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Annotation of Curcumin in Turmeric and its Effects on Human Health.

Jemimah Chan, Erina Hayashi, Amanda Huynh, Allen Ngo, Tam Nguyen
University of California, Davis
Food Science and Technology
Section A02
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Annotation of Curcumin in Turmeric and its Effects on Human Health

Introduction to Curcumin in Turmeric

Curcumin, only found in the turmeric root, is a diarylheptanoid curcuminoid. Turmeric
has been widely used throughout history as a dye, a spice in food, and for its medicinal
properties, among other functions. Although it is well known for its versatility and nutritive
properties, the mechanism of curcumins metabolism and improving its bioavailability are
obstacles still under research. In addition to what has been introduced already, this paper will
also discuss curcumin research in regards to its positive effects on the human psyche and
possible anti-inflammatory benefits on the immune system.

Chemical Structure and History of Curcumin

Curcumin is the primary compound responsible for giving turmeric its vibrant yellow
color. It is a diarylheptanoid curcuminoid that belongs to a class of secondary plant metabolites.
There are two classifications of diarylheptanoids: linear and cyclic. Based on curcuminoids
structures, they belong in the linear class. Turmeric contains three different curcuminoids known
as curcumin, demethoxycurcumin (curcumin II), and bis-demethoxycurcumin (curcumin III);
however, the main one found in turmeric is curcumin (Villupanoor, 2008). The chemical formula
of curcumin is C21H20O6 and the structure contains a seven carbon chain joined by two
aromatic rings at each ends along with various substituents. Curcumin can also exist in enol or
keto form and they both have a melting point of 184-185 degrees Celsius (Villupanoor, 2008).
Turmerics brilliant golden color is contributed by the three curcuminoid substances. To list its
components, curcumin makes up about eighty to 85% of the color, demethoxycurcumin
contributes 10-15%, and bis-demethoxycurcumin makes up approximately 5% (Attokaran,
2011). In water, curcumin is insoluble; however, in the presences of ethanol and or acetone it can
be soluble. The structure of curcumin was first synthesized in 1815. In 1870, the crystalline form
of curcumin was discovered, and then finally, in 1910, the overall curcumin structure was
determined.
Throughout history, turmeric has been used as a spice, dye, and medicine in Asian
cultures. Traditionally this spice was called Indian saffron due its similar peppery, warm, and
bitter flavor to saffron. Ever since turmerics flavor was discovered to be comparable to saffron,
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turmeric has been used as a substitute for saffron since it is a much cheaper alternative. Turmeric
was popularly used for its anti- inflammatory properties to treat conditions such as digestive
disorders, liver problems, skin diseases, arthritis, and healing wounds.

Curcumin Use in Asian Countries and Connections with Current Findings

Curcumins striking orange-yellow hue and rumored medicinal properties were
experienced firsthand by people in Asia (Hamasaki). Cultivation of curcumins source plant,
turmeric, is thought to have originated in the tropical Southeast Asia and found its way into
peoples lives as a fragrant multi-functional staple added in foods and clothing, and its
characteristic bright, orange-yellow color were associated with religious and festive occasions
(Alexander, 2016). This plant grows best in warm, rainy regions which include China, India,
Indonesia, Peru and Jamaica. However, a majority of the worlds production of turmeric occurs
in India, especially South India where the temperatures are highest and monsoons frequent.
About 350,000 tons of turmeric are produced annually in India, indicating the large demand for
turmeric within the country. Turmeric can be produced any time of the year, but the best time to
plant the tubers is June immediately before the rain season. Harvest can occur during February
until April when the weather is the driest. The order of events is such that the post-harvest drying
process can proceed most effectively in the low-moisture weather (Hamasaki).
Curcumin as found in turmeric is known for its health, remedial and even scientific uses.
Many health claims have been associated with curcumin in Asian countries for the past four
thousand years since the Vedic culture of India; the main rumored cosmetic benefits are
decreased external signs of aging and cleared skin blemishes (Simera, 2015). It is unknown if
these rumored benefits are due to direct effects of curcumin, or turmerics use as sunscreen
paste (thereby blocking the skin-sagging and blemish-causing effects of direct sun exposure).
When used to add a yellow color to many food products such as mustard, curry, cooked meat and
fish, traditional pickles and desserts (Turmeric for Food), the curcumin may benefit the consumer
through its antifungal and antibacterial properties (Aggarwal, et. al, 2007). Curcumin is not only
used as an important food colorant, but can be used for rough estimations of alkalinity without
the need for expensive equipment; curcumins yellow color will give way to deep red under
alkaline conditions around pH of 7.4 to 8.6 (Wang, et.al, 1997).
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Current Western science is only beginning to discover the therapeutic possibilities of

curcumin; many relatively new research studies support curcumin as the active compound in
turmeric that is so popular in Asian medicinal traditions (Aggarwal, et.al). For example, in the
Ayurvedic medicine of India, the powdered turmeric has been used to treat swelling and pain of
injured joints and external injuries (Ramdev Food Products). Similarly, turmeric in Chinese
medicine (called jianhuang) is believed to treat arthritis and reduce swelling and pain from
traumatic injuries (Dharmananda). As will be explained in the next section, these claims are
partially validated through current scientific studies showing that curcumin do have anti-
inflammatory effects, thus reducing pain and swelling associated with aggravated tissues
(Aggarwal, et.al).

Curcumin Nutrition, Metabolism, and Bioavailability

To begin with some basic nutrition facts about turmeric, every 100 grams contains: 354
calories, 65 of carbohydrates, 10 grams of fat, and 8 grams of protein. It also holds a significant
amount of minerals, such as calcium and iron, and essential vitamins such as pyridoxine and
riboflavin (Rudrappa, 2016). The fresh turmeric root also contains vitamin C to help remove free
radicals and develop immunity, making it one of the herbs and spices that has the highest known
anti-oxidant strength (Rudrappa, 2016). However, when turmeric is used in cooking, it is
typically used in amounts much less than 100 grams, leading to the question of whether or not
the benefits (such as the antioxidant strength, mineral and vitamin content, in addition to other
ones that will be explained in detail later) of curcumin can be metabolized in a way that is
effectively absorbed by the body. This reality also presents an issue about bioavailability that will
be discussed later in this section.
The research of the mechanism of curcumin metabolism in the human system is still
underway. In one study conducted on the breakdown in the livers and intestines of rats and
humans, and the plasma of mice, led to the observation of two phases. First, curcumin is reduced
to dihydrocurcumin (DHC), then further reduced to tetrahydrocurcumin (THC). Both of the
reduction reactions are NADPH-dependent and catalyzed by enzyme CurA (also known as
dihydrocurcumin reductase or NADPH-dependent curcumin), however CurA does not further
reduce THC, which led to the possibility that CurA does not reduce carbon-oxygen double bonds
and only carbon-carbon double bonds (Hassaninasab, Hashimoto, Tomita-Yokotani, &
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Kobayashi, n.d.). Phase I continues reduction into hexahydrocurcumin and octahydrocurcumin.

Phase II proceeds with curcumin and its metabolites conjugated with glucuronides and sulfates.
Experimentation was extended to human feces because no reports have been made about how
curcumin affects the human gut biome or addressed whether or not gut microorganisms can
metabolize curcumin; it was concluded that E. coli was the microorganism with the highest
metabolic activity, leading to the potential that E. coli may be responsible for curcumin reduction
into THC in the intestines (Hassninasab, et al., n.d.).
Another study observed the incubation of curcumin in the hepatic and intestinal cytosol
collected from rats and humans (Ireson et al., 2002). Upon spectrophotometry of the samples, the
presence of curcumin sulfate and curcumin glucuronide molecules were indicated, as were THC
and hexahydrocurcumin (Ireson et al., 2002). These results support the studies discussed above,
as the same metabolites were found in the livers and intestines of rats and humans in each
respective experiment. The findings were also analyzed showing that conjugation in the intestinal
tissues of humans were much greater than in the same tissue of the rats; however, the reverse
was true upon examination of the hepatic tissues of humans in comparison to the rats (Ireson et
al., 2002). Taken together as a whole, the ability of either intestinal or liver tissues from humans
to reduce curcumin exceeded that in tissues from rat...[suggesting] discrepancies in tissue
enzyme content, and raising the potential issue of whether or not rats are an appropriate model
for the metabolism curcumin in humans (Ireson et al., 2002). The discrepancy should be taken
into account for future research.
In general, curcumin cannot be detected in the human system at less than 3.6 4g/day
(Higdon, 2005). Instability at neutral and alkaline pH, tendency for reductive and conjugative
metabolism, and poor uptake by the lumen of the intestine to circulation are all reasons for
curcumins low bioavailability (Metzler, Pfeiffer, Schulz, & Dempe, 2013). Consumption of
turmeric with black pepper and fat are two ways that have been found to improve bioavailability.
Black pepper contains piperine (responsible for pungency in black pepper), which inhibits
intestinal and hepatic glucuronidation, increasing bioavailability by 2000% in humans (Prasad,
Tyagi, & Aggarwal, 2014). Consumption of turmeric with fat also allows the curcumin molecule
to bypass the liver, enter the lymphatic system, and then into systemic circulation (Greger, 2014).
Both tactics address the issue of curcumin conjugation and absorption to therefore, increase the
bioavailability.
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Psychological Effects
Although perhaps not so obvious, there are several psychological effects of curcumin that
have been researched and accepted. Some of these effects include neurogenesis, stress, fear,
learning, and memory. According to animal research (primarily rats), curcumin can facilitate
neurogenesis, or the birth of new brain cells that occurs in the hippocampus. Neurogenesis is
essential for optimal learning, memory, and mood. A study done by Xu et. al in 2007 showed
increasing neurogenesis with increasing curcumin administration (5-20 mg) in rats after physical
and psychological stress was inflicted. Curcumin is thought to help fight mental illnesses like
depression because it releases neurotransmitters serotonin and dopamine, which helps with good
mood, clear thinking, and a healthy sex drive. Curcumin thus functions as a class of clinical anti-
depression and Alzheimers medications called MAO (monoamine oxidase) inhibitors because
they break down these neurotransmitters. Common MAO inhibitors include Prozac and Effexor,
which have also been shown to possibly cause birth defects. Anhedonia, which is the inability to
feel pleasure, is one way to measure depression, and its reflected by the preference to sucrose. In
a study in 2014 by Lui et. at, it was shown that curcumin increased sucrose consumption in
depressed rats, caused by chronic mild stress. In 2005, Xu et. al tested the effects of curcumin on
depression and mood by doing a forced swim test on rats. The results show that the more
curcumin given to rats, the less time they spent immobilized and tried to escape from the water
they were in. The greatest dose of curcumin (10mg/kg) worked better even to a control anti-
depressant medication, imipramine (10mg/kg). It has been found that dietary curcumin may
impair the formation and short-term consolidation of auditory fear memory. It has also been
shown to prevent the reconsolidation of older, already well-consolidated fear memory. Dietary
curcumin, thus, may be effective for PTSD, which is characterized by strong and persistent fear
memories. Based on a study in 2014 by Chinese scientists, it has also been shown that mice
exposed to curcumin performed better in a Morris water maze test, escaping the maze more
quickly than other conditions. This suggests curcumin has a profoundly positive effect on
hippocampal learning and memory. In 2006, Xu et. al experimented on the effects of curcumin
on chronic stress on rats by using the shuttle-box task, which consists of a patterned shock and
change of physical barriers. Rats in the high curcumin group were able to cope with the stress
best and learn the task more quickly than other conditions.
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Curcumins Anti-Inflammatory Benefits on our Immune System against Chronic Diseases

Curcumin helps relieve our body of chronic inflammation by acting as an anti-
inflammatory. Inflammation is the immune systems primary defense to infections and injuries.
When inflammation is prolonged, persistent, low-grade (small rise in inflammatory markers),
and systematic, it is characterized as chronic inflammation (Egger, 2012). Chronic inflammation
is associated with many chronic illnesses such as cancer and Alzheimers disease. Research has
been conducted on curcumins anti-inflammatory properties, and has revealed its positive impact
on the immune system by reducing chronic inflammation associated with these chronic diseases.
Chronic inflammation has been shown to increases a persons susceptibility to cancer
(Danovi, 2013). Curcumin acts as an anti-inflammatory by suppressing agents causing
inflammation in our body. For example, nuclear factor kappa B (NF-kB), which is a ubiquitous
pro-inflammatory transcription factor (Goepp, 2006). According to Dr. Lartigue, NF-kB
promotes proliferation, cell migration and invasion, and suppresses apoptosis, which are all
known cancer hallmarks. NF-kB is present in both healthy tissues and cancerous tissues. The
activation of NF-kB is the result of toll-like receptors reacting to foreign antigens in the body and
promotion through cytokines. According to Life Extension Magazine in 2011, curcumin
suppresses this transcription factor and effectively promoting apoptosis without affecting healthy
tissues. This makes tumor cells more vulnerable to pharmacological cell-killing agents. It has
also been shown to act in a dose dependent manner against tumor cells; higher the curcumin
uptake, higher the activity against tumor cells (Goepp, 2006). Therefore, curcumin is effective in
weakening all forms of cancer, reducing the need for high dosage of drugs with harmful side
effects.
Alzheimers disease is a progressive neurodegenerative disease that results in behavioral
changes, cognitive deterioration, and a decline in daily living activities. The brain of an
Alzheimers disease patient shows increase in beta amyloid plaque and neurofibrillary tangles
(Giri, 2003). The increase in amyloid plaques interferes cell-to-cell communication, and
neurofibrillary tangles interferes cell-to-cell nutrient transfer. Consumption of curcumin can
possibly slow down the progression, or better yet, counteract the effects of Alzheimers disease.
A study by Giri et. al in 2004 showed that an increase in amyloid plaques promotes the
production of monocyte THP-1, which secretes cytokines like IL-1. Cytokines play an important
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role in cell signaling because they warn other white blood cells of the presence of foreign
substances that need to be destroyed, which cause inflammation. Prolonged inflammation
damage neurons, causing some symptoms of Alzheimers. Curcumin can reduce inflammation by
inhibiting the secretion of cytokines by THP-1 (Giri, 2004). In a study done by Zhang et. al in
2006, macrophages that were treated with curcumin had an improved uptake and digestion of
beta amyloid plaque. The decrease in amyloid plaque leads to less secretion of pro-inflammatory
agents which prevents more neuron damage.

Conclusion
The use of phytochemicals, such as curcumin, will continue to grow if current trends,
such as increased average lifespan or increased incidence of chronic illnesses continue. However,
consumers have limited assurance about its efficacy, quality and safety. Knowledge from ancient
medical systems contribute to current scientific research, and such studies have shown that
curcumin has the capability of improving the human condition through specific immune system
stimulation and its anti-depressive and anti-degenerative effects. However, more research such
as establishment of methods to improve its bioavailability is necessary before curcumin can
earn a prominent place in disease prevention and medical treatment in the United States.
Running Head: Curcumin 9

References

Aggarwal, BB., Sundaram, C., Malani, N., Ichikawa, H. Curcumin: the Indian solid gold. (2007).
http://www.ncbi.nlm.nih.gov/pubmed/17569205

Alexander, Rachel. (2016). What Is the Meaning of Turmeric in Hinduism? Retrieved from
http://classroom.synonym.com/meaning-turmeric-hinduism-6711.html

Chronic IL-1 beta-induced neuroinflammation: Is it really that bad? (n.d.). Retrieved from
https://www.rndsystems.com/resources/artices/ chronic-il-1-beta-induced-neuroinflammation-it-
really-bad

Danovi, S. (2013, February 1). Feeling the heat - the link between inflammation and cancer.
Retrieved from http://scienceblog.cancerresearchuk.org/2013/02/01/feeling-the-heat-the-link-
between-inflammation-and-cancer/

Dharmananda. S., Ph.D. (n.d.) Turmeric: Whats in an Herb Name? How Turmeric (Jianghuang)
and Curcuma (Yujin) Became Confused. Retrieved from
http://www.itmonline.org/arts/turmeri3.htm

Egger, G. (2012). In search of a germ theory equivalent for chronic disease. Retrieved from
http://www.cdc.gov/pcd/issues/2012/11_0301.htm

Geopp, J. G. (2006, July). What is nuclear factor-kappa beta? Retrieved from

http://www.lifeextension.com/magazine/2006/7/report_nuclear/page-03?p=1

Giri, R. K., Rajagopal, V., & Kalra, V. K. (2004). Curcumin, the active constituent of turmeric,
inhibitsamyloid peptide-induced cytochemokine gene expressionand CCR5-mediated chemotaxis
of THP-1 monocytesby modulating early growth response-1 transcription factor. Journal of
Neuochemistry, 91, 1199-1210. http://dx.doi.org/10.1111/j.1471-4159.2004.02800.x
Running Head: Curcumin 10

Giri, R. K., Selvaraj, S. K., & Kalra, V. K. (2003). Amyloid peptide-induced cytokine and
chemokine expression in THP-1 monocytes is blocked by small inhibitory RNA duplexes for
early growth response-1 messenger RNA. The Journal of Immunology, 170(10), 5281-5294.
http://dx.doi.org/10.4049/?jimmunol.170.10.5281

Greger, M. (2014, January 20). Boosting the Bioavailability of Curcumin [Video file]. Retrieved
from http://nutritionfacts.org/video/boosting-the-bioavailability-of-curcumin/)

Hamasaki, Masanori. (n.d.) . .

Retrieved from https://www.house-direct.jp/st/useful/ucon_india

Hassaninasab, A., Hashimoto, Y., Tomita-Yokotani, K., & Kobayashi, M. (n.d.). Discovery of
Curcumin Metabolic Pathway Involving a Unique Enzyme in an Intestinal Microorganism.
Proceedings of the National Academy of Science of the United States of America, 108(16).
http://dx.doi.org/10.1073/pnas.1016217108

Higdon, J. (2005). Curcumin. Retrieved February 28, 2016, from Oregon State University Linus
Pauling Institute website: http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/curcumin
How curcumin protects against cancer. (2011, March). Retrieved from
http://www.lifeextension.com/magazine/2011/3/how-curcumin-protects-against-cancer/page-01

Ireson, C. R., Jones, D. J.L., Orr, S., Coughtrie, M. W.H., Boocock, D. J., Williams, M. L., . .
Gescher, A. J. (2002). Metabolism of the Cancer Chemopreventive Agent Curcumin in Human
and Rat Intestine. Cancer Epidemiology, Biomarkers, and Prevention.

Lartigue, J. D. (2013, June 28). The inflammation link: NF-B remains a difficult but intriguing
target. Retrieved from http://www.onclive.com/publications/Oncology-live/2013/June-2013/The-
Inflammation-Link-NF-B-Remains-a-Difficult-but-Intriguing-Target
Running Head: Curcumin 11

Liu, D., Wang, Z., Gao, Z., Xie, K., Zhang, Q., Jiang, H., & Pang, Q. (2014). Effects of curcumin
on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic
unpredictable stress. Behavioural brain research, 271, 116-121.

Metzler, M., Pfeiffer, E., Schulz, S. I., & Dempe, J. S. (2013). Curcumin uptake and metabolism.
Biofactors, 39(1), 14-20.

Mishra, S., & Palanivelu, K. (2008). The effect of curcumin (turmeric) on Alzheimer's disease:
An overview. Ann Indian Acad Neurol., 11(1), 13-19. http://dx.doi.org/10.4103/0972-2327.40220

Prasad, S., Tyagi, A. K., & Aggarwal, B. B. (2014). Recent developments in delivery,
bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice.
Cancer Research and Treatment, 46(1), 2-18.

Ramdev Food Products (n.d.). Synopsis of Turmerics Healing Properties. Retrieved from
http://www.turmeric.co.in/turmeric_ayurvedic_use.htm

Rudrappa, U. (Ed.). (n.d.). Turmeric Nutrition Facts. Retrieved February 28, 2016, from
Nutrition-and-You website: http://www.nutrition-and-you.com/turmeric.html

Simera. (2015, June). Beauty Benefits of Turmeric. Beautetude.com. Retrieved from

http://beautetude.com/2015/06/24/beauty-benefits-of-turmeric-2/
Turmeric for Food. (n.d.) Retrieved March 6, 2016, from
http://www.turmeric.co.in/turmeric_food_use.htm

Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, Lin JK (1997). Stability of curcumin
in buffer solutions and characterization of its degradation products.J. Pharm. Biomed. Anal. 15
(12): 1867-1876.

Xu, Y., Ku, B., Cui, L., Li, X., Barish, P. A., Foster, T. C., & Ogle, W. O. (2007). Curcumin
reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and
Running Head: Curcumin 12

brain-derived neurotrophic factor expression in chronically stressed rats. Brain research, 1162, 9-
18.

Xu, Y., Ku, B., Tie, L., Yao, H., Jiang, W., Ma, X., & Li, X. (2006). Curcumin reverses the
effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of
CREB. Brain research, 1122(1), 56-64.

Xu, Y., Ku, B.-S., Yao, H.-Y., Lin, Y.-H., Ma, X., Zhang, Y.-H., & Li, X.-J. (2005).
Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of
depression in rats. Pharmacology Biochemistry and Behavior, 82(1), 200-206.

Attokaran, M. (2011). Natural food flavors and colorants Mathew Attokaran. Retrieved February
27, 2016, from https://vpn.lib.ucdavis.edu/store/10.1002/9780470959152.ch98/asset/
,DanaInfo=onlinelibrary.wiley.com+ch98.pdf?
v=1&t=ilivpz3o&s=5b22f7f38d94351eecf09819468f48ad36c2bfe5

P.N. Ravindran, K. Nirmal Babu, & K. Sivaraman (Eds.). (2007). Turmeric - The Golden Spice
of Life. Retrieved February 27, 2016, from
https://vpn.lib.ucdavis.edu/doi/pdfplus/10.1201/,DanaInfo=www.crcnetbase.com+978142000632
2.ch1

Villupanoor A. Parthasarathy, Bhageerathy Chempakam, & T. John Zachariah (Eds.). (2008).

Chemistry of spices Turmeric . Retrieved February 27, 2016, from
https://vpn.lib.ucdavis.edu/CABeBooks/FullTextPDF/2008/,DanaInfo=www.cabi.org+20083217
094.pdf

Zhang, L., Fiala, M., Cashman, J., Sayre, J., Espinosa, A., Mahanian, M., Zaghi, J., Badmaev, V.,
Graves, M. C., Bernard, G., & Rosenthal, M. (2006). Curcuminoids enhance amyloid- uptake
by macrophages of Alzheimer's disease patients. Journal of Alzheimer's Disease, 10(1), 1-7.