Resveratrol Flashcards
Resveratrol
Polyphenolic compound described as
- 354 trihydroxystilbene
- phytoalexin
- plant antibiotic
- still need compound
- fat soluble compound , exists in cis and trans, aglycone and glycoside
Resveratrol history
Traditional in Chinese Japanese herbal product called kojo kon
Primary active ingredient in Japanese knotweed
- one of richest sources of resveratrol
Resveratrol foods
Highest in red grapes and wine
- only in SKIN of grapes
- highest in Pinot noir
Resveratrol bioavailability IMPORTANT
High absorption (70% absorbed after consumption)
BUT low bioavailability due to rapid metabolism to metabolites in the liver
Only trace amounts of unmetabolized Resveratrol in serum after consumption
So Resveratrol metabolites are more biologically relevant BUT there’s been limited research in them
- unlikely humans are exposed to Resveratrol, just its metabolites
- much of the basic research on Resveratrol is done in cell culture using unmetabolized Resveratrol and at levels much higher than found in human blood
Studies have encapsulated resveratrol in a nanoemuslion to enhance bioavailability
Resveratrol and CVD
Core of French paradox
- French have high sat fat diets and smoking rates but lower CVD risk, is it the red wine?
5 ways Resveratrol may improve CVD risk
How Resveratrol may reduce CVD 1
- Regulation of vasodilation and vasoconstriction
- promote vasodilation (increase nitric oxide in isolated cells)
- inhibit vasoconstriction
- inhibits ET
Ratio outcome measure LIKE
- the 2/16 hydroxy thing
- P2 enzymes
- this one
How Resveratrol may reduce CVD 2
- Inhibition of ROS (antioxidant activity)
- Anti inflammatory activity
- inhibits inflammatory enzymes and transcription factors - Inhibition of platelet aggregation
- prevents blood clots - Inhibition of vascular smooth muscle cell proliferation
- prevents atherosclerosis progression
Resveratrol and CVD notes IMPORTANT
Translation of research results in a challenge
All of these effects are demonstrated in cell culture which is not humans
All of these effects are demonstrated at doses not achievable through our diet
All experiments conducted with resveratrol NOT its metabolites
How Resveratrol may reduce cancer
- Estrogenic and anti estrogenic activities
- Effects of biotransformation enzymes
- decreases P1 enzymes, increases P2 - Inhibition of proliferation and induction of apoptosis
- controls and kills cancer cells - Inhibition of tumour invasion
- Inhibition of angiogenesis
- reduced blood flow to cancer cells
Resveratrol and cancer notes EXAM QUESTION
Translation of research results in a challenge
- All effects demonstrated on cell culture not humans
- Effects demonstrated at doses not achievable through diet
- Conducted in Resveratrol not its metabolites
*clear alcohol and Resveratrol have hormesis
Resveratrol and longevity
Relates to Resveratrol ability to mimic caloric restriction
- causes reprogramming of cell metabolism
- increases lifespan 30-70%
- increases insulin sensitivity
- improves CV function
- decreases inflammation
But a challenge for humans
Resveratrol as a CR mimetic
Sirtuin regulator
- increases the genetic expression of the SIR2 enzyme (mimics CR)
Also increases SIRT1 enzyme
- deacetylases a variety of target molecules that help regulate intermediary metabolism, cell survival, vascular health
Also activates AMPK
- AMPK is a critical regulator of energy metabolism and the aging process
Resveratrol and longevity important notes
Translation of research results
- dose is a huge issue as it’s impossible to achieve in diet-
- Resveratrol vs metabolites
- no human studies done
Resveratrol supplements
Most are sourced from root of Japanese knotweed,some from red grape extract
Effective dose for disease prevention is not known
- not included in dietary recommendations for cancer
Doses are more pharmacological yet still considered NHP
Closing notes Resveratrol
Recall importance of
- bioavailability
- translation of research results to humans (3 points)
- need for human clinical trials
- pharmacological doses
