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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5569_Библиотеки_им_академика_М_И_Перельмана
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Table 12.3
pepper community 2011)
Country
India 49,000–49,550
Indonesia 33,000–40,000
Brazil 32,000–38,200
Malaysia 154,000–16,450
Vietnam 88,000–101,750
The production of black pepper in various countries during 2009–2010 (International
2009–2010
Production (metric tons)
12.7.2 Climate Conditions
A number of investigations have reported differences in growth and production of
pepper on the basis of their genetic makeup, agronomic practices and environmental
conditions [43]. Black pepper is a moist tropic plant that needs between 2000 and
3000mm of rainfall, high levels of humidity, tropical temperatures and relatively
constant day length throughout the entire year. The amount and distribution of precipitation have a substantial impact on the yield of pepper crop. The optimum average rainfall for P. nigrum is 2000mm/per year. The ushing and number of owers
started by a rainfall of 70mm over the course of 20days in May–June, but once
these processes get started, rain should remain continue till the P. nigrum is fully
ripe [44].
12.7.3 Fertilizer Practices andSustainable Farming
Black pepper has great demand due to its nutrients and therefore it should be
enriched with these nutrients to obtain high yield [45]. Nutrients uptake of a mature
P. nigrum plant is estimated 13kg P, 202kgN, 18kgMg, 156kgK and 68kg of
calcium/ha [46]. The term “Natural Farming” is not only farming without the
involvement of inorganic fertilizers but it directs multiple dimensions to use microorganisms for improvement of soil quality and soil fertility [47]. Sustainable farming can be dened as “utilization of resources in such a way that they do not affect
the sustainability of ecosystem without any sort of compromise on human health
status [48].
12.7.4 Role ofSoil Microora
The presence of microorganism is only effective when they attain optimum conditions (water, oxygen, pH and temperature) to perform their functions on their substrate [49]. During natural farming, the population of these effective microora is
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made to grow to large scale and then applied to cultivated soil [50]. However, the
benecial effects of microora depend upon the environmental conditions of soil
(temperature, pH, moisture) and appear only when they establish as well as become
dominant to perform their metabolic activities [36]. In case of black pepper, it takes
years to fully establish the microora in the soil. Recurrent month - to - month
administrations, particularly during the initial cropping period, might signicantly
speed up the development of the supplied benecial microbes [51]. It is also reported
that when this microora is isolated from soil, cultured in the lab & then reintroduced into the native soil at enormous population, it is immediately exposed to
antagonistic & competitive effects from the native soil microora and then the population density declined [52]. Therefore, the opportunities to enhance yield, quality
and health status of cultivated crops become high when microora of soil is applied
in mixed form [53].
M. U. Ijaz etal.
12.7.5 Harvest andPost-Harvest
The rst harvest of P. nigrum is performed upto 2 to 3years followed by plantation.
The owering stage of black pepper starts after 1year of plantation but they shed
them to gain more nutrient for subsequent years. The yield of black pepper reach to
the peak in the seventh year followed by plantation but then decline gradually.
However, the yield can remain sustained for 15years if managed according to aforementioned conditions [54]. To achieve high quality black pepper fruits, it should be
handled with appropriate management after harvesting. To make the fruits separation easy, crop should be bagged for half or full day and night period covered under
heaps for complete fermentation. After this period the spikes of pepper separated by
using mechanical thrashers (for large crop) or by trampling under the foot [55].
Processing and storage of black pepper and its derivatives is the crucial step in order
to obtain maximum benets. Since heat, such as that used in domestic cooking procedures, readily depletes piperine, the active principal ingredient therefore, the
method used to store and handle pepper is crucial. Light-induced isomerization
transforms piperine and its isomers into chavicine, isopiperine and isochavicine.
The rate of isomerization rises with exposure time and light intensity. When chavicine is stored, it gradually turns into piperine, losing some of its pungency [56].
The amount of piperine lost from P. nigrum during thermal processing varied
between 16% and 34%, with the maximum loss occurring during pressure cooking,
suggesting decreased accessibility of pepper active ingredients from cooking when
the constituents have only been exposed to high temperature such as boiling or pressure cooking for minimum time duration. Total extractable oleoresin as well as piperine of pepper are degraded according to rst-order thermodynamics [57, 58].
Ionizing radiation has the capacity to purify the black pepper and its derivatives
from microorganisms. A substantial reduction was reported in the viscosity as a
function of radiation dose in the dose range necessary for microbiological
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disinfestations [59]. Antioxidant potential of black pepper is reported to reduce in
response to 10–30kGy of radiation [60].
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12.8 Various Sorts ofDiseases ofP. nigrum
12.8.1 Phytopthora Infection
During the rainy season, fungus (P. capsica) causes the soaking of water and forms
lesions on the margins of leaves which later get enlarged and spread from leaf lamina to stem. The severity of disease becomes higher if the shoots emerge from foot
rot. These runner shoots carry the infectious fungus towards roots [61]. If nursery
conditions are favorable for the fungus, it reproduces thousands of times and infect
the roots to cause root rot disease. To prevent from aforementioned infection, the
removal of runner shoot should be carried out on immediate basis from the garden
or by using different fungicides [62, 63].
12.8.2 Blight & Rot Disease
This condition caused by Pythium sp., Collectotrichum sp. and Rhizoctonia solani
with different appearance after attack. During the attack by R. solani, leaves developed spots of greyish color but the infected leaves remained anchored with each
other. In case of Collectotrichum sp. Attack, the leaves develop yellowish color in
the form of necrotic spots. Both of these conditions can be avoided by eliminating
runner shoots from the lawns and spraying the solution of Bordeaux mixture (1%).
However, the process of Phytosanitations also play crucial role in preventing these
conditions during which infected veins are eliminated from the gardens and eradicated completely [64, 65].
12.8.3 Phyllody andStunted Disease ofBlack Pepper
Phyllody is suspected to cause by a mycoplasma like organism (MLO) which has
tendency to convert the spikes into leaf like structure in contrast to the anatomy of
normal ower. However, the molding of spikes into such shape does not destroy
rather it hamper the berries production. In case of stunted disease, the growth of
vines becomes ceased thus directly affecting the actual yield. The most prominent
signs include molting of leaves, narrowing lamina and reduction in the length of
internode thus referred as little leaf disease [66] (Fig.12.2).
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Fig. 12.2 Flowsheet showing the biological and pharmacological activities of black pepper
M. U. Ijaz etal.
12.9 Biological andPharmacological Applications
ofBlack Pepper
Black pepper is reported to show anti-oxidant [67, 68], anti-cancerous [69] antiapoptotic [70] immune-modulatory [69] antimicrobial [1] and anti-spasmodic [71].
Following are some important biological and pharmacological applications of
black pepper:
12.9.1 Antimicrobial Activities
The antimicrobial action of any spice depends upon certain factors such as quantity,
chemical constituents, type of spice, type of pathogen attacking the spices and
intensity of such attack and storage conditions of spices [72]. Emergence of drug
resistant pathogen led to inefcient response of antimicrobial drugs against them.
The treatment of microbial infections becomes challenging and thus requires new
antimicrobial drugs or therapies [73]. A wide variety of pathogens have been
observed to be resistant to P. nigrum ‘s antimicrobial effectiveness. The sensitivity
of the microorganisms against drug depends upon the concentrations and use of different solvents for black pepper extraction. For instance, Khan etal. investigated
that water extract of black pepper fruit have the highest zone of inhibition (ZOI)
against E. coli whereas the extract of hot water demonstrated the highest ZOI against
S. typhi and S. aureus amongst multiple solvent extracts (hot water, methanol and
cold water) [74]. Additionally, the extract of methanol had the highest degree of
inhibitory activity against P. aeruginosa, S. typhi & E. coli but had no effect against
S. aureus. Another investigation conducted by Karsha and Lakshmi found that use
of acetone for P. nigrum extraction showed highest degree of inhibition against
S. aureus and found to be more active in contrast to the extract of dichloromethane
against numerous bacteria [75]. Furthermore, it was discovered that extraction of
black pepper by using methanol displayed high degree of inhibition against pathogenic fungi [76]. Various pathogens including S. aureus, B. subtilis, E. coli, and
P. aeruginosa showed resistance against n-Hexane extract while inhibited by the
action of ethanol along with acetone extract of P. nigrum. A number of leaf extract
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solvents showed marvelous antimicrobial activities against above mentioned pathogens [77, 78].
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12.9.2 Antioxidant Activity
Numerous in-vitro investigations were designed to examine the antioxidant abilities
of P. nigrum. The ethanol extract exhibited highest ferric reducing abilities as com-
pare to aqueous extract of black pepper but the aqueous extract displayed high
degree of scavenging capabilities against hydrogen peroxide, superoxide anion,
leading to reduced oxidative stress. A number of investigations were conducted by
Shanmugapriya etal. to determine the antioxidant potential of P. nigrum by employ-
ing acetone, ethyl acetate and aqueous solvents [77]. Extract of ethyl acetate represented high degree of scavenging against superoxide anion, DPPH
(2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis
(3-ethylbenzothiazoline- 6-sulfonic acid) while acetone based showed excellent
scavenging activities against nitrous oxide and hydrogen peroxide. Essential oils
(derivatives of black pepper) exhibited inhibitory activities against lipid peroxidation, FRAP (ferric reducing ability of plasma) and DPPH in contrast to the extracts
of ethanol and ethyl acetate [79]. Alcoholic extract of P. nigrum is documented to
enhance the level of anti- oxidant level such superoxide dismutase, glutathione-Stransferase and glutathione peroxidase in rats [80]. Essential oils of P. nigrum is
documented to diminish malondialdehyde (MDA) levels in the hepatic tissues of
rabbits [81].
12.9.3 Anti-cancerous Activity
Scientic community is continuously working to explore new medicines from
plants after the failure of multiple drugs in cancer therapy and plethron of its side
effects on patients more than their benecial impacts. Many researchers demonstrated the anti-cancerous effects of black pepper and its derivatives on various cancer cell lines. For example, chloroform as well as ether extracts of black pepper root
demonstrated cytotoxic activities for the treatment of myeloid leukemia (HL-60
cell) in human after 3days of continuous exposure [82]. Methanol extract from the
fruit of black pepper showed excellent anti-cancerous actions against numerous
cancer lines such as MDA-MB-231 and MCF-7 while the extract of dichloromethane demonstrated similar effects on MDA-MB-468 cell line of breast cancer [83].
Ethanolic extract of black pepper exhibited anti-cancerous activities against various
cell lines of colorectal cancer such as HCT-15, HCT-116 and HT-29 [84].
Pellitorine, a derivative of black pepper root was documented to show cytotoxic
effects in dicancer cell lines (HeLa and MCF-7) [82]. The top-notch derivative of
black pepper which is well-known for its anti-cancerous activities is piperine which
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was found to show suppressive effects against breast cancer gene HER-2. Pipperine
was reported to block the signaling pathway of ERK1/2 and inhibit the activity of
FAS and SREBP-1 gene. It was also reported to suppress the expression of EGF
induced gene MMP-9 by blocking the activation of AP-1 and NF-jB [85]. Cell lines
of prostate cancer such as PC-3, LNCap and DU145 were also reported to be inhibited by piperine. Furthermore, it enhances the formation of LC3B and elevated the
level of LC3B-II [86]. Aforementioned cell lines of prostate cancer were inhibited
by dose dependent effect of piperine. It was reported to enhance the level of p27Kip1
and p21Cip1in both DU145 and LNCaP but PC-3 remain unaffected. Several investigations demonstrated that piperine directly block the potassium channels which
are the key regulator of cancerous cells proliferation. Piperine demonstrated effective results at IC50 = 49.45 μM in human prostate cancer while 39.91 μM in
LNCaP.The blockage of these channels led to the arrest of G0/G1 cell cycle which
ultimately cease the proliferation of cancerous cells and enhance apoptosis [87].
Administration of piperine enhance the activation of PARP-1 and caspase-3 while
inhibit the expression of phosphorylated STAT-3 and NF-kB in various human prostate cancer cell lines such as PC-3, LNCaP and DU-145 [88]. Treatment of pipperine during invivo investigation is proved to reduce tumor formation and level of
serum gamma glutamyl transpeptidase and serum sialic acid in rat. This compound
is also reported to decrease the level of total protein and protein bound carbohydrates which are involved in instigating the lung cancer [89].
Piperine has demonstrated anti-proliferative properties in different types of cancerous cells by arresting the cell cycle in vatious phases such as G0/G1, S or
G2/M.Arrest of cell cycle in S phase only occurrs in leukemia cells [90] while G1
phase is halted in prostate [86, 87], colon [91] and melanoma cancerous cells [92].
The inhibition of G1 phase is correlated with the upregulation of p21 protein while
downregulation of cyclin D. p21 protein inhibits the cyclin-dependent kinases as
well as promote the blockage of phosphorylation of retinoblastoma and reduces the
expression of E2F transcriptional factor 1 [93]. The over expression of p21 is
reported to block the G2/M phase of cell cycle when piperine was provided in ovarian [94], osteosarcoma [95], lung [96] and breast cancer [97, 98]. Furthermore,
piperine is documented to inhibit both G1/S and G2/M transition in a model of
mammalian breast cancer [99].
The capability of malignant cells to invade the other tissues of body is the major
hallmark. Metastasis is a complicated process which need to acquire different stages
such as resistance against apoptosis, proteolysis with the help of metalloproteinases,
enhancing cell mortality and invasion to surround tissues as well as reduction in cell
adhesion [100]. Interestingly, piperine is found to reduce the expression of metalloproteinases in different types of cancerous cells. For example, piperine inhibits
the metalloproteinases-2 and 9in breast cancer cell lines. Inhibitory effects of piperine are not only related with the inhibition of metalloproteinases but it also inhibits the expression of HER2 [85] which is the primary regulator of breast cancer
invasion and enhance the expression of both aforementioned metalloproteinases
[101]. The inhibitory actions of piperine are also relied on the inhibition of Akt
signaling pathway as investigated in the study of brosarcoma, osteosarcoma,
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prostate and breast cancer cell lines [102]. All the aforementioned investigations
were performed in the mammalian model of different carcinoma cell lines [97] in
which piperine inhibited the expression of metalloproteinases-13 [103]. In case of
osteosarcoma cell lines, piperine enhances the expression of TIMP1 and 2 which
directly inhibit the regulation of metalloproteinases2 and 9 [95].
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12.9.4 Anti-inammatory Activity
The Anti-inammatory potential of black pepper and its derivatives were determined
by using plethysmometer [104]. Pipperine was exhibited anti-inammatory response
at different concentrations of doses such as 5, 10 and 15mg/kg of body mass. The
activity was observed maximum at 15mg/kg after 2h of continuous exposure but
still this response was less than the response represented by diclofenac sodium. After
administration of 500mg/kg essential oil of black pepper, paw inammation was
reduced signicantly (about 72%) in rat after 3h of treatment in contrary to the control group while the administration of 100mg/kg reduced the inammation to about
66.1% in same time duration. In case of chronic inammation of paw, a dosage of
500mg/kg reduced the inammation to about 50% while the standard treatment of
diclofenac sodium (10mg/kg) reduced 57.5% of paw inammation [105].
12.9.5 Analgesic andAnticonvulsive Activity
Black pepper has been extensively studied by scientists to be used as safe painkiller
drug. The pain alleviating effects of black pepper and its derivatives were evaluated
in ethanolic and hexane extracts. To evaluate the pain alleviating effects of pipperine
in hexane extract, tail immersion technique was used in which a dosage of 5mg/kg
was administrated in 2h while the analgesy meter test was performed to determine
the pain killing effects of pipperine in ethanol extract at 10mg/kg for 1 h which
demonstrated that ethanol extract proved to be more pain alleviating as compare to
hexane extract [104]. Ethyl alcohol and hexane extract of black pepper were reported
to encounter the duration of seizures in maximal electroshock seizure induced model
and pentylenetetrazol (PTZ) induced model of Wistar rats. Treatment of pipperine
(70mg/kg) has been documented to prevent animals from PTZ induced seizers [106].
12.9.6 Anti-diabetic andHypolipidemic Activity
Administration of aqueous extract of black pepper to diabetic rats for 28days bring
down the blood sugar from 270mg/100mL to 129mg/100mL [107]. Treatment of
methanolic extract of P. nigrum with different doses 100, 200 and 300mg/kg was
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reported to diminish the glucose level in alloxan induced diabetic mice [108]. As
soon as the activity of polyol pathway increases, it enhances the level of aldose
reductase which is directly involved in the complications during diabetic conditions, thus maintaining the level of aldose reductase can inhibit the complications
such as nephropathy, retinopathy and neuropathy. Hyromethanolic extract of black
pepper is documented to reduce the level of aldose reductase to reference range of
25–64 lg/mL, thus showing antidiabetic effects [109].
12.9.7 Neuroprotective Effects
Methanolic extract of black pepper is found to demonstrate anti-depressant as well
as anxiolytic activity in Wistar rats. This extract has tendency to regulate amyloid
beta which causes impairment of spatial memory by reducing oxidative stress in rats
[110]. Pipperine was proved to enhance cognitive functions and motor coordination
[111] as well as its treatment can recover the motor decit and locomotory activity
controlled by motor coordination [112]. Collected information on cognitive and
brain problems is alarming on a global scale. Neural conditions and stress are estimated to impact over 450 million people [113]. Recently, the neuroprotective properties of food products were emerged as a potential treatment for a variety of
diseases. In this regard, black pepper‘s bioactive constituents and antioxidant capability are considered essential for enhancing brain health. Additionally, supplementation with piperine (5, 10, and 20mg/kg body weight/day) improves neuroprotective
properties as well as enhances the cognitive function. It was documented that piperine reduced chronic mild stress brought by uctuations in consumption of sugar
among the individuals [114]. Forced swimming test was reported that piperine demonstrated efcient anti-depressant properties at the dosage of 10–20mg/kg which is
a successful way to prevent brain related disorders such as Parkinson and Alzheimer
and epilepsy [115]. Piperine is also reported to ght against various sorts of neurological and psychiatric diseases. Oxidative stress is considered as the major factor
behind the parthenogenesis of Alzheimer and other neurodegenerative diseases. An
injection of streptozotocin was injected to a rat model of Alzheimer disease which
induced oxidative stress as well as cause the malfunctioning of neurotransmission
[116]. Similar group of rats were administrated with 2.5 mg/kg of piperine for
28days. Piperine suppress the generation of oxidative stress and enhance the synatptic plasticity as well as improve mobility and chlionergic function of streptozotocin injected rats [117, 118].
Furthermore, the administration of piperine suppress the production of Ca
rent [119] which ultimately cease the release of glutamate from nerve endings of
hippocampal, thus improving synaptic plasticity and facilitate paired pulse. It was
reported that administration of piperine expressed the acetylcholine receptors in
hippocampus region which regulate the cognitive functions as well as plasticity of
synaptic nerves. Piperine inhibit the production of acetylcholine esterase [120]
which break down the acetylcholine into choline and acetate (Fig.12.3).
2+
cur-
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Fig. 12.3 Piperine ingestion demonstrated the neuroprotective properties
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The molecular aetiology of the cognitive issues brought on by streptozotocin is
still obscure, but its infusion dramatically raises the levels of synapsin, amyloid, and
tau-phosphorylation [121]. Therefore, it may be assumed that piperine therapy
might affect tau hyperphosphorylations and misfolded proteins. According to a
study, piperine therapy inhibits secretase, which prevents amyloid and tau pathogenesis in addition to improving cholinergic activities [122, 123].
Piperine has been documented through numerous investigators for its curative
action in epilepsy, a neurological disorder characterized via frequent seizures.
Piperine acknowledge signicant consideration in treatment of epilepsy for its
remarkable monoamine oxidase A (MAO) repressive as well as neuro-protective
capabilities. Piperine administration can also maintain the serotonin concentration
as well as moderated MAO along with -amino butyric acid pathway [124]. It is also
revealed that administration of piperine enhances the glycine, GABA along with
taurine level whereas decreases nitrate in the brain & sera of a pilocarpine- instigated
epileptic rats [125].
In a maximal electroshock instigated seizure model of epilepsy, piperine dosage
diminishes the morbidity via negatively maintaining the NA+ ion gates which retard
the beginning of tonic seizures [126], demonstrating that piperine may control the
sodium ion channel to control tonic convulsion as well as morbidity in epilepsy. For
example, blockage of transient receptor potency cation channel family (V) member 1 via piperine-mediated anti-epilepsy activity [127], illustrated that TRPV1 could
also be included in the piperine process, piperine can directly affect the poreforming segment (S6) to escalate opening of these ion’s channel [128]. Furthermore,
co-administration of piperine along with carbamazepine in the patients of epilepsy
displayed a considerable elevation in the bioavailability of carbamazepine, AUC
along with absorption as well as decrease the elimination half-life [129, 130].
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12.9.8 Nutrient Absorption inGastrointestinal Track
From decades, black pepper along with its derivatives are broadly accepted and
utilized in the treatment of gastrointestinal disturbances. After the ingestion,
P. nigrum stimulates the synthesis of hydrochloric acid from the walls of stomach
which aids in the digestion of food by enhancing histamine receptors. Furthermore,
uptake of black peppers was reported to enhance the urination as well as diaphoretic
(promote sweating) condition [131]. Following oral ingestion, pipperine gets
absorbed from the mucosal layer and then enters into intestinal and serosal uids
[132]. Pipperine is found to enhance the absorption of Vit B, Ca, selenium and
β-carotene throughout the gastrointestinal track [133, 134].
12.9.9 Anti-diarrheal Activity ofBlack Pepper
Anti-diarrheal activity of this plant is referred to its pungent pepperine derivative &
numerous reserachers reported anti-diarrheal acitivty of black pepper [135].
Interestingly, a large proportion of people particularly from developing countries
are still using black pepper in severe diarrheal conditions [136]. Moreover, similar
anti-diarrheal effects of black pepper were observed in rats [137].
12.9.10 Cardioprotective Effects ofBlack Pepper
Pipperine is proved to involve in the activation of peroxisome proliferator activated
receptor- γ to enhance cardiac protection against various sorts of cardiac toxicities
[138]. Furthermore, pipperine has been documented to show ameliorative effects
against curcumin induced cardiac toxicity in rat [139]. These investigations suggested the cardio-protective abilities of pipperine against various chemotherapeutic
drugs induced toxicity.
12.9.11 Insecticidal Activity
P. nigrum has demonstrated its insecticidal activity against different insects such as
Amphimallon majal, Scarabaeidae and Coleoptera [2]. Essential oil of black pep-
per (0.2% concentration) demonstrated strong repellent ability against Tribolium
castaneum which is common insect of wheat during storage conditions [140].
Additionally, the repellent potential of P. nigrum was observed to be dose depend
against T. castaneum [141].
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