Black Pepper and Health Claims: A Comprehensive Treatise

Abstract

For millennia, spices have been an integral part of human diets and commerce. Recently, the widespread recognition of diet-health linkages bolsters their dietary importance. The bioactive components present in them are of considerable significance owing to their therapeutic potential against various ailments. They provide physiological benefits or prevent chronic ailment in addition to the fundamental nutrition and often included in the category of functional foods. Black pepper (Piper Nigrum L.) is an important healthy food owing to its antioxidant, antimicrobial potential and gastro-protective modules. Black pepper, with piperine as an active ingredient, holds rich phytochemistry that also includes volatile oil, oleoresins, and alkaloids. More recently, cell-culture studies and animal modeling predicted the role of black pepper against number of maladies. The free-radical scavenging activity of black pepper and its active ingredients might be helpful in chemoprevention and controlling progression of tumor growth. Additionally, the key alkaloid components of Piper Nigrum i.e. piperine assist in cognitive brain functioning, boost nutrient's absorption and improve gastrointestinal functionality. In this comprehensive treatise, efforts are made to elucidate the antioxidant, antimicrobial, anti-inflammatory, gastro-protective, and anti-depressant activities of black pepper. Moreover, the synergistic interaction of black pepper with different drugs and nutrients is the limelight of the manuscript. However, the aforementioned health promoting benefits associated with black pepper are proven in animal modeling. Thus, there is a need to conduct controlled randomized trials (CRT's) in human subjects, cohort studies, and meta-analyses. Such future studies would be helpful in recommending its application in diet-based regimens to prevent various ailments.

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BLACK PEPPER AND HEALTH CLAIMS: A COMPREHENSIVE
TREATISE
Journal:
Critical Reviews in Food Science and Nutrition
Manuscript ID:
BFSN-2011-0286.R1
Manuscript Type:
Review
Date Submitted by the
Author:
10-Mar-2011
Complete List of Authors:
Butt, Masood; National Institute of Food Science and Technology,
University of Agriculture, Faisalabad
Pasha, Imran; University of Agriculture, Faisalabad, National
Institute of Food Science and Technology
Sultan, Tauseef; Bahauddin Zakariya University, Dept of Food
Sciences
Randhawa, Muhammad; University of Agriculture, Faisalabad,
National Institute of Food Science and Technology
Saeed, Farhan; University of Agriculture, Faisalabad, National
Institute of Food Science and Technology
Ahmad, Waqas; University of Agriculture, Faisalabad, National
Institute of Food Science and Technology
Keywords:
Spices, Black pepper, Piperine, Nutraceutical
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TYPE OF ARTICLE: Review article 1
TITLE: BLACK PEPPER AND HEALTH CLAIMS: A COMPREHENSIVE 2
TREATISE 3
4
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1. Masood Sadiq Butt 6
National Institute of Food Science and Technology, 7
University of Agriculture, Faisalabad 8
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2. Imran Pasha 10
National Institute of Food Science and Technology, 11
University of Agriculture, Faisalabad 12
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3. Muhammad Tauseef Sultan 14
Department of Food Sciences 15
Bahauddin Zakariya University, Multan 16
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4. M. Atif Randhawa 18
National Institute of Food Science and Technology, 19
University of Agriculture, Faisalabad 20
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5. Farhan Saeed 22
National Institute of Food Science and Technology, 23
University of Agriculture, Faisalabad 24
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6. Waqas Ahmad 26
National Institute of Food Science and Technology, 27
University of Agriculture, Faisalabad 28
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†Corresponding author 31
Dr. Muhammad Tauseef Sultan 32
Department of Food Sciences, 33
Bahauddin Zakariya University, 34
Multan, Pakistan 35
Contact No. 0092-333-9949100 36
Email: tauseefsultan@hotmail.com 37
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BLACK PEPPER AND HEALTH CLAIMS: A COMPREHENSIVE TREATISE
Masood Sadiq Butt a, Imran Pasha a, M. Tauseef Sultan b, M. Atif Randhawa a,
Farhan Saeed a, and Waqas Ahmed a
a National Institute of Food Science and Technology, University of Agriculture, Faisalabad
b Department of Food Sciences, Bahauddin Zakariya University, Multan
ABSTRACT
For millennia, spices have been an integral part of human diets and commerce.
Recently, the widespread recognition of diet-health linkages bolsters their dietary
importance. The bioactive components present in them are of considerable significance
owing to their therapeutic potential against various ailments. They provide
physiological benefits or prevent chronic ailment in addition to the fundamental
nutrition and often included in the category of functional foods. Black pepper (Piper
Nigrum L.) is an important healthy food owing to its antioxidant, antimicrobial potential
and gastro-protective modules. Black pepper, with piperine as an active ingredient,
holds rich phytochemistry that also includes volatile oil, oleoresins, and alkaloids. More
recently, cell-culture studies and animal modeling predicted the role of black pepper
against number of maladies. The free-radical scavenging activity of black pepper and its
active ingredients might be helpful in chemoprevention and controlling progression of
tumor growth. Additionally, the key alkaloid components of Piper Nigrum i.e. piperine
assist in cognitive brain functioning, boost nutrient’s absorption and improve
gastrointestinal functionality. In this comprehensive treatise, efforts are made to
elucidate the antioxidant, antimicrobial, anti-inflammatory, gastro-protective, and anti-
depressant activities of black pepper. Moreover, the synergistic interaction of black
pepper with different drugs and nutrients is the limelight of the manuscript. However,
the aforementioned health promoting benefits associated with black pepper are proven
in animal modeling. Thus, there is a need to conduct controlled randomized trials
(CRT’s) in human subjects, cohort studies, and meta-analyses. Such future studies
would be helpful in recommending its application in diet-based regimens to prevent
various ailments.
Key words: Spices, Black pepper, Piperine, Functional properties, Nutraceutical
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I. Introduction 1
In the recent era, efforts have been directed to establish scientific rationale for health 2
improving potential of functional and nutraceuticals foods. Innovations in the 3
nutrigenomics and proteomics further reflected the importance of dietary interventions 4
to prevent and cure various maladies. In this regard, prevention of cardiovascular 5
disorders (CVD), cancer insurgence, diabetes mellitus, Alzheimer’s disease, and variety 6
of inflammatory ailments through dietary modules is of prime consideration 7
(Chonpathompikunlert et al., 2010). The list of healthy foods marketed with distinct 8
health claims is long enough. However, spices and their bioactive components are more 9
promising candidates for their inclusion in diet-based regimens to improve human 10
health (Butt et al., 2009).Their different parts including dried seed, bark, fruit, root, and 11
flower are in use as food adjuncts that impart flavor, aroma and color to foods 12
(Srinivasan, 2008; Singletary, 2010). 13
The demarcation line between culinary and therapeutic use of spices has been a bit hazy 14
from ancient times to the present era (Srinivasan, 2005a). The health promoting 15
potential of these foods are numerous but improving digestive system, mediating 16
inflammation, antimicrobial, chemo-protective and neuroprotective tasks are of greater 17
significance (Duessel et al., 2008). Recently, well-documented evidence supported their 18
ability to prevent cancer insurgence (Christine and Kaefer, 2008; Butt and Sultan, 2010). 19
However, the claims are based on animal studies thus, there is a need to study their 20
health claims in human subject in order to warrant their pharmaceutical application to 21
cure various maladies. 22
Of the various spices, black pepper (Piper Nigrum L.) holds a prominent position and is 23
acknowledged as “King of Spices” (Nisha et al., 2009). It has manifold functional uses in 24
the traditional food formulations, kitchens, perfumery, traditional medicine, and even 25
in beauty care (De-Souza et al., 2005; Srinivasan et al., 2004). Black pepper’s pungency 26
and flavor is due to presence of alkaloid piperine, volatile oil, and oleoresins (Zachariah 27
et al., 2010). In Indian folklore medicine, it is mainly used as an immune enhancer (Bang 28
et al., 2009) and to treat against diarrhea, asthma, chronic indigestion, gastric ailments, 29
colic, insomnia, and epilepsy (Chaudhry and Tariq, 2006; Agbor et al., 2006; Fu et al., 30
2010). The review is an effort to present the comprehensive treatise regarding the 31
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botanical classification and rich phytochemistry of black pepper. The health promoting 1
potentials associated with its consumptions are the limelight of the manuscript. The 2
details are described in their respective heading herein. 3
II. Botanical classification and phytochemistry 4
Black pepper belongs to Piperaceae family that comprises over one thousand species 5
with tropical and subtropical distribution (Table 1). It is commonly known as 6
peppermint, black pepper, kaali-mirch and black gold. The coastal areas of India are its 7
prime origin but nowadays its plantation is extended to other parts of the globe too like 8
Vietnam, Ceylon, Malaysia, Indonesia and Brazil (Thanuja et al., 2002; Srinivasan, 2008; 9
Polovka and Suhaj, 2010). 10
Place Table 1 here 11
Black pepper is dried form of un-ripened green berries and heat provided during 12
cooking aids in sudden burst of the cell walls. The process further boosts enzymatic 13
reactions resulting in greater color changes leading to blackish tonality. Black pepper 14
dried fruit is frequently refers as peppercorns (approximately 5 mm in size). The 15
peppercorns are rich in vitamin A and K in addition to dietary fiber, calcium, 16
magnesium, potassium, manganese, phosphorous and β-carotene. Some other products 17
from black pepper are ground pepper; oleoresin and pepper oil (Utpala et al., 2008; 18
Zachariah et al., 2010). 19
Black pepper, with piperine as an active ingredient, contains volatile oil, oleoresins, and 20
alkaloids. Major alkaloids present in black pepper are piperine, chavicine, piperidine, 21
and piperetine (Shaikh et al., 2006). The terpenes, steroids, lignans, flavones, and 22
alkamides are other primary constituents (Musenga et al., 2007; Murthy and 23
Bhattacharya, 2008). Black pepper essential oil contributes towards the aroma, oleoresin 24
contributes towards the overall taste, and the alkaloid piperine imparts pungency 25
(Zachariah et al., 2010). The briefs about the phytochemistry of the black pepper are 26
presented in Table 2. The detailed description of major components is discussed herein. 27
Place Table 2 here 28
A. Piperine 29
In 1820, Danish chemist Hans Christian Orstedt isolated piperine for the first time. The 30
relative m-olecular mass of piperine (C17H19O3N) ([1-[5-[1, 3-benzodioxol-5-yl]-1-oxo-2, 31
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4, pentadienyl piperidine), is 285.33 g mol−1 and it contains 71.55% carbon, 16.82% 1
oxygen, 4.91% nitrogen, and 6.71% hydrogen. It is yellow crystalline substance having a 2
melting point of 128–130°C (McNamara et al., 2005). It is insoluble in water and acts as 3
weak base, which on hydrolysis with nitric acid or aqueous alkali succumb to volatile 4
base piperidine (C5H11N). In contrary, the acidic product of hydrolysis is piperine acid 5
(C12H19O4; m.p. 216–217°C) that further exists in four isomeric forms (Parmar et al., 6
1997). 7
Piperine is tasteless due to the three isomers which are weakly pungent, but its 8
stereoisomer “chavicine” imparts characteristic pungency to the black pepper as stated 9
earlier (Bandhopadhyay et al., 1990). Piperine is highly sensitive to light so solution 10
should not be exposed to direct light. Piperine and its allied components like piperidine 11
and chavicine are responsible for pungent properties of black pepper (Badmaev et al., 12
2000; Kaefera and Milne, 2008). 13
Solvent extraction systems using ethanol as solvent are employed for the extraction of 14
piperine from black pepper (Naseri and Yahyavi, 2008). The reverse phase high-15
performance liquid chromatography (R-HPLC) and spectrophotometer can be used for 16
its estimation. The spectrophotometeric method invariably yields elevated results thus 17
HPLC method is more reliable (Wood et al., 1988; Sowbhagya et al., 1990). 18
The piperine is important for its health provoking potential described in later section of 19
the aritlce. Briefly, it facilitates the digestion and reduces the food passage time in 20
intestine by improving the digestive enzyme stimulation and saliva secretion. In 21
addition to gastric protective functions, piperine extends its services in liver protection 22
and bio-absorption of micronutrients, vitamins and trace elements. It helps increasing 23
the bioavailability of many types of drugs and phytochemicals thus act as nutrient 24
enhancer (Snyman et al., 2001; Capasso et al., 2002; Kumoro et al., 2009). 25
B. Essential oil 26
The essential oil of Black pepper (about 1–3%) appears as a colorless to greenish liquid, 27
with spicy (peppery) aroma. It has characteristic odor reminiscent with flashpoint of 28
54°C, specific gravity (0.860 - 0.884) and refractive index (1.478 - 1.488) at 20°C. The 29
optical rotation (-1° to -23°) of black pepper oil is levorotatory (George et al., 1988; 30
Shankaracharya et al., 1997). The extraction of essential oil can be carried out using 31
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various methods i.e. liquid carbon dioxide, steam distillation and solid-phase micro 1
extraction (SPME). The nutrient and volatile components can be estimated through 2
column chromatography, gas chromatography (GC) and gas-chromatography mass 3
spectrometer (Tipsrisukond et al., 1998; Ferreira and Meireles, 2002). 4
Until now, 46 compounds are discovered. The major components included are (E)-5
ocimene, guaiene, (Z) (E)-farnesol, guaiol and cadinol. Sabinene, carophyllene, and 6
terpinen-4-ol are present in appreciable quantities. Other imperative sesquiterpene 7
hydrocarbons are bisabolene, cadinenes, calamenene, copaene, cubebenes, ar-8
curcumene, elemenes, farnesene, guaiene, humulenes, isocaryophyllene, muurolene, 9
santalene, selinenes, ledene, sesquisabinene and zingiberene (Ao et al., 1998; Zachariah 10
and Parthasarathy, 2008; Renjie et al., 2010). 11
C. Phenolic compounds 12
The black pepper is rich in potent phenolic acids and antioxidants. It is therefore 13
important spice for ameliorating oxidative stress. The phenolic components of black 14
pepper are mixture of the glycosides of phenolic acids and flavonol glycosides (Renjie et 15
al., 2010). Previously, Parmar et al., (1997) listed the flavonol constituents from black 16
pepper i.e. isoquercetin, quercetin, 3-β-D-rutinoside isorhamnetin, kaempferol-3-o-β-17
galactoside, kaempferol 3-arabinoside, and quercetin-3-o-β-D rutinoside. Overall, the 18
black pepper contains the appreciable quantities of certain bioactive molecules that are 19
helpful in reducing the extent of various maladies. 20
III. Nutraceutical and Functional Scenario 21
The black pepper is used in conventional medicines as food adjunct to improve 22
digestive system through various modules i.e. better appetite & absorption, and 23
controlling dyspepsia & fleshiness. However, the existing health problems that concern 24
mankind primarily include cardiovascular disorders, diabetes mellitus, inflammatory 25
disease and cancer insurgence (Chonpathompikunlert et al., 2010). Several animal 26
studies explicated the role of black Pepper as preventive agent against these maladies 27
(Szallasi, 2005; Politeo et al., 2006). Some highlights of the health promoting potential of 28
bioactive molecules present in black pepper are presented in Table 3. However, the 29
details of its potential health promoting benefits are described herein. 30
Place Table 3 here 31
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A. Antioxidant Potential 1
Oxidation is an inevitable process observed in body cells coupled with some 2
undesirable responses that include production of reactive oxygen species (ROS). ROS 3
are widely accepted as the causative agent responsible for various ailments i.e. cancer, 4
inflammation, atherosclerosis, and aging (Butt et al., 2009). Excessive production of ROS 5
outplays the defense capabilities of body resulting in oxidative stress (Seifried et al., 6
2007). A considerable number of spices and aromatic herbs are known to possess 7
antioxidant potential ought to the presence of bioactive molecules in them (Liu and Ng, 8
2000). 9
In this regard, Saxena et al., (2007) established positive correlation between antioxidant 10
activity (AOA) and phenolic contents (PC) present in plants (r=-0.47). However, 11
coefficient of correlation and determination is higher for spices (r=-0.86 and R2 =74%, 12
respectively). Black pepper holds significant antioxidant activity as 50% inhibition of 13
free radicals can be achieved with 0.43mg. In some earlier studies conducted by Gulçin 14
(2005), it was observed that water and ethanol extracts (75 µg/ml) of black pepper show 15
95.5%, and 93.3% inhibition of lipid-peroxidation, respectively. The inhibition ought to 16
total phenolics content i.e. 54.3 and 42.8µg/mg, respectively. Saxena et al. (2007) 17
reported higher quantities of polypheols i.e 191mg/100g. Determination of antioxidant 18
activity through some In vitro trials generated some conclusive evidences. In this 19
regard, (Kapoor et al., 2009) observed high antioxidant activities of black pepper 20
essential oil and oleoresins as compared to synthetic antioxidants. Likewise, Su et al. 21
(2007) indicated that black pepper is a potential dietary source of natural antioxidants. 22
Therefore, presence of these functional ingredients in black pepper makes it a strong 23
candidate to ameliorate oxidative stress (Mittal and Gupta, 2000). Gulçin (2005) 24
attributed these actions to its strong hydrogen-donating ability, metal chelating, and 25
effectiveness to scavenge free radicals. Additionally, synergistic effects of piperine with 26
some other antioxidants like curcumin also assign valuable position to black pepper in 27
disease prevention strategies related to ROS and allied species (Aggarwal, 2010). 28
The animal modeling using high-fat diets can be utilized to assess the antioxidant 29
activities of plants. In this regard, the production of thiobarbituric acid reactive 30
substances (TBARS) and conjugated dienes (CD) is used as indices of oxidative damage. 31
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Whilst, imbalance in activities of antioxidant enzymes including superoxide dismutase 1
(SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GPx) 2
and glutathione contents are indices of reduced antioxidant status of the body 3
(Ramasamy and Namasivayam, 2006). Vijayakumar et al. (2004) reported that 4
supplementation of black pepper/piperine lowered oxidative damage and modulated 5
the enzyme systems functioning in the body (Vijayakumar and Nalini, 2006). Rauscher 6
et al. (2007) used diabetes mellitus induction as a model of oxidative damage and 7
application of piperine @ 10mg/kg/day i.p. reversed the diabetes mediated changes in 8
Sprague Dawley rats. The effects are attributed to presence of antioxidants that further 9
results in reduced LDL-oxidation via modulation of prostaglandins and leukotrienes 10
synthesis (Srinivasan, 2005b). 11
In the nutshell, black pepper holds antioxidant potential but needs further testing 12
through controlled randomized trials (CRT’s). The results from such studies would 13
guarantee utilization of black pepper and its bioactive molecules as natural antioxidant 14
in food chain and diet based strategies to prevent various maladies. 15
B. Anti-inflammatory Potential 16
The process of inflammation can lead to the development of various ailments that 17
include arthritis, Alzheimer’s, Parkinson’s disease, and even cancer insurgence is also 18
linked with inflammatory burst. The mechanism to cope with the inflammation 19
comprises of many pathways that also include inhibition of enzymes responsible for 20
inflammatory cascade (Mueller et al., 2011). Diets containing functional ingredients 21
hold anti-inflammatory potential (Monika et al., 2010). Recent pharmacological studies 22
conducted at animals and cell levels have shown that black pepper and its active 23
ingredients piperine might be useful against these undesirable responses (Gupta et al., 24
2000; Selvendiran et al., 2003; Sabina et al., 2011). 25
Eventually, anti-inflammatory activities of black pepper are reported for the first time 26
some two decades ago. Mujumdar et al. (1990) indicated that piperine mitigate the acute 27
inflammatory process, through stimulating the pituitary adrenal axis. Later, Bang et al. 28
(2009) strengthened the anti-inflammatory activities of piperine (20 & 100 mg/kg/day) 29
through some in vitro trials. They postulated that inhibition of interlukon (IL6), matrix 30
metalloproteinase (MMPs), prostaglandin E2 (PGE2), and activator protein 1 are 31
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possible routes for their said properties. Recently, Sabina et al. (2011) reported that 1
piperine (50/100ug/ml) suppressed the level of β-glucuronidase and lactate 2
dehydrogenase in dose-dependent manner. Piperine along with some other 3
components can inhibit the expression of enzymes like 5-lipoxygenase and COX-1 that 4
are responsible for leukotriene and prostaglandin biosynthesis. These effects 5
collectively are valuable to prevent degenerative disorders like rheumatoid arthritis too 6
(Stohr et al., 2001; Lee et al., 2008). 7
Overall, the anti-inflammatory perspectives of black pepper and its active ingredients 8
should be tested in disease prevention and control associated with inflammation. 9
C. Antimicrobial Potential of Black Pepper 10
If we turn the pages of history, we can see that since long plants were employed as 11
antimicrobial agents (Irkin and Korukluoglu, 2009). Utilization of natural products 12
especially spices as antimicrobials is allied with dual benefits i.e. prevention of 13
infectious disorder, and improving health. Phytochemicals present in these products 14
hold antimicrobial potential and extensively explored in the recent epoch. Amongst, 15
phenolics possess well-documented antimicrobial potential (Weerakkody et al., 2010). 16
Black pepper and piperine hold antimicrobial properties and can remarkably limit the 17
growth of Staphylococcus aureus (Sangwan et al., 2008), S. epidermidis and Salmonella typhi 18
(Arora and Kaur, 1999). Additionally Singh et al. (2005) further strengthened the notion 19
by the proof against Bacillus cereus and B. subtilis. Recently, Weerakkody et al. (2010) 20
enumerated the significant antimicrobial potential of black pepper. Some extracts of 21
black pepper displayed excellent growth inhibition of bacteria like Staphylococcus, 22
Bacillus and Streptococcus with minimum inhibitory concentrations (MIC) of 125, 250 and 23
500ppm, respectively (Karsha and Lakshmi, 2010). Likewise, pseudomonas was more 24
susceptible to black pepper followed by Escherichia coli, Klebsiella and Salmonella (62.5, 25
125 and 250ppm MIC, respectively). 26
In this regard, Mc-Mahon et al. (1995) also reported the anti-parasitic behavior of black 27
pepper’s alkaloids against Giardia and Entamoeba species. Similar studies by various 28
other scientists concluded their potential against trypanosomes and plasmodia. One of the 29
interesting roles of black pepper is related to repellent potential against various insects 30
and rodent. Scott et al. (2002) observed that black pepper and other freshly ground 31
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peppers are sprinkled to repel many mammals. It is also reported to be effective against 1
houseflies along with its ability to depress egg-laying (MacKinno et al., 1997). The 2
extracted essential oil from black pepper can also be applied to protect grains from 3
insect damage and control worm infestations (Dorman and Deans, 2000). Some 4
bioactive molecules of black pepper find their application in allelopathic control of 5
insect-pests owing to their efficacy (Gbewonyo et al., 1993). Black Pepper oil also 6
demonstrated significant antimicrobial activity against animal pathogens (Bonjar, 2004). 7
Overall, black pepper holds substantial antimicrobial activity against various 8
microorganisms and can find different applications ranging from preserving foods to 9
prevent infections. 10
D. Gastrointestinal health and nutrient absorption 11
Black pepper and its active ingredients are commonly employed as traditional remedies 12
against gastric disturbances from time immemorial. It is widely accepted that black 13
pepper is instrumental to prevent and cure gastrointestinal problems. The black pepper 14
enhances the production of hydrochloric acid from stomach thus improving digestion 15
through stimulation of histamine H2 receptors. In addition, black pepper has 16
diaphoretic (promotes sweating), and diuretic (promotes urination) properties (Johri et 17
al., 1992; Ononiwu et al., 2002). 18
As far absorption of piperine is concerned, it is absorbed from mucosal side (44-63%) 19
that could be traced in intestinal tissue and serosal fluids (Suresh and Srinivasan, 2007). 20
Piperine improves the functionality of gastrointestinal tract. The mechanisms of action 21
include enhanced absorption of nutrients, improved enzymes synthesis, and perk-up 22
defense capabilities. The examples include enhanced intestinal absorption of 23
methionine & calcium ions, trace elements (selenium), vitamins B and β-carotene 24
(Badmaev et al., 2000; Capasso et al., 2002). The amplified nutrient absorption is 25
dependent upon the positive changes in permeability of intestinal cells membranes 26
(Srinivasan, 2007). Moreover, it protects intestinal membranes from gastric secretions 27
and ROS damage owing to antioxidant potential. Moreover, black pepper significantly 28
enhanced the activities of antioxidant enzymes i.e. SOD, catalase, GR, and GST. These 29
mechanisms collectively lead to balanced mucosal health to provide gastro-protection 30
(Irani, 2005; Chaudhry and Tariq, 2006; Prakash and Srinivasan, 2010). In addition to 31
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above, black pepper and its active ingredients improve expression of some digestive 1
enzymes along with increase in the secretion of saliva. These collectively lead to 2
facilitated digestion with reduced transit time in gastrointestinal tract (Kumoro et al., 3
2009; Bang et al., 2009; Kaefera and Milne, 2008). 4
Recently, Okumura et al. (2010) presented the hypothesis that piperine intake may 5
decrease body weight and visceral fat accumulation through increased expression of 6
thermogenic protein uncoupling protein-1 in the mice. Badmaev et al. (1999) showed 7
that black pepper could speed the metabolic procedures that generate energy in the 8
human body. Although, the same process is responsible for sustaining weight loss but 9
recognized as playing an essential role in modulating nutrients absorption from diet. 10
Moreover, piperine increases the oxygen uptake when administered to perfuse hind 11
limbs of experimental rats (Srinivasan, 2007; Eldershaw et al., 1994). Pepper juice 12
amplifies intestinal absorption of different nutrients, and piperine dose-dependently 13
restrained fatty acid oxidation in rat liver microsomes (Platel et al., 2003; 14
Tachakittirungrod et al., 2007). 15
Black pepper along with its bioactive molecules can be used in constipation and 16
diarrhea. The mode of action of black pepper and its bioactive molecules involves 17
concentration-dependent & atropine-sensitive stimulant effect, spontaneous 18
contractions similar to loperamide and nifedipine, inhibition of naloxone-sensitive 19
effect, Ca(2+) channel blocking (CCB) activity, relaxant effect, K+ (80 mM)-induced 20
contractions. These mechanisms collectively leads to spasmodic (cholinergic) and 21
antispasmodic (opioid agonist and Ca (2+) antagonist) effects as narrated by Lambert et 22
al. (2004) and Mehmood and Gilani (2010). Overall, the results are quire conclusive to 23
warrant the utilization of black pepper and its ingredients to prevent and cure various 24
gastro-intestinal disorders. 25
E. Improvement in drugs & phytochemicals delivery 26
The phytochemicals and nutrients are important to maintain the human health but issue 27
of their bioavailability needs researcher’s attention. Some bioactive molecules work 28
synergistically to improve the absorption of each other. Black pepper and piperine 29
improved the bioavailability of some phytochemicals like curcumin, catechins, etc. The 30
mechanisms for claimed effects include 1) ability to promote the rapid absorption, 2) 31
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protection from chemical reactions in the gastrointestinal tract and 3) protection against 1
oxidative damage (Agbor et al., 2010; Singletary, 2010). 2
The black pepper and piperine improve the bioavailability of many drugs. In this 3
regard, piperine enhances the oral bioavailability of carbamazepine and phenytoin 4
(drugs used to cure epilepsy) by improving their absorption (Pattanaik et al., 2009). 5
Previously, Pattanaik et al. (2006) provided evidences for synergistic effects of piperine 6
(20mg) administered with phenytoin. Likewise, supplementation of 120 mg coenzyme 7
Q10 with piperine for 21 days produced a statistically significant (p = 0.0348) greater 8
area under the plasma curve (30%) as compared to coenzyme Q10 alone (Badmaev et 9
al., 2000). The results of efficacy studies conducted by Jin and Han, (2010) suggest that 10
piperine significantly augments the oral exposure of fexofenadine in rats probably due 11
to the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal 12
absorption (Lee et al., 2006). In some studies, utilization of black pepper or its active 13
ingredients including piperine increased the bioavailability of nimesulide (anti-14
inflammatory drug). Acute toxicity studies on mice revealed a reduction in lethal dose 15
(LD50) of the combination (980 mg kg-1) as compared to nimesulide (1500 mg kg-1) alone 16
(Gupta et al., 2000). Likewise, drugs like ampicillin and Norfloxacin mediate variety of 17
bacterial infections and co-administration of 20 mg/kg of piperine can enhance their 18
effectiveness (Janakiraman and Manavalan, 2008). 19
Piperine also boosts the bioavailability of important phytochemicals contained in other 20
foods e.g. bioactive components present in curcumin and green tea (Selvendiran et al., 21
2003). Curcumin has been widely used as food additive and herbal medicine 22
throughout Asia. The combination of piperine (2.5 mg/kg, i.p., 21 days) with curcumin 23
(20 and 40 mg/kg, i.p., 21 days) showed improved anti-immobility, neurotransmitter 24
enhancing and monoamine oxidase inhibitory (MAO-A) effects of curcumin (Bhutani et 25
al., 2009; Suresh and Srinivasan, 2010). The combination of curcumin and piperine is 26
most likely to inhibit CYP3A, CYP2C9, UGT, and SULT metabolism within the 27
intestinal mucosa (Volak et al., 2008). 28
Conclusively, addition of black pepper or piperine to recipes & meals can improve the 29
restorative worth of various spices and other foodstuffs (Nakatani et al., 1986; 30
Selvendiran et al., 2003). Black pepper can enable us to reap optimum benefits from the 31
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medicinal phytochemicals found in other dietary spices. Its bioavailability enhancing 1
properties makes black pepper one of the most important spices. 2
F. Neuroprotective potential of black pepper 3
Globally, statistics are alarming regarding the mental and brain ailments. According to 4
estimate, more than 450 million people suffer from some nervous problems (Gupta et 5
al., 2000). Amongst, depression is leading source of distress and discomfort for more 6
than 20% of global population (Kessler et al., 1994). Humans in a bid to find the way out 7
to these conditions have devised many possible methods yet are not so successful in this 8
arena (Dorman et al., 2000; Fu et al., 2010). 9
The neuroprotective role of functional foods has been highlighted in the recent past to 10
cure number of ailments. In this regard, antioxidant potential of black pepper and its 11
bioactive molecules is of considerable importance to improve brain function 12
(Wattanathorn et al., 2008). Furthermore, the supplementation of piperine (5, 10 and 13
20mg/kg body/day) provides neuro-protection including improved cognitive function 14
(Hanumanthachar and Miland, 2005; Lee et al., 2005). Li et al. (2007) previously 15
investigated the antidepressant-like effect of piperine (2.5, 5 and 10 mg/kg). Their 16
results revealed that piperine ameliorated the chronic mild stress due to changes in 17
sucrose consumption, plasma corticosterone level, and open field activity. They 18
commented that up-regulation of the progenitor cell proliferation of hippocampus, and 19
cytoprotective activities are responsible for antidepressant-like effect of piperine. Later, 20
Li et al. (2007) added that piperine treatment up-regulated brain-derived neurotrophic 21
factor (BDNF) and mRNA expression. Additionally, Hu et al. (2009) indicated that 22
piperine (10 & 20 mg/kg) improved the depression through reduction in ACTH and 23
CRH levels thus ultimately leading to modulating hypothalamic-pituitary-adrenal 24
(HPA) axis.. Recently, Bhutani et al. (2009) suggested to use piperine in combination 25
with curcumin for the treatment of depressive disorders. The behavioral studies using 26
forced swimming test (FST) and tail suspension test (TST) revealed that piperine is 27
potent anti-depressant agent @ 10 & 20 mg/kg (Lee et al., 2005; Mohit et al., 2009; Liao 28
et al., 2009). 29
Currently, the number of patients suffering from Alzheimer’s disease is one of the 30
biggest challenges being faced by mankind (Filley, 1995; Zarotsky et al., 2003; Liston et 31
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al., 2004). The scientists over the globe attempted to isolate some natural products 1
suitable against such disorders (Galli et al., 2002; Youdim et al., 2002; Jabeen et al., 2007). 2
In one such study, Chonpathompikunlert et al., (2010) studied the effects of piperine in 3
rat modeling and observed that piperine (5, 10 and 20 mg/kg BW) significantly 4
improved memory impairment and neurodegeneration in hippocampus. Piperine and 5
its analog (methyl piperate) have ability to restrain the monoamine oxidases (MAO) (Li 6
et al., 2007; Naseri and Yahyavi, 2008) that is one of suitable strategy to prevent 7
neurodegenerative problems such as Alzheimer’s and Parkinson’s (Kong et al., 2004; 8
Edmondson et al., 2007; Lee et al., 2008). However, the effects of piperine on 9
neurogenesis are not well demonstrated in human subjects but modes of actions could 10
possible be reduced extent of lipid peroxidation and acetylcholinesterase enzyme 11
(Youdim et al., 2002). 12
Black pepper and its active ingredients can be supportive in treating various disorders 13
related to nervous systems that include depression, Alzheimer, epilepsy, etc. However, 14
its pharmaceutical application cannot be warranted now owing to less number of 15
scientific investigations in human subjects. Therefore, as earlier stated that controlled 16
randomized trials should be conducted keeping in mind the above discussion to bring 17
meticulousness of the issues. 18
G. Black pepper against cancer 19
According to an estimate, the prevalence of cancer can be reduced (30 to 40%) with the 20
dietary habits (Anto et al., 2002; Zhou et al., 2003). Some population-based studies also 21
indicated that consumption of foods rich in bioactive molecules can decrease the risk of 22
various ailments especially cancer. In this regard, consumption of spices is positively 23
correlated with reduced risks of cancer incidence in Asian and Mediterranean regions 24
(Mohandes et al., 1999). Even the higher risk of malignancies in developing economies 25
can be linked with the reduced intake of spices (Fleischauer et al., 2000; Sloan, 2005; 26
Selvendiran et al., 2005). 27
The anticancer perspectives of black pepper include modulation of phase-I, phase-II 28
detoxification systems, inhibition of lipid peroxidation, and indeed improvement in 29
antioxidants status (Selvendiran and Sakthisekaran, 2004). In this regard, Zhou et al. 30
(2003) presented the evidences that the positive anticancer effects of piperine against 31
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benzo-pyrene induced lung carcinogenesis in mice model are due to its ability to 1
interaction with cytochrome P450 enzyme syste,. Later, Selvendiran et al. (2004) 2
explicated that piperine exhibited in vitro and in vivo dose-dependent inhibition of 3
phase-I detoxification system (Bhardwaj et al., 2002). Moreover, piperine modulated the 4
mitochondrial tricarboxylic acid cycle and glutathione-metabolizing enzymes in animal 5
model lung carcinogenesis (Thirunavukkarasu et al., 2001; Vijayakumar et al., 2004; 6
Suresh and Srinivasan, 2006). Later, Vellaichamy et al. (2009) examined the 7
chemopreventive potential of piperine (50mg/kg) against 7,12-8
dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis. Piperine modulated 9
the phase I & II detoxification system effectively thus ameliorating lipid peroxidation. 10
In addition to aforementioned effects, the improvements in antioxidants status to 11
normal are of significant importance for health care. Likewise, Krishnakumar et al. 12
(2009) observed similar results in oral cancer bearing animals. Earlier, Nalini et al. 13
(1998) observed that black pepper may protect the colon cancer by decreasing the 14
activity of β-glucuronidase and mucinase. Pellitorine (terpinoids present in black 15
pepper) showed strong cytotoxic activities against HL60 and MCT-7 cell lines (Ee et al., 16
2010). Black pepper also counteracts cancer development directly (Selvendiran et al., 17
2004) through modification in enzyme kinetics to control the protein level in blood 18
(Polovka and Suhaj, 2010). In another study, Bogomolny et al. (2008) supported some 19
earlier studies that piperine owing to its potent antioxidant property can reduce protein 20
expression thus modulating cell proliferation and transformation (Selvendiran et al., 21
2006). Research has revealed that pepper exerts a free-radical scavenging activity that 22
assists in controlling the progression of some cancers. In some conditions, the same 23
property can be useful in reducing the growth of cancer cells (Yadav and Bhatnagar, 24
2007). More recently, Liu et al. (2010) postulated that nearly all bioactive molecules of 25
black pepper can suppress TNF-induced NF-kappaB activation. The extracts of black 26
pepper at 200 microg/mL and its compounds at 25 µg/mL inhibited lipid peroxidation 27
by 45-85%, COX enzymes by 31-80% and cancer cells proliferation by 3.5-86.8%. 28
Piperine when used in combination with curcumin yielded some promising results as 29
their combination restored the status of lipid peroxidation, antioxidants and detoxifying 30
agents in DMBA-induced bone marrow cancer (Manoharan et al., 2009). Furthermore, 31
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black pepper and cardamom extracts collectively enhance the cytotoxic activity of 1
natural killer cells that indicate their potential anti-cancer effects (Majdalawieh and 2
Carr, 2010). 3
The black pepper and its components are also effective in reducing the extent of toxicity 4
of certain components. The drastic effects of some toxic compounds like DMBA, carbon 5
tetrachloride, tert-butyl hydroperoxide, dioxin, and AFB1 are mediated by black pepper 6
and piperine (60 µM) as elaborated by some scientists (Reen et al., 1997; Koul and Kapil, 7
1993; Amakura et al., 2003; Han et al., 2008). The undesirable effects of aforementioned 8
toxic metabolites are of serious concern for human & animal health as they enter 9
through food chain and cause reproductive toxicity, teratogenicity, immune 10
dysfunction, hepatotoxicity, and endocrine changes (Schecter et al., 2006; Ishida et al., 11
2008). Researchers hypothesized that piperine may hinder hydrolysis of glucuronide 12
conjugates, causing toxins and mucinase to be degraded (Kobayashi et al., 2003; Nalini 13
et al., 1998; Srinivasan, 2007). The black pepper and its bioactive molecules hold 14
potential to prevent cancerous growth and are of important for their anti-genotoxicity 15
perspectives. 16
H. Other Health Benefits 17
The hypocholesterolemic and antioxidant property of black pepper has far-reaching 18
nutraceutical worth (Tachakittirungrod et al., 2007). The increased levels of 19
triglycerides, total & low-density lipoprotein (LDL) cholesterol are major risk factors for 20
cardiovascular disorders. Some dietary strategies can prevent prevalence and 21
pathogenesis of CVD’s. The improvement in peroxisome proliferators-activated 22
receptor (PPAR)-α is one possible route to improve the lipid profile. The piperine 23
exerted the highest trans-activational activities with EC (50) values of 84 µM and 49 µM, 24
respectively (Mueller et al., 2011). Earlier, Taqvi et al. (2008) explored underlying 25
mechanism behind cardiovascular effects of piperine (1 to 10 mg/kg). It caused a dose-26
dependent decrease in mean arterial pressure (MAP) through inhibition of K+ (80 mM) 27
precontractions & phenylephrine (PE) and Ca2+ channel blockade. Piperine (20 28
mg/kg/day) decreased the blood pressure caused by the blockage of voltage-29
dependent calcium channels (Hlavackova et al., 2010). 30
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One of the main common ailments in the world, diabetes mellitus, enforces a fabulous 1
health and social burden (McDonnell and Archbold, 1996). The pathogenesis of diabetes 2
is dependent on many factors and glycation of the various proteins in the body is of 3
considerable importance. The glycation of albumins and allied protein might lead to 4
change in nature, structure and their biochemical activity. Black pepper has inhibitory 5
effects on albumin glycation reaction (Dearlove et al., 2008; Singletary, 2010). Likewise, 6
Saraswat et al. (2009) reported inhibition of 40 to 90% (piperine @ 1.0 mg/ml) in the 7
formation of advanced glycation end-products (AGE) to lens proteins. Black pepper 8
(IC50: 0.2mg/mL) showed excellent selectivity towards aldose reductase inhibition. The 9
aforementioned discussion portrayed the message that inclusion of black pepper in 10
dietary strategies can be beneficial in management of diabetes and its complications 11
(Vijayakumar et al., 2004; Saraswat et al., 2008). However, there is still needs for some 12
community-based trials for meticulousness. 13
Black pepper extract has been studied by (Venkatasamy et al., 2004) to treat skin 14
disorders i.e. vitilago that is characterized by lesions of depigmentation. Ebihara et al. 15
(2006) suggested that black pepper excavate and its main alkaloid piperine endorse 16
stimulatory effects on melanocyte proliferation and dendricity thus it can be used for 17
the treatment of vitiligo (Soumyanath et al., 2006; Lin et al., 2007). In humans, black 18
pepper oil is one the strongest appetizer; inhalation stimulates the swallowing in post 19
stroke patients with dysphagia. Some other studies are also available regarding health 20
promoting potentials of black pepper. However, many of them are limited in their 21
applications owing to lack of animal studies. 22
Conclusion 23
In the recent epoch, much focus has been paid to functional and nutraceutical food. The 24
health promoting prospective of such products is ought to bioactive components 25
present in them. Black pepper owing to functional ingredients like piperine, oleoresins, 26
and essential oil is helpful in regulating gastrointestinal functionality. It is also helpful 27
in mediating inflammation. Black pepper can provide neuro-protection thus defending 28
the body from depression and Alzheimer’s. The synergistic effect of black pepper in 29
enhancing the bioavailability of nutrients and drugs is of considerable importance. 30
Overall, the nutraceutical perspective of black pepper is of key importance for health 31
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care consultants. However, researcher concentration is immediately required to asses its 1
health promoting potential through controlled randomized trials (CRT’s) and cohort 2
studies. Additional efforts are also required to asses its proper utilization in different 3
products and results of such studies would bring meticulousness of the concerns. 4
References 5
Agbor, A. G., Vinson, A. J., Oben, E. J., and Ngogang, Y. J. (2010). Antioxidant effect of 6
herbs and spices on copper mediated oxidation of lower and very low density 7
lipoprotein. China J. Nat. Med. 8: 114-120. 8
Agbor, G. A., Vinson, J. A., Oben, J. E., and Ngogang, J. Y. (2006). Comparative analysis 9
of the in vitro antioxidant activity of white and black pepper. Nutr. Res. 26: 659-10
663. 11
Aggarwal, B. B. (2010). Targeting inflammation-induced obesity and metabolic diseases 12
by curcumin and other nutraceuticals. Annu. Rev. Nutr. 30: 173-199 13
Amakura, Y., Tsutsumi, T., Sasaki, K., Yoshida, T., and Maitani, T. (2003). Screening of 14
the inhibitory effect of vegetable constituents on the aryl hydrocarbon receptor-15
mediated activity induced by 2,3,7,8 tetrachlorodibenzo-p-dioxin. Biol. Pharm. 16
Bull. 26: 1754-1760. 17
Anto, R. J., Mukhopadyah, A., Denning, K., and Aggarwal, B. B. (2002). Curcumin 18
induces apoptosis through activation of caspase-8, BID cleavage and cytochrome 19
c release; its suppression by ectopic expression of Bcl-2 and Bcl-xl. Carcinogenesis. 20
23: 143-150. 21
Ao, P., Hu, S., and Zhao, A. (1998). Essential oil analysis and trace element study of the 22
roots of Piper Nigrum L. Zhongguo. Zhong. Yao. Za. Zhi. 23: 42-63. 23
Arora, D. S. and Kaur, J. (1999). Antimicrobial activity of spices. Int. J. Antimicrob. 24
Agents. 12: 257-262. 25
Badmaev, V., Majeed, M., and Norkus, E. (1999). Piperine, an alkaloid derived from 26
black pepper increases serum response of beta-carotene during 14-days of oral 27
beta-carotene supplementation. Nutr. Res. 193: 381-388. 28
Badmaev, V., Majeed, M., and Prakash, L. (2000). Piperine derived from black pepper 29
increases the plasma levels of coenzyme Q10 following oral supplementation. J. 30
Nutr. Biochem. 11: 109-113. 31
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Bandhopadhyay, C., Narayan, V. S., and Variyar, P. S. (1990). Phenolics of green pepper 1
berries Piper Nigrum L. J. Agric. Food. Chem. 38: 1696-1699. 2
Bang, J. S., Oh da, H., Choi, H. M., Sur, B. J., Lim, S. J., Kim, J. Y., Yang, H. I, Yoo, M. C., 3
Hahm, D. H., and Kim, K. S. (2009). Anti-inflammatory and antiarthritic effects of 4
piperine in human interleukin 1beta-stimulated fibroblast-like synoviocytes and 5
in rat arthritis models. Arthritis. Res. Ther. 11: R49. 6
Bhardwaj, R. K., Glaeser, H., Becquemont, L., Klotz, U., Gupta, S. K., and Fromm, M. F. 7
(2002). Piperine, a major constituent of black pepper, inhibits human p-8
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carcinogenesis in Swiss albino mice. Pulm. Pharmacol. Ther. 19: 107–111. 30
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Vijayakumar, R. S. and Nalini, N. (2006). Efficacy of piperine, an alkaloidal constituent 17
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Vijayakumar, R. S., Surya, D., and Nalini, N. (2004). Antioxidant efficacy of black 20
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UK. 13
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metabolites in the leaf and berries of selected black pepper varieties. Sci. Horti. 16
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Table-1: Botanical Classification of black pepper
Groups Name
Kingdom Plantae
Subkingdom Tracheobionta
Superdivision Spermatophyta
Division Magnoliophyta
Class Magnoliopsida
Subclass Magnoliidae
Family Piperales
Order Piperaceae
Genus Piper L
Specie Piper nigrum L.
Source: USDA, NRCS. 2010. The PLANTS Database (http://plants. usda.gov, 9 May 2010).
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Table 2: Rich phytochemistry of the black pepper
Sr. No. Researcher Chemical Components Percentage
1. Lee et al. (2004)
Singletary (2010)
Essential oil
Piperine
Chavicine
Piperidine
Fatty oils
Resin
Starch
1-2.5%
5-9%
1%
8%
6-8%
0-5%
22-42%
2. Ravindran and Johny,
(2001)
Essential oil
Piperine
Starch
Oleoresin
0.4 to 7.0%
2.0 to 7.4%
15-45%
3.5-12
3. Murthy and Bhattacharya
(2008)
Essential oil (limonene, β-
caryophyllene, sabinene and β-pinene)
4. Singh et al. (2005) Acetone extract
Piperine
Piperolein
Piper amide
Guineensine
33.5%
13.7%
3.4%
3.23%
5. Utpala et al. (2008) Phenol contents 0.3 to 0.8 mg/g
6. Orav et al. (2004)
Musenga et al. (2007)
Essential oil
β-caryophyllene
Limonene
β-pinene
∆-3-carene
Sabinene
α-pinene
Eugenol
Terpinen-4-ol
Hedycaryol
β-eudesmol
Caryophyllene oxide
α-phellandrene
1.4-70.4%
2.9-38.4%
0.7-25.6%
1.7-19.0%
0-12.2%
0.3-10.4%
0.1-41.0%
0-13.2%
0-9.1%
0-9.7%
0.1-7.2%
NA
7. Jirovetz et al. (2002) Elemol
Germacrene-D
Limonene
Β-pinene
α-pinene
β-ocimine
β-pinene
α-phellandrene
αhumulene
∆-carene
Βphellandrene
T-muurolol
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Table 3: Functional & Nutraceuticals Effect of Bioactive Compounds of Black Pepper
Bioactive
compounds
Functional & Nutraceuticals Role Researchers
Piperine
1. Bio-absorption of vitamins and trace elements.
2. Effective against acute inflammatory process
3. Antimicrobial properties
4. Improved functionality of gastrointestinal tract.
5. Decreased body weight and visceral fat accumulation
6. Improved bioavailability of curcumin and catechins
7. Enhanced bioavailability of many drugs
8. Piperine ameliorate the chronic mild stress
9. Reduce risk of cancer
10. reducing the extent of toxicity of certain components
Kumoro et al., 2009/
Capasso et al., 2002
Bang et al., 2009
Sangwan et al., 2008
Badmaev et al., 2000
Okumura et al. 2010
Singletary, 2010
Pattanaik et al., 2009
Li et al. 2007
Vellaichamy et al. 2009
Han et al., 2008
Essential oil
1. Contributes aroma
2. Control worm infestations
Zachariah et al., 2010
Dorman and Deans, 2000
Phenolics 1. Reduce oxidation process
2. Ameliorating oxidative stress
Renjie et al., 2010
Saxena et al., 2007
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Journal: Critical Reviews in Food Science and Nutrition
Manuscript ID: BFSN-2011-0286
Manuscript Title: BLACK PEPPER AND HEALTH CLAIMS: A COMPREHENSIVE
TREATISE
Dear Editor,
I have seen the reviewer’s comments eagerly and made the following changes in the
article as per desired.
Query 1. The some text in the article should be written again as language should be
simple and lucid for the readers and researchers. The use of same
sentences/concepts /aspects at multiple places should be avoided.
Answer 1. Corrections have been made. Now, appropriate words are used for
specific purpose.
Query 2. Health benefits should be checked again and each aspect should be
discussed only at one place. I would suggest the authors to add up one or
two table regarding the health promoting potential of the black pepper.
Answer 2. Every aspect related to health endorsing effects of black pepper has been
discussed separately only at one place. Table regarding health benefits of
black pepper has now been added in the manuscript.
Query 3. Finally yet importantly, grammatical errors should be removed.
Answer 3. All grammatical errors have been eliminated from the text.
Query 4. The first line of the abstract should be as “For millennia, spices have been
an integral part of human diets and commerce. Recently, the widespread
recognition of diet-health linkages bolsters the dietary importance of
spices and herbs”
Answer 4. It has been changed according to reviewer’s comments
Query 5. The words selection should be appropriate especially in the abstract
section e.g. “hold” is used twice that should be avoided
Answer 5. Proper and suitable words has been incorporated in text especially
abstract portion and duplication has been removed.
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Query 6. Page 1, Line 24: The sentence use should “Black pepper (Piper nigrum L.)
is an important healthy food owing to its antioxidant & antimicrobial
potential and gastro-protective modules”
Answer 6. Now, sentence is according to reviewer’s suggestions.
Query 7. From abstract, “More recently, cell-culture studies and animal modeling
predicted the role of black pepper against number of maladies” can be
omitted as its duplication of same concepts mentioned earlier.
Answer 7. We all authors have discussed and suggested that this sentence has
different meanings and not considered as duplication
Query 8. Page 1, Line 37: Component should be replaced with components in the
abstract. Accordingly, the complete sentence should be re-written.
Answer 8. The word “components” has remained same as it means different
components of piper nigrum.
Query 9. Meta-analysis represents single expression or experiment so it should be
changed to meta-analyses
Answer 9. Changes has been incorporated according to reviewer’s comments
Query 10. First and second paragraph can be combined into one. I think following
could be one possibility “In the recent era, efforts have been directed to
establish scientific rationale for health improving potential of functional
and nutraceuticals foods. Amongst, prevention of cardiovascular
disorders (CVD), cancer insurgence, diabetes mellitus, Alzheimer’s
disease, and variety of inflammatory ailments through dietary modules is
of prime consideration. Moreover, emerging findings in the nutrigenomics
and proteomics further reflected their importance in a deeper sense
(Chonpathompikunlert et al., 2010). The list of healthy foods marketed
with distinct health claims is long enough. However, spices and their
bioactive components are more promising candidates for their inclusion in
diet-based regimens to improve human health (Geoffrey, 2006; Butt et al.,
2009). Their different parts including dried seed, bark, fruit, root, and
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flower are in use as food adjuncts that impart flavor, aroma and color to
foods (Srinivasan, 2008; Singletary, 2010)”.
Answer 10. First and second paragraph of manuscript has now been combined
Query 11. Chonpathompikunlert et al., 2010 should be checked again. Is paper
published in 2010 or 2009 as two references are given in reference section?
Answer 11. Chonpathompikunlert et al., 2010 has been published in 2010.
Query 12. Why authors written these sentence e.g. “Being the sole reason for many
of the attacks in the ancient ages, still considered instrumental in the
economies of many nations across the globe (Srinivasan, 2005)” and
“During the era of industrialization and globalization, these commodities
were traded in the western countries that led to wide bloom in their
production” as they must be deleted. I would suggest authors to look into
introduction again and reduce its length to 3/4th. Moreover, the sentences
should be linked with each in the same paragraphs.
Answer 12. The Correction has been and these sentences were deleted from the text
Query 13. Page 3, Line 1: Human subject should be replaced with human subjects
Answer 13. It has been done according to suggestions
Query 14. The last two paragraphs can also be merged up into one.
Answer 14. Both paragraphs has been combined
Query 15. Functional uses can be replaced with applications
Answer 15. Changes has been incorporated according to comment
Query 16. The first paragraph should be re-written again. Last sentence can be
deleted. The authors should delete the reference “DM, 2009”
Answer 16. Changes have been made in first paragraph. Reference has also been
deleted.
Query 17. The authors should be specific is use of unit systems as mol−1 is not right
as it should be mol−1. Please check the manuscript again
Answer 17. Unit has been written properly. All manuscript has now been carefully
written.
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Query 18. “Piperine and its allied components like piperidine and chavicine are
responsible for pungent properties of black pepper (Badmaev et al., 2000;
Bhattacharjee and Sengupta, 2009)” should be adjusted at the end of first
paragraph of heading “piperine”
Answer 18. Correction has been made accordingly
Query 19. Page 6, Line 17: “Black pepper essential oil contributes towards the aroma,
oleoresin contributes towards the overall taste, and the alkaloid piperine
imparts pungency (Zachariah et al., 2010)” should be adjusted in the first
paragraph of the main heading.
Answer 19. All has been incorporated according to reviewer’s suggestion
Query 20. The section of essential oil & phenolics should be re-written
Answer 20. This portion has now been re-written again
Query 21. The introduction of each aspect/sub-heading should be deleted. It will
reduce the length of the article considerably. The same point is valid for
some other parts of the manuscript too e.g. Page 7 (Line 13-19), Page 10
(Line 4-10), Page 14, Line 7-21), Page 18 (Line 28-30), etc. The text should
be reduced in all these cases.
Answer 21. All sub headings has been deleted from the text.
Query 22. Humanity should be replaced with mankind as humanity is property not
noun.
Answer 22. Humanity has now been replaced with mankind
Query 23. “using different assays i.e. thiobarbituric acid value (TBA), DPPH radical
scavenging, and total antioxidant activity (FTC method)” can be deleted
Answer 23. It has been done according to reviewer’s comments
Query 24. “In addition, the inhibitory action as observed through FTC method
strengthened the claims for strong antioxidant activities of essential oil
and oleoresins” can also be deleted
Answer 24. It has been done according to reviewer’s comments
Query 25. Page 8, Line 18: Paragraph needs re-phrasing to make it lucid
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Answer 25. Paragraph has been re-phrased
Query 26. “Spices and herbs are traditional remedies to cure some maladies and
diseased conditions in South Asian territories” is duplication thus should
be removed
Answer 26. All duplicate sentences have been removed from the text.
Query 27. Re-arrange the section “Anti-inflammatory Potential” to make it lucid and
introductory details should be avoided. e.g. “They postulated that
inhibition of interlukon (IL6), matrix metalloproteinase (MMPs),
prostaglandin E2 (PGE2), and activator protein 1” need further clarity
Answer 27. The paragraph has been re-arranged and cleared completely
Query 28. C. Antimicrobial Potential of Black Pepper. Reference support is limited
Answer 28. More references has now been added in this portion
Query 29. Gastrointestinal health and nutrient absorption needs revision in first and
last paragraph to clear the evidences presented
Answer 29. The literature regarding gastrointestinal health and nutrient absorption
has been revised properly.
Query 30. Page 13, Line 5-21. Can data be presented in Tabular form?
Answer 30. The details are mentioned in the text. Therefore, its tabular presentation
would be only duplication of findings not else
Query 31. “Several research interventions resulted in finalizing the assumption that
the depressed state is result of many factors that act into play; of which,
patho-physiological changes of depression includes the increased
glucocorticoid secretion followed by decreased level of brain derived
neurotrophic factor in the hippocampus” can be deleted
Answer 31. The section has been deletec
Query 32. “The combination of all these parameters can lead to the state where
reduction of hippocampal volume occurs thus resulting in depression and
allied discrepancies” can also be deleted
Answer 32. The section has been deletec
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Query 33. “Chronic stress procedure (CSP) induction in rats is suitable model used
worldwide to assess the potential of dietary components and drugs
against depression” can also be deleted.
Answer 33. The section has been deletec
Query 34. “The efficacy of drugs is limited as they are effective in the initial stages
but unable to stop the cascade of events going on the central nervous
system” can not be claimed as most of ailments are treated with the
pharmaceuticals
Answer 34. The section has been deleted and suggestion has been incorporated
Query 35. Last paragraph at Page 15 should be re-written
Answer 35. The last paragraph has been skipped as it was carrying information
supported by only one or two references
Query 36. First paragraph at “Black pepper against cancer” should be revised.
Answer 36. The paragraph is revised and its now writes as “According to an estimate,
the prevalence of cancer can be reduced (30 to 40%) with the dietary habits
(Anto et al., 2002; Zhou et al., 2003). Some population-based studies also
indicated that consumption of foods rich in bioactive molecules can
decrease the risk of various ailments especially cancer. In this regard,
consumption of spices is positively correlated with reduced risks of cancer
incidence in Asian and Mediterranean regions (Mohandes et al., 1999).
Even the higher risk of malignancies in developing economies can be
linked with the reduced intake of spices (Fleischauer et al., 2000; Sloan,
2005; Selvendiran et al., 2005)”.
Query 37. The citations like “Zhou et al. (2003)”, Vellaichamy et al. (2009), and
Krishnakumar et al. (2009) needs little elaboration regarding their findings
and mechanisms of action. Its looks only addition of references, as their
results is not properly elaborated.
Answer 37. The results of researchers suggested above are mentioned in the text.
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Query 38. The section “Other Health Benefits” needs some greater considerations as
authors just piled up information and literature rather made conclusive
discussion. The section can be completely omitted. However, if authors
want to retain the text than a Table/figure can be more useful
Answer 38. The section is reviewed again and duplications and unnecessary details
are now skipped from the text.
Query 39. Paragraph starting from Vanilloid receptor (TRPV1) should be completely
omitted ass its just contains three studies and no clear links are discussed
with special reference to nutrition point of view.
Answer 39. The complete paragraph has been deleted
Query 40. In my view, “Some other studies are also available regarding health
promoting potentials of black pepper. However, many of them are limited
in their applications owing to lack of animal studies” should be added at
the end of heading “Other health benefits”
Answer 40. The answer is same as to mentioned in Suggestion 35
Query 41. Authors should check references section again for style and etc. Some
references needs to be cited in the text and vice versa
Answer 41. The references style has been checked again and mistakes observed are
corrected.
I would like accept that mistakes removed from the article considerably and indeed I
am looking forward for better write-up and presentation skills in the future. Lastly, I
would like to request to kindly accept the manuscript as it has been considerably
improved.
Corresponding authors
M. Tauseef Sultan
Assistant Professor
Bahauddin Zakariya University
Multan
Email: tauseefsultan@hotmail.com
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