piper nigrum L. acquires powerful analgesic performance
besides being an anti-inflammatory agent.117, 119 Piperine
from black pepper may well assist in getting better the blood
sugar metabolism. Several researches have established the
fact of piperine and some of its derivatives having anti-
diabetic potential. 120, 121A research postulated that piperine
averted diabetes by glucose transporter protein type 4
translocation through a hike in the intracellular calcium level
and creation of reactive oxygen species.122 Piperine has
reported to appreciably improve allergic conditions like
sneezing and redness tempted by sensitization of nerve
endings generated from histamine release in rejoinder to
antigen-antibody effects in animal models. There also been
reports of reduction in eosinophil infiltration due to
suppression of histamine and interleukin production. Thus
Black pepper can be used in anti-allergic remedies as
well.123,124The powerful antitussive and bronchodilator
features of Black pepper have been recognized quite a few
times and several home remedies of cough includes a certain
portion of black pepper.4, 25, 107Piper plants have been used in
treatment of parasitic diseases since long and piper nigrum
has particularly been beneficial against Leishmania species,
Trypanosoma cruzi and Plasmodium falciparum, which are
the causing agents for malaria fever. 92, 93, 12 5Hence the
antimalarial use of Black pepper can also be added to its
credit.
The pungent piperine has indicated to have some role in
fertility with marked increase in serum gonadotropin
hormone levels when examined on the testis of albino
mice.126There has been incidences of secretion of
catecholamines from brain cortex of experiemental rats post
piperine infusion treatment.127 The promising role of Black
pepper in hypertension is intervened most likely through
calcium channel blocking has been documented in a number
of lietatures.3, 128, 129, 130Piperine is also accounted to display
anti-platelet activity mediated by different mechanisms.131,
128 Piperine can also be administered to cancer patients prior
to radiotherapy thanks to its defensive effect against
radiation.132 The protective effect of black pepper is in
accordance with its antioxidant potential.43 Research datas
have also confirmed that piperine have an effect on mood,
memory and cognitive disorders.133, 134Moreovers, Black
peppers’ role as growth encourager, thermogenic, anti-
thyroid agent, insecticidal, chemo-preventive, fertility
improving with antitumor and rubefacient properties has
Goswami et al Journal of Drug Delivery & Therapeutics. 2020; 10(3):312-321
ISSN: 2250-1177 [318] CODEN (USA): JDDTAO
also been identified in a number of literatures. Being rich in
antioxidants, Black pepper is steadily gaining attention in the
cosmetic industries particularly in hair and skin cosmetics.
135, 5, 8, 25
Use of Black pepper in formulations
The “King of Spices” Black pepper has evolved a lot from
merely enhancing the taste of foods to being one of the most
important natural compound with diversified
pharmacological actions. Largely human clinical studies are
being focused on the bioavailability augmentation by co-
administration of piperine with a variety of drugs. But the
safety in terms of dose is a crucial factor as in preclinical
studies, there has been evidences of mild toxicity in very high
doses. Moreover, there are certain challenges like little water
solubility, low absolute oral bioavailability and extensive
first-pass metabolism is also considered in oral delivery of
piperine. Different newer forms of dosage are now being
designed for the safe and effective use of this condiment.136,
112,113A number of patents have also been filed regarding the
newer utilization of piperine in therapeutics.137, 138 Further
investigations particularly clinical trials in humans will
establish more on the diversified use of the plant and its
mechanism ways for safe and effective clinical delivery.
CONCLUSION
Black pepper is one of the foremost spice seasoning used
worldwide in diets. It is obtained as dried young berries from
recurrent, evergreen woody climbers of Piper nigrum L. plant
belonging family Piperaceae. The spice is mostly cultivated in
tropical parts of India and Southeast Asia. This is a natural
food additive that supply enormously to the savour and
essence of foods, and have been recognised to own several
therapeutic assets and hence is successfully used in the
native classifications of medicine in various parts of the
globe. Besides their conventional use, a multitude of
advantageous physiological consequences have come front
by broad animal studies and numerous human trials
throughout the past era. Among these are their antioxidant
and cancer fighting potential, antimicrobial, and
immunomodulatory, anti-inflammatory, digestive,
cholesterol lowering, digestive, antidiarreal, antidepressant,
anxiolytic, antidiabetic and bioavailability enhancing
properties have been elicited vividly. At present several
investigators have been using different novel formulations
with pepper as the focal constituent for specific delivery to
organs. Piperine has been a leading constituent of Black
pepper which has shown promising biological effects in
numerous in vitro and in vivo studies and in clinical trials as
well. Wide ranges of promise are open for the expansion of
purposeful foods and pharmaceuticals based on black pepper
and for that extensive standardised and well-designed
research is the utmost need. This review anticipates finding
its utility in academia, systematic explore and existent
industrialized application in signifying the black pepper is in
reality the ‘King of Spices’.
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... these minerals are essential elements for the day-to-day activities of humans. In addition, black pepper also has a significant concentration of vitamins such as Vitamins C, B1, B2, and B3 [8]. Nigerian black pepper had a tannin concentration ranging from 2.11 to 2.80 mg /100 g [1]. ...
... Black pepper is commonly used in different fields such as agronomics, pharmaceuticals, food, and cosmetics [8]. Black peppers have a wide variety of compounds like antioxidant, antibacterial, antifungal, anti-inflammatory, and antitumor properties and insecticidal agents [20]. ...
... Oral administration of black pepper extracts helps to suppress cancers [5]. Furthermore, this spice shows immunity-enhancing, antidiabetic, hepatoprotective and anti-obesity properties [5,[10][11][12][13][14][15]. Piperine in black pepper can be used to treat neurodegenerative illnesses such as depression, Alzheimer's and Parkinson's diseases [6]. ...
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Chemistry in Sri Lanka. Vol. 41 No. 3, September 2024, Pg 14-17. (Watch more; https://www.youtube.com/watch?v=kZ0yPhGR5ko&t=79s). Black pepper is known all over the world as “King of Spices”, since it is not only an ingredient to make mouthwatering food, but also rich in immense medicinal value. The pepper name is derived from the “Pippali” in Sanskrit. According to history, Greek people have used pepper as currency in fourth century and is the first spice that gained the value. Black pepper is used to heal cough, asthma, kidney inflammations and joint pains in India and China as a folk medicine. Scientists have discovered many types of phytochemicals e.g., alkaloids, flavonoids, polyphenols, tannins, saponins etc., are present in this plant which contains miraculous medicinal value.
... 9 Additionally, lignans and flavonoids have also been found in this condiment. 10 Because most natural products are biosynthesized in only trace quantities and need time-consuming processes for isolation, their application as drugs or as a basis for semi-synthesis of newer therapeutic molecules is constrained. Nonetheless, considering its abundance and simplicity of isolation, piperine has an advantage over these restrictions. ...
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As the major naturally occurring alkaloid in pepper with a pungent taste, piperine is known for its beneficial biological functions and therapeutic effects. In this work, the bioavailability and biological activities of piperine were presented and discussed. Novel delivery systems for enhancing the bioavailability of piperine were also reviewed. This study could provide a better understanding of the physiological and biochemical aspects of piperine to be further developed in the food and nutraceutical industries.
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Black pepper (Piper nigrum L.) is known as king of spices and it's sharp taste is due to the presence of piperine which is the main bioactive alkaloid in the fruit. In the present study both of piperine and black pepper oil in different concentrations evaluated for their antimicrobial activity against Staphylococcus aureus (G+ coccoid shaped bacteria), Bacillus subtilis (G+ long spore forming bacteria), Salmonella sp and E.coli (G- short rod bacteria). The inhibition activity was measured by using agar well diffusion method. Piperine and black pepper oil showed antibacterial activity with all tested Gram positive bacteria with zones ranged from 8.23-18.1mm and 3.14-10.43,respectively. The results showed that piperine is an excellent antibacterial agent with all tested bacteria.
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Introduction: Piperine, the major bioactive component from black pepper, has gained increasing attention for its beneficial effects in the central nervous system (CNS). However, its related pharmacodynamics and brain pharmacokinetics, as well as its interaction with other CNS drugs are lacking, which may hinder its therapeutic and safe use. Areas covered: The current review provides an updated summary on CNS activities of piperine, including anti-epileptic, anti-depressive and neurodegeneration protection effect. The brain pharmacokinetic properties of piperine together with the approaches to enhance its aqueous solubility were summarized. Considering the wide use of black pepper and the well-reported alteration on CYP and transporters by piperine, interactions between piperine and CNS drugs are also illustrated for the first time. Expert opinion: Although the CNS beneficial effects of piperine have been extensively studied in preclinical models, clinical evidence on its CNS application is barely available, which may be attributed to its limited aqueous solubility, unclear pharmacokinetic properties in humans and potential toxicities during long-term use at higher doses. Although beneficial interactions between piperine and certain CNS drugs were often reported in preclinical studies, more mechanistic studies with clinically relevant doses should be conducted to provide guidance on their clinical combination use.
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