Articles

Piper nigrum

Synonyms

No documentation

Vernacular Names:

Malaysia: Lada, Lada sulah, Lada Hitam, Lada Putih
English:  Black Pepper
Indonesia:  Marica (Java); Lada, Pedes (Sunda); Lada, Lado, Ketek, Lado kobon (Sumatra)
Thailand:  Priktai
India:  Maricha, Ushana, Hapucha, Pipali
China:  Hu Jiao
Hong Kong:  Woo Jiu
Japan:  Kosho
Korea:  Hu Chu Na Mu
French:  Poivre Noir [1]

General Information

Description

Piper nigrumis a climbing/trailing plant of the Piperaceae family. The stem is jointed and forked, of a green colour but woody texture. When trailing on the ground, every joint bears roots. The leaves are ovate, entire, smooth, sessile, roundish and coriaceous; each with seven nerves; upper surface is dusky green while underneath is of paler green. The petiole is short. Flowers are small and monopetalous, divided into three segments at the end, having no peduncles, but are placed in cluster on the stalk. The fruit which succeeds is a berry; twenty to thirty crowding one stalk, at first green, then red, and afterwards black, but white internally. [1]

Plant Part Used

Pepper is the fruit of the plant P. nigrum. The black pepper is dried unripe fruit while white pepper is dried ripe fruit with the pericarp removed. These are the medicinal and culinary part of the plant that is most commonly used. Leaves, stems and roots are sometimes used. [1] 

Chemical Constituents

1(7),2-p-menthadien-4-ol; 1(7),2-p-menthadien-6-ol; 1,1,4-trimethylcyclohepta-2,4-dien-6-one; 1,8(9)-p-menthadien-4-ol; 1,8(9)-p-menthadien-5-ol; 1,8-menthadien-2-ol; 1-terpinen-4-ol; 1-terpinen-5-ol; 2,8-p-menthadien-1-ol; 2-methyl-pentanoic-acid; 2-undecanone; 3,8(9)-p-menthadien-1-ol; 5,10(15)-cadinen-4-ol; b-caryophyllene-alcohol; borneol; carvacrol; caryophylla-2,7(15)-dien-4-beta-ol; caryophylla-2,7(15)-dien-4-ol; caryophylla-3(12),7(15)dien-4-beta-ol; cis-2,8-menthadien-2-ol; cis-p-2-menthen-1-ol; methyl-carvacrol; methyl-eugenol; isopulegol; limonen-4-ol;linalol; myrtenol; nerolidol; p-cymene-8-ol; 3-methyl-butyric-acid; a-linolenic-acid; ascorbic-acid; benzoic-acid; butyric-acid; cinnamic-acid; hexanoic-acid; isochavinic-acid; oleic-acid; oxalic-acid; phenylacetic-acid; lauric-acid; linoleic-acid; myristic-acid; palmitic-acid; piperonic-acid; 4,10,10-trimethyl-7-methylene-bicyclo-(6.2.0)decane-4-car; a-cis-bergamotene; a-copaene; a-guaiene; a-humulene; a-pinene; a-santalene; a-selinene; a-terpinene; a-thujene; a-trans-bergamotene; a-curcumene; b-bisabolene; b-carotene; b-caryophyllene; b-elemene; b-farnesene; b-pinene; b-selinene; calamene; calamenene; camphene; cis-ocimene; d-limonene; d-3-carene; d-cadinene; d-elemene; epoxydihydrocaryophyllene; g-cadinene; g-muurolene; g-terpinene; isocaryophyllene; l- a-phellandrene; l-limonene; myrcene; p-cymene; sabinene; sesquisabinene; terpinen-4-ol; terpinolene; a-cubebine; b-cubebine; chavicine; cubebine; n-methyl-pyrroline; piperanine; piperidine; piperettine; piperyline; pellitorine; (E)-1-[3',4'-(methylenedioxy)cinnamoyl]piperidine; piperine; paprazine; dehydropipernonaline; b-pinone; carvetonacetone; carvone; caryophyllene-ketone; cryptone; dihydrocarvone; m-methyl-acetophenone; n-butyophenone; p-methyl-acetophenone; methyl-cyclohepta-2,4-dien-6-one; ubiquinone; cepharadione A; boron; chlorine; chromium; camphor; caryophyllene-oxide; methyl-caffeic-acid-piperidide; retrofractamide A; pipercide; piperchabamide D; dehydroretrofractamide C; 2,4-tetradecadienoic acid isobutyl amide; sylvamide; cis-sabinene-hydrate; citronellyl-acetate; eugenol; geranyl-acetate; isobutyl-caproate; isobutyl-isovalerate; linalyl-acetate; methyl-cinnamate; methyl-heptanoate; methyl-octanoate; trans-sabinene-hydrate; terpinyl-acetate; citral; citronellal; myrtenal; perillaldehyde; piperonal; heliotropin; myristicin; niacin; piperin; piperolein-a; piperolein-b; piperolein-c; riboflavin; thiamine; pellitorin; n-nonadecane; n-nonane; n-tridecane; p-cymene-8-methyl-ether; phytosterols; safrole; 1,8-cineole; a-terpineol; cis-carveol; dihydrocarveol; trans-carveol; trans-pinocarveol; piperolactam D [6]

Traditional Use:

P. nigrum is a spice and a medicine much revered throughout the world since it was introduced to the western culture a long time ago. It had been used a currency at one time being exchanged in similar manner as gold. Famous physicians of the past had said many good things of the medicinal values of this spice. 

Piper nigrum L. is acrid and is easily recognizable when applied to the tongue. Upon swallowing it creates a sensation of warmth in the stomach assisting digestive functions. It is a stimulant of the secreting system. It is given in cases of vomiting, abdominal pain, diarrhoea and anorexia. The Japanese use pepper to treat acute gastroenteritis. In Chinese Traditional Medicine the roots and stems are used to treat vomiting and abdominal pain by giving a decoction of it orally.  [1][2] 

On the skin it acts as a rubefacient and a vesicant. It also promotes diaphoresis and is an excitant to the mucous surfaces. For these effects it is used to treat common cold, cough with expectoration and fever in general and morbid cholera. An infusion of previously toasted peper is very effectual for this purpose. [3] 

P. nigrum is one of the acrid species recognized when we apply it to the tongue. On the skin it acts as a rubefacient and vesicant. Swallowed, it stimulates the stomach, creates a sensation of warmth in this viscus, and, when used in small doses, assists the digestive functions, but if given in large quantities induces an inflammatory condition. Thirty white peppercorns, taken for a stomach complaint, induced violent burning pain, thirst, and accelerated pulse, which continued for three days, until the fruits were evacuated. It is a stimulant to the vascular and secreting systems. It accelerates the frequency of the pulse, promotes diaphoresis, and acts as an excitant to mucous surfaces. It is regarded as a stimulant for the uro-genital apparatus. 

P. nigrum is being used in the treatment of inflammatory diseases like gout and rheumatism. In these cases large doses of the drug is being prescribed. [4] Dioscorides recommend its use in infective inflammatory process like tonsillitis and scrofulous tumour. [5] The Chinese physicians are in agreement with Dioscorides in its use to treat tonsillitis but they recommend its use in the more serious form i.e quincy. [6] 

P. nigrum is considered an abortifacient by Dioscorides. He made pessaries which is inserted intra-vaginally as a contraceptive method. [5] 

Chinese physians recognizes its anticonvulsant and sedative properties and recommend its use in the treatment of various forms of palsies. Its anticonvulsive property has a slow onset taking 2 – 3 days of continuous administration to show an effect. [6] 

Pre-Clinical Data

Pharmacology

Melanocyte proliferative and melanin synthesis activity

The ability of a substance to induce the proliferation of melanocytes is an essential element in the treatment of vitiligo. Lin et.al first reported such activity in the aqueous extract of P. nigrum. They isolated piperine (1-piperoylpiperidine) an alkaloid and found that both this compound and the total extracts has the ability to not only stimulate the proliferation of melanocytes but also caused morphological changes with more and longer dentrite formations. This augmentation of growth seems to be mediated through the protein kinase C signaling pathway. [7] In a recent study they found that the crude chloroform extract was more effective than an equivalent concentration of the pure compound piperine in stimulating the proliferation of melanocytes. They identified the following compounds in the extract to be responsible for this effect i.e. piperine, guineensine and pipericide. It is concluded the methylenedioxyphenyl function with the presence of an amide group is essential for the melanocyte stimulatory activity. [8] 

While piperine was able to stimulate proliferation of melanocytes, they are not able to excite the synthesis of melanin. Soumyanath A et. al found that by exposure to UVA resulted in photoisomerization of piperine which causes loss in its abilty to stimulate melanocyte proliferation and its binding ability to serum albumin. This suggest that exposure to sunlight after application of piperine to the skin should be avoided. They also suggest that should UVA be incorporated in the treatment of vitiligo using piperine, then irradiation and application of piperine should be staggered in order to effectively induce pigmentation. [9] Earlier to this Matsuda et. al had isolated two lignans from the leaves of P. nigrum which showed significant stimulatory activity of melanogenesis without any significant effects on cell proliferation. These two lignans were identified as (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin. [10] 

Anti-inflammatory and antimicrobial activity

In evaluating the anti-inflammatory activity of piperine it was found that it acted on the early acute phase of inflammatory processes and also on the chronic granulative process but not the exudative processes. This action was found to be partially due to the stimulation of the pituitary adrenal axis. [11] 

While screening 21 species of alimentary plants for their antimicrobial activity against Streptococcus aureus, studies found that extracts of P. nigrum was effective in inhibiting the growth of this bacteria. [12] Studies found that a number of compound they isolated from the petroleum ether extract of the berries of P. nigrum were active against Bacillus subtilis, Bacillus sphaericus, and Staphylococcus aureus amongst Gram + ve bacteria, and Klebsiella aerogenes and Chromobacterium violaceum among Gram -ve bacterial strains. These compounds were 2E, 4E, 8Z-N-isobutyleicosatrienamide (1), pellitorine (2), trachyone (3), pergumidiene (4) and isopiperolein B (5). [13] 

Anti-oxidant activity

P. nigrum has been used in the treatment of many conditions and one of the activities attributed to it that contributed to these medicinal values is its antioxidant activity. Investigation of anti-oxidant activity of black pepper and piperine in rats with high fat diet induced oxidative stress. It is reported that supplementing the diet with black pepper and/or piperine significantly reduced thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and maintained the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione (GSH) in the liver, heart, kidney, intestine and aorta. This indicates that the supplementation was successful in reducing hig-fat diet induce oxidative stress to the cells of rats. [14] Further demonstration showed that the water and ethanol extracts of P. nigrum has anti-oxidant and radical scavenging activities as proven by their series of assays including the following - total anti-oxidant activity, reducing power, 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, and metal chelating activities. [15] Another study concluded the fact that amongst the plants they tested for their anti-oxidant activities P. nigrum proved to be the one with the highest activity. [16] 

Antispasmodic activity

It was observed that the hot water extract of P. nigrum was able to inhibit spasm of isolated rat ileum induced by KCl. Study suggested that the spasmolytic effects was possibly mediated via Ca2+ influx. [17] 

Bioavailability enhancement activity

Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals. This is attributed to its ability to inhibit enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucoronyl transferase. [18] Administration of piperine together with beta-lactam antibiotics (amoxicillin trihydrate and cefoxamine sodium) enhanced the bioavailability of these antibiotics. This is reflected in various pharmacokinetic parameters viz. tmax, Cmax, t(1/2) and AUC of these antibiotics. [19] Almost similar effects were seen when it was given together with phenobarbitone to rats. The sleeping time was potentiated and the blood and brain levels of phenobarbitone were higher. [20

Hypotensive and vasomodulator activity

Piperine is the dominant alkaloid in black pepper. It has been shown to have hypotensive and vasomodulator effects on the cardiovascular system. Intravenous administration of piperine resulted in a decrease in the Mean Arterial Pressure (MAP) in normotensive anaesthetized rats and this is followed by a small rise in MAP after each dose. It also caused a partial inhibition of force and rate of ventricular contractions and coronary flow. Piperine inhibited high K= (80 mM) pre-contractions and partially inhibited phenylephrine indicating it has a Ca2+ channel blockade activity. In a Ca2+ free medium piperine exhibited vasoconstrictor effect. There is endothelial-independent vasodilator effect more potent against high K+ percontractions than phenylephrine. It is concluded that piperine has hypotensive effects mediated via Ca2+ Channel Blockade (CCB), the decrease is limited by associated vasoconstrictor effect. [21]

Toxicities

No documentation

Clinical Data

Clinical Trials

No documentation

Adverse Effects in Human:

No documentation

Use in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

No documentation

Read More

  1) Botanical Info

  2) Cultivation

  3) Malaysian Herbal Plants

  4) Essential Oil

References

  1. P. Jonathan. The Elements of Materia Medica and Therapeutics. pg. 387-388 Longman, Brown, Green and Longmans London 1855
  2. K.S. Chung, K. Takeatsu, P.H.B. Paul, G. Ji-Xian. International Collation of Traditional and Folk Medicine: Northeast Asia. World Scientific Publishing 1997 pg 48
  3. C. Nathaniel. Elements of therapeutics and materia medica, Volume 2. Carey & Lea Philadelphia 1831 pg. 97
  4. J.T. Robert. A new family herbal. R & R Crosby and Co. London 1814 pg. 33 – 34
  5. A. Tess. Osbaldeston Dioscorides De Materia Medica. IBIDIS Press 2000 Pg. 316 – 318
  6. C.H. Kee, M.W. Walter. The pharmacology of Chinese herbs. CRC Press Boca Raton 1999 pg. 164
  7. Z. Lin, J.R. Hoult, D.C. Bennett, A. Raman. Stimulation of mouse melanocyte proliferation by Piper nigrum fruit extract and its main alkaloid, piperine. Planta Med. 1999 Oct;65(7):600-3.
  8. Z. Lin, Y. Liao, R. Venkatasamy, R.C. Hider, A. Soumyanath. Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation in-vitro. J Pharm Pharmacol. 2007 Apr;59(4):529-36.
  9. A. Soumyanath, R. Venkatasamy, M. Joshi, L. Faas, B. Adejuyigbe, A.F. Drake, R.C. Hider, A.R. Young. UV irradiation affects melanocyte stimulatory activity and protein binding of piperine. Photochem Photobiol. 2006 Nov-Dec; 82(6):1541-8.
  10. H. Matsuda, Y. Kawaguchi, M. Yamazaki, N. Hirata, S. Naruto, Y. Asanuma, T. Kaihatsu, M. Kubo. Melanogenesis stimulation in murine B16 melanoma cells by Piper nigrum leaf extract and its lignan constituents. Biol Pharm Bull. 2004 Oct;27(10):1611-6.
  11. A.M. Mujumdar, J.N. Dhuley, V.K. Deshmukh, P.H. Raman, S.R. Naik SR. Anti-inflammatory activity of piperine. Jpn J Med Sci Biol. 1990 Jun;43(3):95-100.
  12. C. Pérez, C. Anesini. Antibacterial activity of alimentary plants against Staphylococcus aureus growth. Am J Chin Med. 1994;22(2):169-74.
  13. S.V. Reddy, P.V. Srinivas, B. Praveen, K.H. Kishore, B.C. Raju, U.S. Murthy, J.M. Rao. Antibacterial constituents from the berries of Piper nigrum. Phytomedicine. 2004 Nov;11(7-8):697-700.
  14. R.S. Vijayakumar, D. Surya, N. Nalini. Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress. Redox Rep. 2004;9(2):105-10
  15. I. Gulcin. The antioxidant and radical scavenging activities of black pepper (Piper nigrum) seeds. Int J Food Sci Nutr. 2005 Nov;56(7):491-9.
  16. K.S. Natarajan, M. Narasimhan, K.R. Shanmugasundaram, E.R. Shanmugasundaram. Antioxidant activity of a salt-spice-herbal mixture against free radical induction. . J Ethnopharmacol. 2006 Apr 21;105(1-2):76-83
  17. M.K. Naseri, H. Yahyavi. Antispasmodic effect of Piper nigrum fruit hot water extract on rat ileum. Pak J Biol Sci. 2008 Jun 1;11(11):1492-6.
  18. K. Srinivasan. Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr. 2007;47(8):735-48.
  19. A.R. Hiwale, J.N. Dhuley, S.R. Naik. Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats. Indian J Exp Biol. 2002 Mar;40(3):277-81.
  20. A.M. Mujumdar, J.N. Dhuley, V.K. Deshmukh, P.H. Raman, S.L. Thorat, S.R. Naik. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp Biol. 1990 May;28(5):486-7.
  21. S.I. Taqvi, A.J. Shah, A.H. Gilani. Blood pressure lowering and vasomodulator effects of piperine. J Cardiovasc Pharmacol. 2008 Nov;52(5):452-8.