Introduction to Toxicology

EV 460/660 & BI 460/660

Fall 2014

Biological Activity of Tumeric

Presentation by Amy Sirk

Background info on curcumin (turmeric)

Turmeric (cucurmin longa) a tropical plant - member of the ginger family. The root (rhizome) is dried and ground into a powder.
Cultures that cook with it -India, China, Southeast Asian countries.
Medicinal use- Ayurvedic literature documents (3000 BC) the use of turmeric for many illnesses, including obesity. Commonly used for its antiseptic properties .

Background info on obesity, metabolic syndrome
CDC – 66% of American adults are overweight. 33% of American adults obese, one in 6 children obese.
Obesity related deaths 300,000 per year. 2008- $147 billion spent on obesity related diseases.
Obesity associated with low grade chronic inflammation. Adipose tissue primarily affected. Development of inflammation and oxidative stress in adipose tissue leads to insulin resistance.
Metabolic syndrome- abdominal fat, Type-2 diabetes, hypertension, insulin resistance, high BMI. 47 million US Adults have metabolic syndrome –CDC.

Active compounds in turmeric
More than 100 compounds isolated from turmeric
Main active components are a volatile oil containing turmerone and the coloring yellow curcumin – concentrations of 3-5% in turmeric powder.
interacts with proteins released by white adipose tissue (WAT)- lipase, resistin, TNF, MCP-1
Increases insulin-stimulated glucose uptake in adipocytes
Inhibits adipogenesis

Tumor Necrosis Factor (TNF)

TNF –multifunctional proinflammatory protein that induces death in tumor cells.

Affects lipid metabolism, exerts major influence over inflammation, obesity, insulin resistance.

TNF blocking medications used to treat rheumatoid arthritis and Crohn’s disease - Enbrel, Humira

Genetically obese mice – adipose tissue overexpresses TNF

TNF level high in most obese humans, levels decrease as subjects lose weight.

TNF interferes with insulin receptors in adipocytes through serine phosphorylation of insulin receptor substrate

Inverse relationship between TNF and lipase levels
Correlation in obese individuals between TNF levels and C-reactive protein levels (systemic inflammation marker)

Turmeric inhibits TNF accumulation, suppresses transcription and secretion

increase insulin sensitivity
reverse hyperglycemia

hyperlipidemia

Leptin

Leptin- hormone that regulates appetite, increases SNS activity-stimulates fatty tissue to burn energy.
Leptin is secreted by adipose tissues - levels higher in animal and human obesity but the body seems to be resistant to leptin. Turmeric downregulates leptin levels while reducing leptin resistance.

MCP-1

Inhibits release of MCP-1. MCP-1inflammatory cytokine involved in insulin resistance

Animal testing
2012 study Weijuan Shao et al.
published by Public Library of Science.

36 5-week old male mice were randomly divided into three groups.
Curcumin, a low-molecular weight polyphenol derived from the spice turmeric, was purchased from Sigma in St. Louis

Group A were fed with the low fat control diet(LFD) 10% Kcal from fat
Group B were fed a high fat diet (HFD) 45% Kcal from soy bean fat
Group C were fed HFD with curcumin (4g/kg diet) added 2 days/week (Mondays and Thursdays)

Image source: Shao 2012

Because this study used a 45% fat diet instead of the usual 60% fat accumulation and insulin resistance were slower to manifest.
Long term dietary curcumin administration prevented HFD-induced body-weight gain and obesity
Weight gain occurred up until the 16th week. From week 16 to week 28 oral curcumin supplementation prevented the effect of HFD on weight-gain.

Image source: Shao 2012

Curcumin improved insulin sensitivity and whole body glucose disposal

High blood glucose levels present in HFD-fed animals. Curcumin-administered animals exhibited blood glucose levels more consistent with LFD.


Curcumin improved insulin signaling in adipose tissue and hepatocytes

In the presence of glucose oxidase curcumin dose-dependently restored the stimulatory effect of insulin


Turmeric Research Paper – Q & A

1. Name the active compound in Turmeric : yellow curcumin
Extra credit- what concentrations of the active compound are present in turmeric powder: 3 – 5%

2. Name two ways in which TNF influences obesity: TNF overexpressed in adipose tissue, induces insulin resistance, inverse relationship between TNF and lipase, interferes with insulin receptors, exerts major influence over inflammation.

3. Name two ways in which turmeric affects adipose tissues: stimulates glucose uptake, inhibits release of inflammatory protein (Extra credit-name the protein: MCP-1)