Mareecham-Black pepper (Piper nigrum) Part 4
Mareecham-Black pepper (Piper nigrum) Part 4
In this article, I discuss the phytopharmacology of
some more phytochemicals found in Mareecham-Black pepper (Piper nigrum)
Piperidine
Molecular
formula: (CH2)5NH, C5H11N
Structural
formula:
[169]
Piperidine is heterocyclic amine. It is a colorless
liquid with a disagreeable or objectionable odor. Piperidine was first reported
in 1850 by the Scottish chemist Thomas Anderson and in 1852 by the French
chemist Auguste Cahorus. Both obtained piperidine by reacting piperine with
nitric acid. Pyridine can also be reduced to piperidine via a modified Birch
reduction using sodium in ethanol. Piperidine itself has been obtained from
Mareecham-Black pepper (Piper nigrum)
[170]
Pharmacokinetics of Piperidine
Piperidine a colorless liquid
can be absorbed through intestine via breath, skin and all mucous membranes.
While piperidine is metabolized in the liver and excreted by kidney, it can
damages both the organs.
Anti-inflammatory
and Antioxidant activity of Piperidine
To investigate anti-inflammatory activity of
piperidine, paw edema was induced in rats by using carrageenan. To one group,
piperidine was administered orally at 100, 250 and 500mg/kg body weight doses.
To another group, dexamethazone was administered intraperitoneally (IP) at the
dose of 2mg/kg body weight. The study indicated that piperidine had a potent
anti-inflammatory activity comparable to that of dexamethasone.
Furthermore antioxidant activity of piperidine was
investigated by standard methods. The study revealed that piperidine exhibited
antioxidant activity comparable to ascorbic acid, a commercial synthetic
antioxidant. [171]
Immonomodulatory
activity of Piperidine
Piperidine and its derivatives display glycosidase
inhibiting and immunosuppressive activities. Glycosidase inhibitory activity
was studied against α-glucosidase, α-galactosidase and α-mannosidase with
reference to known standard N-hydroxyethyl 1-Deoxynojirimycin (DNJ: trade name
Miglitol). Immunosuppressive activity was evaluated in vitro by the ability of piperidine derivatives to inhibit the
proliferation of human lymphocytes in the Mixed Lymphocyte Reaction (MLR) and
to inhibit the production of Immunoglobulin G (IgG). [172]
Antibacterial activity of Piperidine
Piperidine, sodium piperidine
and some of its synthetic derivatives showed in vitro antibacterial activity against Staphylococcus aureus ATCC 1501, Bacillus subtilis ATCC 6633, Yersinia
enterococolitica ATCC 1501, Escherichia
coli ATCC 11230 and Klebsiella
pneumoniae [173]
Recently six novel derivatives
(No. 5 to10) have been synthesized. They show strong antioxidant activity. Due
to this they are potent antibacterial agents. Of these compound 6 showed the
strongest inhibitory activity against seven bacteria tested. [174]
Piperidine-4-one, a new
derivative of piperidine has been synthesized recently. Its antimicrobial
activity was characterized by using Fourier-transform infrared spectroscopy
(FTIR), hydrogen-1 nuclear magnetic resonance (1H-NMR), 13C nuclear magnetic
resonance (13C NMR), mass spectroscopy and zone of inhibition. It was found to
be a potent antibacterial agent against Bacillus
subtilis. [175]
Antiviral
activity of Piperidine
Researchers have developed a series of
N(2)-(1-(substituted-aryl)piperidin-4-yl)-N(6)-mesityl-9H-purine-2,6-diamine
derivative (piperidine derivative). Further study revealed that the compound
showed antiviral activity against HIV, influenza A/H1N1 (strain A/PR/8/34) in
Madin-Darby canine kidney cells. [176]
Antifungal
activity of Piperidine
Piperidine, sodium piperidine and some of its
synthetic derivatives showed in vitro
antifungal activity against Candida
albicans. [177]
Recently six novel derivatives
(No. 5 to10) have been synthesized. They show strong antioxidant activity. Due
to this they are potent antifungal agents. Compounds 5, 6, 9 and 10 reveal
varying degree of inhibition against Aspergillus
niger, Aspergillus flavus, Saccharomyces cervisiae and Candida albicans. At
1000 μg/ml compound 8 demonstrates the highest scavenging capacity of 78% and
compound 6 the least scavenging potential of 49%. [178]
Piperidine-4-one, a new
derivative of piperidine has been synthesized recently. Its antimicrobial
activity was characterized by using Fourier-transform infrared spectroscopy
(FTIR), hydrogen-1 nuclear magnetic resonance (1H-NMR), 13C nuclear magnetic
resonance (13C NMR), mass spectroscopy and zone of inhibition. It was found to
be a potent antifungal agent against Candida
albicans. [179]
Actions of
Piperidine against Parasites
A series of 44 derivatives of 4-aminipiperidine was
screened in vitro for antiprotozoan
activity. The study showed that they were active against Trypanosoma brucei rhodesienses, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. [180]
Piperidine derivative R. D. 7098 was tested for its
efficacy against intestinal amoebiasis in 30 patients. R. D. 7098 showed a
definite clinical improvement in 73% of patients. The clinical improvement was
supported by stool examination and sigmoidoscopic examination. Toxic reactions
were nausea and epigastric pain. [181]
Piperidine and its derivatives were found to be
effective against the human parasite Giardia
intestinalis. [182]
Actions of
Piperidine on wound healing
Naturally occurring piperidine, synthetic piperidine
and synthetic derivatives of piperidine were screened for their wound healing
activity on Swiss albino rats. The study showed that epithelization and wound
contraction was faster in wounds treated with these compounds than the
untreated wounds. The tensile strength of the scar significantly increased. The
results were similar to the wounds treated with Nitrofurazone. [183]
Actions of
Piperidine on the Breast
Naturally occurring piperidine, synthetic piperidine
and synthetic derivatives of piperidine were screened for their activity
against breast cancer. The results showed that they were effective in
controlling ER-positive and ER-negative breast cancer. This effect is
attributed to their potent antioxidant and oxygen-free-radical scavenging
activities. [184]
Actions of
Piperidine on Hematopoetic system
Naturally occurring piperidine, synthetic piperidine
and its synthetic derivatives showed myelo-stimulatory activity. [185]
Actions of
Piperidine on Eyes
When injected intravenously piperidine caused
contraction of the nictitating membrane in cats and dogs. [186]
Actions of
Piperidine on Endocrine System
In two series
of experiments, piperidine produced pressor action by liberation of adrenaline
or another pressor compound from the adrenal glands. [187]
Actions of
Piperidine onMusculoskeletal System
Piperidine displays antidegenerative activity. Its
antioxidant, anti-inflammatory and analgesic properties can be useful for the
treatment of arthritis.
Actions of
Piperidine on Nervous System
Larger doses of tetraethyl ammonium chloride i. e. 20
and 30mg/kg body weight reversed the responses to piperidine.
In cats under chlorarose anesthesia, sympathectomy
reduced the pressor response to piperidine.
Cocaine administered prior to sympathectomy slightly
increased the responses to piperidine.
Piperidine and its derivatives display analgesic
effects. [188]
Alzheimer’s disease is associated with decrease in the
activity of the cholinergic system in the cerebral cortex and other areas of
the brain. It is caused by reduced synthesis of acetylcholine by
cholinesterase. A study shows that piperidine inhibits cholinesterase and
stabilizes the levels of acetylcholine in the brain. Thus piperidine can be
useful for the prevention and treatment of Alzheimer’s disease. [189]
Actions of
Piperidine on Cardiovascular System
In experiments on cats, piperidine was found to
stimulate the liberation of acetylcholine from the perfused superior cervical
ganglion. Intravenous injection of 5mg of piperidine hydrochloride to cats was
found to release acetylcholine and reduce blood pressure.
In study on dogs, 10 mg of piperidine reduced elevated
blood pressure. Tetraethyl ammonium bromide did not abolish the depressor
responses to piperidine. [190]
Actions of
Piperidine on Respiratory System
Piperidine exerts stimulant
action on respiration. [191]
Actions of
Piperidine on Gastrointestinal System
Piperidine hydrochloride at the dose of 0.5 mg
stimulated the contractions of rabbit’s intestine. This effect was very similar
to that of nicotine and was not abolished by atropine. [192]
Actions of
Piperidine on Female Reproductive System
In three experiments piperidine caused increase in
tone in the horns of guinea pig uterus. In non-pregnant cat uterus piperidine
caused increase in tone which was ineffective in the presence of atropine
sulphate. [193]
Antitumor
activity of Piperidine
Piperidine and its derivatives display anti-tumor
activity against drug-resistant tumors. [194]
Interactions
of Piperidine
A study on mice demonstrated that simultaneous
administration of nitrite and piperidine led to marked increase in the
incidence of the cancer of urinary bladder [195]
Toxicity of
Piperidine
· Contact with piperidine can severely irritate and burn
the skin and eyes with possible eye damage.
· Breathing piperidine can cause irritation of nose,
throat, trachea and lungs causing sneezing, coughing and wheezing.
· Exposure to piperidine can cause dizziness, headache,
irritability, depression, fatigue and muscle weakness.
· Exposure to piperidine can cause salivation, nausea,
vomiting and griping pain in abdomen.
· Piperidine can cause liver and kidney damage. [196]
Dose of Piperidine
By intra venous (IV) route: 0.06mg/kg body weight
By subcutaneous route: 0.1mg/kg body weight [197]
Chavicine
Molecular
formula: C17H19NO3
Structural
formula:
Chavicine is an alkaloid found in Mareecham-Black
pepper (Piper nigrum). It is one of
the four geometric isomers of piperine. [198]
Chavicine was believed to cause the peculiar taste of
pepper.
On storage chavicine is slowly transformed into
piperine.
Actions of Chavicine
on Nervous System
Aluminum, especially Aluminum Chloride (AlCl3)
is neurotoxic agent. It causes oxidative stress that leads to accumulation of
amyloid-plaques in the brain. Chavicine protects the brain from aluminum
induced neurotoxicity. Chavicine also acts as memory enhancer. [199]
Many
pharmaceutical activities of Chavicine are similar to Piperine and Piperidine.
Dipiperamide
D
Molecular formula:
C36H40N2O6
Structural
formula:
Dipiparamide
D an alkaloid from Mareecham-Black pepper (Piper
nigrum) belongs to the class of organic compounds known as benzodioxoles.
These are compounds containing a benzene ring fused to either isomers of
dioxoles. Dioxole is a five-membered unsaturated ring of two oxygen atoms and three
carbon atoms.
[200]
Two
new bisalkaloids, dipiperamides D and E were isolated as inhibitors of a drug
metabolizing enzyme cytochrome P450 (CYP) 3A4
from the white pepper, Piper nigrum.
Their structures were elucidated by spectroscopic methods. Dipiperamides D and
E showed potent CYP3A4 inhibition with IC50
values of 0.79 and 0.12 uM, respectively, and other metabolites from the pepper
were moderately active or inactive. [201]
Dipiperamide
E
Molecular
formula: C34H38N2O6
Structural
formula:
[202]
Pharmacological
properties of Dipiperemide D and Dipiperamide E are similar to those of
Piperine and Piperidine.
Some Testimonials from Modern Research
Pharmacokinetics
of Piper nigrum
Mareecham-Black pepper (piper nigrum) is a bioenhancer par excellance so it should be used
regularly in clinical arena. Mareecham-Black pepper (Piper nigrum) should be used in combination with drugs acting on
nervous system, GI system, respiratory system, cardiovascular system etc,
especially with antibiotics and anticancer drugs. [203], [204]
Anti-inflammatory and analgesic activities of Piper nigrum
In a study anti-inflammatory activity of hexane
extract of Mareecham-Black pepper (Piper
nigrum) was evaluated against carrageenan-induced paw inflammation in rats,
analgesic activity was determined by tail immersion method. The study showed
that Mareecham-Black pepper (Piper nigrum)
displayed anti-inflammatory and analgesic activities. [205]
Antipyretic activity of Piper nigrum
To evaluate antipyretic activity of alcoholic extract
of Mareecham-Black pepper (Piper nigrum)
in Wistar albino rats, pyrexia was induced in rats by injecting 15% w/v
Brewer’s yeast suspension. Administration of 100, 250 and 500mg/kg body weight
of the extract showed antipyretic activity. [206]
Antioxidant activity of Piper nigrum
Methanolic extract of Maricham-Black pepper (Piper nigrum) L fruits display a potent
antioxidant activity by inhibiting lipid peroxidation, lipoxygenase and
arresting hydroxyl and superoxide free radicals. [207]
When there is imbalance between free radical
generation and antioxidant activity, oxidative stress is generated which is
harmful to our body, causing simple health problems to genesis of cancers.
Different kinds of free radicals can attack cell membrane, alter membrane
permeability, damage cell membrane, cause oxidation of lipids, cause loss of
enzymatic activities and ultimately disrupt cell function and body physiology
which may cause cancer. Plants are a potent source of antioxidant activity that
protects body systems. Maricham-Black paper (Piper nigrum) is one such antioxidant that protects body by
antagonizing oxidative stress at various levels. [208], [209]
Immuunomodulatory activity of Piper nigrum
The aqueous extracts of Mareecham-Black pepper (Piper nigrum) significantly enhance
splenocyte proliferation in a dose-dependent fashion. The extracts enhance T
helper (Th) 1 cytokine release by splenocytes. Experimental evidence suggests
that Maricham-Black pepper (Piper nigrum)
displays a potent immunomodulatory activity. [210]
Antibacterial activity of Piper nigrum
Qualitative analysis of methanol and chloroform
extracts of Maricham-Black pepper (Piper
nigrum) showed the presence of alkaloids, tannins, flavonoids and cardiac
glycosides. The presence of phytochemicals in the extracts showed antibacterial
activity against Staphylococcus aureus,
Salmonella typhi, Escherechia coli and Proteus species. [211]
In another study Maricham-Black pepper (Piper nigrum) showed antibacterial
activity against Streptococcus mutans
isolated from tooth decay and inflammation of the teeth and Eschericiia coli from patients with
diarrhea. [212]
A group of researchers isolated phytochemicals (1)
2E.4E, 8Z-N-isobutyleicosatrienamide (2) pellitorine (3) tracheone (4)
pergumidiene and (5) isopiperolein B from the berries of Maricham-Black pepper
(Piper nigrum). All the
phytochemicals were active against Bacillus
subtilis, Bacillus sphaericus and
Staphylococcus aureus, Gram positive
bacteria; and Chromobacterium violaceum and
Klebciella aerogenes, Gram negative
bacterial strains. [213]
In another study the researchers found that
Maricham-Black pepper (Piper nigrum)
altered the membrane permeability of the cells there by acting as antibacterial
agent against Staphylococcus aureus, Bacillus cereus, Streptococcus faecalis, Pseudomonas
aeruginosa, Salmonella typhi and Escherichia coli.[214]
The chloroform extract of Maricham-Black pepper (Piper nigrum) when incubated with Escherichia coli and Staphylococcus aureus inhibited the
bacterial growth. The extract enhanced permeability of bacterial cell membrane,
affected the metabolic rate of glycolysis, disrupted the normal metabolism of
bacteria and disrupted the bacterial respiration. [215]
Recently by using nanotechnology, silver nanoparticles
of leaf and stem extracts of Maricham-Black pepper (Piper nigrum) have been synthesized. They show antibacterial
activity against Gram positive and Gram negative bacteria. [216]
Antifungal activity of Piper nigrum
At concentration of 25 mg/mL methanol and petroleum
ether extracts of Maricham-Black pepper (Piper
nigrum) displayed antifungal activity against Candida albicans while at concentrations of 12.5 mg/mL the methanol
extract of the leaf of Maricham-Black pepper (Piper nigrum) displayed antifungal activity against Aspergillus species. [217]
In another study, cold water, hot water extracts and
pepper soup of the leaf of Maricham-Black pepper (Piper nigrum) displayed antifungal activity against Candida albicans. This activity was
attributed to the presence of tannins, flavonoids and alkaloids in the leaf of
the plant. [218]
A group of researchers screened ethanolic extract of
Maricham-Black pepper (Piper nigrum)
for antifungal activity against Candida
albicans by disc diffusion method. They found that at concentrations 500,
1000 and 2000μg the extract displayed antifungal activity against Candida albicans. [219]
Antiprotozoal activity of Piper nigrum
Visceral leishmaniasis is a life-threatening disease.
Ethanolic and Hexane extracts of seeds of Mareecham-Black pepper (Piper nigrum) showed profound
leishmanicidal activity against Leishmania
donovani promastigoates and amastogoates via apoptosis. [220]
Anthelmintic activity of Piper nigrum
In experimental phytopharmacology the anthelmintic
activity of a phytochemical is evaluated against earthworm instead of round
worm.
The alcoholic extract of the dried fruits of
Mareecham-Black pepper (Piper nigrum)
was found to kill earthworm (Pheritima
prosthuma). The anthelmintic activity was comparable to that of
Albendazole. Hence researchers concluded that Mareecham-Black pepper (Piper nigrum) had anthelmintic activity
against round worms (Ascaris lumbricoides).
[221]
Actions of Piper nigrum on Nervous system
Day by day the incidence of anxiety-depression and
Alzheimer’s disease is increasing. Modern drugs used for their treatment have
many untoward side effects. Hence search is on for safer herbal drugs to treat
these neurological disorders.
A study shows that methanolic extract of fruit of
Mareecham-Black pepper (Piper nigrum)
significantly exhibits anxiolytic and antidepressant activities by attenuating
oxidative stress. Further the extracts improve the clinical picture of
Alzheimer’s disease. [222]
Another study was done in corticosteroid induced
depression model of mice. After administration of Mareecham-Black pepper (Piper nigrum)/Piperine the depression
and behavioral changes significantly improved. [223]
A study showed that Mareecham-Black pepper (Piper nigrum) significantly improved the
memory in aluminum trichloride (AlCl3) induced neurotoxicity mouse
model. These effects were attributed to the phytochemical chavicine present in
Mareecham-Black pepper (Piper nigrum).
[224]
Actions of Piper nigrum on Cardio Vascular System
In
another experimental study on rats, Maricham-Black pepper (Piper nigrum) was administered to the animals in 250mg/kg and 500
mg/kg body weight for 10 weeks. The lipid profile showed a significant
reduction in total cholesterol, phospholipids, free fatty acids and
triglycerides thus preventing the risk of atherosclerosis. [225]
Actions of Piper nigrum on Respiratory System
Mareecham-Black pepper (Piper nigrum) shows antitussive and bronchodilator properties. The
addition of little amounts of powdered Mareecham-Black pepper (Piper nigrum) in green tea significantly
reduces bronchial asthma. [226], [227]
Actions
of Piper nigrum on Gastrointestinal
Systen
Mareecham-Black pepper
(Piper nigrum) increases the
production of saliva, activates salivary amylase, promotes gastric secretion
and decreases gastric transit time. [228]
Oral administration of
1.5 G of Mareecham-Black pepper (Piper
nigrum) to healthy volunteers significantly increased pepsin and parietal
cell secretion, gastric cell exfoliation and potassium (K+) loss.
[229]
Oral administration of
aqueous extract of Mareecham-Black pepper (Piper
nigrum) at doses of 75, 150 and 300 mg/kg body weight displayed
antimotility, antisecretory and antidiarrheal effects. The effect was dependent
on dose administered. The authors concluded that this effect was due to
alkaloids present in Mareecham-Black pepper (Piper nigrum). [230]
Further some
researchers had showed antibacterial activity of Mareecham-Black pepper (Piper nigrum) causing diarrhea. [231]
Actions
of Piper nigrum on Liver
Oral administration of
the methanol extract of fruit of Mareecham-Black pepper (Piper nigrum) at 100 and 200 mg/kg body weight for 15 days
decreased the hepatotoxicity induced by ethanol and carbon tetrachloride (CCl4)
in Wistar rats. Administration of Mareecham-Black pepper (Piper nigrum) significantly decreased the elevated levels of
Triglycerides (TG), Aspartate Aminotransferase (AST), Alanine Aminotransferase
(ALT), Alkaline Phosphatase (ALP) and Bilirubin. [232]
In another study liver
toxicity was induced with D-galactosamine. Administration of Mareecham-Black
pepper (Piper nigrum) protected the
liver from major liver damage. [233]
Actions
of Piper nigrum on Metabolism
In anti-adipogenesis
study Mareecham-Black pepper (Piper
nigrum) extract inhibited the adipocyte differentiation without affecting
normal cells. [234]
Actions
of Piper nigrum against Diabetes
Mareecham-Black pepper
(Piper nigrum) lowers elevated levels
of serum glucose due to its antioxidant property. [235]
Actions
of Piper nigrum on Male Reproductive
System
Administration of 25
and 100 mg/kg body weight of fruit powder of Mareecham-Black pepper (Piper nigrum) for 20 and 90 days to male
mice showed spermicidal activity. The histopathological study of testis showed
non-uniform degenerative changes in the seminiferous tubules. The seminiferous
tubules showed intraepithelial vacuolation, loosening of germinal epithelium,
occurrence of giant cells and mixing of spermatids of different stages of
spermatogenesis; in severe cases, the tubules were lined by mainly a layer of
Sertoli cell. These changes were dose and duration dependent. The treatment for
20 days did not cause appreciable alterations in histological appearance of epididymis,
while the treatment for 90 days caused detectable alterations in the duct.
Fifty six days after cessation of treatment the organs and their functions
returned to normal. [236]
Antitumor
activity of Piper nigrum
In many experimental
studies, Mareecham-Black pepper (Piper
nigrum) has been reported to display anticancer activity. It inhibits
formation of tumor at various stages of tumoergenesis. This activity was
attributed to antioxidant and immunomodulatory property of the herb. [237]
Further research showed
that phytochemicals, especially piperine present in Mareecham-Black pepper (Piper nigrum), arrests proliferation and
G1/S transition of tumor cells causing their death without harming normal
cells. This is due to inhibition of angiogenesis. [238]
Mareecham-Black pepper
(Piper nigrum) displayed anticancer
activity against androgen dependent and nondependent prostate cancer.
Mareecham-Black pepper
(Piper nigrum) also exhibited
anticancer activity against lung cancer and breast cancer. Further it was to be
useful in arresting metastasis of these cancers. This activity was attributed
to anti-inflammatory, anti-oxidant, free radical scavenging and
immunomodualting properties of the plant. [239], [240]
Toxicity and adverse effects of Piper nigrum
The ethanol extract of
the plant was not toxic to rats up to 5000mg/kg body weight. This suggests that
these levels could be safe for human consumption. Mareecham-Black pepper (Piper nigrum) was devoid of toxicity up to
2000 mg/kg body weight in experimental mice. [241]
Traditional
and Ayurvedic Uses of Mareecham-Black pepper (Piper nigrum)
Traditionally, as
household medicine and in Ayurveda; Mareecham-Black pepper (Piper nigrum) is used----
·
as appetizer
·
as digestant
·
to relieve hyperacidity and heartburn
·
as antiflatulent and carminative agent
·
as antidiarrheal agent
·
to relieve constipation
·
as detoxicating agent
·
as health stimulant
·
as spice
·
for respiratory disorders as
decongestant
·
as anthelmintic
·
for weight loss
·
as antidiabetic agent
·
to reduce fever
·
to treat rheumatism and arthritis
·
for skin care especially in vitiligo
Uses
in Modern Medicine
In modern medicine, Mareecham-Black
pepper (Piper nigrum) is used----
·
as a bioenhancer
·
as anti-inflammatory, antioxidant and immunomodulatory
agent
·
to improve absorption of food and drugs
·
as memory enhancer
·
as antipsychotic and antidepressant
·
as an adjunct to many groups of drugs
such as antibiotics, anticancer drugs
·
to lower lipid levels
·
as anti-obesity drug
·
to treat diabetes
·
for contraception in males
Formulations
and doses:
Trikatu: Equal parts of
Shunthi (Zingiber officinale),
Mareecham (Piper nigrum) and Pippali
(Piper longum)
Dose: Adults: 500 mg to 3 grams per day to be divided in 3-4 doses up to 7 days
Children: One to two
pinchful 3-4 times a day up to 7 days
Marichi Choorna
(Powder of Black pepper):
Marichyadi Vati:
Marichi Taila,
Mareechyadi Taila: For
skin care alopecia, vitiligo, psoriasis
References:
171. K. Tharini and P. Sangeetha,
Antioxidant and anti-inflammatory activity of 3,3-Dimethyl 2,6-Dimethyl
Piperidine 4-one oxime, Int. J. Chem. Sci.: 13(4), 2015, 1794-1804
172.
Pramod R Markand et al, γ-Hydroxyethyl Piperidine Iminosugar and N-Alkylated Derivatives: A study of
their activity as glycosidase inhibitors and as immunosuppressive agents
173. Arsian S et al,
Antimicrobial activity studies on some piperidine and pyrrolidine substituted
halogenobenzene derivatives, J Enzyme Inhib Med Chem. 2006 Apr; 21(2): 211-4
174. Leeantha Naiker
et al, Antimicrobial and antioxidant activities of piperidine derivatives,
African Journal of Pharmacy and Pharmacology, Vol. 9(31), pp783-792, August
2015
175. Pandurangan
Perumal et al, Characterization and Antimicrobial Activity of Piperidine-4-one
Derivative, Inventi Rapid: Med Chem Vol. 2014, Issue 3, May 2014.
176. Kang D et al, Synthesis and
Preliminary Antiviral Activities of Piperidine-substitutes Purines against HIV
and Influenza A/H1N1 Infections, Chem Biol Drug Des 2015 Oct; 86(4): 568-77
177. Arsian S et al,
Antimicrobial activity studies on some piperidine and pyrrolidine substituted
halogenobenzene derivatives, J Enzyme Inhib Med Chem. 2006 Apr; 21(2): 211-4
178. Leeantha Naiker
et al, Antimicrobial and antioxidant activities of piperidine derivatives,
African Journal of Pharmacy and Pharmacology, Vol. 9(31), pp783-792, August
2015
179. Pandurangan
Perumal et al, Characterization and Antimicrobial Activity of Piperidine-4-one
Derivative, Inventi Rapid: Med Chem Vol. 2014, Issue 3, May 2014.
180. Dardonville C et al, Antiprotozoal
activity of 1-phenethyl-4-aminopiperidine derivatives, Antimicrob Agents
Chemother 2009 Sep; 53(9): 3815-21
181. B. D. Pimperkar, P Raghavan, S. S.
Satoskar, A clinical trial of 1-dichloroacetyl-4-methylpiperidine (R. D. 7089)
a new anti-amoebic drug, Transactions of the Royal Society of Tropical Medicine
and Hygiene, Volume 60, Issue 2, 1966, Pages 237-240
182. Bahadur V et al, O (2)-dependent
efficacy of novel piperidine- and piperazine-based chalacones against the human
parasite Giardia intestinalis, Antimicrob Agents Chemother. 2014; 58(1): 543-9
183. K Vinaya et al, Evaluation of in vivo
wound-healing potential of
2-[4-(2,4-dimethoxy-benzoyl)-phenoxy]-1-[4-(3-piperidine-4-yl-propyl)-piperidine-1-yl]-ethanone
derivatives, European Journal of Medicinal Chemistry 44(8): 3158-65, April 2009
184. Arun A et al, New piperidine
derivative DTPEP acts as dual-acting breast cancer agent by targeting ERα and
downregulating PI3K/Akt-PKCα leading to caspase-dependent apoptosis, Cell
Prolif 2018 Dec 2018 51(6): e12501
185. Tynyshtyk K. Iskakova, Synthesis and
Myelostimulatory Activity of 1-(2-Ethoxyethyl) Piperidine Derivatives, Procedia
Chemistry, Volume 10, 2014, Pages 358-363
186. Mary F Lockett, Some Pharmaceutical
Actions of Piperidine, Pyrrolidone and of Pressor Concentrates from Dog Urine,
Brit. J. Pharmacol. (1949), 4, 111
187. Mary F Lockett, Some Pharmaceutical
Actions of Piperidine, Pyrrolidone and of Pressor Concentrates from Dog Urine,
Brit. J. Pharmacol. (1949), 4, 111
188. Mary F Lockett, Some Pharmaceutical
Actions of Piperidine, Pyrrolidone and of Pressor Concentrates from Dog Urine,
Brit. J. Pharmacol. (1949), 4, 111
189. Sharon L. Rogers, Cholinergic Basis
for Alzheimer Therapy pp 314-320; E2020- The Pharmacology of a Piperidine
Cholinesterase Inhibitor
190. Mary F Lockett, Some Pharmaceutical
Actions of Piperidine, Pyrrolidone and of Pressor Concentrates from Dog Urine,
Brit. J. Pharmacol. (1949), 4, 111
191. Mary F Lockett, Some Pharmaceutical
Actions of Piperidine, Pyrrolidone and of Pressor Concentrates from Dog Urine,
Brit. J. Pharmacol. (1949), 4, 111
192. Mary F Lockett, Some Pharmaceutical
Actions of Piperidine, Pyrrolidone and of Pressor Concentrates from Dog Urine,
Brit. J. Pharmacol. (1949), 4, 111
193. Mary F Lockett, Some Pharmaceutical
Actions of Piperidine, Pyrrolidone and of Pressor Concentrates from Dog Urine,
Brit. J. Pharmacol. (1949), 4, 111
194. Yanqun Zeng et al, Design and synthesis
of piperidine derivatives as novel human heat shock protein 70 inhibitors for
the treatment of drug-resistant tumors, European Journal of Medicinal
Chemistry, Volume 97, 5 June 2015, Pages 19-31
195. BG Chemie; Toxikologische Bewertung
Nr. 72, Piperidine
196. https://nj.gov/health/eoh/rtkweb/documents/fs/1543.pdf
196. https://nj.gov/health/eoh/rtkweb/documents/fs/1543.pdf
New Jercy Department of Health and Senior
Services, Hazardous Substance Fact Sheet, September 1999
197. https://www.sciencedirect.com/topics/neurosciences/piperidines
198.
https://en.wikipedia.org/wiki/Chavicine
199. Ghazala Iqbal et al, Memory Enhancing
Effect of Black Pepper in the AlCl3 induced Neurotoxicity Mouse
Model is Mediated Through Its Active Component Chavicine, Current
Pharmaceutical Biotechnology, Volume 17, Number 11, 2016
201. Sachiko T
Sukamoto, CYP3A4 Inhibitory Activity of New Bisalkaloids, Dipiperamides D and
E, and Cognates from White Pepper, Bioorganic and Medicinal Chemistry, Volume
10, Issue 9, September 2002, Pages 2981-2985.
202.
https://pubchem.ncbi.nlm.nih.gov/compound/Dipiperamide-E
203. Han HK, The effects of black pepper on
intestinal absorption and hepatic metabolism of drugs, Expert Opin Drug Metab
Toxicol, 2011 Jan; 7(6): 721-9
204. Patil T. S. and Wele A. A., Significance of
pharmacokinetics and pharmacodynamics of Piper nigrum L (Marich) as an
ingredient and possible marker of Ayurvedic Formulations, Indian Drugs; 44(5)
May 2007
205. Tasleem F et al, Analgesic and anti-inflammatory activities of
Piper nigrum L, Asian Pac J Trop Med. 2014 Sep; 7S1: S461-8
206. A. Nagateja Pavani et al, Antipyretic activity of piper nigrum in
Wistar albino rats; https://www.semanticscholar.org/paper/Antipyretic-activity-of-Piper-nigrum-in-Wistar-rats-Pavani
207. Zoheir A Damanhouril et al, A Review on Therapeutical of Piper
nigrum L. (Black Pepper): The King of Spices, Med Aromat Plants, Volume 3,
Issue 3, 1000161
208. Duangjai A et al, Black pepper and piperine recuce cholesterol
uptake and enhance translocation of cholesterol transporter pproteins, J Nat
Med. 2013; 67: 303-310
209. Nahak G and Sahu RK Phytochemical evaluation and antioxidant
activity of Piper cubaba and Piper nigrum, J Applied Phar. Sci. 2011; 1(8):
153-157
210. Amin F. Majdalawieh and Ronald I Carr, In vitro Investigation of
the Potential Immunomodulatory and Anti-Cancer Activities of Black Pepper (Piper nigrum) and Cardamom (Elettaria cardamomum); Journal of
Medicinal Food, Vol 13, No. 2
211. P. Ganesh et al, Phytochemical analysis and antibacterial activity
of Pepper (Piper nigrum L.) against some hyman pathogens, Scholats Research
Library Central European Journal of Experimental Biology, 2014, 3 (2): 36:41
212. Zahraa Mohammad Kaho et al, Evaluation of Antibacterial Activity
of Piper nigrum Extract against Streptococcus mutans and Escherichia coli, J.
Pharm. Sci. & Res. Vol. 11(2), 2019, 363-370
213.
S. Venkat Reddy et al, Antibacterial constituents from the berries of Piper
nigrum, Phytomedicine, Volume 11, Issues 7-8, 25 November 2004, Pages 697-700
214. Karsha et al, Antibacterial activity of black pepper (Piper nigrum Linn) with special
reference to its mode of action on bacteria, IJNPR Vol. 1 (2) June 2010
215. Wenxue Chen et al, Effects of Black Pepper (Piper nigrum L.)
Chloroform Extract on the Enzymatic Activity and Metabolism Escherichia coli
and Staphylococcus aureus, Journal of Food Quality, Volume 2018, Article ID
9635184, 9 pages.
216. Kanniah Paulkumar et al, Piper nigrum Leaf and Stem Assisted Green
Synthesis of Silver Nanoparticles and Evaluation of Its Antibacterial Activity
Against Agricultural Plant Pathogens, The Scientific World Journal, Volume
2014, Article ID 829894, 9 pages.
217. Mohd. Sayeed Akthat et al, Antimicrobial activity of Piper nigrum L. and Cassia didymobotyra L. leaf extract on selected food borne
pathogens, Asian Pacific Journal of Tropical diseases, Volume 4, Suppliment 2,
September 2014, Pages S 911-S919
218. Lovet T et al, Antimicrobial efficacy of leaf extracts of Piper
nigrum against Escherichia coli, Staphylococcus aureus and Candida albicans,
Journal of Basic Pharmacology and Toxicology, 2017; 1(2): 32-36
219. Gayathri Karthikeyan, Antimitotic activity of Piper nigrum on
clinical isolates of candida, International Journal of Research in
Pharmaceutical Sciences, Volume 10 Issue 2 2019
220. Chouhan G et al, Leishmanicidal activity of Piper nigrum bioactive fractions is interceded via apoptosis in vitro and substantiated by Th1
immuno-stimulatory potential in vivo, Frontiers in Microbiology, 2015; 6: 1-19
221. L. E. Sheeja George et al, Anthelmintic activity of the alcoholic
extract of the dried fruits of Piper
nigrum, Indian J. Sci. Res. 19(2): 62-64, 2018
222. Hritcu L et al, Anxiolytic and
antidepressant profile of the methanolic extract of Piper nigrum fruits in
beta-amyloid (1-42) rat model of Alzheimer’s disease, Behaviorial and Brain
Function, 2015; 11 (13): 1-13
223. Mao QQ et al, Piperine reverses the
effects of corticosterone on behavior and hippocampal BDNF expression in mice,
Neuro Chem Int. 2014; 74: 36-41
224. Gazala Iqbal et al, Memory Enhancing
Effect of Black Pepper in AlCl3 Induced Neurotoxicity Mouse Model is
Mediated Through Its Active Component Chavicine, Current Pharmaceutical
Biotechnology, 2016, 17, 000-000
225.
Vijaykumar RS et al, Hypolipidemic effect of Black pepper (Piper nigrum) in Rats Fed High Fat Diet, J Clin. Biochem. Nutr.
2002; 32: 31-42
226. Majeed M et al, Use of piperine as
bioavailability enhancer, United State Patent, 1999; (5): 972, 382
227. Ahmad N et al, Biological role of Piper nigrum (Black pepper): A review,
Asian Pacific Journal of Tropical Biomedicine, 2012; 1945-1953
228. Singh A and Duggal S, Piperine- Review of
advancec in pharmacology, Int. J. Pharm. Sci. Nanotech. 2009; 2: 615-620
229.
Myers BM et al, Effect of red pepper and black pepper on the stomach, Am J
Gastroenterol, 1987; 82: 211-214
230.
Shamkuwar PB et al, Evaluation of anti-diarrheal effect of Black pepper (Piper nigrum L), Asian Journal of Plant
Science and Research, 2012; 2: 48-53
231.
Sapam R et al, Screening of phytochemicals and determination of total phenolic
content, antioxidant and antibacterial activity of methanolic extract of Piper
nigrum, Indo American Journal of Pharmaceutical Research, 2018; 8(2):
1354-1360
232.
Nirwane AM and Bapat AR, Effect of methanolic extract of Piper nigrum fruits in ethanol-CCl4 induced hepatotoxicity in Wistar
rars, Der. Pharmacia. Lettre, 2012; 4: 795-802
233.
Singh A and Duggal S, Piperine- Review of advancec in pharmacology, Int. J.
Pharm. Sci. Nanotech. 2009; 2: 615-620
234. Park UH et al, Piperine a
component, of Black pepper, inhibits adepogenesis by antagonizing PPARγ
activity in 3T3-L1 Cells, J Agrc. Food Chem. 2012; 60: 3853-3860
235.
T Khaliq et al, Recent Progress for the Utilization of Curcuma longa, Piper
nigrum and Phoenix dactylifera Seeds against Type 2 Diabetes, West Indian Med J.2015
Dec; 64(5): 527-532
236.
Mishra RK et al, Antispermatogenic and antifertility effects of fruits of Piper
nigrum L in mice, Indian J Exp Biol. 2009 Sep; 47 (9): 708-714
237.
Damanhouri ZA et al, A review on therapeutic potential of Piper nigrum (Black pepper): The King of Species, Medicinal and
Aromatic Plants 2014; 3(3): 1-6
238.
Doucette CD et al, Piperine a dietary phytochemical, inhibits angiogenesis, The
Journal of Nutritional Biochemistry 2013; 24: 231-239
239.
Selvendiran K et al, Chemopreventing effect of piperine modulating lipid
peroxidation and membrane bound enzymes in benzo (a) pyrene induced lung
carcinogenesis, Boimedicine and Pharmacotherapy 2004; 58: 264-267
240.
Sriwiriyanjan S et al, Anticancer and cancer prevention effects of
piperine-free Piper nigrum extract on
N-nitrosomethylurea-induced mammary tumerogenesis in rats, Cancer Prev. Res.
2016; 9(1):74-82
241.
O. Onyesife Chioma et al, Toxicological Assessments of Piper nigrum on Alloxan
Induced Diabetic Rats, American-Eurasian Journal of Toxicological Sciences 6
(2): 30-34, 2014
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