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12.9.12 Anti-obesity andCarminative Effects ofBlack Pepper
Obesity is becoming the world one of the largest health problem due to different
conditions such as gastric or other metabolic disorders. P. nigrum is proved to be
efcient in reducing obesity along with other non-pharmaceutical approaches such
as exercises, yoga and diet maintenance [142]. Moreover, black pepper has potential
to stimulate strong carminative responses which ultimately causes the secretion of
saliva, enhance appetite and secretion of gastric juice for efcient digestion. In
many countries these are employed as condiments on skin due to their ability to
dilate the supercial vessels of skin which ultimately reduced the body temperature [143].
12.9.13 Anti-pyretic Effects ofBlack Pepper
In India, different herbal medicines such as folklore, Yunani and ayurvedic uses
black pepper against various sorts of treatment or conditions such as pain, cold,
neuritis, fever, throat infections and malaria therefore, known for its anti-pyretic and
anti-analgesic actions [4]. The anti-pyretic actions of black pepper have been
reported after successful experimentation in different medications [144].
12.9.14 Hepatoprotective andGastrointestinal Activity
Researchers have conducted a number of investigations to determine the various
biological impacts of black pepper‘s extracts or its active ingredient, piperine, during the past few decades to establish the scientic explanation for the pharmacological effectiveness of P. nigrum. Thus, a wide range of pharmacological activity and
health-promoting aspects of black pepper have been described in several researches
[145, 146] such as hepatoprotective, anticonvulsant, chemo preventive antiinammatory, hepatoprotective, antidiarrheal, immunomodulating and antioxidant
properties. Although there were apparently some conicting ndings on the safety
of P. nigrum as a food additive, it seems to be safe even at dosages much higher than
the average human intake. Previous investigations have highlighted concerns about
piperine’s possible carcinogenic effects due to its structural resemblance to natural
carcinogens such methyleugenol, safrole and estragole [147, 148].
Treatment with P. nigrum or its derivative (pipperine) has been documented to
enhance activity of metabolic and intestinal enzymes which ultimately increase the
bioavailability of therapeutic drugs in the body [4]. The uses of herbal medicines are
increasing continuously, an estimation provided by WHO demonstrated that homeopathic medicines contributed about 30 to 50% of total medicines consumption in
which China is consuming about 70% [149]. In the jejunal mucosa, the brush
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Fig. 12.4 Dose dependent effects of piperine on the secretion of gastric juice
M. U. Ijaz etal.
boundary transmembrane enzymes such as glutamyl transpeptidase, glycyl-glycine
dipeptidase, alkaline phosphatase and leucine amino peptidase were also activated
by black pepper and piperine [150]. Additionally, piperine and supplementary black
pepper increased the activity of intestinal Na+ and K+ ATPase by 111% and 52%
respectively. All the aforementioned ndings imply that piperine is capable of altering membrane dynamics because of its nonpolar nature by interacting with nearby
lipids & hydrophobic protein regions, which may reduce the likelihood that membrane lipids will act as steric hindrance to enzymatic proteins and change the conformation of the aforementioned enzymes. Additionally, scanning electron
microscopy ultra- structural investigations showed that piperine increased microvilli length and proposed that piperine may cause changes to membrane dynamics
and permeation characteristics and it stimulates the production of various proteins
which are regulators of cytoskeletal function which ultimately increases the small
intestine absorptive surface and facilitates effective drug absorption through the epithelial layer [151]. Piperine is reported to elevate the level of gastric acid secretion
against dose dependent effects of piperine in albino rats when the dose concentration reduces from 20 to 142mg/kg. Piperine is documented to induce the secretion
of gastric acid 22.8% and 334.6% the in response to 20mg/kg and 142 mg/kg of
dose respectively. Cimetidine 1mg/kg reported to counteract the effects induced by
piperine and thus proved to involve in cholinergic receptors. However, there is possibility that piperine is responsible for the activation of H2 receptors which ultimately elevate the acidity level [131] (Fig.12.4).
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12.9.15 Immuno-modulatory andAnti-allergic Effects
Piperine exhibited immune-modulatory and anti-allergic activity and documented
to inhibit the proliferative response which was induced by the antibodies (lipopolysaccharide and immunoglobulin) during invitro studies. Piperine is documented to
inhibit the expression of aforementioned antibodies as well as reduced the differentiation of CD86 [152]. An investigation conducted by Lee etal. reported that combine therapy of piperine along with gamma-aminobutyric acid up-regulate the IL-10
and NF-kB by mediating the expression of JNK MAPK and p28 which ultimately
enhance the activation of EPO and EPO-R [153]. In contrast to upregulation of
immune response, piperine signicantly reduces allergic rhinitis in rats which were
provoked by ovalbumin. Piperine substantially decreased allergy symptoms such as
rubbing and redness brought on by nerve ending hypersensitivity brought on by
histamine released as a result to antigen-antibody reaction but it also diminishes
nitric oxide (NO) thresholds because eosinophil transition into nasal epithelial tissue was less pronounced. It was discovered that piperine administration diminished
swelling, redness, and disturbance of alveoli and bronchioles, much like in the histopathological portion of the nasal mucosa [154]. Piperine therapy inhibited eosinophil invasion and attenuated airway hypersensitivity in an ovalbumin-induced
asthma model by inhibiting T cellular activities production of Th2 cytokine and
Th2 [155].
12.9.16 Anti-thyroidal Activity ofBlack Pepper
Combine administration of piperine along with carbimazole elevated the density of
lipoproteins while reduced the level of plasma proteins and lipoproteins [136]. In
another investigation, piperine is reported to induced the level of testosterone while
lowered the level of Apo B and TSH (88). Furthermore, another study conducted by
Panda and Kar demonstrated that administration of piperine to albino rat reduces the
level of T3 and T4 [156].
12.9.17 Effects ofBlack Pepper andIts Derivatives
onMetabolic Enzymes
There are several studies which demonstrated the that black pepper and its derivatives directly effect on intestinal and hepatic metabolic enzymes by altering the
biotransformation pathways of these enzymes. Piperine is demonstrated dose
depended response on oxygenase system of liver in rats. The activity of different
hepatic enzymes such as benzphetamine, aminopyrine N-demethylase and cytochrome P450 signicantly reduced in response to intraperitoneal (100 mg) and
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intragastric (800 mg) administration of piperinein rats [157]. The substantial
decrease in the activity of oxygenase system of liver is induced by several mechanisms including inhibition of D-aminoleyulininc acid synthetase, reducing hepatic
heme and by binding with cytochrome P450. The levels of hepatic microsomal
cytochrome P450 and cytochrome b5, NADPH-cytochrome-C reductase, benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase were
signicantly increased in rats when the intragastric dose was reduced to 100mg/kg.
These ndings imply that piperine, depending on the administration dose and
method of administration, has both inhibitory and stimulatory effects on the cytochrome P450-mediated activities of the microsomal monooxygenases [158]. All the
aforementioned results indicate that piperine is not a hepatotoxic substance because
none of the treatments signicantly increased the activities of aspartate aminotransferase, isocitrate dehydrogenase and serum sorbitol dehydrogenase. In another
investigation, the effects of black pepper were assessed after providing the feed
comprisinf of 0.5, 1.0 and 2% of P. nigrm for 10 and 20days of duration [159]. In
response to aforementioned dosage, the level of glutathione S-transferase and sulfhydryle content was increased in response to 0.5% of black pepper containing feed.
Black pepper is reported to exhibit chemo-preventive role against different carcinogenic substances. The level of hexobarbital hydroxylase was signicantly increase
in piperine treated rats [160].
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12.9.18 Effects ofBlack Pepper onCholesterol Level
P. nigrum and its derivatives accelerated the translocation process of cholesterol
transporters as well as elevated the rate of fats break down into simple and digestible
molecules to prevent their accumulation into the surrounding tissues of body [161].
Use of P. nigrum along with highly fatty meal (40mg/kg) substantially reduced the
weight of body as well as VLDL, triglycerides, total cholesterol and LDL but
enhance the value of HDL.Daily uptake of P. nigrum and piperine lowers the risk
of getting arthrosclerosis [162].
12.9.19 Preservation ofOrange Juice by P. nigrum
Essential Oil
Citrus fruits are signicant source of vitamins specically vitamin C and A along
with calcium, folic acids, iron as well as thiamine. They also have remarkable concentration of avonoids and carotenoids. Juice of citrus fruits such as oranges is
very nutritious and contains fundamental preserving capabilities for the fruits of
Rutaceae family. However, without appropriate preservation fruits can decays
whereas its taste, color and aroma could be affected severely [79]. Preservation of
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this juice may be carried out via thermal pasteurization, pulsed electric and high
hydrostatic pressure mechanism. Chemicals comprising of sodium benzoate and
potassium sorbate along with natural preservative including organic acids, bacteriocins, phenolic acids and essential oils could also be employed for their preservation
[163]. Essential oil of P. nigrum can be signicant if employed in industries as a
result of its ability to escalates the shelf-life of orange juice. Besides this, orange
juice having essential oils of P. nigrum exhibits considerably reduced microbial
load, titratable acidity, pH, percent loss as well as nano-enzymatic browning
whereas reduces the content of ascorbic acid when compare with fruit juices stored
by employing ethanol along with oleosins [79].
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12.9.20 Bioavailability andPotential ofPiperine
Piperine, the alkaloid component of long and black peppers is currently recognized
as an enhancer of bioavailability of numerous therapeutically as well as structurally
diverse drugs along with various other substances. The therapeutic action of piperine to escalate the bioavailability of pharmaceutical drugs in humans is of great
clinical importance. A signicant mechanism accounts for its bioavailability mediating potential is still not well understood. Atal etal. have analyzed the scientic
basis of the usage of the trikatu group of acrids (black pepper, long pepper as well
as ginger) in the enormous prescriptions in the native ayurvedic system of medication [164]. Long pepper increases the level of blood of vasicine, test drug by approximately 233% under the potential of piperine test’s blood level indicating that these
acrids contains the capability to elevates the bioavailability of specic drugs. It is
concluded that the trikatu group of drugs enhances the bio-availability of pharmaceuticals either by mediating the rapid absorption from the gastro-intestinal tract or
via preventing the drug from being metabolized in the passage through the hepatic
tissue after being absorbed. Piperine has been documented to have a signicant
effect on the activation as well as de-activation of exogenous constituents [165].
12.10 Other Health Advantages
Levels of LDL cholesterol and triglycerides are all signicant risk factors behind
coronary vascular disorders. Certain dietary suggestions can help in prevention of
CVDs. Increasing the function of the peroxisome proliferator-activated receptor is
one of the top approaches to enhance the lipid prole. The highest transactivation
activity was demonstrated by piperine having values of EC (50) were 84 M and
49M, respectively [166]. It has been investigated that the use of black pepper extract
is proved to be successful in treating a skin disorder called vitiligo which is characterized by lesions on the skin and lack of skin pigmentation. Primary alkaloid of
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Fig. 12.5 Benets of black pepper
M. U. Ijaz etal.
black pepper promotes the growth of melanocytes as well as involved in the promotion of swallowing hence worked as strong appetizer [167] (Fig.12.5).
12.11 Conclusions
In the current era, spices are not only conned to use in food for taste, aroma and
color but become the part of ayurvedic, Unani and numerous other herbal medicines
against the treatment of different disorders. Black pepper (King of Spices) and its
bioactive compounds have been successfully investigated in several studies which
demonstrated their role in the maintenance of nutritional balance as well as to show
potential anti-inammatory, anti-microbial, anti-cancerous, anti-diarrheal, antipyretic and anti-analgesic properties. Additionally, both in-vivo and in-vitro studies
proved their signicant role in different diseases of respiratory, digestive and circulatory system as well as against chronic conditions such as in metastatic cancer.
Black pepper is reported to prevent the protein aggregation in the brain and protect
from Alzheimer’s conditions. Different extracts of black pepper showed multiple
pharmacological and biological activities in different animal models.
Pharmacological uses of black pepper are enhancing the importance of black pepper
all over the world. Future studies should be conducted on different extracts of black
pepper to ascertain its safety and effectiveness in detail.
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