The first slide presentation on black pepper was posted in June 2019. It has since attracted more than 10,000 viewers. This is an update on recent advances for the viewers and followers.

1. SPICE AS MEDICINE:
BLACK PEPPER UPDATE 2023
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 Providers April 2023

2. Presentation outline: Black Pepper 2023
▪ 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
India

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

7. Major pepper producing countries (2022)
https://www.researchgate.net/figure/The-Worlds-Top-Black-Pepper-Producing-
Countries-by-Benjamin-Elisha-Sawe-on-June-7-2019_fig2_343416656

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

9. From pepper fruit to peppercorn and pepper

10. Difference between peppercorn and pepper

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

12. Number of articles (black pepper) published in PubMed from
1945 to 2022
https://pubmed.ncbi.nlm.nih.gov/?term=black+pepper

13. ▪ NUTRIENT COMPOSITION
▪ BIOACTIVE COMPOUNDS

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

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

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

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

18. SOME 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

19. PRECLINICAL STUDIES ON PIPERINE
▪ TRPV1 & TRPA1 CHANNELS
▪ ANTISEIZURE
▪ BLOOD PRESSURE
▪ GLUCOSE
▪ CHOLESTEROL
▪ PLATELET AGGREGATION
▪ ANTI BACTERIAL
▪ ANTICANCER

20. Piperine

21. Effects of piperine on ion channels in sensory nerves

22. Piperine produces a greater degree of desensitization than
capsaicin (2005)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1576058/#:~:text=Immediately%20following%20ingestion%2C%20piperine%20is,heat%20and%20capsaicin%20receptor%20TRPV1.

23. Modulatory Effects of Piperine on Inflammatory
mediators
CGRP
©DRKEVINNG

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

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

26. 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

27. 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

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

29. Black pepper and piperine reduce cholesterol uptake and enhance
translocation of cholesterol transporter proteins in vitro (2012)

30. 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/

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

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

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

34. 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

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. 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

37. 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

38. Summary of Targets of Piperine (2022)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796742/#:~:text=Piperine%20is%
20a%20type%20of,bioavailability%20and%20fertility%2Drelated%20activities.

39. PHARMACOKINETICS

40. 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.

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

42. 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.

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

44. CLINICAL STUDIES

45. 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/

46. 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

47. Herbal formulation "turmeric extract, black pepper, and ginger"
versus Naproxen for chronic knee osteoarthritis:
A randomized, double-blind, controlled clinical trial (2020)
▪ Osteoarthritis is the most common articular disease that can lead to chronic pain and
severe disability. Curcumin-an effective ingredient in turmeric with anti inflammatory
property-plays an important role in protecting the joints against destructive factors.
Gingerols and piperine, are the effective ingredients of ginger and black pepper, which
may potentially enhance and sustain the effect of curcumin in this direction. To
determine the effect of cosupplementation with turmeric extract, black pepper, and
ginger on prostaglandin E2 (PGE2 ) in patients with chronic knee osteoarthritis,
compared with Naproxen. Sixty patients with two different levels of knee osteoarthritis
(Grade 2 and 3) were studied. Individuals were randomly assigned to receive daily
turmeric extract, ginger, and black pepper together or Naproxen capsule for 4 weeks.
PGE2 was evaluated by ELISA method. 24-hr recall was also assessed. All of participants
completed the study. PGE2 decreased significantly in both groups (p < .001), but there
was no significant differences between groups. The results of this study indicated that
intake of the selected herbs twice a day for 4 weeks may improve the PGE2 levels in
patients with chronic knee osteoarthritis similar to Naproxen drug.
▪ Keywords: Naproxen; black pepper; ginger; knee osteoarthritis; prostaglandin E2;
turmeric extract.
https://pubmed.ncbi.nlm.nih.gov/32180294/

48. SAFETY ISSUES

49. 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

50. 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

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

52. Examples of some delicious black pepper cuisine

53. 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.