Spice as Medicine: Turmeric, Curcuma longa

SPICE AS MEDICINE
TURMERIC
CURCUMA LONGA
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 Oct 2019

Outline of Lecture
▪ What is turmeric?
▪ History, production, consumption
▪ Classification
▪ Nutrient composition
▪ Bioactive compounds
▪ Pharmacological actions
▪ Clinical studies, meta-analysis
▪ Summary

What is Turmeric?
Turmeric is a 5–6 ft plant
(Curcuma longa L.), which sends
out rhizomes that are used either
fresh or dried and powdered.

Milestones in history of turmeric, Curcuma longa

Discovery of curcuminoids
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288651/

The number of publications published since 1995 on
(i) curcumin, (ii) curcumin and clinical trials or animal studies, (iii) curcumin and
formulations, and (iv) curcumin and analysis. (2019)
https://www.mdpi.com/1420-3049/24/16/2930/htm

Curcumin: Total-Scale Analysis of the Scientific Literature
The top ﬁve contributor journals, organizations, and countries/territories
of the 18,036 manuscripts. (2019)
Molecules 2019, 24, 1393; doi:10.3390/molecules24071393
Journals
Organizations
Countries

Scientific misconduct on publications especially those of
curcumin authored by Bharat Aggarwal (2012-2018):
▪ As of April 2018, 19 papers had been retracted.
▪ As of 2019, 28 papers published by Aggarwal have been
retracted, 10 others have received an expression of
concern, and 17 others have been corrected
https://en.wikipedia.org/wiki/Bharat_Aggarwal

Major turmeric producing countries (2011-12)
http://www.commoditiescontrol.com/eagritrader/commodityknowledge/turmeric/turmeric.htm

Major countries that import turmeric
https://www.quora.com/Which-is-the-major-country-for-exporting-turmeric

Scientific classification of Turmeric

Anatomy of Turmeric (rhizome)
https://www.etsy.com/listing/640160754/turmeric-plant-poster-floral-wall-decor
Leaf
Flower
Flower
Rhizome

Nutritional Value of Turmeric, Curcuma Longa
http://www.phytojournal.com/archives/2017/vol6issue1/PartA/6-1-17-211.pdf

Major phytoconstituents of extracts of Curcuma longa
https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.6b00975

Chemical structures of key volatile components in the
essential oil from Curcuma spp. rhizomes. (2018)
Turmeric root EO from Kerala, India contained ar-turmerone (46.8%)
Nutrients 2018, 10, 1196

Difference between curcumin and ar-turmerone

Anatomy of the gastrointestinal tract

First by-pass effect through the liver
Liver
systemic circulation

Bioavailability of curcumin: < 1%
Liver
systemic circulation
curcumin 100%
Curcumin <1%
< 1%

Influence of Piperine on the Pharmacokinetics of
Curcumin in Human Volunteers (1998)
Serum concentrations µg/ml (mean ±
SEM) of curcumin 2g oral alone and
with piperine 20mg in humans (n= 8).
Significance as compared to curcumin
alone; *P <0.01 **P <0.001.
https://lumaforlife.com/wp-content/uploads/2018/06/P1.Influence-of-Piperine.pdf
Curcumin
Curcumin+Piperine

Pharmacokinetic parameters (mean ± SEM) of oral curcumin 2 g/kg
alone and in combination with piperine 20 mg/kg in
normal healthy volunteers (n=8)) (1998)
https://lumaforlife.com/wp-content/uploads/2018/06/P1.Influence-of-Piperine.pdf

Reported half-lives of curcumin at a variety of conditions
(2017)
https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.6b00975/suppl_file/jm6b00975_si_001.pdf

Metabolite derivatives of curcumin
molecules-21-00264 (2)

Modeled time concentration plots of curcumin conjugates detected in
plasma from 12 human subjects treated with a single 10 g (2008)

Curcumin conjugate pharmacokinetic parameters (2008)

Summary of absorption, distribution and excretion of
curcumin in rats. (1980)
Adapted from https://www.ncbi.nlm.nih.gov/pubmed/7423534

Major areas of scientific research on
curcumin and ar-turmerone
▪ Cancer
▪ Breast
▪ Colon
▪ Colorectal
▪ Pancreas
▪ prostate
▪ Inflammation
▪ Immuno-modulation
▪ Oxidative stress
Molecules 2019, 24, 1393

Pharmacological actions of
curcumin and ar-turmerone
▪ Antioxidant activity
▪ Antimicrobial activity
▪ Anti-inflammatory activity
▪ Anti-diabetic activity
▪ Anti-cancer activity
▪ Effects on biotransformation enzymes
▪ Inhibition of proliferation and induction of apoptosis
▪ Inhibition of tumor invasion and angiogenesis
▪ Neuroprotective activity
https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/curcumin

Effect of curcumin on inflammatory process
https://www.semanticscholar.org/paper/Curcumin%3A-An-Anti-Inflammatory-Molecule-from-a-
on-Basnet-%C5%A0kalko-Basnet/cfd9e11203d1a1c21d073fde514778dd72ae5cf9/figure/5
Aspirin

Molecular basis of curcumin action on inflammatory process
https://www.ecrjournal.com/articles/anti-inflammatory-action-curcumin-use

Curcumin Extract Inhibits Gene Expression
(CCR7, MMP9, and COX2) in MCF7 (Mammary Tumor-Derived Lung Metastasis Cells). 2019

The effects of turmeric (curcumin) on tumor suppressor protein (p53)
and estrogen receptor (ERα) in breast cancer cells. (2017)

The Effect of Curcumin in the HER-2-Overexpressed Breast Cancer:
An In Vitro and In Vivo Comparison Study with Herceptin
https://www.hindawi.com/journals/ecam/2012/486568/
cancer cell lines

Curcumin inhibits skin SCC cell growth in vitro and in vivo
https://www.hindawi.com/journals/jsc/2012/147863/fig1/

Effect of Piperine on Skin Permeation of Curcumin from a
Bacterially Derived Cellulose-Composite Double-Layer Membrane for
Transdermal Curcumin Delivery (2018)
https://www.mdpi.com/2218-0532/86/3/39
Piperine increased the permeation rate of curcumin by about 1.89 times
Curcumin

Recent research on pharmacological actions of ar-turmerone
▪ Anti-inflammation activities
▪ Cytokines
▪ Enzymes
▪ Anti-cancer activities
▪ Angiogenesis
▪ Cell proliferation
▪ Nerve cell regeneration

Anti-inflammatory effects of aromatic-turmerone through
blocking of NF-κB, JNK, and p38 MAPK signaling pathways
in amyloid β-stimulated microglia. (2012)
https://www.ncbi.nlm.nih.gov/pubmed/22728094

Aromatic‐turmerone attenuates invasion and expression of
MMP‐9 and COX‐2 through inhibition of NF‐κB activation in
TPA‐induced breast cancer cells (2012)
▪ Abstract
▪ Recent evidence suggests that breast cancer is one of the most common forms of malignancy in females,
and metastasis from the primary cancer site is the main cause of death. Aromatic (ar)‐turmerone is present
in Curcuma longa and is a common remedy and food. In the present study, we investigated the inhibitory
effects of ar‐turmerone on expression and enzymatic activity levels of
12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced matrix metalloproteinase (MMP)‐9 and
cyclooxygenaase‐2 (COX‐2) in breast cancer cells. Our data indicated that ar‐turmerone treatment
significantly inhibited enzymatic activity and expression of MMP‐9 and COX‐2 at non‐cytotoxic
concentrations. However, the expression of tissue inhibitor of metalloproteinase (TIMP)‐1, TIMP‐2, MMP‐2,
and COX‐1 did not change upon ar‐turmerone treatment. We found that ar‐turmerone inhibited the
activation of NF‐κB, whereas it did not affect AP‐1 activation. Moreover, The ChIP assay revealed that in vivo
binding activities of NF‐κB to the MMP‐9 and COX‐2 promoter were significantly inhibited by ar‐turmerone.
Our data showed that ar‐turmerone reduced the phosphorylation of PI3K/Akt and ERK1/2 signaling,
whereas it did not affect phosphorylation of JNK or p38 MAPK. Thus, transfection of breast cancer cells
with PI3K/Akt and ERK1/2 siRNAs significantly decreased TPA‐induced MMP‐9 and COX‐2 expression.
These results suggest that ar‐turmerone suppressed the TPA‐induced up‐regulation of MMP‐9 and COX‐2
expression by blocking NF‐κB, PI3K/Akt, and ERK1/2 signaling in human breast cancer cells. Furthermore,
ar‐turmerone significantly inhibited TPA‐induced invasion, migration, and colony formation in human breast
cancer cells. J. Cell. Biochem. 113: 3653–3662, 2012. © 2012 Wiley Periodicals, Inc.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.24238

Aromatic-turmerone induces neural stem cell
proliferation in vitro and in vivo (2014)
Ar-turmerone increases NSC proliferation in vitro
After i.c.v. injection of 3 mg (1 mg/μl) ar-turmerone,
significantly more DCX-positive neuroblasts

Curcumin combined with turmerones, essential oil components of
turmeric, abolishes inflammation‐associated mouse colon
carcinogenesis (2012)
Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We
recently reported that ar‐turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the
present study, we explored the molecular mechanisms by which ATM attenuates NO generation and
examined the anti‐carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including
ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)‐induced expression of inducible forms of both
nitric oxide synthase and cyclooxygenase (iNOS and COX‐2, respectively). A chase experiment using
actinomycin D revealed that ATM accelerated the decay of iNOS and COX‐2 mRNA, suggesting a
post‐transcriptional mechanism. ATM prevented LPS‐induced translocation of HuR, an AU‐rich
element‐binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model,
oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)‐induced shortening of
the large bowel by 52–58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR,
and their combinations using a model of dimethylhydradine‐initiated and DSS‐promoted mouse colon
carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both
doses suppressed adenocarcinoma multiplicity by 63–69%. Interestingly, the combination of CUR and TUR
at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that
TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination
with CUR may become a powerful method for prevention of inflammation‐associated colon carcinogenesis.
© 2012 BioFactors, 2013
https://iubmb.onlinelibrary.wiley.com/doi/abs/10.1002/biof.1054

Current use of Turmeric
Powdered root
Spice
Curry
Dye
Essential oil
Aromatherapy
Topical use
Medicine
Chinese
medicine
Ayurvedic
medicine

Medical use of turmeric or curcumin supplements
▪ Disease prevention
▪ Cancer
▪ Type 2 diabetes mellitus
▪ Disease treatment
▪ Cancer
▪ Inflammatory disease
▪ Rheumatoid arthritis
▪ Radiation dermatitis
▪ Ulcerative colitis
▪ Oral health
▪ Oral submucous fibrosis
▪ Cognitive decline and Alzheimer’s disease
▪ Major depressive disorder
▪ Premenstrual syndrome
https://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/curcumin

Problems of ingesting turmeric for health benefits
▪ Only 1 to 6 percent of turmeric is curcumin.
▪ Oral bioavailability of curcumin is about 1%.
▪ Curcumin taken orally is not well-absorbed and is quickly eliminated from the body.
▪ Turmeric may be contaminated with heavy metals such as lead,
▪ Curcumin supplements are not regulated in the same way as medications.
▪ Curcumin may interact with certain medications, such as blood thinners.
▪ Curcumin has never been shown to be conclusively effective in a randomized,
placebo-controlled clinical trial for any indication.
https://www.consumerreports.org/dietary-supplements/does-turmeric-really-reduce-inflammation/

Number of publication articles in PubMed on Turmeric, curcumin and
studies on effect of curcumin on diabetes, arthritis and cancer
https://www.ncbi.nlm.nih.gov/pubmed/?term=curcumin%2C+cancer
Turmeric, curcumin
Diabetes, arthritis
Cancer
No data available for ar-turmerone

Cognitive Function of Nondemented Elderly Subjects
and Their Self-Reported Curry Consumption
According to the study authors, “although the results are suggestive of a biological therapeutic effect, we emphasize that they
do not establish a clear and direct causal effect of curry consumption on improving cognitive function.” The difference in
MMSE between those who rarely use turmeric and those that often use it is not significant

A Potential Role of the Curcumin in
Alzheimer’s Disease (2005)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1702408/?_escaped_fragment_=po=11.4035

Effect of oral Curcuma extract in patients with
colorectal cancer. (2001)
https://www.ncbi.nlm.nih.gov/pubmed/11448902/

Curcumin: A Review of Its’ Effects on Human Health (2017)
▪ Turmeric, a spice that has long been recognized for its medicinal properties, has received interest
from both the medical/scientific world and from culinary enthusiasts, as it is the major source of
the polyphenol curcumin.
▪ It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis,
anxiety, and hyperlipidemia.
▪ It may also help in the management of exercise-induced inflammation and muscle soreness, thus
enhancing recovery and performance in active people.
▪ In addition, a relatively low dose of the complex can provide health benefits for people that do not
have diagnosed health conditions.
▪ Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects.
▪ Ingesting curcumin by itself does not lead to the associated health benefits due to its poor
bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid
elimination.
▪ There are several components that can increase bioavailability. For example, piperine is the major
active component of black pepper and, when combined in a complex with curcumin, has been
shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides
multiple health benefits.

How does curcumin work with poor bioavailability?
Clues from experimental and theoretical studies.(2016)
Inhibitive effects of human fAβ(1–42) formation by curcumin, its degradation products mixture and ferulic acid, evaluated by ThT fluorescence
assay.
fAβ=amyloid-β peptide fibril
Curcumin degradation products

Efficacy of Turmeric Extracts and Curcumin for
Alleviating the Symptoms of Joint Arthritis:
A Systematic Review and Meta-Analysis of Randomized Clinical Trials. (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003001/figure/f2/
Mean differences in PVAS
between curcuma and placebo.
Mean differences in PVAS and
WOMAC between curcuma and
placebo
Mean differences in PVAS and
WOMAC between curcuma
and pain medicine.
PVAS=pain visual analogue score
WOMAC=Western Ontario and McMaster Universities OA Index

Meta-analysis for comparison of plasma Total cholesterol
concentrations between experimental and control groups (2017)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637251/figure/Fig5/
Although a random-effect model was used,
pooled analysis of data from 6 studies [15,
23–27] showed no significant between-group
differences in terms of plasma TC
concentrations (P = 0.054), ostensibly owing
to the significant heterogeneity among these
studies (I 2 = 73.8%, n = 218 for both
experiment and control groups,

Meta-analysis for comparison of plasma LDL-C concentrations
between experimental and control groups (2017)

Meta-analysis for comparison of plasma Triglyceride
concentrations between experimental and control groups (2017)

Meta-analysis for comparison of plasma HDL-C concentrations
between experimental and control groups (2017)

Meta-analysis of glycemic outcomes in
prediabetes and type 2 diabetes mellitus. (2019)
This study indicated that daily administration of 1500 mg curcumin has positive
effects in reducing fasting blood glucose and weight in patients with type 2 diabetes.
prediabetes
type 2 DM

Anticoagulant activities of curcumin and its derivative (2012)

Curcumin in Treating Breast Cancer: A Review. (222016)

Commercial products of turmeric

Side Effects, Contraindications and Precautions
http://www.phytojournal.com/archives/2017/vol6issue1/PartA/6-1-17-211.pdf

Summary
▪ Turmeric is the rhizome of a plant belonging to the species Curcuma longa.
▪ The bioactive compounds of turmeric are non-volatile curcuminoids and volatile
essential oil.
▪ The main non-volatile curcuminoid is curcumin whereas the main volatile constituent
is aromatic(ar-) turmerone.
▪ Multiple pharmacological activities have been shown in these bioactive compounds:
▪ Antioxidant, antimicrobial, anti-inflammatory, anti-cancer,
▪ Anti-hyperlipidemic, anti-diabetic
▪ Neuroprotective, hepatoprotective
▪ The low oral bioavailability of curcumin makes it unsuitable for therapeutic use.
▪ However, its flavor, aroma and medicinal properties have been used as a culinary
spice and traditional Chinese and Ayurvedic medicines for thousands of years.

ANY QUESTION?
Please contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com
61

Spice as Medicine: Turmeric, Curcuma longa

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