Midterm 1 Flashcards
What plants products are used for human health?
Food grains such as lentils (high in protein); fruits and veggies; wheat, rice, and other grains (carbs); flowers; and spices and fragrances.
What can trees help with?
The most apparent benefit is they provide us with clean air by absorbing carbon dioxide and releasing oxygen. In addition, they provide shelter. However, trees also provide spiritual needs and mental needs as they can reduce depression and anxiety just by a walk in the fresh air.
What does the opium plant do?
Derived to make morphine, which is a pain management agent.
What does dandelion do?
An extract of its roots aid in cancer treatment.
What does the yew tree/shrub do?
One of its compounds-taxol-is used in chemotherapy for cancer.
What do fenugreek seeds do?
They have anti-diabetic activity.
What does mountain ash do?
They have anti-diabetic activity.
What do ashwagandha roots do?
They are neuro-protectant.
What is the most important antibiotic drug? Where does it come from?
Penicillin which is derived from fungi.
What is important to note about all the plants talked about in NHP?
They are all scientifically proven as they have go through research trials and clinical trials.
What have medicinal chemistry advances helped with?
Led to synthetic derivatives of the natural compounds and compounds targeted to certain proteins.
Why is research on natural health products important?
Discover novel therapeutics for some of the major chronic diseases.
What are the troubles with the increases in NHP support?
Even though a great amount of the general public has been more inclined towards non-traditional medicine, the medical system has not been properly educated on such. Therefore, with little to no education and limited scientific/clinical knowledge and validation, proper recommendation cannot be given.
Phytotherapy
Treatment of diseases using plant extracts.
What are the main non-traditional medicine cultures?
- Chinese traditional medicine
- Ayurvedic medicine (traditional Indian medicines)
- Jamu (Indonesian traditional medicines)
- Kampo (traditional Japanese medicines)
- Traditional Medicine for Canada’s first peoples
When can herbal medicines move to clinical validation?
Once they are scientifically validated through scientific studies.
Do we know the oldest traditional medicine?
No, as they are considered to be prehistoric.
What is the known oldest traditional medicine?
Shown in chimps.
What is meant by traditional medicine?
Knowledge about plants that is passed down generations.
What did Babu Kalunde observe?
That young porcupines with stomach upset and pain ingested roots of a plant called mulengelele.
What plant did porcupines eat?
Mulengelele, a toxic plant in the Tazanian community known as Aeschynomene cristata.
What did Babu do with the plant that porcupines ate?
He used it as medicine, treating dysentery (a gastrointestinal infection) as an illness.
What did Huffman and Mohamedi Seifu Kalunde observe (first plant)?
That sick chimps chewed bitter pith (Vernonia amygdalina) and seen to be improved in health afterwards.
What did Huffman and Mohamedi Seifu Kalunde observe (second plant)?
That sick chimps swallowed leaves of Aspilia mossambicensis and observed whole leaves coming out in the excreta with disease causing worms stuck to it. Specifically, their mother showed them.
Zoopharmacognosy
The act of animals using plants to cure themselves.
How could aspilia mossambicensis pull out worms?
Due to the microthorns on the leaves, worms would adhere to them.
What is the downfall with aspilia mossambicensis?
Cannot be chewed completely or they won’t work. This is because the micro-thorns need to be present.
Was the act of swallowing of leaves knowledge or instinct?
It was knowledge as it was done by trial and error, and they passed on from generation to generation.
What did Dr. Youyou Tu discover?
An antimalarial drug from herbal extract.
What did Dr. Tu study?
Sweet wormwood
What did Dr. Tu extract from sweet wormwood? Benefits?
A compound known as artemisinin, which inhibits malaria parasite.
What did Prof. Satoshi Omura discover?
A drug that fought against worm infections (roundworm).
What did Prof. Omura study?
Soil bacteria, specifically Streptomyces bacteria.
What did Prof. Omura isolate from streptomyces bacteria? Benefit?
Ivermectin, which fights against roundworm infections.
How are plants identified?
By their own army of compounds they produce.
How was covid infection rate in Himalayan people?
Those that lived in that area had a low infection rate (not as lethal when infected too).
Why did Himalayan people have a low infection rate?
They made tea from Rhododendron arboreum petals.
What happened to the infection rate with the aqueous extract?
It had 80% inhibition at 1mg/ml.
What did the isolated compound extracts of Rhododendron arboreum show?
They prevented viral infection of cells.
What happened in vitro culture of the petals of Rhododendron arboreum?
The viral load did not go into cells, showing inhibition of the proteases in the viral load.
What are the only two solvents used in extraction procedures?
Water and ethanol.
What needs to happen with Rhododendron arboreum now?
It needs to be clinically validated. It would be assumed to use the natural extract since the synthetic compounds might be toxic.
What are the three categories of herbal products?
- Herbal drugs or plant extracts derived from specific parts of medicinal plants (NHP)
- Natural products (purified compounds) isolated from nature
- Nutraceuticals or functional foods
What are herbal drugs?
They are the natural extract where it’s just using the plant itself (no purification or isolation). This is using the roots, leaves, etc.
What part of St. John’s wort is used for medicine (herbal drugs)?
The aerial parts.
What does St. John’s wort treat?
Mild to moderate depression.
What part of the Gingko biloba plant is used for medicine (herbal drugs)?
The leaves
What does gingko biloba treat?
For cognitive deficiencies such as memory impairment.
What are Ashwagandha roots used for (herbal drugs)?
Brain tonic
What part of chemomile is used for medicine (herbal drug)?
Flowerhead
What does chemomile treat?
Gastrointestinal complaints and is an anti-inflammatory agent.
What are natural health products (NHP)?
Pure chemical isolated from any natural source.
How is opium poppy a natural product?
Morphine extracted to be a pain killer.
How is foxglove a natural product?
Digoxin and other digitalis extracted to treat heart failure.
How is pacific yew a natural product?
Taxol extracted from the bark to be used in anti-cancer therapies.
Nutraceuticals
Any substance that is a food or part of a food that provides medicinal and health benefits.
What herbs and spices are nutraceuticals?
Garlic, ginger and tumeric are antioxidants.
Why is cocoa and red wine nutraceuticals?
Contain anthocyanins that reduce inflammation and aid in cancer protection.
Why are tomatoes and carrots nutraceuticals?
They contain carotenoids that have antioxidant properties.
Food
Provides energy and co-factors of vitamins.
Functional food
Food that provides health functions beyond the basic nutrition.
What does the world health organization do?
They provide universal health coverage and integration of safe and effective traditional providers and complementary services into self-care practices and healthy service delivery with a focus on herbal medicines.
How many people in the UK use herbal medicine?
Between 20-33% of people use it alone or in combination with conventional medicines.
What is the european market for herbal medicines?
7.4 billion USD
Where is the huge market of herbal use as medicine?
In India and China.
Are herbal medicines licensed?
In some countries they are licensed and used under medical supervision while in other countries there is no medical supervision (ex. people using dandelion tea without dr. recommendation).
What are the concerns of herbal medicines?
- Quality and efficacy (benefits in a controlled setting - lab)
- Safety of the NHPs in children, pregnant women, and breastfeeding mothers.
- Herb-drug interactions for those people on conventional treatment (grapefruit juice can decrease drug absorption)
Explain how gingko biloba changes in NHP regulations.
- Food category in UK but now follows under as a “Traditional Herbal Medical Product”
- In Germany, it is a “Herbal Medicine Product”
- In USA it is regulated as a food supplement
Licensed herbal products (UK)
Product license right (PLR) issued to herbal products already in use based on bibliographic evidence to support efficacy and safety (using for long periods of time).
Traditional Herbal Products registered under the European Traditional Herbal Medicinal Product Directive (UK)
Manufacturers can register their product as medicinal product to make restricted claims on the package and patient information provided certain criteria.
What is the criteria to list register a product under the European Traditional Herbal Medicinal Product Directive?
- Evidence that a corresponding herbal product has been used traditionally for at least 30 years (15 in non EU) - indicates safety
- Bibliographic data on safety with an expert report (tested)
- A quality dossier (indication on testing, safety, etc.)
- Details on patient information leaflet (PIL) - dosage and indicates no other contamination
What is unlicensed herbal medicines (UK)?
Those products that are exempt from licensing. They are distributed by herbalists based on their own recommendations.
What do unlicensed herbal medicines consist of?
Dried, crushed, or fragmented plants (must contain no chemical interference).
How are unlicensed herbal medicines sold?
Under their botanical names with no written recommendation for use.
How does Australia classify herbal products?
The Therapeutic Goods Administration (TGA) classifies them as low risk or high risk.
AUST-L
Low risk herbal and complementary medicines registered in the Australian Register of Therapeutic Goods (ARTG).
AUST-R
Higher risk medicines that undergo full pre-market evaluation for safety and efficacy registered in the Australian Register of Therapeutic Goods (ARTG).
When did Canada start licensing herbal products?
2004, Natural Health Products Regulation act.
When can herbal products be used in medicine in Canada?
Allowed based on evidence of claims:
- detailed information on medical ingredients, source, potency, non-medical ingredients, and recommended use
What happens once the product is assessed in Canada?
Health Canada grants a Market Authorization and Natural Product Number (NPN) - single pure compound.
NHPN
Natural Health Product Number for identification.
Where are herbal medicines in the USA?
Regulated as dietary supplements by the FDA. This means they are in the food category and not tightly controlled.
How are herbal medicines assesesd in the US?
- Do not have to be assessed for safety and effectiveness
- Limited therapeutic claims may be made (research done if - pre-clinical)
What statement is placed on herbal products in the US?
This statement has not be evaluated by FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.
What happens when the herbal product is in the market (US)?
FDA monitors claims on safety and if not satisfied, it will cancel the license.
What is required in the US for herbal product licensing?
A good manufacturing practice.
What extract to prepare if active ingredients are hydrophobic?
Ethanol
What extract to prepare if active ingredients are water soluble?
Water
How does NHP differ from natural compounds?
NHP = isolation of total extract
Natural compounds = purify single compounds
How to prepare NHP extracts?
Grinded, immersed with water or ethanol, and then could be fermented if necessary.
How to isolate natural compounds?
By activity-based purification and then determine the structure.
What is similar between NHP and natural products?
The evuation of bio-activities using:
- different enzymatic activities
- cellular models of diseases
- animal models of diseases
- evaluate toxicity and tolerability (not needed in CAN for NHP)
What do the bio-activities of the extracts or compounds need to show?
The mechanism of action of activities (how it does what it does).
What do first people think of traditional healers?
Think they are highly knowledgeable and inspired individuals. When they administered remedies, it was a rule they were devoid of adverse side-effects.
What is reliance on in herbal medicine of first people?
The created organic alkaloids, phytochemical properties, and synergistic action of whole plants (how all biocompounds interact). Also the understanding of the requisites of human physiology.
Besides herbal medicine, what other practices do first nation people practice?
Further preventive and therapeutic practices include daily water bathing and the abundant drinking of water to improve fever; deep breathing; physical and spiritual exercises to boost immunity; and special geriatric and child rearing methods.
What are the three approaches to healing in Traditional Indigenous culture (KNOW)?
- Consider in an integrated manner the mental, social, spiritual, physical, and ecological dimensions of health and well being (holistic approach)
- Central importance is placed upon the concept of maintaining healthful balance, within the individual and between the individual, society, and the natural world
- Imbalance and breakdown arise with the breaching of sacred natural laws and the inter-connectedness of life, inevitably resulting in discomfort and disease
How can imbalance be fixed in indigenous culture?
Diet can restore health and well-being since most foods are used for their healing values. Also, simple lifestyle and environmental factors like sound nutrition, exercise, clean air and water, positive mental attitudes, and abstention form toxic drugs (vaccines) help with health.
How many populations did WHO estimate to employ indigenous ways of medicine?
In some countries as many of 80 to 90 % of the population use their medicinal practices for health care needs.
Why employ traditional indigenous medicine?
- More affordable
- More closely corresponds to the patient’s values and beliefs
- Less paternalistic (reduced autonomy) than allopathic medicine
- Is effective
Is the Indigenous population more healthy?
No, they have worse health and the term crisis is being used. For instance, it is six times more likely for diabetes to be common in a native person.
Why did CAN renew interest in Indigenous medicine?
Rosy periwinkle has bee used to attain an 80 % recovery level for childhood leukemia and effective in treating Hodgkin’s disease.
What extracts of rosy periwinkle does the western medicine use?
Vincristine and vinblastine.
How was it discovered that periwinkle helps to treat childhood cancer?
Accidentally as Indigenous people used it to treat flu-like symptoms. Modern scientists found this for a treatment option for kids since they cannot use strong medicines.
Ametra
Application of traditional medicine
Who does the Ametra Project work with?
The Shipibo Conibo people in the rainforests of Eastern Peru.
What is the key objective of the Ametra Project?
To employ and investigate the relative efficacy of the traditional methods of healing to hopefully integrate them into hospitals.
How did the Ametra Project work?
- brought Shipibo-Conibo village health workers and university store pharamacologist together to examine and put to test various traditional plant remedies as recommended by their traditional healers
- once the relative efficacy, safety, and methods of use are documented, this information is incorporated into healthy care training course materials which are then being used educationally in various Indigenous communities (enrich in their own knowledge; success)
What did Indigenous people claim about psychedelics?
Claimed that when using you can talk to the Gods when you take them (become spiritual)
ex. marijuana leaves
What did the Council on Rural Health CAN say about Indigenous medicine?
Their traditional medicine must be integrated into the current health care so that all of their people have the choice of being able to obtain access to traditional medicine (education both ways).
What is skunk cabbage used for (Indigenous)?
To stimulate the removal of phlegm in asthma.
What is bronchitis?
Bacterial infection of the air windpipe.
What is creosote bush used for (Indigenous)?
A teat of leaves used for bronchial and other respiratory problems.
What is pleurisy wood used for (Indigenous)?
A tea of boiled roots used as a remedy for pneumonia and later used to promote the expulsion of phlegm.
What was wormwood used for (Indigenous)? What changed?
A tea of boiled leaves used to treat bronchitis. Found to have no anti-bacterial resistance.
What are yellow-spined thistle used for (Indigenous)?
Blossoms boiled and the liquid is applied to burns and skin sores.
What is boneset used for (Indigenous)?
Tea used to reduce fever; stomachache; body pain; and to alleviate fever and colds.
What is wild carrot used for (Indigenous)?
The blossoms are steeped in warm water and when in full bloom can be drank for diabetes prevention. Also a tea of the root bark offsets the effects of diabetes (Devil’s Club).
What is pokeweed used for (Indigenous)?
A tea of boiled berries to cure rheumatism. The dried root can reduce inflammation.
What is bloodroot used for (Indigenous)?
The tea of the root is used as a rheumatism remedy. This is because natural material fixes autoimmune cells and protects joint cells from dying (needs to be tested).
What is dandelion used for (Indigenous)?
A tea of its roots drunk for heartburn; general tonic (feel better); and anti-cancerous
What is yellow root used for (Indigenous)?
A tea from the root was used as a stomachache remedy.
What is the most ancient medical disciplines out of them all?
Ayurveda (traditional Indian medicine).
What extra element does First peoples medicine include?
A nature element, so there must be a balance between nature, spirit, mind, and body to prevent diseases.
How old is Ayurveda? Documentation?
It is 5000 years old with documentation as part of their religious text (Vedic literature).
What is a common feature of all ancient medicine?
Combination of spirit, mind, and body for healing.
NOTE: Indigenous medicine includes nature
What philosophy is Ayurveda founded on?
Prakruti and Purush (nature and creatures/consciousness).
What is Prakruti and Purush?
Prakruti = nature (influenced by the five elements)
Purush = creatures/consciousness
An imbalance between the two leads to disease. When we ignore or suppress our true self (Purusha), it creates disharmony within us which ultimately manifests as physical or mental ailments. Understanding one’s Prakruti helps in identifying potential health risks associated with specific dosha imbalances early on.
How is pregnancy represented in native culture?
The couple IS pregnant as a higher spirit chooses them to be parents.
Sweat lodges
Treatments native people use to treat diseases but hard to scientifically prove (remove sweat = cleanses body).
Panch Bhuta
Five basic elements that represent the manifestation of cosmic energy (not in balance = disease).
What are the five elements of Panch Bhuta?
- The ether (space)
- Air
- Fire
- Water
- Earth
What are the five basic elements related to?
The five senses (hearing, touch, vision, taste, and smell).
What is the seven Dhatu?
Organs and tissues in indian medicine that have been translated to modern medicine.
List the seven Dhatu.
- Rasa (serum)
- Rakta (blood cells)
- Mansa (muscles)
- Medda (fat/adipose tissue)
- Asthi (bones)
- Majji (marrow nervous system)
- Skukra (male reproductive system)
- Artar (female reproductive system)
Rasa
Serum
Rakta
Blood cells
Mansa
Muscles
Medda
Fat/adipose tissue
Asthi
Bones
Majja
Marrow/nervous system
Shukra
Reproductive system (male)
Artar
Reproductive system (female)
Tridosha
The three humors/principles which govern the function of our bodies on the physical and emotional level.
What are the three humors?
Vata, pitta, and kapha.
Vata
Affiliated to air or ether.
What does vata control?
Biological movements like CNS, breathing, blinking, heart beat, and nervous impulse.
Pitta
Affiliated to fire and water
What does pitta control?
Controls body temp, metabolism, digestion, excretion, blood production, the endocrine system, intelligence, and understanding.
Kapha
Affiliated to water and earth.
What does kapha control?
It’s related to physical structure and biological strength, so it controls immunity, mucus production, joint lubrication, wound healing, and vigour (good health) and memory.
How does tridosha relate to disease?
Imbalance of them can cause disease.
What does tridosha determine?
Defines people’s personality and what treatment they get (personalized medicine). This is because you may be dominant in one, and then have less of the others.
Prakruti
Individual human constitution
Malas
The three waste products: urine, feces, and sweat.
Can the malas cause disease?
Yes, an imbalance in them can cause disease.G
Gunas
The attributes
What are treatments used in Ayurveda medicine?
Diet, fasting, bloodletting, skin applications, enimas, stimulating vomiting, yoga, and breathing.
Why are there breathing exercises in all traditional medicines?
They increases nitric oxide which performs signal transport to keep the heart healthy.
Rasayana
Remedies that affect many systems of the body and have a positive effect.
Give examples of rasayana remedies.
Asparagus, amla (india gooseberry), long pepper (best anti-cancer effects), haritaki, guduchi, and aswagandha.
What properties do most of the rasayana remedies have?
Anti-inflammatory and anti-oxidant properties.
What Indian medicine balances the tridosha?
Indian gooseberry (amla).
What does indian gooseberry do?
Improves memory and intelligence, tonic.
What does sweet flag do (Ayurveda medicine)?
It pacifies (calms down) vata and kapha to act as a nerve stimulant and digestive.
What does trailing eclipta do (Ayurveda medicine)?
It pacifies kapha and pitta aiding in skin and hair disorders.
How are most of the extracts prepared in Ayurveda medicine?
Water extract, where it’s usually boiled to make a tea.
What are different ways medicines can be prepared in the Ayurvedic culture?
Cold infusion (water for long periods of time); hot infusion (boiled); powder; juice (pressed); and milk extract.
How does the milk extract work?
It extracts lipophilic compounds due to the hydrophobic properties of it (boiled and filtered).
How is most medicine given to babies?
The mom either ingests it or they place it in the mother’s breastmilk (double the nutrients). This is so the medicine is safe enough for a baby to take now.
How old are written documents in traditional Chinese medicine?
500 BC
What is the philosophy of traditional Chinese medicine based on?
Holistic approaches including the physical, emotional, and spiritual aspect of a person’s illness. Balance and harmony is important.
What physical and spiritual exercises are practiced in traditional Chinese medicine? Why?
Kung fu since it can calm you down and build muscle at the same time.
What extra aspect of holistics is included in native medicine?
Ecology (Mother Nature).
What is qi?
The essential life force in traditional Chinese medicine.
Where is qi?
It is everywhere:
- from food and drinks - digestion extract - transferred to the body
- from air - through breathing - transferred to lungs
- from lung and body meet in the blood - and qi of blood can circulate through the body
What are main remedies in traditional Chinese medicine?
Diet and breathing exercises (Kung Fu), and herbal medicines.
Yin
Negative, passive, dark, female, and water.
Yang
Positive, active, bright, male, and fire.
What is stronger: yin or yang?
Yin is stronger because the fire of yang can be extinguished by the water of yin; however, water is indestructible.
Do yin and yang need to be in balance?
For no illness to happen. Usually they are in balance. If one is strong at one time, the other is weak.
What are the five elements in traditional Chinese medicine?
Fire
Wood
Earth
Metal
Water
Fire in TCM.
Heart
Wood in TCM
Liver
Earth in TCM
Spleen
Metal in TCM
Lungs
Water in TCM
Kidneys
How does anatomy and organ description compare in TCM and Ayurveda medicine?
TCM = not important as the dissection of the human body was thought to be insulting to ancestors
Ayurveda = detailed anatomy and very much dissection-heavy culture
What relationship is important in TCM?
Qi, yin, and yang.
What are NOT the cause of diseases in traditional medicines?
Bacteria, viruses, and chemicals.
What is the reason of disease in traditional medicines?
Weakness of an organ or system.
What are the 7 emotional forces in TCM?
Joy, anger, anxiety, concentration, grief, fear, and fright.
What are the 6 external cosmological forces in TCM?
Wind, cold, summer heat, dampness, dryness, and fire.
How do they diagnose in TCM?
Through touch by tongue, pulse (rate, pressure, or frequency), palpation of internal organs (detect masses and tenderness), massage, and interviewing.
What is the treatment in TCM?
Rectify harmony (calm down spirit, body, and mind); restore qi through diet; and balance yin/yang through physical exercises and herbal treatment.
What are cold diseases caused by in TCM?
Those such as coughs, cold in lungs, nausea and vomiting are caused by a deficiency of Yang.
What are cold diseases treated by in TCM?
Warming herbs (yang herbs) like ginger.
What are hot diseases caused by in TCM?
Those like fever, malaria, or congestion of the chest (overeating and lung infection), are caused by deficiency of Yin.
What are hot diseases treated with in TCM?
Cooling herbs (yin herbs) like arctium lappa L.
What disease in TCM affects all 3 balances?
Empty which is fatigue or diabetes causes deficiencies in qi, yin, and yang.
What restores deficiencies in all 3 balances in TCM?
A nourishing tonic (boost qi and warm yang and cool yin).
What does Aconitum taste like? What does it belong to?
A pungent taste of hot yang.
What does aconitum help with?
Heart tonic, diarrhea, and as an analgesic (pain reliever).
What does sweet wormwood and rhubarb taste like? What does it belong to?
Bitter taste of cold yin.
What does sweet wormwood help with?
Malaria and fever.
What does rhubarb help with?
Constipation, burn, and jaundice.
What is the purpose of important herbs in TCM being listed for the entire world?
Demonstrates that since this knowledge of herbs has been used for long periods of time, they must be good; well-tolerated; and used for these certain diseases. This allows the modern world to test them for scientific validation.
What is KAMPO?
Japanese Traditional Medicine (JTM)
How long has Japanese traditional medicine been practiced for?
1500 years
What is JTM dervied from?
Ancient TCM.
What is the relationship in JTM?
Body and its environment.
What causes disease in JTM?
Imbalance of normal state of equilibrium.
What is the purpose of treatment in JTM?
To restore balance.
What are the forms of treatment in JTM?
Herbal formulations, where five to nine herbs co-exist together. Therefore, it can be used for several different conditions.
ex. Ningiome = cough formulation of 14 herbs including ginger
What is sho-saiko-to?
A herbal formula with 7 herbs used for treatment.
What is sho-saiko-to used for? Why?
Acute fever, pneumonia, branchitis, influenza, chronic hepatitis, and chronic gastrointestinal disorders. A great deal of these are inflammatory disorders in which the seven herbs have anti-inflammatory effects. In addition, the first four are infectious diseases where the immune system needs to fight, so it can be understood that the herbs have immunomodulatory effects.
What are the herbs in sho-saiko-to?
Bupleurim root, pinellia, scutellaria root, jujube fruit, ginseng, licorice root, and ginger.
Innocent remedies
Those that help the body and do not provide any side-effects.
Where is western herbal medicine practiced most?
In greek cultures.
What are the humors and temperatures in western herbal medicine?
Blood, black bile, yellow bile, and phlegm with hot, cold and damp temperatures.
What does illness result from in western herbal medicine?
Imbalance of the humors.
How is illness corrected in western herbal medicine?
Herbs
What is the best way to detoxify?
Eat fibre
What does western herbal medicine not include?
NO exercise, so no mental or physical aspect.
What is Culpeper’s Herbal?
The first comprehensive compilation of medical and pharmaceutical knowledge on plant medicine.
What is modern herbalism?
Medical herbalists use traditional knowledge and apply herbal medicines in a modern context.
What do modern herbalists do?
They prescribe herbal medicine using modern medicinal practices. For instance, they have a modern rational/scientific phytotherapeutic approach where they use knowledge of causes, consequences of diseases, and modern diagnostic tools in conventional medicine.
What are traditional herbalists?
Those who refer to mainly the older traditions and philosophy. They use herbs to treat diseases and are licensed to prescribe herbal medication (UK + EU).
Holistic therapy
A patient’s psychological, emotional, and physical health is considered for treatment (all traditional medicine).
Personalized treatment
Herbalists select herbs on individual basis for each patient.
What is important in treatment strategy?
There needs to be identification of underlying of the patient’s illness (usually viruses).
What are herbs used for in traditional medicine?
To increase the body’s healing capacity and strengthen the body’s capacity to correct imbalances/disturbed function rather than just the symptoms. Also to detoxify and stimulate circulation.
What is the importance of stimulating circulation?
Prevents cardiovascular problems.
How to stimulate circulation through food?
Spices contain a fibrinin compound that gives brightness of cheeks.
Do plant compounds act together?
Yes, it is believed that different chemical constituents of a medicinal plant act together in some way that has beneficial effects (not always).
What are the conditions treated in modern herbalism?
Mostly chronic conditions like allergies, autoimmune (MS, lupus, Chron’s), infections, fatigue, emotional and mental health, etc.
What is the treatment strategy in western medicine?
Use herbs to relieve symptoms, reduce inflammation, stimulate immune system, detoxification, and hormonal balance.
How do herbalists in western medicine prescribe herbal treatment?
Through consultations, case history, and discussion of diet and lifestyle. They arrange diagnostic tests as well.
How many herbs do herbalists prescribe?
A combination of different herbs (4 to 6).
What is ration phototherapy?
Science or evidence-based herbal medicine that have evidence of efficacy and safety.
What are health foods?
Total extracts, so multiple compounds.
What is health food?
Non-toxic, generally well-tolerated nutritional compounds.
What are the pros of multiple compounds?
- Could act together to enhance the efficacy
- Some compounds may inhibit toxicity of others (reduced toxicity due to multiple compounds requiring lower doses)
ex. plants used in anti-cancer treatment will not be attacked because the plant cells have an antidote to the anti-cancer compound
What are the cons of multiple compounds in herbal medicine?
- How do you know what compounds do what?
- Poor patent ability
- High dosage as a pure compound = toxicity
Potent herbal medicines
Bioactive compounds targeting specific components, toxic to certain pathways.
When are conventional medicines and herbal ones combined?
In certain cases, HIV infection requires triple therapy, and cancer, as multiple compounds are given as chemotherapy.
Polyvalent action
Ability to interact with, or act against, more than one type of microorganism, antibody, toxin, or antigen.
What are three scenarios of polyvalent action?
- Several compounds affecting a single target directly or indirectly
- A single compound affecting multiple targets
- Multiple compounds affecting multiple targets
Loewe additivity
Drugs have similar mechanisms and effects on the same target. If two drugs are additive, combining them should produce the same effect as increasing the dose of either drug alone.
ex. if drug one causes 50% of death of cancer 50 mg and drug two causes 50% of death at 100 mg, drug one at 25mg and drug two at 50 mg would still give 50% effectiveness
OR
if drug one causes 50% of death of cancer and drug two causes 50% of death, together they would cause 100%
Bliss independence
Drugs act independently on different targets. Assumes that two drugs act independently of each other, each contributing to the overall effect without interference.
ex. one killing cells by inducing caspase activation, the other killing cells by inducing oxidative stress
Combination index (CI)
Measures the degree of drug interaction and the extent of synergy or antagonism in a drug combination.
CI < 1
The doses of the drugs in the combination are lower than expected, indicating synergy.
Synergy
The combined effect of two drugs is greater than the sum of their individual effects (occurs when the drugs enhance each other’s activity, often by targeting different steps in a biological pathway).
CI > 1
The doses of the drugs in the combination are higher than expected, indicating antagonism.
CI = 1
The doses of the drugs in the combination are as expected, indicating additivity.
Additivity
The combined effect of two drugs is equal to the sum of their individual effects.
Antagonism
Occurs when one drug reduces or inhibits the effect of another drug.
What do ispahgula or psyllium husk treat?
Constipation and diarrhea.
How do ispahgula or psyllium husk have a laxative effect?
Due to the fiber and gut-stimulatory effect of seed constituents (bowel movements going).
How do ispahgula or psyllium husk have a anti-diarrhea effect?
Due to gut inhibitory effects of compounds in ispaghula.
What else can ispahgula and psyllium husk help?
Improve glycemic control in Type 2 diabetes and have anti-amoebic constituents.
What does liquorice act as?
Synergistic agent.
What does the whole extract of liquorice inhibit?
Angiogensis (generation of new vessels, which cancer induces).
What promotes angiogenesis?
Glycyrrhizin (a purified compound of liquorice).
Give an example of synergy with THC extract and THC pure compound.
The total extracting containing the same amount of THC as the purified compound, showed better activity. This could be due to other compounds in the total extract enhancing the effect. CBD playing a role.
What is salicin used in?
Aspirin
What is salicin found in?
Willow bark
What is salicin used as?
Anti-inflammatory
Ethnobotany
The study of how plants and humans interact and the knowledge of plants and its use in medical, food, technology, and spirituality.
What were the past attitudes about ethnobotany?
Often ridiculed and dismissed as a descriptive survey of interesting but dying and irrelevant traditions.
What are the present attitudes about ethnobotany?
WHO traditional medicine program and national programs now integrate traditional and modern health care; traditional medicine provides 80% of health care products.
Ethnopharmacology
The study of biological activity/pharmacology of traditionally used plants and the relation between traditional and modern science.
What are the applications of ethnopharmacology?
A proven route to drug discovery; bring safe cultural practices forward to modern day; and to support and respect First Nation culture.
What is not a priority of medicinal plants in healing cultures?
Drug development
Do the Indigenous societies document their medicines?
No, they do not have well documented literature. Instead, they pass their traditions, present today, on by oral traditions.
What is Indigenous medicine based on?
Observation over scientific method.
What do traditional societies down without access to outside resources?
Traditional healers remember and pass down by oral tradition to family members. Over 200 species of medicines.
How many species can a culture maintain knowledge of?
800-1000 species
What kind of world view do Indigenous societies have?
A cosmocentric one, where they have a way of seeing the world with an importance of nature, based on their traditional tribal religion.
What is the contrast with the documentation of TCM, Ayerveda, and European herbalism?
They are well-documented in literature, thus they don’t have to be passed on from generation to generation.
How does the diversity of well documented cultures compare to the ones that aren’t?
Well documented cultures are less botanically and culturally diverse.
How quickly are documented culture integrated into modern medicine than the ones that aren’t?
Much quicker.
ex. TCM practitioners are regulated in several provinces like BC and ON
Naturopathy
Evidence based herbal medicine
Homeopathy
Alternative medicine based on diluted extracts with inverse dose dependence (more diluted = more effective = anti-scientific).
Where is integrative medicine common?
Cancer centers because chemotherapy tends to lower quality of life, whereas these traditional medicines may provide some release at the end of life (palliative care).
What are practices in Neowestern herbalism?
Chelation therapy; aromatherapy (smells = calming effect); energy therapies; mind body interaction like yoga, etc.
Neowestern herbalism
Individual herbal medicine based on popular culture. It uses those that back modern science.
Biodiversity
The total diversity of living things, at genetic, species, and ecosystem levels.
Cultural diversity
The total diversity of human cultures.
Biosphere
The entire are of the earth - land, water, and air - inhabited by living things.
Ethnosphere
The sum of total human though, language, beliefs, and institutions made manifest by the myriad of world cultures (all ethnicity).
What is being diluted in the world out of all the cultures?
Ethnodiversity and biodiversity.
What is being lost at a great rate?
Ethnosphere
What is the indicator of ethnosphere loss?
A key indicator is language loss (over 50%).
What is language?
A set of grammatical rules and body of vocabulary AND the flash of the human spirit, the soul of each particular culture becoming a material realm AND knowledge acquired over time.
How can preservation of indigenous cultures and biological diversity go together?
Conservation groups and indigenous cultures can have alliances that protect the rights of vulnerable people, and preservation and stewardship of biodiversity and tropical forest.
What happens with the preservation of culture for local people?
They gain income, medicines, construction material, and preservation of cultural heritage and language.
Where is the most important plant diversity?
68% of plant diversity exists in tropical areas.
How many people in the tropics rely on traditional medicine?
More than 80%.
What is happening to biodiversity as populations grow?
It is shrinking since people are overthrowing areas and clearing out trees and greenery to build.
How many indigenous people and languages worldwide?
300 million indigenous people worldwide with 6000 languages.
How many of the world languages and intellectual heritage do indigenous people count for?
60% of languages and more than half of human intellectual heritage.
How much loss of language is there for indigenous culture?
Over 50% loss.
Where is Indigenous cultural diversity extirpated from?
US, Europe, Japan, Canada, China, and India.
Where does Indigenous diversity remain high?
SE Asia, Central and S America, Africa, Indonesia, circumpolar regions, and BC Canada.
Who are healers in Borneo?
Either male or female elders.
How do healers in W Africa learn their knowledge?
Hold university degrees OR they can learn the trade in the form of apprenticeship from elders.
What is the third pillar of traditional medicine?
Spirituality
What does the tree of life represent in Mayan culture?
Heaven, Earth, Man, and the Underworld, showing the interconnectedness of all things.
What is the tree of life?
Yaxche: Ceiba tree
How is health and disease seen in Mayan culture?
Mental, physical, and spiritual balance.
What are the culture bound syndromes in Mayan culture?
Awuas, Bilis, Pasmo, Susta, and Evil winds.
What does fire do in Mayan cultures?
Ancients put copal incense into sacred fire as a healing ceremony. It pleased the Gods, combining spirituality and plant use.
What are the directions in Mayan cultures?
Earth, air, water, and fire.
How extensive is the indigenous knowledge of plants?
Great amount of knowledge with hundreds to thousands of species for medicinal, dye, food, etc, but over 10s of thousands of different uses.
How was Amazonian medicinal culture shown?
Schultes collected over 2000 of estimated 20,000 medicinal plants of the Amazon and listed their uses. They are all scientifically validated.
What is Sangre de Drago do (Amazonian)?
Wounds
What does cat’s claw do (Amazonian)?
Anti-inflammatory
What is Ayahuasca?
An orally administered hallucinogen used for ritual healing and religious use.
What do the Ecuador people speak about Gods?
Back in the day, men could speak to the gods.
What does Ayahuasca do?
It restores the ability to speak to the gods and allows the healer and patient to travel to the spirit world and invoke the spirits to cure disease.
What happens when regular people use Ayahuasca?
They did not speak to gods, instead they talked to themselves and repented their sins (crying).
What is Ayahuasca used in modern medicine? Why?
Treatment of addiction because it is not an addictive drug.
ex. treatment of drug addicts in Vancouver
What did brain scans of those who used Ayahuasca show?
Increase in the levels of serotonin transporters, thus decreasing the levels of depression.
What are serotonin transporters (5-HT) associated with?
Alcoholism, violent behaviour, depression, and eating disorders.
What is arthritis?
Pain, swelling, and inflammation in the joints.
Systematic disease
Those that affect the entire body rather than a single part or organ.
Who does arthritis affect the most?
People over 65.
Rheumatoid arthritis
An autoimmune disorder that occurs when the body’s immune system attacks the tissues of the body, specifically connective tissue, leading to joint inflammation, pain, swelling, stiffness and degeneration of the joint tissue.
What can rheumatoid arthritis affect?
Several joints and damage the surface of the joints and underlying bone through inflammation.
What cells are reactive in inflammatory arthritis?
Inflammatory cytokines.
How does inflammatory arthritis occur?
Self-reactive immune cells are killed but some can survive, forgetting their job and attack the body.
What is osetoarthritis?
The common degenerative joint disease that affects the cartilage, joint lining and ligaments, and the underlying bone of a joint.
Where does osteoarthritis occur most often? Why?
Knee because a great amount of body weight burdens this area. It is used so frequently that it wears and tears.
How does osteoarthritis occur?
As we age, cartilage disappears because the bones constantly rub against each other. These tissues breakdown and there is pain joint and stiffness.
NOT by immune cells.
When are you experiencing pain in both kinds of arthritis?
Inflammatory = all the time
Osteoarthritis = when walking not when sitting
Can osteoarthritis have inflammation?
Yes.
What are causes of arthritis?
- Age (osteo)
- Injury (wear and tear) (osteo)
- Abnormal metabolism, leading to gout
- Inheritance (osteo)
- Infections
- Immune system dysfunction (RA)
What is the issue in the treatment of arthritis?
Over time, taking a lot of these drugs can be toxic.
Treatment for rheumatoid arthritis.
Disease-modifying antirheumatic drugs (DMARDs).
ex. trexall and plaquenil
What do DMARDs do?
They try to suppress the immune system in certain areas (locally) from attacking the joints.
What are the pros about corticosteroids?
To treat arthritis and reduce inflammation and suppress the immune system almost instantly when injected (cortisone).
What drugs are used in combination with DMARDs?
Biologics (monoclonal antibodies).
Biologics (monoclonal antibodies)
Genetically engineered drugs that target various protein molecules involved in the immune response.
ex. enbrel and remicade
What doe NSAIDs do?
They reduce both pain and inflammation such as advil or aleve.
What do analgesics do?
Pain reducing medications like tylenol or oxycontin.
What are treatments for arthritis?
Drugs, exercise and physiotherapy, and joint replacement surgeries for osteoarthritis.
How does exercise help with arthritis?
Can build the muscles around the joint and bone. Could can damage locally (inflammation), causing a repair response that brings down pain and inflammation.
What medicinal plants can help for rheumatoid arthritis?
Turmeric, garlic, ginger, black pepper, and green tea have anti-inflammatory properties. Just need more scientific validation.
What plant showed scientific effects in treating osteoarthritis?
Curcumin and boswellic acid.
How can fruits help with arthritis?
They have polyphenolic flavonoids that have been associated with antioxidant, anti-inflammatory, and analgesic effects.
ex. pomegranates, and berries
Are fruits validated?
Yes, they are pre-clinically, clinically, and epidemiological studies on OA and RA.
What compound in broccoli help with arthritis?
A compound called glucoraphanin gets converted to sulforaphane.
What has sulforphane been shown to do?
Represses matrix-degrading proteases and protects cartilage from destruction in vitro and vivo cases.
What does interleukin do in arthritis?
It’s an inflammatory cytokine that increases the production of metalloproteinase and other factors that destroy cartilage.
What does SFN in broccoli do?
Inhibits the production of metalloproteinase, therefore preventing the degeneration of cartilage and inhibiting the production of other inflammatory cytokines.
What did the arthritis experiment in vitro include?
Cultured osteocytes and chrondocytes from articular joints.
What did SFN show in vivo?
Protected against surgically induced osteoarthritis in mice and inhibited cartilage destruction in a bovine explant model.
Who did they gather for the broccoli/arthritis study?
Those who had booked a day to get a knee replacement surgery with a wait period of 6 months to a year.
What was the dosage of broccoli people should eat?
100 mg
What did they look at for the broccoli arthritis patients?
Looked at the knee joint that was replaced.
What did they find in the broccoli/arthritis study?
A diet of broccoli (high in SFN) can stabilize cartilage and reduce inflammation in humans as the isothiocyanate (like SFN) was increased in the knee joints of patients.
What compound in many fruits/veggies helps with arthritis?
Quercetin is an anti-oxidant, anti-inflammatory, and inhibits apoptosis.
What is diabetes?
The inhibition of glucose uptake by tissues, leading to high blood sugar, urine sugar, and other symptoms.
Why has diabetic populations increased?
Increase in processed foods, decrease in physical activity, and every year they count the total people who already have diabetes, are counted again.
Type 1 Diabetes
Deficiency of insulin, no insulin production, so diagnosed early in life.
Type 2 Diabetes Meletus
The most common form where people become resistant to insulin. They are diagnosed later in life (40-50y).
Risk factors for T2DM.
- Food habits, excess calories, obesity
- Lack of exercise
- Genetic background
- Age
Why are South Asian people more genetically susceptible to diabetes?
Because they store fat in different spots.
How does glucose enter the cell?
Phosphorylation of the IRS-1 via the insulin receptor undergoes multiple changes that allow GLUT-4 transporters to go the cell membrane and allow glucose to come ingto the cell.
What are two symptoms of diabetes?
- High blood glucose level (spill into the urine)
- Ketosis (high level of alpha ketone acids)
What increases in the tissues in diabetes?
Fat hydrolysis, gluconeogenesis, ketone body formation, and fatty acid oxidation.
What does the high level of ketone bodies lead to?
Increase in hydrogen ions that increase the acidity of blood pH. There is an increase in the excretion of hydrogen and potassium ions that lead to dehydration and excessive thirst.
What results in the maturity onset diabetes of the young (MODY)?
Mutation in glucokinase which usually co-ordinates insulin release with glucose levels.
When does gestational diabetes occur?
During the second half of pregnancy.
How does gestational diabetes transfer to the baby?
Excess glucose in the mom’s blood means excess sugar feeding to the fetus. Extra glucose gets stored as fat and the fetus becomes obese in the uterus.
How is gestational diabetes caused?
There is a hormonal change during pregnancy in the placenta (estrogen, cortisol, etc.). These can block the effect of insulin leading to a reduced response of the body cells to the sugar and therefore increase in blood glucose.
How is T2DM caused?
The insulin receptor wears and tears over time becoming desensitized to insulin.
What can be done to avoid T2DM?
Diet and exercise (same in coventional and traditional medicine).
What does metformin do?
It’s a drug with different mechanisms of action:
- inhibits gluconeogenesis from the liver
- inhibits absorption of glucose from intestine
- may stimulate insulin secretion from the pancreas
What does sulfonylurea do?
Stimulates insulin production
What did phlorizin come from?
The root bark of the apple tree.
What did scientists find phlorizin could do?
Increase glucose in the urine, lower blood glucose levels, and prevent reabsorption of glucose.
What does phlorizin inhibit?
SGLT1/2, which are transporters in the kidneys and intestines that aid in absorbing glucose.
What did they target phlorizin to?
SGLT2.
What do insulin injections do?
They increase the insulin concentration by 10, 100, or 1000x fold, which forces binding between the insulin and its receptor.
What are possible mechanisms of fenugreek seed in diabetes?
- Inhibit absorption of glucose into the bloodstream
- Stimulates hypoglycemic effects through glucose-dependent insulin secretion
- Lowers LDL and total cholesterol
- Sensitizes the insulin-receptor interaction
How much fiber do fenugreek seeds have?
50% fiber with 30% insoluble and 20% soluble.
What does fiber in fenugreek seeds do?
It inhibits the absorption of glucose from the GI, reducing the amount that re-enters the bloodstream. It also inhibits sucrase and amylase digestion, which slows down sugar breakdown and release.
What component in fenugreek seeds leads to glucose-induced insulin release?
4-hydroxyisolucine
What is glucose-induced insulin release?
Process by which the pancreas (islet cells-beta cells) releases insulin in response to rising blood sugar levels after eating.
What did human studies of fenugreek reveal?
Reduced plasma glucose and increased the number of insulin receptors.
What component in fenugreek seeds help with cholesterol levels?
Sapogenin
What does sapogenin do?
Increase biliary cholesterol excretion.
What is biliary cholesterol excretion?
More cholesterol is being removed from the body through bile, which is a digestive fluid produced by the liver.
How does cholesterol relate to diabetes?
Insulin resistance increases LDL and trigylcerides, which builds up in arteries
What was a clinical study for type 1 diabetes?
10 patients with type 1 were given 100 gms of fenugreek seed powder in two doses (lunch and dinner) for 10 days. The other group was given regular meal without fenugreek powder.
What were the results of the type 1 diabetes clinical study?
54% reduction in 24hr urine glucose level. There was a reduction in fasting serum glucose levels (15.1 mMol/L to 10.9 mMol/L). This indicated that fenugreek seed powder caused release of insulin.
What was the downside of the type 1 diabetes clinical trial?
A bigger trial in terms of people and time is needed (10 days is not enough to gather and prove evidence).
What was a clinical study for type 2 diabetes?
FSP given in amounts (25 gm or 100 gm with food). Studies had the patients with or without standard treatments.
What were the results of the clinical type 2 diabetes study?
Significant reduction in fasting glucose levels as well as urinary levels were observed. Other studies T2DM patients had observed decrease in total cholesterol, LDL-C, and triglycerides.
What was the toxicology study of T2D?
60 T2D patients with 25 gm FSP/day for 24 weeks.
What did the toxicology study of T2D show?
Did not show toxic effects on kidney, and liver.
Does FSP interact with other medications?
No it does not.
Is FSP expensive?
No, it’s a cheap NHP treatment.
What is the problem the Cree and First Nations people face in terms of medical diseases?
Adult onset diabetes is increasing 10 fold.
What are the complications relating to diabetes?
Stroke, heart disease, eye damage, kidney damage, difficulty passing urine, and numbness and reduced blood supply.
What is the difference in lifestyle between native people back then and now?
Used to eat traditional foods with an active lifestyle and now they eat refined food with a sedentary life.
What did the Cree Health Board request?
Scientific studies of traditional medicines for T2D to address safety and efficacy issues.
Who were the source of knowledge for the Cree studies?
Cree healers.
What are pre-diabetic symptoms?
Extreme hunger, hand shaking, and fatigue.
What was the elder knowledge of diabetes?
They didn’t know what diabetes is, but they do treat the symptoms for it.
What are pharmacological targets for T2D (uptake)?
Increase glucose uptake in muscle cells (metformin).
What are pharmacological targets for T2D (lipids)?
Promote healthy lipid metabolism through adipogenesis and increased insulin sensitivity (rozaglitizone).
What are pharmacological targets for T2D (G6P)?
Inhibit hepatic glucose 6 phosphase, a rate limiting enzyme for glucose production = chops off the phosphate that releases glucose from the liver.
What are pharmacological targets for T2D (Hb A1c)?
Inhibit reaction of glucose with proteins to form glycated end products like Hb A1c. HbA1c (hemoglobin with glucose attached). Higher AbA1c = higher glycation = higher blood sugar.
What law involves first nation people and traditional medicine?
The use of traditional medicine on reserves.
What was the ethnobotany study of anti-diabetic medicine in Cree people?
2 communities of 65 Cree elders were interviewed based on 15 symptoms associated with T2D, and asked what plant they used. Calculated the SIV.
What is SIV?
The syndromic importance value quantifies the significance of a treatment.
How does SIV relate to diabetes?
The higher the SIV = the more the plant is used in lost of symptoms. Therefore, this plant must be important in treating diabetes-like symproms.
How many plants were identified with a high SIV?
8
ex. sorbus decora - mountain ash; picea mariana - black spruce; and alnus incana - speckled alder.
What part of SDE is used for diabetes?
Inner bark.
What does mountain ash do?
It has metformin like activity where it enhances the glucose uptake in muscles.
How did they study mountain ash?
Using a bioassay guided isolation where they used the total extract (activity based purification), and then used the fraction that was the best to further purify them. Done this until they could identify the compound.
Explain the glucose uptake assay.
- C2C12 muscle cells were grown in cultures
- add treatments like insulin or other compounds to observe effects of glucose uptake
- treated with 2-deoxi-D[1-3H] glucose
- stop intake by using an inhibtor
- lyse and wash cells
- quantify radioactive signal
Why use 2-deoxi-D[1-3H] glucose instead of glucose?
2-deoxi-D[1-3H] glucose won’t metabolized and remains intact when absorbed so we can observe its uptake afterwards.
Explain how the bioassay-guided fractionation scheme works.
- take dried shredded extraction material (bark of sorbus decora)
- extract with ethanol
- crude extract tested for biological activity but first extracted with hexanes, ethanol, or water
- fractioned using column chromatography
- each fraction tested again for biological activity; positive = further processed and purified to isolate specific compounds
- once a pure active compound is isolated, its biological activity can be confirmed using a different set of bioassays = consistent activity = identification as the bioactive compound in the plant extract
What is the best fraction of SDE?
FB7, FB7-4
What is the best compound of SDE?
Compound 2
What does metformin do?
Increase the absorption of glucose.
How does SDE compare to metformin?
Stimulated glucose absorption better than metformin.
What did SDE-B and C show?
SDE-B fractions had high activity of glucose uptake, whereas C fractions weren’t as good.
What were the two purified fractions of SDE-B? How did they do?
SDE-B10 (best) and SD-B10-D (a little worse). Better than all previous fractions.
What compounds of SDE-B did well?
Compound 2
What was the SDE study with mice?
Mice were fed the SDE for 7 days and measured blood for glycemic index.
What can the purified compound of SDE be given to mice?
May be toxic and have to go through many different regulations to get it approved (too much time).
What did the SDE study with mice show?
The ones who took SDE showed a decrease in the glycemic index, which means a smaller increase in blood sugar following foods (glucose absorbed quicker).
What does the pitcher plant (Sarracenia purpurea) do for diabetes?
Inhibits glucose 6 phosphatase which is a rate limiting step for glucose production in the liver.
How many compounds isolated in the pitcher plant (Sarracenia purpurea)?
11 active compounds isolated with 1 and 10 being new compounds.
What did SPE show in a study?
Inhibits G-6Pase activity but insulin brought it down by 75%.
What did compounds 1 and 10 of SPE do?
Reduced G-6-Pase activity (not as much as insulin though).
What do tamarack compounds do?
Stimulate adipogenesis (healthy fat cells).
How does adipogenesis relate to diabetes?
Adipogenesis helps store excess free fatty acids (FFAs) in the body as triglycerides within fat cells. When fat cells are able to store excess FFAs through adipogenesis, they reduce circulating levels of free fatty acids in the blood, which can help improve insulin sensitivity. This can reduce insulin resistance, a hallmark of type 2 diabetes.
What compound in tamarack helps with adipogenesis?
23-oxo-3-hydroxycyloart-24-en-26-oic acid.
How did they study obesity prevention and treatment in mice?
Standard diet gives 4% of energy from fats.
High-fat diet given 35% of energy from fats.
- first 4 weeks everyone got regular food
- between 4-12 weeks given a high fat diet
- treatment for different lengths
- added plant (tamarack) extract after 4 weeks to high fat diet to see if it could treat diabetes
- other group given plant extract at same tie to see if it would prevent diabetes
What did the tamarack plant extract show in the mice trials?
It reduced glycemia and ratio of leptin to adiponectin, which are two important adipokines involved in appetite control and insulin sensitivity.
What does leptin do in relation to diabetes?
Leptin helps regulate appetite and energy balance by signaling to the brain when the body has enough energy stored in fat. Higher levels of leptin are often seen in insulin resistance. In conditions of obesity, leptin can become resistant, meaning the brain doesn’t respond to it properly, leading to increased appetite and weight gain.
What does adiponectin do in relation to diabetes?
It enhances glucose uptake and fat oxidation, helping the body use energy more efficiently. Higher levels of adiponectin are usually associated with lower risk of type 2 diabetes because it helps increase insulin sensitivity and decrease fat accumulation in the liver and muscles.
What does leptin maintain besides hunger?
Skin temperature because healthy lipid cells breakdown fat to generate heat.
What did measuring skin temp in mice show using the tamarack extract (prevention group)?
That in prevention when a higher amount was given (250 mg) there was an increase in temp (lipid cells doing their job and burning fat).
What did measuring skin temp in mice show using the tamarack extract (treatment group)?
In the treatment group, it was given for longer after obesity already caused. Even a low dose had an effect on increasing temp, indicating healthy lipogenesis (125 mg).
What are the steps in studying plant extracts for diabetes using metabolomics?
- Screen plant extracts for biological activity (those by Aboriginal communities of lake Mistissini QC)
- Develop non-targeted analysis by UPLC MS QTOF
- Perform discriminant statistical analysis of signals for markers (which signals are unique to active plants)
What extracts showed higher glucose uptake activity?
Both ethanol and hot water extracts, but the plants extracted with ethanol had higher activity (above 100%); highest were S.purpurea and S.decora.
What does mass spectometry do?
Identify compounds.
What compound did MS identify? What does it do?
Quercentin-3-O-arabinoside and found that it was more active than metformin and insulin in glucose uptake.
What was the antidiabetic compound in tamarack called?
Awashishic acid.
What is happening with the Cree community now with diabetics?
Cree healers using the plants for public health and working with 4 communities to restore traditional food and medicines. 5 plants in very effective in diabetic animal models (safe).
Where is the biodiversity hotspot for phytochemicals?
Mesoamerican corridor.
Why is there greater diversity in tropical areas for plants?
Greater variation in alkaloid defenses due to insects.
What should be the range of Hb A1C?
Between 5 and 6.
What Mayan plant was the most active in anti-diabetic activity?
Chibiyal vine.
What compound in chibiyal vine aided in anti-diabetic/glycosation activity?
Verbascoside
Cell differentiation
Cells split into different tissues to do different jobs.
Necrosis
A passive cell death phenomenon where it’s pathological (external damage), traumatic (cell membrane disruption and release of contents into environment; immune attack), and inappropriate (not meant to happen).
Apoptosis
Programmed cell death that is physiological (those no longer needed or dead) and appropriate.
What happens to the cell contents in apoptosis?
Taken up by neighbouring cells and cleaned.
What is apoptosis characterized by?
Cell shrinkage, nuclear condensation, DNA fragmentation, flipping of phosphatidyl-serine to the outer leaflet of PM, and activation of caspases.
What are examples of apoptosis?
- uterine lining shed monthly
- cells with DNA damage infected with virus
- skin cells replacing themselves
- gut epithelium tissue turnover
- thymus = self reactive immune cells
What causes DNA damage?
UV, chemotoxins, and replication error.
What are the three safeguards of DNA repair/cancer?
- DNA damage is repairable = repair
- Too much damage to repair = apoptosis
- Can’t repair itself or can’t die = senescence (no more dividing or growth)
What causes a tumor?
When the three safeguards fail and the cell continues to replicate uncontrollably with corrupted DNA.
How has cigarette consumption and lung cancer progressed over the years?
Both increased exponentially until 2000, where there was a dip in both. This is because of the known injury it does cause now.
How does cancer develop?
- Uncontrollable cell division
- Blockage of cell death mechanisms caused by DNA abnormalities
- Acquiring immortality
- Induction of blood capillary formation or angiogenesis (need blood supply to live)
- Detachment from the tissue, invasion of other tissues
- Mutations leading to escape from immune system
How does uncontrolled cell division occur?
- Mutation leading to activation or overproduction of oncogenes (cell division promoting signalling molecules)
- Mutation leading to inactivation or underproduction of cell blocking genes/tumor suppressor genes/anti-oncogenes
What are common DNA abnormalities in cancer?
p53 mutation and over production of Bcl2 genes.
How to know number of cell division?
Telomere length at the end of chromosomes shortens each replication cycle.
How do telomeres work in cancer cells?
The telomere length is kept constant by telomerase, so they cells become immortal.
When can mutations yield excessive proliferation?
- activating mutation in one copy
- inactivating mutation in both copies
What does the first mutation of a gene do?
Cell seems normal but is predisposed to proliferate excessively (NOT cancer).
What does the second mutation do?
Cells begins to proliferate too much but still normal.
What does a third mutation in a cell do?
Cell proliferates more rapidly; it also undergoes structural changes.
What does a fourth or later mutation do?
Cells grows uncontrollably and looks obviously deranged (CANCER).
Hyperplasia
When cells divide faster than normal; not cancer.
Dysplasia
A buildup of abnormal cells; may be cancer or may not be.
In situ cancer
Localized cancer.
Invasive cancer
Tumor cells can invade nearby blood vessels and travel to other areas of the body.
Polyps
Abnormal growth of tissue that contain cells that are either malignant or cancerous. Removing them can reduce cancer by 95%.
What does p53 do?
It induces cell apoptosis and takes away proofreading abilities.
What gene is mutated in all polyps and advance colon cancers?
APC (ademona polyposis coli) gene mutation.
What gene is mutated second in polyps of colon cancer?
Oncogenic mutations of a Ras gene.
What gene mutations determine cancer of colon?
Loss of p53 and DCC.
After and before what mutations can polyps still be removed?
Loss of APC and before RAS loss/mutation.
What chromosome/gene is in all brain cancers?
Chromosome 17 or p53.
What is lost in the later stages of brain cancer?
Chromosome 9
What does the loss of chromosome 9 do?
Contains genes that encode interferons, proteins involved in triggering immune response. These mutations may help the cancer cells escape the immune system. Includes multiple tumor supressors -1 and 2 (MTS-1/2) as well; those involved in regulating cell division
What is lost in the most aggressive form of brain tumors?
One copy of chr. 10.
What did the survival rates of mutating DNA polymerase S show?
The loss of one copy decreased survival rates by only 10%, whereas a loss of both copies reduced survival rates in mice by more than 50%. Both survival chances dropped as the mice aged.
What does the oxidation of DNA bases cause?
When nucleotides get oxidized, their bases are transformed, causing mutation. It will make the wrong pair, which is bad for replication.
What does dG oxidize to?
8-oxo-dG
What did metabolic rate and DNA oxidation study show?
The more thymidine glycol you have in your urine, means that the more your DNA is damaged (oxidized from cystoine).
What is DNA damage more common in? Why?
Mice because they consume more oxygen allowing bases with a higher likelihood of being oxidized.
How can radiation cause DNA damage?
It activates paths and cross-links two adjacent nucleotides. This makes replication difficult.
How do we know if a particular compound is carcinogenic?
A biochemical test on bacteria. If the chemical causes a mutagen of the genes in bacteria, then it’s called a mutagen.
Why are some mutagens in humans not found as mutagens in bacteria?
We have a good detoxification system in the liver, specifically cytochrome p450, that can modify compounds into carcinogens. Many SNPs cause differential activity of the cytochrome based on mutations.
What is benzopyrene?
A pre-carcinogen in bacteria that does nothing, but in humans is gets converted to the ultimate carcinogen (BPDE) by CYP1A1.
What does BPDE do?
It modifies nucleotides.
What is aflatoxin?
Fungal toxin
What does aflatoxin cause?
Liver cancer.
Why is there a higher risk of liver cancer in China, Qidong peninsula?
The humid environment causes fungi growth that produces aflatoxin. Increased exposure from the air, food, and water, and when people are exposed to it, this can cause liver cancer.
Is aflatoxin a carcinogen?
Not in bacteria but in the human system cytochrome p450 converts it to a carcinogen, resulting in changes to the DNA material (2 changes detoxify it).
What are toxins that affect cancer?
Chemotoxicity, radio toxicity, and oxidative toxicity.
What genes are bad in cancer development?
Mutations in DNA repair genes as they as more errors proliferate, cancer has a greater chance of developing.
What are common DNA repair genes?
BRCA1/2 in breast cancer, WRN in several cancers (werner), TP53 in other cancers (li-Fraumeni), and BLM in solid tumors.
What does BRCA1/2 do? How does it cause cancer?
Homology-directed repair of dsDNA bonds. Both copies need to be mutated to cause cancer.
What does WRN do?
exonuclease and DNA helicase.
What does TP53 do?
DNA damage alarm protein, triggering DNA repair response for minor damage or cell death for major.
What does BLM do?
DNA helicase (no DNA repair without it) and replication
What does XPb cause? How?
Skin induced cancer due to a mutation in nucleotide excision repair genes.
Adenoma
Outgrowths and lumps that can be removed in colon cancer to reduce the risk.
How does the removal of polyps help with cancer?
It specifically helps with lowering the risk of colon cancer to less than 1%.
How can growth factors and receptors cause cancer?
Factor = constant binding leading to cell proliferation
Receptor = increased interaction with signals leading to constant signalling and division (automatic activation)
What happens to growth factors after a certain stage?
Stops producing, the receptors are inactive (cell should be dead or differentiating, should not be dividing).
What are growth factors and receptors called?
Proto-oncogenes
How can proto-oncogenes become oncogenes? What does this mean?
When proto-genes are mutated inapprioately it leads to overproduced factors or mutated receptors that leads to hyper-proliferation.
How to help with growth factors in cancer?
Target the receptors, so the signal to divide doesn’t happen.
What are examples of growth factors/receptors in cancer (those that tumors make to signal)?
Factor = HGF (breast and lung), IGF-2 (colon), VEGF-A (prostate), and TGfalpha (squamous cell lung and breast)
Receptor = Met, IGF-1R, VEGF-R, and EGF-R
What growth factors/receptors are involved in tumor pathogenesis?
Factor = PDGFa, EGFb, VEGFf
Receptor = PDGF-R, EGF-Rc, VEGF-Rg
What happens if p53 is mutated?
Cells don’t die, so that that have DNA repair mutations continue to develop and grow.
What are anti-oncogenes?
p53 and RB
What does RB do? Mutated?
When bound to a transcription factor, it does not allow transcription of early cell cycle genes. When mutated, there is no control over transcription.
What proposed the discovery of RB?
Retinoblastoma
How is RB activated?
Cyclin D binds to CDK to activate it –> phosphorylates RB –> transcription factor released
What is p53?
A transcription factor that also activates other genes.
What genes does p53 activate?
p21
What does p21 do?
Super duper blocker of the cell cycle.
How does the p53-p21 interaction work?
p53 senses damage –> activates p21 to shut down the cell division processes –> p53 waits until DNA damage is repaired before it allows the cells to start replication process again
What happens if there is too much damage? Who does p53 activate?
BAX, which is a pro-apoptotic protein which causes the induction of apoptosis.
What can p21 interact with?
- shut down cyclin E-CDK 2 complex
- blocks cyclin B = completely stopping cell division so there is no time to repair the gene
How does the karotype of cancer look like?
There are truncations, more than two copies per chromosome.
Why is cancer hard to kill?
Cancer cells become fit, so there are many methods developed to kill cancer, which actually kill healthy cells first.
What does K-ras mutation do?
Hyperproliferation that leads to tumor initiation.
How does phorbol ester or TPA cause cancer?
Activates protein kinase c:
1. Activates Fos and Jun (cell cycle genes)
2. NF-kB is let free; transcription factor which activates genes involved in inflammation
3. Phosphorylation of MAPK
- therefore activation of inflammation and cell division
How does inflammation cause cancer?
It pushes cells to divide, and with more dividing, more ability for error to occur.
What does helicobacter hepaticus cause?
Uclers
What does ulcers activate?
Inflammation
Why do people with arthritis have a higher risk of cancer?
Because inflammation occurs in the condition leading to hyper-proliferation over time.
How are ulcers a bacterial disease?
The pH is low, around 2, where the bacteria grows very high.
How can hepatitis B/C cause cancer?
Inflammation in them.
What does the mdr mutation cause?
Inflammation –> hyper-prolieration
What can ibuprofen do?
It can lower the risk factor of cancer as it is an anti-inflammatory. Stops hyperproliferation.
What did mice with the mdr mutation show?
Hyperproliferation and inflammation like symptoms that leads to hepatcellular carcinoma (liver).
What are the four biochemicals causes of cancer?
- Oxidative stress
- Chemotoxins
- Radiation
- Inflammation
NOTE: last one has nothing to do with DNA damage
How does the mutation of mdr (loss of function) lead to cancer?
activates TNF-alpha –> binds to IKK –> phosphorylates the inhibtor NF-kB:IkB –> NF-kB is released (inflammatory transcription factor):
- transcribes TNF-alpha (inflammation)
- anti-apoptotic genes (Bcl-2 genes)
- increases cell replication through cyclin D (mitogenesis)
Where does aspirin come from?
Weeping willow tree
What does aspirin inhibit?
COX-2 enzyme by using salicylate compound to bind to arachidonic acid
What can arachidonic acid be converted to? What does this mean?
Prostaglandin E2 modified by COX-2 enzyme. This compound causes inflammation, which over time if sustained, can increase the risk of cancer.
What happened to the mice given prostaglandin E2?
The mucosal layer in the intestine had hyperproliferated cells that resulted in intestinal cancer.
What can activate COX-2?
NF-kB
How does prostaglandin E2 cause cancer?
- Loss of contact inhibition (cells touching each other can prevent replication)
- Anchorage-independent proliferation (lets cells divide when alone and accelerates metastasis)
- Loss of E-cadherin (protein to which cells are attached to each other)
- Increased proliferation
What hormone increases can cause cancer?
Estrogens and testosterone.
How can infectious agents lead to cancer?
Lead to inflammation
ex. helicobactera pylori, hepatitis B/C
What are cancer causing agents?
Hormones, drugs (diuretics), infectious agents, chemical agents (bile, chewing tobacco), physical or mechanical trauma (head injury, gallstones), and chronic irritaion/inflamation (tropical ulcers).
Which of the four factors of cancers can we try to prevent?
Inflammation and oxidative stress.
How to reduce inflammation and oxidative stress?
Many NHPs like flavonoids (broccoli and curcumin) to help with anti-inflammatory activity and eat colourful fruits and veggies that keep down oxidative stress too.
What helps in reduction of cancer rates?
Mammograms, prostate examination, and polyps by colonoscopy.
What does glucose and cancer show?
Cancer cells eat a lot more glucose, and doctors can diganose how advanced stage cancer is.
What new developments are used in early diganosis?
Gene microarrays and protein microarrays.
What is a challenge in cancer?
Early diganosis.
How to prevent cancer?
Fiber rich and anti-inflammatory/oxidant food.
How can curcumin/tumeric help prevent inflammaton?
GIT will be exposed to it and locally decrease inflammation. All food is digested and absorbed in teh colon quicker (many inflammatory products can worsen and stay here longer).
Treatments for cancer.
Surgery, chemotherapy, and radiotherapy.
How do chemotherapy and radiotherapy work?
They induce apotosis in fast dividing cells through DNA damage. It does kill normal cells too.
What does taxol do?
It disrupts tubulin polymerization and inhibits growth/induce cell death in dividing cells.
What are new therapeutic treatments of cancer?
- Targeted delivery of chemotherapeutic agents via liposomes containing specific anti-cancer antibodies
- Delivery of photo-senstitive chemotherapeutic agents conjugated to specific targets
- Localized laser targeted radiotherapy
