Ethnobiology and Pharmacognosy PDF

Ethnobiology and Pharmacognosy Prepared by: Fleurdeliz Maglangit Bio 134  Ethnobiology is the scientific study of dynamic relationships among peoples, biota, and environments. the scientific study of the way plant...

Ethnobiology and Pharmacognosy Prepared by: Fleurdeliz Maglangit Bio 134  Ethnobiology is the scientific study of dynamic relationships among peoples, biota, and environments. the scientific study of the way plants and animals are treated or used by different human cultures. the study of traditional or folk knowledge and practices related to the use of natural resources, particularly for medicinal purposes. This field includes studying plants as medicines, alternative methods for healing, wild foods, and agricultural crops. 2 Bio 134  Research Objectives of Ethnobiology Catalog and Document Traditional Knowledge Systems Systematically catalog and Explore and analyze the methods by which document the diverse range of traditional knowledge about plants and animals is plants and animals, including their acquired, preserved, and organized within different traditional preparations and uses, cultures. across different cultures. 3 Bio 134  Research Objectives of Ethnobiology Sustainable Management Domestication and Agriculture Assess and develop strategies for the Investigate the processes and historical sustainable management of plant and animal origins of species domestication, focusing on populations that are important for human use. how plants and animals have been selectively This involves evaluating traditional and bred and managed. Study the development of modern practices for conserving biodiversity agricultural practices and their impact on and ensuring the long-term availability of human societies and ecosystems. these resources. 4 Bio 134  Pharmacognosy Definition Origin the study of medicine derived from two Greek words: derived from natural o Pharmakon - a drug sources o Gnosis - acquire knowledge of 5 Bio 134  American Society of Pharmacognosy The American Society of Pharmacognosy definition: Pharmacognosy is “the branch of knowledge concerned with medicinal drugs obtained from plants or other natural sources”. ASP is a scientific society founded in 1959 that promotes the growth and development of pharmacognosy through a presentation of research achievements and the publication of meritorious research. 6 Bio 134  "And the earth brought forth grass, and herb yielding seed after his kind, and the tree yielding fruit after his kind, whose seed was in itself, and after his kind: and God saw that it was good." -Genesis 1:12 “The trees will provide food and their leaves will be used for healing people..." -Ezekiel 47:12 7 Bio 134  History Pharmacognosy has developed from ancient civilizations and used parts from local flora and fauna for their survival. By trial and error, primitive man had acquired biological knowledge that was useful in determining which plants and animals possess food value and which of them to avoid because they were unpalatable, poisonous, or dangerous. 8 Bio 134  Trial and Error Christopher McCandless (1968-1992) Abandoned his conventional life, donated his savings of $24,000 to charity, discarded most of his possessions, and set out on a journey across America. 24-yo McCandless died in the Alaska wilderness 114 days of hunting game and foraging edible plants. Before going to Alaska, he weighed 140 lbs. 3 weeks after his death his remains weighed 67 lbs and lacked discernible subcutaneous fat. Movie based on a true story 9 Bio 134  Trial and Error Christopher McCandless (1968-1992) Theories of death: Starvation Hedysarum alpinum seeds Journal entry: EXTREMELY WEAK. FAULT OF POT[ATO] SEED. MUCH TROUBLE JUST TO STANDUP. STARVING. GREAT Movie based on a JEOPARDY true story 10 Bio 134  Trial and Error Hedysarum alpinum Common names: wild potato, Alaska carrot 11 Bio 134  Trial and Error Theories of McCandless death: 2. Swainsonine in H. alpinum seeds Swainsonine o 2007: Dr. Thomas Clausen - "I tore that plant apart. There were no toxins. No alkaloids. I'd eat it myself.” 12 Bio 134  Trial and Error Theories of McCandless death: 3. ODAP in H. alpinum seeds Lathyrism - a tropical disease marked by tremors, muscular weakness, and paraplegia, especially prevalent in South Asia beta-N-oxalyl-L-alpha-beta diaminoproprionic acid (ODAP) o 2013: The seeds contained 0.394 % beta-ODAP by weight, a concentration well within the levels known to cause lathyrism in humans, although the interpretation of the results were disputed by other chemists 13 Bio 134  Trial and Error Theories of McCandless death: 4. L-canavanine in H. alpinum seeds L-canavanine o 2015: High levels of L-canavanine (an antimetabolite toxic to mammals) in the H. alpinum seeds caused the death of Mc Candless 14 Bio 134 L-canavanine 15 Bio 134 Presence of L-Canavanine in Hedysarum alpinum Seeds and Its Potential Role in the Death of Chris McCandless (sagepub.com) 16 Bio 134  Happiness is only real when it is shared. 17 Bio 134  History of Pharmacognosy Mesopotamia Ancient Egyptians Greece and Rome Ancient India made clay models possessed a knowledge describe many plants that described more than of the human body of medicinal uses of were known to have 1000 plants, example and early writing many plants, like medicinal properties such snakeroot which is indicate that they morphine from opium in as atropine and used for the treatment were aware of a Papaver somniferum hyoscine which were of high blood pressure. medicinal effects which is used as hypnotic used as mydriatic agents of many plants. and analgesic. in Atropa belladona family Solanaceae. 18 Bio 134  Century of Pharmacognosy (18th century) Johann Adam Schmidt (1759-1809) Carl Linnaeus Published Lehrbuch der Materia Medica in 1811 which Naming and classifying was a work on medicinal plants and their properties plants In this book the term "pharmacognosy" was originally coined. 19 Bio 134  Century of Pharmacognosy (18th century) At the end of the 18th century, crude drugs were still being used as: o Powders o Simple extracts, or o Tinctures. Crude drugs – are vegetable or animal drugs that consist of natural substances that have undergone only the processes of collection and drying. Natural substances – are those found in nature, including whole plants, herbs, and their parts; vegetable saps, extracts, and secretions; animal glands, organs, extracts, and secretions; and substances that have not had changes made in their molecular structure as found in nature. 20 Bio 134  Era of pure compounds The era of pure compounds (In 1803, a new era in the history of medicine) Morphine from opium Strychnine (1817) from Strychos nux-vomica used to treat moderate to severe pain a pesticide, particularly to kill rats 21 Bio 134  Era of pure compounds The era of pure compounds (In 1803, a new era in the history of medicine) Quinine (1820) from cinchona bark Caffeine (1820) Treatment of malaria Friedlieb Ferdinand Runge, the godfather of caffeine; first isolated caffeine from coffee beans and the first to isolate quinine 22 Bio 134  Era of pure compounds The era of pure compounds (In 1803, a new era in the history of medicine) Nicotine (1828) from tobacco Addictive stimulant Atropine (1833) from plants of the nightshade family Anticholinergic medication used to treat the symptoms of low heart rate, reduce salivation and bronchial secretions before surgery, or as an antidote for certain poisoning 23 Bio 134  Era of pure compounds The era of pure compounds (In 1803, a new era in the history of medicine) Cocaine (1855) from Coca plant addictive stimulant drug Cocaine hydrochloride (Goprelto), an ester local anesthetic, was approved for medical use in the United States in December 2017 24 Bio 134  19th century In the 19th century, the chemical structures of many of the isolated compounds were determined. In the 20th century, the discovery of important drugs from the animal kingdom, particularly hormones and vitamins. Microorganisms have become a very important source of drugs. 25 Bio 134  26 Bio 134 Current Opinion in Microbiology 2019, 51:72–80 27 Bio 134  Most clinically relevant classes of antibiotic are derived from natural products. 28 CurrentBio 134 in Microbiology 2019, 51:72–80 Opinion  The History of Antibiotics Repeat 29 Bio 134  The Present Bio 134 X Repeat 30  What is Antibiotic Resistance? The ability of bacteria or other microbes to resist the effects of an antibiotic. 31 Bio 134  How do bacteria become superbugs? 1. Mutation: Bacteria can spontaneously develop mutations in their DNA that make them resistant to a specific antibiotic. These mutations can then be passed on to their offspring. 32 Bio 134  How do bacteria become superbugs? 2. Horizontal Gene Transfer: Bacteria can acquire resistance genes from other bacteria through processes like: Conjugation Transformation Transduction (direct transfer between (uptake of free DNA) (transfer by bacteriophages) bacteria via a pilus) The transfer of DNA from one donor The uptake of free DNA from the The transfer of genetic material from one bacterium to one recipient bacteria, environment by a recipient bacterium, host cell to another via a bacteriophage which involves cell-to-cell contact leading to the expression of a new trait. during infection. 33 Bio 134  How do bacteria become superbugs? 3. Selective Pressure: The overuse or misuse of antibiotics in healthcare, agriculture, and animal husbandry creates an environment where only the resistant bacteria survive and multiply. This selective pressure encourages the proliferation of resistant strains. 34 Bio 134 Microbial Evolution and Growth Arena plate (MEGA-plate) allowed visual observation of mutation and selection in a migrating bacterial front Bacteria Evolution on a MEGA Petri Plate – Michael Baym – Harvard Medical School (2016) | Natural History Nature Documentary (naturedocumentaries.org) 35 Bio 134  Antibiotic Resistance It is estimated that by 2050, antimicrobial resistance (AMR) could be a bigger kill than cancer, with 10 millions deaths annually. 36 Bio 134  Bad Bugs, No Drugs 37 Bio 134  38 Bio 134  Antibiotic introduced Antibiotic resistance identified Gap year Sulfonamides (protonsil) 1936 1942 6 Penicillin 1943 1940 -3 Tetracycline (chlortetracycline) 1952 1950 -2 Chloramphenicol 1948 1950 2 Erythromycin 1951 1955 4 Vancomycin 1958 1960 2 Rifampicin 1958 1962 2 Methicillin 1960 1962 2 Gentamicin 1967 1979 12 Ciprofloxacin 1968 1968 0 Imipenem 1985 1998 13 Ceftazidine 1987 1987 0 Levofloxacin 1996 1996 0 Linezolid 2000 2001 1 Daptomycin 2003 2005 2 Ceftaroline 2010 2009 -1 39 Bio 134  Bio 134 40 Bio 134  WHO priority pathogens list for R&D of new antibiotics Priority 1: CRITICAL Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae*, carbapenem-resistant, 3rd generation cephalosporin-resistant Priority 2: HIGH Enterococcus faecium, vancomycin-resistant Staphylococcus aureus, methicillin-resistant, vancomycin intermediate and resistant Helicobacter pylori, clarithromycin-resistant Campylobacter, fluoroquinolone-resistant Salmonella spp., fluoroquinolone-resistant Neisseria gonorrhoeae, 3rd generation cephalosporin-resistant, fluoroquinolone-resistant Priority 3: MEDIUM Streptococcus pneumoniae, penicillin-non-susceptible Haemophilus influenzae, ampicillin-resistant Shigella spp., fluoroquinolone-resistant * Enterobacteriaceae include: Klebsiella pneumonia, Escherichia coli, Enterobacter spp., Serratia spp., Proteus spp., and Providencia spp, Morganella spp. 41 Bio 134  Antimicrobial Resistance: The Silent Pandemic 72 % of Covid-19 patients received antibiotics even when it is not medically prescribed, worsening the AMR crisis. Antibiotics 2021, 10(6), 738 42 Bio 134  Natural Products as Sources of New Drugs from 1981 to 2014 Over 50 % of the approved 67, 6% drugs from 1981 to 2014 are 420, 35% natural compounds or those 320, 27% based on NP scaffolds Natural products are the 172, 14% source of the most complex and fascinating chemical structures. 223, 18% Natural product (NP) unmodified NP derivative Mimic of NP Synthetic drug (NP pharmacophore) Synthetic drug 43 J. Nat. Prod. 2016, 79, 629−661 Bio 134  What are Natural Products? Bio 134  What are Natural Products? Chemical characteristics ❑ Compounds produced by plants, animals, or microbes that usually have a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design. ❑ Methods of extraction and purification are generally SIMILAR to the techniques used for organic compounds (e.g., TLC, column chromatography, HPLC, GC) ❑ Methods of structural determination NMR, MS, IR, X-ray, UV 45 Bio 134  What are Natural Products? Chemical characteristics ❑ Compounds are unique to only one species or family of organisms. ❑ Classified as “secondary metabolites” in contrast to “primary metabolites” ❑ Excludes amino acids, proteins, carbohydrates, lipids, nucleotides, all compounds found in major metabolic pathways (primary metabolites) 46 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: color (identification) Anthocyanins impart red, blue or purple colors to most Theobroma cacao, cocoa fruits and flowers Mimicry of dead leaves. Bitter taste to deter herbivores. Pigments may also act as a sunscreen for young leaves. 47 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: color (attraction) Pollinator attractants 48 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: color (attraction) Nesocodon mauritianus (E)-Nesocodin red nectar Phelsuma ornata 49 Bio 134  What are Natural Products? Coloured nectar - visual signal for lizard pollinators e.g., endemic Phelsuma Mauritian coloured nectar no longer a mystery: a visual geckos signal for lizard pollinators | Biology Letters (royalsocietypublishing.org) 50 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: color (attraction) Nesocodon mauritianus Pollinator attractants Coloured nectar - visual signal for lizard pollinators e.g., Mauritian coloured nectar no longer a mystery: a visual signal for lizard pollinators | Biology Letters produces a natural red nectar endemic Phelsuma geckos (royalsocietypublishing.org) 51 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: Color/taste (antifeedant) Anthocyanins as antifeedants Antifeedants are organic compounds produced by plants to inhibit attack by insects and grazing animals. Lactuca sativa, lettuce 52 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: Color/taste (antifeedant) Anthocyanins as antifeedants Antifeedants are organic compounds produced by plants to inhibit attack by insects and grazing animals. 53 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: Scent (attraction/repulsion) Pollinated by a hornet, Vespa bicolor which also preys on honeybees. The orchid produces a chemical that mimics a honeybee pheromone to attract Dendrobium sinense hornets for pollination. Orchid Mimics Honey Bee Alarm Pheromone in Order to Attract Hornets for Pollination - ScienceDirect 54 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: Social communication Jasmonates are plant hormones produced when tissues are wounded. Growth is slowed and specialised defense molecules are produced to repair damage. Methyl jasmonate Q&A: How does jasmonate signaling enable plants to adapt and survive? BMC Biology, 2016, 14(79) 55 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: Defense and protection (e.g., toxins, antibiotics) Physical defense Predators 56 Bio 134  What are Natural Products? Biological characteristics ❑ No nutritional or structural function. Functional roles may include: Defense and protection (e.g., toxins, antibiotics) Was first isolated in 1971 from the bark of the Pacific yew (Taxus brevifolia), hence its name “taxol”. Approved for medical use in 1993. Used to treat a number of types of cancer. Paclitaxel from Pacific yew bark 57 Bio 134  but many still have UNKNOWN function in the organism in which they are found… Bio 134  Compounds from natural sources play THREE significant roles in modern medicine: Source of extremely useful drugs that are difficult, if not impossible, to produce commercially by synthetic means (e.g., Vincristine). Madagascar periwinkle (Catharanthus roseus) vincristine Vincristine is used to treat acute leukemia and other cancers. 59 Bio 134  Compounds from natural sources play THREE significant roles in modern medicine: Source of compounds that may be modified to render them more effective or less toxic (e.g., hydromorphone) narcotics morphine hydromorphone Hydromorphone is 5× to 10× times more potent than morphine. 60 Bio 134  During synthetic tailoring, the core of the antibiotic is left intact, preserving its activity, but the chemical groups at its periphery are modified to IMPROVE the drug’s properties. New generations are often designed to be ACTIVE against pathogens that have become resistant to the previous generation. 61 Bio 134  The complex chemical structure of vancomycin took nearly 30 YEARS by several groups to fully elucidate. The emergence of RESISTANT BACTERIA has seen a sharp REDUCTION in the effectiveness of vancomycin antibiotic. Thousands of derivatives have been CHEMICALLY ENGINEERED to produce MORE POTENT versions of vancomycin and related glycopeptides. Vancomycin antibiotic medication used to treat a number of bacterial infections. ACS Med. Chem. Lett. 2018, 9, 66–67 62 Bio 134  Compounds from natural sources play THREE significant roles in modern medicine: Their utility as prototypes/models for synthetic drugs possessing physiologic activities similar to the originals (e.g., procaine from cocaine) anesthetic cocaine procaine first and subsequently best-known substitute for cocaine. It is not addictive, toxic or irritating. Removing complex non-pharmacophoric molecular fragments (i.e., the auxophore) simplifies the lead’s structure while retaining biological activity. 63 Bio 134 Natural products in drug COLLECT ORGANISM discovery EXTRACT SEPARATE COMPONENTS ACTIVE TEST FOR BIOLOGICAL ACTIVITY ACTIVE NOT ACTIVE PURE COMPOUND FIND STRUCTURE GET MORE NO MODIFY APPROVAL YES £££££££££ 64 Bio 134  How a compound becomes a drug time frame (years) lead discovery (isolation, synthesis) 1-2 pharmacological tests / screening 3-5 toxicity, analytics 6-9 clinical trials 10 - 15 approval  introduction on the market  for 100,000 tested compounds, one will eventually become a drug!  cost for development approximately $ 400 M  after launch, patent coverage will last on average for another 8 years 65 Bio 134  Stages of clinical trials preclinical trials on animal populations  dose-finding, metabolism, toxicity phase I small group (20-80) of healthy volunteers  safety, tolerability, metabolism phase II on larger groups (20-300)  clinical efficacy, dosing requirements phase III large patient groups (300–3000)  efficacy in comparison with current standard treatment approval phase IV post-launch safety surveillance 66 Bio 134  67 Bio 134  THE COMPLETE HISTORY OF MEDICINE “That root is heathen. 1985 AD “Here, eat this ROOT” Here, say this PRAYER instead” 1940 AD 1850 AD N O W 2000 BC 1000 AD “That prayer is nothing but superstition. Here, swallow this POTION instead” “That potion is nothing but snake oil. Here, swallow this PILL instead” “That pill is totally ineffective. Here, take this ANTIBIOTIC instead” “That antibiotic is no longer effective. Here, eat this ROOT” 68 Bio 134  Natural Products Drug Discovery Bio 134 Course Description: Survey, extraction, screening, isolation, screening, and characterization of bioactive compounds from plants and other natural resources traditionally known to have pharmacological applications Survey Extraction Screening Isolation Characterization -traditional knowledge -Solvent extraction -Metabolomics -Chromatography -Mass spectrometry and partitioning (SPE, TLC, column, -Nuclear magnetic -folklore medicine -Biological assays HPLC, GC) resonance -Infrared -dereplication spectroscopy -UV -X-ray 69 Bio 134  Natural products is at the intersection of many fields: 70 Bio 134  Research areas in natural products: 1. Structure elucidation 2. Biological activity o Ecological o Pharmaceutical properties/drug discovery o Healthcare and cosmetics products 3. Metabolomics 4. Biosynthesis 5. Molecular biology and biotechnology 6. Quantitative natural products chemistry 71 Bio 134  Ethnobotanical Documentation of Medicinal Plants Used by the Indigenous Panay Bukidnon in Lambunao, Iloilo, Philippines ❑ A total of 131 medicinal plant species were used to address 91 diseases. o Curcuma longa L. o Artemisia vulgaris L. o Annona muricata L. o Blumea balsamifera (L.) DC. o Chromolaena odorata (L.) R.M. Frontiers in Pharmacology. 2022, 12, 790567 72 Bio 134  End of discussion 73 Bio 134