Botanicals PODA 1

how much did consumers spend on herbal supplements?

$11.26 billion

total dietary supplements sales in US?

$54 billion -included herbs, botanicals, meal supplements, minerals, specialty products, sports nutrition products, and vitamins

-established for vitamins and minerals -important for vitamin A = leads to birth defects in excess

- regular daily allowance (RDA) - tolerable upper limits (TUL)

what are the top 5 selling single herbal products in the natural channel?

1. CBD 2. elderberry 3. tumeric 4. grass 5. mushrooms

national stakeholders for dietary supplements

1. FDA 2. NIH 3. NIST 4. Uniformed services university of health sciences 5. USP

what were issued by the FDA to warn consumers of fraudulent products that were masquerading as DS but were Rx drugs? -these products were for weight loss, sexual enhancement, and body building -stroke, liver failure, heart palps, death

1. GMPs (good manufacturing practices) 2. AERs (adverse event report)

identification of botanicals

1. ID of raw plant material 2. reference material can be obtained

unsafe phytochemicals in DS antraquinones examples?

1. aloe vera 2. senna

what do true alkaloids exhibit?

1. basic character 2. heterocyclic N atoms present 3. biosynthesized from amino acids or immediate precursors 4. limited distribution in the plant kingdom 5. toxic, primarily on CNS -most structurally diverse of secondary metabolites

process for botanical harvesting

1. collection/harvesting 2. drying 3. garbling 4. grinding 5. extraction 6. concentration 7. drying 8. QC/QA analytical methods 9. manufacturing the final formulation in the desired dosage form

steps of getting the drug from nature

1. crude drug (opium) 2. extractive (tincture) 3. pure constituent (morphine powder) 4. semi-synthetic derivative (heroin)

steps of herbal preparations

1. decoction 2. infusion 3. tincture 4. essential oils 5. percolation

reasons why kava is used in oceania with apparent impunity

1. deviation from the tradition water extraction method used in pacific vs. organic solvent use in western 2. inclusion in western products of more toxic plant parks other than roots 3. genetic differences in people 4. western practice of consuming alcohol with kava may modify hepatic metabolism through cytochrome P450

largest sales of botanical dietary supplements?

1. direct to public 2. natural and health food channel 3. mass market channel

botanical products that are regulated by the FDA

1. drug products (CDER) 2. dietary supplements 3. Food (CFSAN) 4. cosmetics, devices

what are top selling herbal singles in the mainstream?

1. elderberry 2. horehound 3. cranberry 4. tumeric 5. apple cider vinegar

2 early indicators that botanical DS have toxicity?

1. ephedra (CNS toxicity) 2. Aristolochia species (renal toxicity)

what are manufacturers responsible for under DSHEA?

1. evaluating the safety 2. labeling of their products before marketing

products that are considered natural but not botanical dietary supplements?

1. fatty acids, omega, fish oils, metabolites, steroids 2. chondroitin and glycosamine 3. lutein and lycopene 4. adenosyl methionine

secondary metabolites in herbal tea prepared with hot water could be...?

1. glycosylated flavonoids 2. complex phenols (vegetable tannins) 3. glycosides 4. simple phenols 5. isoprenoids -alkaloids are toxic to CNS so not seen in DS

galenic formulation

1. granulation process (micro-granulated powder) 2. compression processes 3. raw materials and finished products are systemically monitored before batches are released

botanicals that cause liver toxicity?

1. green tea 2. comfrey 3. kava

herbal products / botanical drug examples

1. green tea/ polyphenon E 2. crofelemer

the sampling gross sample must be ?

1. homogeneous 2. randomly selected 3. represent overall sample quantity

ways to monitor the potential toxicity of DS?

1. hospital ED 2. data from poison control centers

what is required on dietary supplements label?

1. identity 2. net quantity 3. structure function claim and statement 4. directions 5. supplements facts panel 6. other ingredients 7. name of manufacturer, packer, or distributor

major groups of secondary metabolites (natural products)?

1. isoprenoids 2. phenolics 3. alkaloids - thousands of secondary metabolites may be present in a given botanical DS

types of examination of botanicals

1. macroscopic (outside) 2. microscopic (inside)

sources of botanicals

1. natural habitat 3. cultured species

active principles of the 2 current FDA approved botanical drug products

1. phenols 2. polyphenols

key components of a skin care lotion, cream, or gel emulsion

1. the aqueous and oily phase 2. emulgent to prevent separation of these two phases 3. drug substances

FDA monitors supplement safety via

1. voluntary adverse effect labeling 2. labeling claims 3. product literature 4. occasional lab testing

how many days to report a serious adverse event to the FDA?

15 days

how many dietary supplement products marketed may be classified as botanical dietary supplements?

55,000

-renal disease, treated with dialysis or kidney transplantation tumors (e.g., of the bladder),even after transplantation -renal disease was evidenced by extensive interstitial fibrosis, with atrophy and loss of the tubules "Chinese herb nephropathy" -Chemical analysis of the slimming regimen showed the presence of aristolochic acids I and II

Aristolochia species

-mixture of these compounds has been shown to cause cancers -mixture acts as a powerful nephrotoxic and carcinogenic agent -adducts have been detected in the kidneys and ureters of patients with "Chinese herb nephropathy" -FDA issued a "Consumer Advisory"

Aristolochic acid I and Aristolochic acid II

-FDA has responsibility of taking action against any adulterated or misbranded DS after reaches market -authority to take legal action against unsafe DS products

DS safety and advertising

-poison is primarily solanocapsine, alkaloid -other cherries from same fam used in gout and inflammatory processes -gastric problems, vomiting, gastroenteritis

Jerusalem cherry (solanum psedocapsicum)

-U.S. FDA published a Consumer Advisory due to potential for liver toxicity - never banned by FDA -banned by the countries of the European Union and Canada. -ban was overturned in Germany, which should stimulate the re-approval elsewhere -anxiolytic dose is quite high -hypnotic dose is low -if have liver problems or take med that affect liver avoid this

Kava

-mission to strengthen knowledge and understanding of dietary supplements by evaluating scientific info -provide fact sheets, computer access to research, and dietary supplement ingredient database -offering research support and providing analytical methods and reference materials, evidence based reviews, and ingredient and label databases

NIH office of dietary supplements (ODS)

-microscopy and staining techniques to identify ground samples -chemical constituents -low tech (colorimetric tests) -high tech or increasing levels of complexity -herbs -TLC, HPLC, GC, MS, FTIR -qualitatively/quantitatively analyze presence of active compound -create reliably reproducible pattern of the source's complex mix of constituents

USP/NF methods

-contain sildenafil, sibutramine, and synthetic steroids -cause adverse effects on misuse -FDA issued consumer alert with sibutramine -marketed for sexual enhancement, weight loss, or body building

adulteration of DS with prescription drugs

soluble in CHCl3 at high pH (8.5)

alkaloid free bases

soluble in water at low pH (3.5)

alkaloidal salts

-occur in the plant in the form of salts complexed with small organic acids -water soluble -trivial names end in "ine" -solubility can be manipulated during extraction according to pH of solvents used

alkaloids

treat symptoms of diseases primarily through Rx drugs

allopathy

-whole leaf extract possibly carcinogenic to humans (group 2b) in the colon -topically to heal wounds and for various skin conditions -orally as laxative

aloe vera

-sold to satisfy those intending to lose weight or build muscle -arginine, lysine, ornithine = increase human growth hormone -safe if taken at recommended doses but may interfere with protein metabolism if consumed at excess

amino acids as DS

-large group of glyocosides used medicinally -laxatives used as DS -recognize parent ring system, aglycone, and entire glycoside -O-glycoside linkage and C-glycosides forms -safety is questioned

anthraquinone glycosides

uses essential oils extracted from medicinal plants to treat various health conditions -oils are diluted, then used topically, internally, or to stimulate olfactory senses

aromatherapy

combines natural therapies with a highly personalized, holistic approach to the treatment of disease

ayurvedic medicine

-yellow salts -quaternary alkaloid -readily soluble in water but insoluble in ether -antiemetic, antibacterial, and anti-inflammatory activity -major constituent of herbal remedy goldenseal

berberine

botanical drug that is not recognized as safe and effective for its therapeutic claims

botanical drug under NDA

botanical product (safe and effective) marketed for a material time and to a material extent for a specific OTC indication

botanical drug under OTC monograph

-more soluble in boiling water than cold water -pure powder available but death has occurred

caffeine

-used internally for gastrointestinal problems, stomach ulcers -externally is it used in the form of a poultice or ointment for wound healing, bruising, and sprains -Both the leaves and rhizomes/roots contain 1,2-dehydropyrrolizidine alkaloids, which are based on the necine base (amino alcohol), retronecine -his alkaloid may be metabolized to a toxic pyrrole metabolic form in the liver, which is able to interact with nucleophiles, such as proteins and nucleic acids, and thus cause harmful effects -levels of pyrrolizidine alkaloids are higher in roots than the leaves -produce serious veno-occlusive disease in the liver -Allantoin and rosmarinic acid responsible for external

comfrey

-mix of these "sinecatechins" (veregen) was first botanical drug -form polymers or pranthocyanidins (not easily hydrolyzed by acids) -polymers based on gallic acid produce "hydrolysable tannins" (easily hydrolyzed by acids but not as stable) -water soluble and astringent when tasted -form week bonds with proteinaceous substances

condensed tannins

-topical preparations usually for application to the skin -semi-solid emulsions that are mixtures of oil and water 1. oil in water 2. water in oil -calendula/marigold, chamomile, comfrey, acne-n-pimple

creams

-complex mix of proanthocyanidins are the active compound -plant of origin = dragons blood -approved as botanical drug as antidiarrheal agent -FDA approved for chemotherapy induced diarrhea for dogs -highly resistant to acid hydrolyses -taken orally (tab) -acid hydrolysis under rigorous conditions the average monomer has 7 catechin units

crofelemer

natural products which are not pure compounds -plants/ parts of plants, extracts, and exudes

crude drug

-used ornamentally and contain alkaloid poison lycorine -used in suicide attempts -salivation, acute abdominal pains, n/v, diarrhea, neuro and CV events, trembling, convulsions, and paralysis -death in large quantities

daffodil (narcissus poeticus)

-made from boiling plant material in water -may be used therapeutically -natural dyes made this way

decoction

product intended to supplement the diet -ORALLY ONLY -vitamin, mineral, herb, botanical, amino acid -supplement the diet by increasing the total daily intake -food NOT drugs -do not need approval from FDA before marketed but are regulated

dietary supplement

protect from fungal contamination

dried material storage

-pure substance or combo of pure substance intended to mitigate, treat, cure, or prevent a disease in humans

drug

-prescription drugs and botanical drugs -purified single chemical entity compounds -paclitaxel, polyphenon E, crofelemer

drug products (CDER)

-common ornamental plant -contain needle shaped calcium oxalate crystals (raphides) -crystals cause temp. burning sensation and erythema, numbing, oral irritation, excessive drooling, and localized swelling

dumbcane (dieffenbachia oerstedii)

experienced stroke symptoms, myocardial infarction, and sudden death -used for athletic performance, increased energy, and weight loss -U.S. FDA banned dietary supplements containing this

ephedra

-bronchodilator -protoalkaloids -ephedra used at DS for those wanting to lose weight but FDA issued final rule banning the sale due to toxicity

ephedrine

-aromatic volatile oils extracted from the leaves, stems, flowers, and other parts of plants -therapeutic use generally includes dilution of highly concentrated oil

essential oils

unsafe phytochemicals in DS pulegone -tea for non-ulcer dyspepsia, dysmenorrhoea, abortifacient, diaphoretic -pure= pulegone can't be added to foodstuffs -regulation european commission = mint/peppermint in food and drink -possibly carcinogenic to humans (group 2B) -USA: isn't authorized as authorized as a synthetic flavoring substance

european and american pennyroyal

regulates dietary supplement advertising for false and misleading health claims -small, independent law enforcement agency to mandate a stop to deceptive and unfair practices -filed 125 major cases challenging health claims made for supplements -investigate companies producing DS products that have deceptive claims of treating

federal trade commission (FTC)

-typical plant phenols and may occur in the plant in the free form (aglycone) or more water soluble form (glycosides) such as ginkgo -green tea: esters but still quite water soluble due to large number of hydroxy groups -catechins (parent phenolic molecules are esterified with small phenolic acid (gallic acid)) -EGCG is major one (potent antioxidant and most highly studied natural product molecules)

flavonoids

essences are used internally or topically to balance emotional states

flower essences

general name that may be shared by a number of related plants

genus

-consumption of when used for weight control with hepatotoxic reactions -contains catechin (phenolic) components, with the most abundant one being epigallocatechin gallate (EGCG)

green tea

-the agent (mixture) is carcinogenic to humans -Sufficient evidence of carcinogenicity in humans -Aristolochia species

group 1

-the agent (mixture) is probably carcinogenic to humans -Limited evidence of carcinogenicity in humans, but in animals -aristolochic acids

group 2A

-the agent (mixture) is possibly carcinogenic to humans -Limited evidence of carcinogenicity in humans, and less than sufficient in animals

group 2B

-The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans -inadequate evidence for humans and animals

group 3

uses plants or plant derived preparations to treat, prevent, or cure various health conditions and ailments -dietary supplements

herbal medicine

infusion or tisane of leaves, flowers, fruit, herbs, or other plant material that contains NO camellia sinensis -black, green, passion flower, rose hips, sarsaparilla, saw palmetto

herbal tea

what is responsible for cases of hepatotoxicity?

herbals and dietary supplements -prescription drugs -anabolic steroids -multi-ingredient nutritional supplements -green tea -Chaparral, Germander, Skullcap

what causes hepatotoxicity?

herbs

crude drugs of vegetable origin utilized for the treatment of disease states often a chronic nature, or to attain or maintain a condition of improved health

herbs (tyler)

-based on theory "like cures like" -consist of remedies of diluted substances from plants, minerals, and animals

homeopathy

-made by pouring water over plant material then allowed to steep -water is usually boiling but cold is also an option -may be used therapeutically (hot tea)

infusion

-involves mashing and boiling in water -plant material is strained -differs based on type -cinnamon, dong quai, white tiger herbal

internal decoction

-based on isoprene (C5H8) with monoterpenes and sesquiterpenes found in volatile oils -units attach head to tail and compounds may be oxygenated

isoprenoids

-dangerous levels of tropane alkaloids (atropine, hyoscyamine, scopolamine) -risk of fatal overdose is high amongst recreational users who ingest the plant for its psychoactive effects -delirium, hallucination, hyperthermia, tachy, severe mydriases that causes painful photophobia for days

jimson weed (datura stramonium)

-topical preparations intended for application to unbroken skin -low to medium viscosity -aloe vera, anti-inflammatory like arnica, calendula, goldenseal

lotions

-contains toxic lectin viscumin -structure of protein is similar to ribosome inactivating proteins that resemble ricin -strongly inhibits protein synthesis by inactivating 60s ribosomal subunit -poisonous if eaten in large numbers

mistletoe (viscum album)

treats health conditions based on what is believed to be the body's innate ability to heal

naturopathy

is CBD a dietary supplement?

no -first investigated as a drug via publicly available research -nasal spray not oral but oral hemp oil is still violating FDA

does the FDA take a position on a dietary supplements efficacy?

no since it is regulated as food -does regulate both finished dietary supplements and dietary ingredients

-sterilization -refrigeration

non topical storage

keep in cool, airtight amber glass containers, protect from light, heat and moisture

oil based formulation storage

-composed of small droplets of oil dispersed in a continuous aqueous phase - more comfortable and cosmetically acceptable as they are less greasy and more easily washed off

oil in water cream

-combines oil (80%) and water (20%) -effective barrier against moisture loss -polyphenon E and betulinic acid

ointments

-most poisonous commonly grown garden plants -contains oleandrin and oleandrigenin (cardiac glycosides) which have narrow therapeutic index and toxic when ingested (increase intracellular Ca) -GI: n/v, excess salivation, stomach pain, diarrhea -CV: irregular hr, racing heart then slows -CNS: drowsiness, tremors, shaking, seizures, collapse, coma -antidote -death of 2 children and mortician kills rival

oleander (nerium oleander)

examine product based on sight, touch, smell, taste and sound -herbs

organoleptic evaluation

-extract the soluble constituents of a plant with assistance of gravity -material is moistened and evenly packed into tall, conical vessel -solvent poured onto material and steeps for certain amount of time -allow the extract to slowly flow out of the vessel -marc may be discarded -many tinctures and liquid extracts are prepared this way

percolation

-study of natural products (plants, animal, organism, or mineral) -used as drugs or for the preparation of drugs

pharmacognosy

-diverse types of aromatic phenolic compounds in plants with propyl side chain

phenylpropanoids

type of phytochemical with some influence on estrogenic activity or hormonal system in humans

phtoestrogens

chemical compounds or chemical constituents formed in the plant's normal metabolic processes

phytochemicals

medicinal substances that originate from plants, including certain phytochemicals as well as whole plants or herbal preperations

phytomedicinals

-very common and soluble in water -acetals with OH of the sugar is condensed with OH of the non sugar moiety -only beta are in plants -most common: Beta-D -yield one or more sugars among the products of acid hydrolysis as well as aglycone

plant glycosides

-used topically in the form of an ointment -combo catechin monomers are the active molecules -major catechin present is EGCG -sinecatechins (veregen) from leaves of green tea

polyphenon E

example of proto and pseudoalkaloids

proto: mescaline, sudafed, and ephedrine pseudo: caffeine

-not having a heterocyclic nitrogen ring

protoalkaloids

not being biosynthesized from amino acid

pseudoalkaloid

chronic exposure to low levels found in DS and as contaminants in foods (such as milk and honey) may contribute to progressive liver disease leading to cirrhosis, among other health problems

pyrrolizidine alkaloids

-common plant in subtropical countries and grows as an ornamental plant in temperate countries -seeds contain glycoprotein, ricin -latent period for several days and then severe gastroenteritis ending in death in 6-8 days -use as agent of biological warfare (shot a king) -listed as C-1 under biological weapons convention -no specific antidote and easy to obtain

ricin communis (castor bean)

-small organic compounds (less than 2,000) obtained from plants, microbes, and animals -relatively non-polar compounds -do not play a role in primary metabolism of the producing organism -plants have ecological role and exist in the correct chiral form to exhibit biological activity

secondary metabolites

-cathartic or laxative -antraquinones -melanosis/ epithelial hyperplasia of colon due to use of laxatives

senna

-volatile oils (plants) used in formulation, perfumery, and medicinally -some solubility in water and add flavor to herbal teas -complex mix of isoprenoids and phenylpropanoids

simple isoprenoids

-found in several species of plant fam solanaceae

solanceous alkaloids

name that is specific to that individual plant

species

non essential sulfur containing amino acid with antioxidant and heart contraction activity and used in energy drinks

taurine

-made by soaking herbs in a dark place with a desired amount of either glycerine, alcohol, or vinegar for 2-6 wks -liquid is strained from the plant material and then used therapeutically

tincture

-most effective method in production of herbal medicine -herb dried or fresh -incubate in jar with a spirit of 40 C pure ethanol -macerate for 2-3 weeks -ginger, ephedra, black cohosh

tinctures for internal use

airtight, light-resistant containers, and void exposure to direct sunlight and excessive heat

tinctures, extracts and decoction storage

-sterilization of all equipment and containers -use of plastic squeeze bottles or pump dispenser -use of preservatives agents -refrigeration

topical storage

liquid, or gaseous substance that has an inherent property to destroy life or impair health.

toxin

addresses how illness manifests itself in a patient and treats the patient not the ailment or disease

traditional chinese medicine

incorporations various methods of botanical and animal medicines as well as specific ceremonial rituals of a culture to cure a disease

tribal medicine

-water soluble and oil soluble, macronutrient, and micronutrient -not needed for normal healthy individuals on reg diet

vitamins and minerals as DS

-deposited in a herbarium for reference -completed by the original supplier or collecting entity for wild crafted material -identification based on crude, semi-purified, or purified natural product

voucher specimen

-composed of small droplets of water dispersed in a continuous oily phase -more difficult to handle but many drugs which are incorporated into creams are hydrophobic and will be released more readily -more moisturizing as they provide an oily barrier which reduces water loss from the skin

water in oil cream