Black pepper, King of spices, Piper nigrum, difference between pepper and chili pepper, origin of black pepper, pharmacology of piperine, benefits of black pepper, bioenhancer

1. SPICE AS MEDICINE:
BLACK PEPPER “KING OF SPICES”
PIPER NIGRUM
By
Kevin KF Ng, MD, PhD
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, Miami, FL, USA
Email: kevinng68@gmail.com
A slide presentation for HealthCare Provider Seminar June 2019

2. Outline of Lecture: Black Pepper
▪ Difference between pepper and chili pepper
▪ History, scientific classification
▪ Nutrient composition
▪ Bioactive compounds
▪ Bioavailability
▪ Pharmacology of piperine
▪ Side effects, safety, interactions
▪ Commercial products
▪ Summary

3. Difference between Pepper and Chili Pepper

4. What is Black Pepper?
▪ Black pepper is a flowering vine in the family Piperaceae.
▪ It is cultivated for its fruit, known as peppercorn.
▪ The fruit is dried and used as a spice and seasoning.
▪ Varieties:
▪ black peppercorns
▪ white peppercorns
▪ black pepper essential oil
▪ ground black pepper

5. Common names of pepper (piper nigrum )
https://www.botanical-online.com/en/botany/black-pepper-characteristics

6. Origin and Habitat of Black Pepper
http://bioweb.uwlax.edu/bio203/2011/haggerty_adam/habitat.html
Kerala
India

7. Spice Trade Map of Dutch East India Company and
British India Company
http://zhang.digitalscholar.rochester.edu/mapping/wp-content/uploads/2018/09/Spices_Ahn-Doyoung-min.png

8. Major pepper producing countries (2012)
http://www.commoditiescontrol.com/eagritrader/staticpages/index.php?id=69

9. Breakdown of Global Consumption of Pepper by Region
398,000 tons (2014)
https://www.nedspice.com/upload/docs/Nedspice_Pepper_Crop_report_2015.pdf

10. From pepper fruit to peppercorn and pepper

11. Difference between peppercorn and pepper

12. Scientific classification of pepper plant (Piper nigrum)
https://plants.usda.gov/java/ClassificationServlet?source=display&classid=PINI3

13. Number of articles (black pepper) published in PubMed from
1945 to 2018: 1076
https://www.ncbi.nlm.nih.gov/pubmed/?term=black+pepper

14. What have we learned over the years 1945 to 2018 ?
▪ Nutrient composition
▪ Bioactive compounds
▪ Piperine
▪ Bioavailability
▪ Pharmacological actions
▪ Health benefits

15. Nutrient composition of black pepper
based on 100 g
Adapted from https://ndb.nal.usda.gov/ndb/foods/show/02030

16. Percentage nutrient composition in black pepper:
Bioactive compound: Piperine & volatile oil
Adapted from USDA National Nutrient Database for Standard Reference 1 April 2018

17. Physical and Chemical Properties of Black Pepper Berries
https://www.researchgate.net/figure/Physical-and-Chemical-Properties-of-Black-Pepper-Berries_tbl1_235718895

18. Major chemical compounds responsible for the
aroma and pungency of the black pepper.
https://www.omicsonline.org/scientific-reports/images/srep129-t004.html

19. SOME OF THE IMPORTANT CHEMICAL CONSTITUENTS OF P. NIGRUM
http://ijpsr.com/bft-article/a-review-on-diversified-use-of-the-king-of-species-piper-nigrum-black-pepper/?view=fulltext

20. Basic and clinical research on piperine
▪ Activation of the heat- and acidity-sensing TRPV ion channels,
TRPV1 and TRPA1, on the pain-sensing nerve cells.
▪ Bioavailability enhancer of food and dietary supplements:
▪ curcumin,
▪ resveratrol,
▪ CoQ10
▪ others
▪ Health benefits:
▪ Antimicrobial
▪ Anti-inflammatory
▪ Immune-modulation
▪ Anti-cancer
▪ Anti-depressant
▪ Anti-0besity

21. Piperine

22. General overview of TRPV channels (2016)
https://pubs.rsc.org/en/content/articlehtml/2016/cs/c5cs00916b

23. PHARMACOKINETICS OF PIPERINE IN RAT
▪ Oral : 97% of piperine was absorbed after oral administration of piperine at a dose
of 170mg/kg to the male albino rats.
▪ It is metabolized rapidly by liver and other tissue and maximum plasma
concentration was attained at about 6 hr
▪ 3% of the administered dose was excreted up to 4 days as piperine in the feces and
it is not detectable in urine
▪ Half life (t½) was found to be 18.24 hr.
▪ About 36% of the orally administered piperine was excreted as conjugated phenols
in urine and 62% as methylenedioxyphenyl metabolites
Asian Journal of Biomedical and Pharmaceutical Sciences, all rights reserved. Volume 4, Issue 36, 2014.

24. Pharmacological actions of piperine

25. Bioavailability enhancement of
drugs and supplements by piperine
Adapted from Asian Journal of Biomedical and Pharmaceutical Sciences, all rights reserved. Volume 4, Issue 36, 2014.

26. Antibacterial Activity of Piperine and Black Pepper Oil (2018)
http://www.biotech-asia.org/vol15no4/antibacterial-activity-of-piperine-and-black-pepper-oil/

27. Effect of piperine on the production of proinflammatory mediators by
synovial cells derived from patients with rheumatoid arthritis (2009)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688199/

28. Piperine inhibits cytokine production by
human peripheral blood mononuclear cells (2012)
http://www.funpecrp.com.br/gmr/year2012/vol11-1/pdf/gmr1656.pdf
iL-2 IFN-‫ץ‬

29. Mean percent blood glucose reduction by piperine in
normal rats (2018)
Extracted from https://pdfs.semanticscholar.org/fb68/37d52cfec668d514bbd487b8163ccccc41a0.pdf

30. Black pepper and piperine reduce cholesterol uptake and
enhance translocation of cholesterol transporter proteins (2012)
https://www.ncbi.nlm.nih.gov/pubmed/22736065

31. Effects of piperine and verapamil on Blood Pressure
in normotensive anesthetized rats
verapamil
BP
https://www.semanticscholar.org/paper/Blood-pressure-lowering-and-vasomodulator-effects

32. Inhibition of platelet aggregation by piperine (2014)
https://www.mdpi.com/2072-6643/6/8/3336

33. Inhibition of platelet aggregation by piperine (2014)
https://www.mdpi.com/2072-6643/6/8/3336 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145312/

34. Inhibitory effect of piperine on Helicobacter pylori
growth and adhesion to gastric adenocarcinoma cells (2014)
https://www.researchgate.net/publication/270962245_Inhibitory_effect_of_piperine
_on_Helicobacter_pylori_growth_and_adhesion_to_gastric_adenocarcinoma_cells

35. Piperine, a Component of Black Pepper, Inhibits Adipogenesis
by Antagonizing PPARγ Activity in 3T3-L1 Cells (2012)
https://pubs.acs.org/doi/full/10.1021/jf204514a

36. Piperine exerts anti-seizure effects via the TRPV1 receptor in
mice (2013)
https://www.sciencedirect.com/science/article/pii/S0014299913005633

37. Cytotoxicity of piperine on AGS (stomach cancer cells):
24 hours (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846933/

38. Piperine treatment down regulates PSA expression in
Prostate cancer (LNCaP) cells (2013)
https://www.researchgate.net/figure/PSA-assay-results-showed-that-
piperine-has-dose-dependent-effects-on-the-secretion-of-PSA_fig2_245028614

39. Antitumor efficacy of piperine in the treatment of human
HER2-overexpressing breast cancer cells. (2013)
▪ Piperine is a bioactive component of black pepper, Piper nigrum Linn, commonly used for daily
consumption and in traditional medicine.
▪ Here, the molecular mechanisms by which piperine exerts antitumor effects in HER2-overexpressing
breast cancer cells was investigated.
▪ The results showed that piperine strongly inhibited proliferation and induced apoptosis through
caspase-3 activation and PARP cleavage.
▪ Furthermore, piperine inhibited HER2 gene expression at the transcriptional level.
▪ Blockade of ERK1/2 signaling by piperine significantly reduced SREBP-1 and FAS expression.
▪ Piperine strongly suppressed EGF-induced MMP-9 expression through inhibition of AP-1 and NF-κB
activation by interfering with ERK1/2, p38 MAPK, and Akt signaling pathways resulting in a
reduction in migration.
▪ Finally, piperine pretreatment enhanced sensitization to paclitaxel killing in HER2-overexpressing
breast cancer cells. Our findings suggest that piperine may be a potential agent for the prevention
and treatment of human breast cancer with HER2 overexpression.
https://www.ncbi.nlm.nih.gov/pubmed/23870999

40. Piperine is a potential inhibitor of cancer stem cells (CSCs) self-renewal (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818432

41. Modulation of TRP channels with agonists induces intracellular
Ca2+ overload, with subsequent cell death. (2016)
https://pubs.rsc.org/en/content/articlehtml/2016/cs/c5cs00916b
Capsaicin, Piperine, 6-Gingerol, 6-Shogaol

42. Piperine triggers apoptosis and causes cell cycle arrest (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818432/

43. Does Piperine Have Health Benefits?
The Current Research Examined (2018)
▪ There are only 21 clinical trials on piperine..
▪ Studies have shown that piperine can increase the absorption of anti epileptic
medications (phenytoin), blood pressure medications (propanolol), treatments for
tuberculosis (rifampicin), painkillers (diclofenac) and some anticancer drugs.
▪ Available data on piperine-nutrient interactions only supports the fact that piperine
increases the beta-carotene.
▪ There are no human clinical trials looking at the effect of piperine on ‘the immune
system
▪ There is no hard clinical information on the anticancer properties of piperine.
▪ Three small clinical studies suggest that piperine may help with weight reduction.
However these studies looked at piperine in combination with other agents.
https://healthybutsmart.com/piperine-benefits-research/

44. BioPerine® (95% piperine) increased the absorption of
beta-carotene in human volunteers
https://www.sabinsa.com.au/index.php/products-from-sabinsa/131-bioperine

45. Piperine: a natural bioavailability enhancer for nutrients
https://www.sabinsa.com.au/index.php/products-from-sabinsa/131-bioperine

46. Possible mechanisms for increased nutrient bioavailability
using BioPerine (95%piperine)
https://www.sabinsa.com.au/index.php/products-from-sabinsa/131-bioperine

47. Acute toxicity of piperine in adult mice (1983)
▪ The LD50 values of piperine in adult male mice were:
▪ Intravenous 15.1 mg/kg
▪ Intraperitoneal 43 mg/kg
▪ Subcutaneous 200 mg/kg
▪ Intragastric: 300 mg/kg
▪ Intramuscular 400 mg/kg
▪ Most animals given a lethal dose died of respiratory paralysis
within 3-17 min
▪ Histopathologic changes included severe hemorrhagic necrosis
and edema in gastrointestinal tract, urinary bladder and adrenal
glands.
https://www.ncbi.nlm.nih.gov/pubmed/6857729

48. Piperine Drug Interactions
▪ Piperine ( 20 mg/day) may increase plasma concentrations of
▪ carbamazepine
▪ midazolam
▪ Diclofenac
▪ Fexofenadine
▪ It is not clear whether dietary use of black pepper would result
in clinically significant drug interactions
https://www.pharmacytimes.com/publications/issue/2017/july2017/piperine-drug-interactions

49. Black pepper commercial products
▪ Whole pepper
▪ Coarse pepper
▪ Grind pepper
▪ Fine grind pepper
▪ Black pepper essential oil

50. Examples of some delicious black pepper cuisine

51. Summary of Black pepper, “King of spices”
▪ Black pepper is a seed from the plant piper annuum.
▪ It has been used for culinary and health purposes for
hundreds of years.
▪ Originated from Kerala of India, it is now grown and used as
spice all over the world.
▪ The major bioactive compound is known as piperine.
▪ Piperine is a flavoring agent with multiple pharmacological
actions.
▪ Black pepper is safe when used as a spice in food.
▪ There is not enough clinical trials to determine its efficacy
in medical use.