23 resveratrol

Question 1

what is resveratrol

Answer 1

polyphenolic compound

• 3,5,4-trihydroxystilbene
• phytoalexin produced by plants due to stress
• plant antibiotic

Question 2

stilbene compound

Answer 2

class of polyphenols

• fat soluble
• cis and trans forms
• aglycone or glycoside

Question 3

resveratrol history

Answer 3

herbal product called Kojo Kon
- active ingredient - polygonum cuspidatum

used to treat wide range of afflictions
fungal diseases, skin inflammations, heart diseases, liver, blood vessels

Question 4

resveratrol found in

Answer 4

only in the skin of grapes

• red wine
• highest in pinot noir
• fermentation intensifies content

Question 5

bioavailabilty

Answer 5

high absorption 70%
low due to rapid metabolism
- unlikely that human tissues are exposed
- most likely resveratrol metabolites

Question 6

resveratrol metabolites

Answer 6

resveratrol monosulphate
resveratrol monoglucuronide (2 isoforms)
dihydroresveratrol monosulphate
dihydroresveratrol monoglucuronide

Question 7

research on health

Answer 7

cvd
cancer
longevity

Question 8

french have high SFA, alcohol and smoking rates but low CVD

Answer 8

alcohol 20-30% reduction for no more than 2 drinks/day

Question 9

How resveratrol may help CVD

Answer 9

1. promote VD and inhibit VC
   - stimulate eNOS for nitric oxide production
   - inhibit ET-1 gene secretion, mRNA levels and promotor acitivity
2. inhibit ROS
   - direct antioxidant activity
   - scavenges free radicals and inhibits LDL oxidation
3. anti-inflammatory activity
   - inhibit enzymes
   - cyclooxygenase and lipoxygenase
4. inhibit platelet aggregation
5. inhibit myocardial infarction proliferation
   - prevent athlerosclerosis

Question 10

Important notes about CVD studies

Answer 10

demonstrated in cell culture
doses obtain through diet
with resveratrol not metabolites

Question 11

How resveratrol may reduce cancer

Answer 11

1. estrogenic/antiestrogenic
   - similar to synthetic E agonist DES
2. biotransformation enzymes
   - phase I and II
3. Normal cell cycle regulation
   - DNA repair
4. Inhibit proliferation - induce apoptosis
5. inhibition of tumour invasion
   - matrix metalloproteinases, help cancer invade normal tissue
6. inhibit angiogenesis

Question 12

important notes about resveratrol studies

Answer 12

cell culture
doses not achievable in diet
resveratrol not metabolites

Question 13

resveratrol and longevity

Answer 13

ability to mimic caloric restriction

• reduce calories without malnutrition can extend life span in animals 30-70%
• dramatic reprogramming of cellular metabolism
• increase insulin sensitivity
• improve cardiovascular function
• reduce age related muscle wasting
• reduce age related disease

Question 14

various categories of caloric restriction mimetics

Answer 14

glycolytic inhibitors
antioxidants
sirtuin regulators
lipid regulators
autophagic enhances
insulin sensitizers

Question 15

resveratrol as a CR mimetic

Answer 15

1. sirtuin regulator
   - increase SIRT1 enzyme
   - NAD dependent enzyme
   - deacetylases a variety of target molecules that help regulate fat metabolism, gluconeogenisis. glycolysis, vascular health and cell survival
2. induction of AMPK
   - AMP protein kinase
   - enhances fatty acid oxidation
   - down regulates HMG-CoA reductase (cholesterol)

Question 16

Hormesis

Answer 16

stimulatory at low doses and detrimental at high doses

- alcohol and resveratrol

Question 17

Doses of resveratrol are considered?

Answer 17

pharmacological rather than dietary

- considered a drug vs a supplement