[01.24] Principles of Ethnopharmacology (TG10-CG02)(V2) - Joseph Carl Louis Laroga.pdf

Principles of Ethnopharmacology Module 01: Principles and Perspectives II Popo Soller, MD-MBA |Asynchronous TABLE OF CONTENTS I. INTRODUCTION I. INTRODUCTION................................................................................ 1 A. WHO GLOBAL REPORT........................................

Principles of Ethnopharmacology Module 01: Principles and Perspectives II Popo Soller, MD-MBA |Asynchronous TABLE OF CONTENTS I. INTRODUCTION I. INTRODUCTION................................................................................ 1 A. WHO GLOBAL REPORT................................................................. 1 A. RATIONALE OF STUDYING ETHNOPHARMACOLOGY....................1 II. ETHNOPHARMACOLOGY................................................................. 2 A. REINTEGRATION OF HERBS IN MEDICINE.................................... 2 B. ADVANTAGES OF USING HERBAL MEDICINE................................ 2 III. PHILIPPINE SETTING....................................................................... 2 IV. PLANT AS MEDICINAL SOURCES......................................................2 V. PRODUCTS AND METHODS OF SEPARATION.................................... 3 A. CLASSIFICATION........................................................................... 3 B. TYPES OF PREPARATION...............................................................3 B. STEPS OF PREPARATION.............................................................. 4 VI. TEN COMMON HERBS.................................................................... 4 A. SAMBONG....................................................................................4 B. LAGUNDI...................................................................................... 4 C. ULASIMANG BATO........................................................................5 D. TSAANG GUBAT............................................................................5 E. NIYOG-NIYOGAN ......................................................................... 5 F. AMPALAYA.....................................................................................5 G. BAWANG......................................................................................6 H. AKAPULKO................................................................................... 6 I. BAYABAS........................................................................................ 6 J. YERBA BUENA............................................................................... 6 VII. NINE BEST-SELLING MEDICAL HERBS..............................................7 A. GINGKO BILOBA........................................................................... 7 B. ECHINACEA...................................................................................7 C. GARLIC......................................................................................... 7 D. GINSENG...................................................................................... 7 E. SAW PALMETTO............................................................................7 F. ST. JOHN’S WORTS........................................................................ 7 G. VALERIAN.....................................................................................7 H. CRANBERRY................................................................................. 7 I. BLACK COHOSH............................................................................. 8 VIII. SAFETY......................................................................................... 8 IX. REGULATION OF HERBAL MEDICINE................................................9 A. STANDARDIZATION OF MEDICAL PLANT MATERIALS................... 9 B. WHO HERBAL DRUG LABELLING REQUIREMENTS....................... 9 C. CHALLENGES IN HERBAL PREPARATION....................................... 9 D. ADVERTISING: R.A. 7394..............................................................9 QUESTIONS....................................................................................... 10 ANSWER KEY..................................................................................... 10 RATIONALE........................................................................................10 APPENDIX......................................................................................... 12 ● WHO’s 13th General Programme of Work (GOPW) for 2019-2023 ○ Strategic priority: reaching 3 billion more people to move towards SDG 3 (Sustainable Development Goals) ▸ SGD 3: Good Health and Well-Being ▸ Ensuring healthy lives and promoting well-being for all ages ⎻ Done by achieving UHC (Universal Health Care) ○ Role of the Traditional and Complementary Medicine (T&CM) ▸ Part of the provision of essential health services ▸ Important to be recognized and to incorporate in actual practice or in the UHC ⎻ Especially in the Philippines, where a lot of communities rely on complementary medicine LEARNING OBJECTIVES 1. Describe and differentiate the different methods of preparing herbal medications 2. Enumerate the 10 commonly used herbs and their therapeutic uses 3. Properly label and advertise herbal preparations to ensure safety and prevent misinformation YL6:01.24 A. WHO GLOBAL REPORT ON TRADITIONAL AND COMPLEMENTARY MEDICINE 2019 Figure 1. Member States with a Registration System for Herbal Medicines (2018) ● As of 2018, the Philippines has a registration system for herbal medicines ● Unfortunately, we still only have 10 recognized herbal medicines in the country ○ In the market, though, there are a lot of options B. RATIONALE OF STUDYING ETHNOPHARMACOLOGY ● Low-cost and effective alternatives compared to the drugs that are available in the market ○ They are at par with the drugs in the market ● Need to study because many people use them ○ To guide patients and prevent misconception ▸ A lot of patients would ask about these medications ▸ You need to be aware of their uses and how they should be given to the patient ○ To guide patients in making informed decisions about the use of herbal medicine TG10: Beltran, Bugtas, Castro, Co, Figueroa, Laroga, S. Lim, Reyes, S. So, Te, Valencia, Vallar CG02: Aniban, Del Rosario, Echegoyen, Longno, Martinez, Mendoza, Rafael, Ronase, Sta. Cruz, Tan, Valoria, Viovicente 1 II. ETHNOPHARMACOLOGY ● Study of people’s use of plants, fungi, animals, microorganisms, and minerals and their biological and pharmacological effects based on the principles of pharmacology ○ This lecture will only focus on plants ○ Note: Ethnopharmacology also spans other types of medicine ● Evidence-based and credible ○ Not just voodoo and practice that has been passed on ○ Scientific-based A. REINTEGRATION OF HERBS IN MEDICINE ○ Accessible ▸ You can plant them in your gardens ○ Affordable ▸ Cheaper compared to the drugs that are available in the market ○ Acceptable ▸ Already been part of our culture ○ Appropriate ▸ Appropriate for our culture ▸ Appropriate for the different diseases Take Note! ● Dr. Soller said that maybe the reason why herbal medicines are not used mainstream is because they’re not as known to most people ○ Even some doctors do not know them properly, that’s why they don’t easily recommend them ○ There are very effective drugs available in the market as well III. PHILIPPINE SETTING A. NATIONAL POLICY ON TRADITIONAL & COMPLEMENTARY MEDICINE (T&CM) Figure 2. Reintegration of Herbs in Medicine ● Traditional Medicine ○ Knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures ○ Herbs are used in traditional medicine ▸ E.g., tribes, indigenous cultures, ones in the mountains, ones that don’t have easy access to modern medicine ● Complementary and Alternative Medicine ○ AKA Integrative medicine ○ Use of non-mainstream approaches along with conventional medicine ○ Uses herbs in complementary treatment, as an adjunct for modern types of drugs ○ Very wide branch of medicine ○ E.g., meditation practices, qi gong, yoga, massage, naturopathy, homeopathy B. ADVANTAGES OF USING HERBAL MEDICINE ● Traditional Medicine Unit of DOH (1992) ○ Philippines’ Traditional Medicine Program ● Traditional and Alternative Medicine Act (TAMA Law) ○ Enacted in December 1997 ○ Aims to improve the quality and delivery of healthcare services through the development of traditional and alternative healthcare (TAHC) and its integration into the national health delivery system ● Philippine Institute of Traditional and Alternative Health Care (PITAHC) ○ Established in 2000 ○ Works with Philippine Food and Drug Administration (PFDA), serving together as the national office of T&CM ○ Strategic Map (2017-2021) B. PHILIPPINE TRADITIONAL KNOWLEDGE DIGITAL LIBRARY ON HEALTH ● 2008: Regulation of acupuncture providers ○ Soon for other modalities ● 2017: ○ 16,690 documented medicinal plants ▸ Yet we still only have 10 recognized herbal medicines (halamang gamot) ○ 66 healing practices ▸ AKA rituals ○ 509 traditional healers ○ 43 research sites ● 2018: Laws and regulations on T&CM practice ● 2020: No health insurance coverage for T&CM (as of 2020) IV. PLANTS AS MEDICINAL SOURCES Figure 3. Advantages of Using Herbal Medicine ● Culturally responsive ○ Available ▸ Readily available in the Philippines ▸ E.g., sampung halamang gamot ⎻ Recommended because they are locally available YL6:01.24 Principles of Ethnopharmacology ● Some of the available drugs in the market have botanical origins ● 25% of modern pharmaceutical drugs have botanical origins ○ Foxglove (Digitalis lanata) ▸ Source of Digoxin ⎻ Drug that decreases heart rate ⎻ Used for the ff: ▪ Atrial fibrillation 2 ▪ Atrial flutter ▪ Heart failure ○ Deadly Nightshade (Atropa belladonna) ▸ Source of Atropine ⎻ Very potent ⎻ For pupillary dilation ⎻ Causes death by slowing heart rate (anticholinergic) ○ Chondrodendron tomentosum ▸ Source of Tubocurarine ⎻ Anesthetic drug ⎻ Causes paralysis as a result of acetylcholine inhibition Figure 4. Plants as Medicinal Sources: Foxglove (left); Deadly Nightshade (middle); Chondrodendron tomentosum (right) V. PRODUCTS AND METHODS SEPARATION A. CLASSIFICATION ● Crude products ○ Powder, tea or herbal collections ○ Refer to whole herbs: ▸ Either dried and encapsulated or processed and preserved in alcohol or another solvent ● Crude extract ○ Active component of the plant is removed ○ Usually in the form of galenicals (e.g. of tinctures and fluid extracts) ○ One or more components present in a specific guaranteed amount ▸ Usually expressed as a percentage ● Primary processed plant product ○ Available in the form of volatile and fixed oils or resins ● Individual plant metabolites ○ Metabolites are extracted from the plant ▸ Alkaloids ⎻ E.g. morphine, quinine, atropine ▸ Glycosides ⎻ E.g. digoxin B. TYPES OF PREPARATIONS DNA EXTRACTS (POWDERED EXTRACTS) ● Solid preparations obtained by condensing and drying fluid extracts ○ Generally, 95% of the extract is solid, 5% water residue (moisture) ● Native dry extract ○ Composed of only plant extract material and is free of additives ○ E.g. ⎻ Compress ▪ Contains the plant extract ⎻ Poultice ▪ Use mortar and pestle to pound the plant and apply it as a compress YL6:01.24 Principles of Ethnopharmacology ⎻ Dry powder ⎻ Can also be incorporated in tablets and capsules Figure 5. Different applications of dried extracts. From left to right: tablets and capsules; poultice; compress LIQUID EXTRACTS ● Natural products like steroids, alkaloids, various anti-cancer agents, oils from seeds, and caffeine from coffee beans can be extracted by solvents in various supercritical fluids like CO2, ethane, NO2, and ethylene ○ Supercritical fluid: Any substance at a temperature and pressure above its critical point giving it properties between a gas and a liquid ● Classified further into: ○ Aqueous extract ▸ Infusion ▸ Decoction ○ Alcohol extract (Tincture) ○ Oil extract Aqueous Extract ● Extracting agent: water ● Easiest to perform ● Extract: mainly contains water-soluble constituents and a few lipid-soluble components ● Disadvantages: ○ Individual constituents are relatively unstable ○ Microorganisms can multiply rapidly since you are just using water Infusion ● Use of soft tissue plant parts (flower, leaves, green stems, crushed seeds, powdered roots, powdered resins) ● Pouring water or soaking the herb ● Typical dose: 1 teaspoon of dried herb: 1 cup hot water ● E.g., chamomile, lemon balm, peppermint, Chinese formulas ○ Infused like tea Decoction ● Herbs are simmered in a water bath (10-15 minutes) ○ Boil in low flame (high heat can denature some proteins) ● Typical formulation: 4 teaspoons of dried herb: 1 cup of water ● Do not use stainless steel utensils (can alter the components/extracts) ● Use: earthen, enameled, or glass utensils ● Do not cover the pot Alcohol Extract (Tincture) ● Extract using ethanol and water at various ratios and concentrations ○ Generally: 95% solids + 5% water residue (moisture) OR 1 water: 5 ethanol ● Alcohol can also kill some microorganisms ● Preparation: Drug is repeatedly steeped in the extract, strained, and concentrated until completely extracted ● Advantages: ○ Able to isolate lipophilic drug constituents (e.g., essential oils) ○ Longer preservation period up to 2-3 years (alcohol has antimicrobial properties) ○ Alcohol assists in rapid absorption of the active ingredients 3 Oil Extract ● Dissolving fat-soluble constituents of medicinal plants in oil (e.g., olive oil, almond oil, peanut oil) ● Preparation: ○ Immerse freshly cut or dried plant parts in vegetable oil ○ Allow to stand at room temperature until fat-soluble constituents have been extracted ● Disadvantages: ○ Relatively unstable ▸ Should be prepared in small quantities ▸ Therefore, prepare right before it will be used ○ Cannot be stored for longer periods of time unlike tinctures C. STEPS IN PREPARATION 1. Plant collection ○ Go organic ▸ Do not collect those with pesticides ○ Harvest on sunny mornings ▸ Avoid picking fruits, leaves, or nuts during or after heavy rainfall (constituents may have been washed away) ○ Leaves, fruits, flowers, or nuts must be mature before harvesting ▸ Less medicinal substances are found on younger plant parts (< 2 years old) ○ Collection considerations: ▸ Flowers: before blooming (more active ingredients) ▸ Seeds and Bark: dry season, plant must be > 2 years old ▸ Stem: plant is ready to bloom, more mature stems have less mineral content ▸ Leaves: when plant is ready to bloom ○ Harvest flowers, stems, and leaves at the same time: before / when the plant is about to bloom 2. Washing and cutting 3. Drying ○ Methods: ▸ Air dry: leaves and flowers ▸ Sun dry: fruits, seeds, bark, branches, roots ▸ Heat dry: least desired → may destroy most of the active ingredients; makes use of ovens 4. Storage ○ For Dry Preparations: ▸ Use sealed plastic bags or brown bottles ▸ Use a moisture absorbent material (charcoal) ▸ Store in a cool dry place without sunlight ▸ Can last up to 6 months ○ For Decoctions: ▸ Dispose after 1 day ▸ After boiling, use the decoction immediately ▸ If there’s any excess, discard ▸ To keep fresh during the day, keep in a flask or thermos 5. Extraction VI. TEN COMMON HERBS TEN COMMON HERBS BY THE DOH]: SLUT NA BABY ● Sambong ● Lagundi ● Ulasimang Bato ● Tsaang Gubat ● Niyog-niyogan ● Ampalaya ● Bayabas ● Akapulko YL6:01.24 Principles of Ethnopharmacology ● Bawang ● Yerba Buena A. SAMBONG ● ● ● ● Name/s: Blumea camphora Scientific name: Blumea balsamifera Ingredients: Coumarins, flavonoids Preparation: Leaves (tea) ○ Tablets are also available ● Use/s: ○ Diuretic ○ Common cold ○ Anti-urolithiasis [SAMBONG] ● Someone Like You by Adele ● “Nevermind I’ll pee, Sambong like you” ● Pee because sambong is a diuretic Figure 6. Sambong B. LAGUNDI ● Name/s: Chinese chastetree ● Scientific name: Vitex negundo ● Ingredients: ○ Volatile oil, resin, alkaloid, lichen acids, glucoside ○ Constituents of oil: sabinene, linalool, terpinen-4-ol, b-caryophyllene, a-guaine ad globulol ● Preparation: Leaves → capsule or syrup ● Use/s: ○ Mucolytic ○ Asthma (Mostly for expectorant; makes mucus easier to cough out) ○ Cough and colds ○ Fever ○ Diarrhea ○ Boils [LAGUNDI] ● The scientific name vitex negundo sounds like a spell in Harry Potter ● If you shout “vitex negundo!”, the spell will be cast on someone and they will cough out phlegm ● This is to remember that lagundi is a mucolytic 4 ● Ingredients: Palmitic oil, oleic acids, saponins, quisqualic acid, sitosterol, glucosides, hydrocarbons, galactose, arabinose, rhamnose ● Preparation: Seeds, bark, leaves ● Use/s: ○ Purgative ○ Antihelminthic (e.g., Ascaris) ○ Tonic, astringent ○ Diarrhea ○ Skin diseases Figure 7. Lagundi [NIYOG-NIYOGAN]: antihelmNNNNthic – puro N ● toNNNNNic ● astriNNNNNNNgent ● skiNNNNNNNN diseases C. ULASIMANG BATO ● Name/s: Pansit-Pansitan, Pepper elder ● Scientific name: Peperomia pellucida ● Ingredients: Alkaloids, tannins, flavonoids, steroid, triterpenoids ● Preparation: Leaves ● Use/s: ○ Arthritis and gout ○ Anti-inflammatory, analgesic ○ Antibacterial, antifungal [ULASIMANG BATO] ● Ulasimang Bato → gout inflammations look like rocks Figure 10. Niyog-niyogan F. AMPALAYA Figure 8. Ulasimang Bato (left), Gout Inflammation (right) D. TSAANG GUBAT ● Name/s: Fukien tea tree/Philippine Tea Tree ● Scientific name: Ehretia microphylla Lam. ● Ingredients: Phytochemicals, flavonoids, glycosides, terpenoids, saponins, alkaloids ● Preparation: Leaves (marketed as tea) ● Use/s: For diarrhea, stomach pain, mouthwash, analgesic, antimicrobial, antiplasmodic, antidiabetic [TSAANG GUBAT] : TG ● Tatae sa Gubat (Tsaang Gubat is for diarrhea and stomach pain) . ● Name/s: Bitter gourd, bitter melon ● Scientific name: Momordica charantia ● Ingredients: Charantins (insulin-like properties), steroidal saponins ● Preparation: Fresh leaves, fruits ● Use/s: ○ Lowers blood pressure ○ Antipyretic, purgative (anti-helminthic or pampurga for worms) ○ More commonly advertised as an agent of lowering blood sugar [AMPALAYA]: amPALaya ● Purgative ● Antipyretic ● Lowers blood sugar Figure 9. Tsaang Gubat E. NIYOG-NIYOGAN ● Name/s: Chinese honeysuckle, Rangoon creeper ● Scientific name: Quisqualis indica L YL6:01.24 Principles of Ethnopharmacology Figure 11. Ampalaya 5 G. BAWANG ● Name/s: Garlic ● Scientific name: Allium sativum ● Ingredients: Sulfur compound, allilin, saponins, flavonoids, S-allyl cysteine ● Preparation: Tablet, or as is (some recommend 2 cloves of garlic once or twice a day) ● Use/s: ○ Antihypertensive for blood pressure control ○ Lowers cholesterol [BAWANG]: Boy Bawang ● Oily (for dyslipidemia and salty for hypertension) ○ Copper (famous for antimicrobial property, e.g. copper mask) ○ Vitamins C, K, E ○ Anthocyanins ○ Flavonoids ○ Carotenoids (Antioxidants) ● Preparation: ○ Mouthwash ○ Poultice ○ External wash ● Use/s: ○ Antiseptic ▸ Patients who will be circumcised (tuli) are asked to swallow bayabas leaves ⎻ These leaves are also used to wash their genital area ○ Diarrhea [BAYABAS]: BAhABAS ● Where will you be when diarrhea hits? ○ Baha ang toilet = diarrhea ○ Dirty baha = antiseptic Figure 12. Bawang H. AKAPULKO ● ● ● ● ● Name/s: Ringworm bush, Bayas-bayasan Scientific name: Cassia alata Main ingredient: Chrysophanic Acid Preparation: Poultice, ointment, soaps, lotions Use/s: ○ Fungal infections ○ Scabies ○ Eczema [AKAPULKO]: AKA-PUNGAL ● Aca-scuse me? (Excuse me from Pitch Perfect) ● Akapulko, Aka-pungal, Aka-fungal (anti-fungal) Figure 14. Bayabas J. YERBA BUENA ● Name: Peppermint ● Scientific name: Mentha arvensis, Clinopodium douglasii ● Ingredient/s: ○ Oil-menthenol ○ Limonene ○ Pulegone ○ B-carophyllene ○ Saponins ○ Glycosides ○ Tannins ● Preparation: Leaves ● Use/s: ○ Analgesic for body pains (sprays, menthol flavor) ○ Antispasmodic ○ Stimulant ○ Sudorific (pampapawis) [YERBA BUENA]: Nyerba ● Nyebe = snow = cold ○ Stimulant ○ Cold compress = good for body pains = analgesic, antispasmodic ● Olaf melting = sudorific ● Olaf is vibrant = stimulant Figure 13. Akapulko Leaves and Flower I. BAYABAS ● Name: Guava ● Scientific name: Psidium guajava ● Ingredient/s: YL6:01.24 Principles of Ethnopharmacology 6 ● Adverse effects: ▸ Breath and body odor ▸ Heartburn ▸ Upset stomach ▸ Allergic reactions D. GINSENG Figure 15. Yerba Buena VII. NINE BEST-SELLING HERBS Take Note! ● Even herbal medications have adverse effects ● The list below can be found globally and not just locally. Some of these are even available in the market. ● Uses: ○ Well-being and stamina, improving both mental and physical performance ○ Also marketed for ▸ Hypertension (HPN) ▸ Blood glucose ● Adverse effects: ○ Headaches ○ Sleep ○ Gastrointestinal problems A. GINGKO BILOBA ● Uses: ○ Brain tonic = vasodilator ○ Memory ○ Asthma ○ Bronchitis ○ Fatigue ○ Tinnitus ● Adverse effects: ○ Bleeding tendencies ○ Headache ○ Nausea ○ Gastrointestinal upset ○ Diarrhea ○ Dizziness ○ Allergic skin reactions Figure 16. Gingko biloba B. ECHINACEA ● Uses: ○ Treat or prevent colds, flu, and other infections ● Adverse effects: ○ Allergic reactions E. SAW PALMETTO ● Uses: ○ Prostatic disorders ▸ Specifically, for benign prostatic hyperplasia (BPH) ● Adverse effects: ○ Mild stomach discomfort ○ Decreased libido ○ Impotence F. ST. JOHN’S WORT ● Uses: ○ Depression ● Adverse effects: ○ CYP inducer G. VALERIAN ● Uses: ○ Insomnia ○ Anxiety ● Adverse effects: ○ Headaches ○ Dizziness ○ Upset stomach ○ Tiredness H. CRANBERRY ● Uses: ○ Urinary disorders ▸ Highly debated ▸ Said to be used for urinary tract infection (UTI) ○ Diarrhea ○ Diabetes ● Adverse effects: ○ Excessive amounts could cause gastrointestinal upset or diarrhea I. BLACK COHOSH Figure 17. Echinacea C. GARLIC ● Uses: ○ Hypercholesterolemia ○ Hypertension ○ Antiseptic YL6:01.24 Principles of Ethnopharmacology ● Uses: ○ Rheumatism ○ Menopausal symptoms ● Adverse effects: ○ Hepatitis / liver failure ○ Stomach discomfort ○ Headache ○ Rash 7 VIII. SAFETY A. SAFETY ISSUES 1. Purity of the herbal supplement ○ 1 – 100s of active chemical substances ▸ There are a lot of substances or “laman” that may cause adverse effects 2. Drug contamination ○ Growth, production, bottling, etc. ○ Heavy metals, bacteria, pesticides ○ E.g., Contamination may occur when prepared close to microbes 3. Toxic side effects 4. Interactive effects with other drugs or herbs PRECAUTIONARY MEASURES ● Be aware of adverse effects of herbal medicines ● Follow the general guide for intake of herbal medicines ○ Be wary of the following: ▸ Active ingredients ▸ Appropriate extraction method ▸ Allergic reactions ▸ Contamination ● Always consult with a doctor if symptoms persist or new symptoms develop ○ Always advise patients to tell you if they are using a herbal medications B. INTERACTIONS WITH OTHER DRUGS OR HERBS ● Affected by genetics and polymorphisms in drug metabolism ○ Specific DNA regions on various chromosomes influence hepatic metabolism ○ Polymorphism gives rise to at least 2 distinct groups in the population that differ in their ability to perform certain drug biotransformation reactions ● Interactions affect both pharmacokinetics and pharmacodynamics of drugs Take Note! (01.22, 2026) ● Some herbal medications are CYP450 inducers ○ These affect metabolism of drugs ○ You might need to stop the usage of herbal medications in order to get the therapeutic levels of various drugs Nice to Know! ● Hyperforin ○ An active constituent ○ A ligand for the xenobiotic pregnane X receptor (PXR) ▸ PXR: a nuclear receptor regulating the expression of proteins that transcriptionally regulate CYP450 3A4 Pharmacodynamic Interactions ● Can lead to serotonin syndrome ● SSRI & MAO inhibitors, such as SJW, cause excess serotonin activity ○ SJW combined with SSRI & MAO can lead to the following adverse effects: ▸ Restlessness, nausea, vomiting, tachycardia, and hallucinations ▸ Case reports: especially when taking serotonin with buspirone, loperamil, nefazodone, paroxetine, sertraline, venlafaxine ● Can cause possible adrenergic crisis ○ Sudden increase in serum levels of adrenal hormones secondary to MAO inhibition ST. JOHN'S WORT (SJW) Pharmacokinetic Interactions ● For mild-moderate depression ● Has fewer adverse effects compared to that of conventional drugs ○ Has both selective serotonin reuptake inhibitor (SSRI) and monoamine oxidase (MAO) inhibitor activity ○ Can lead to restlessness, nausea, vomiting, tachycardia, and hallucinations ● Increases expression of P-glycoprotein (PgP) ○ PgP acts as a pump to remove drugs from cells ○ Regulates MDR-1 (multidrug resistance gene-1) and other drug transporters ○ SJW induces CYP450, thus removing drugs from cells ▸ CYP450 Mechanism ⎻ Induces cytochrome P450 3A4, C29, and 1A2 → creates changes in metabolism → in the long term: produces induction ⎻ If SJW is combined with various drugs such as theophylline, oxycodone, or digoxin, the concentrations of these drugs are reduced to subtherapeutic levels due to hastening of metabolism YL6:01.24 Principles of Ethnopharmacology Figure 18. St. John's Wort GRAPEFRUIT Pharmacokinetic Interactions ● Contains furanocoumarin compounds that can selectively inhibit CYP A ○ By inhibiting CYP, you prevent immediate metabolism of the drug → increase bioavailability ▸ If Drug A (e.g., grapefruit) inhibits something (CYP) that metabolizes Drug B (e.g., terfenadine), then Drug B will be more available in the circulation ○ Increase bioavailability of certain drugs (terfenadine, cyclosporine, felodipine) leading to adverse effects ▸ Note: Felodipine is a hypertensive drug 8 B. WHO HERBAL DRUG LABELLING REQUIREMENTS Figure 19. Grapefruit WARFARIN + HERBS Pharmacokinetic Interactions ● Decreased absorption from GI tract due to mucilage (comfrey, Iceland moss) or laxative herbs ○ E.g., senna, rhubarb ● CYP450 2C9 inhibition/induction, which metabolizes the active S-enantiomer of Warfarin (saw palmetto, kava) ● Recall: Warfarin is an anticoagulant and can cause bleeding Pharmacodynamic Interactions ● Herbs that decrease platelet aggregation (e.g., Ginkgo biloba) ○ Recall: Ginkgo biloba can cause bleeding problems ○ Combining Ginkgo biloba with warfarin can allow for a higher risk of bleeding problems ● Decreased thromboxane synthesis ○ Herbs with coumarin content (though coumarin is a relatively weak anticoagulant) C. SIGNIFICANT HERBAL INTERACTION ● Potential herbal interactions can be detected ● American ginseng (Panax quinquefolius) ○ Induces CYP2C9 ▸ Increases warfarin and other 2C9 substrate effects ● Garlic and Ginkgo ○ Should not be taken with antiplatelet adhesion drugs/aspirin/warfarin due to risk of bleeding ○ Pharmacodynamic effect ● Echinacea ○ May induce CYP1A2; may lower 1A2 substrates IX. REGULATION OF HERBAL MEDICINE A. STANDARDIZATION OF PLANT MATERIAL ● Institutions have released/published quality control methods to establish standards and qualifications of herbal materials ○ EU - Quality of Herbal Medicinal Products ○ WHO - Quality Control Methods for Medicinal Plant Materials ○ Pharmacopoeia Monograph ▸ Book recognized by the government as legal authority for drug standardization RA 8423 ● Traditional and Alternative Medicine Act (TAMA) of 1997 ● Creation of the Philippine Institute of Traditional and Alternative Health Care (PITAHC) ○ To accelerate the development of traditional and alternative health care in the Philippines with provisions for a development fund YL6:01.24 Principles of Ethnopharmacology ● Required elements that should be present on the packaging of any herbal preparations ○ Complete scientific name of the plant (genus, species, subspecies, variety, author); commonly used synonyms may be mentioned ○ Name & quantity of active ingredient(s) (in dried weight when relevant) ○ Dosage form ○ Directions for use (including indications, dosage, mode of administration, duration of use, age group limitations, and use during pregnancy/lactation) ○ Warning statements and relevant contraindications, adverse effects, if any, and overdose information when relevant ○ Batch number ○ Expiry date ○ Storage conditions ○ Name and address of manufacturers and/or importers ○ Registration or notification (listing) number C. CHALLENGES IN HERBAL PREPARATION ● Efficacy ○ Sufficient, exact, and consistent concentration of active compounds ○ Titration and standardization methods ○ Many preparations across different provinces; not very standardized, especially for those outside the Sampung Halaman list ○ Hard to gauge the exact concentration; especially in crude products compared to crude extracts ● Safety ○ Raw materials and final products must meet certain hygiene requirements ○ Free of contaminants (pollutants - psychopharmaceutic residues, heavy metals, aflatoxin) ● Standardization ○ Consistent level of active ingredients, repeatable in every production batch ○ Complete with labeling and advertising guidelines D. ADVERTISING: R.A. 7394 ● Consumer Act of the Philippines - should be familiar with this upon entry into pharmaceutical industry ● Article 112 ○ (a) No claim in the advertisement may be made which is not contained in the label or approved by the concerned department. ○ (b) No person shall advertise any food, drug, cosmetic, device, or hazardous substance in a manner that is false, misleading or deceptive or is likely to create an erroneous impression regarding its character, value, quantity, composition, merit, or safety. ▸ Why companies put “no therapeutic claims” or promote products as a wonder drug; scientific basis required ○ (c) Where a standard has been prescribed for a food, drug, cosmetic, or device, no person shall advertise any article or substance in such a manner that it is likely to be mistaken for such product, unless the article complies with the prescribed standard or regulation. (Guidelines on the Use of Nutrition and Health Claims [CAC/GL23-1997 (Rev 1- 2004)]) 9 QUICK REVIEW QUESTIONS 1. Why is there a need to study Ethnopharmacology? A. To be able to advise patients against the use of herbal medicines B. To guide patients in making informed decisions about the use of herbal medicine C. To promote the superiority of herbal medicines over manufactured medicines D. All of the above 2. All of the following institutions and laws helped in establishing the National Policy on Traditional & Complementary Medicine (T&CM) except: A. Traditional and Affordable Medicine Act (TAMA Law) B. Philippine Food and Drug Administration C. Traditional Medicine Unit of DOH D. Philippine Institute of Traditional and Alternative Health Care 3. Which of the following drugs correspond to their herbal sources? A. Tubocurarine: Atropa belladonna B. Atropine: Chondrodendron tomentosum C. Digoxin: Digitalis lanata 4. A supercritical fluid is substance at a temperature and pressure above its critical point giving it properties between a gas, a liquid, and semi-solid. Oil extracts cannot be stored for long periods of time. A. Only statement 1 is true B. Only statement 2 is true C. Both statements are true D. Both statements are false 5. Which of the following sets of plant parts should be harvested once they reach maturity? A. Nuts, flowers, fruits, leaves B. Leaves, bark, roots, flowers C. Flowers, fruits, roots, stem D. Stem, bark, fruit, roots 6. Which is the common use of a Rangoon creeper and Momordic charantia? A. Tonic B. Antipyretic C. Purgative D. Lowers blood sugar 7. Sammy recently bought an analgesic for body pains that was advertised as containing a natural herb component. Which of the following might she find in the list of ingredients? A. Mentha arvensis B. Psidium guajava C. Gingko biloba D. Cassia alata 8. Which of the following herbal medications is incorrectly matched to at least one of its use/s? A. Cranberry : urinary disorders B. Garlic : antiseptic C. Saw palmetto : prostatic disorders D. Valerian : depression YL6:01.24 Principles of Ethnopharmacology 9. St. John's Wort decreases intracellular drug concentrations by: A. Selectively inhibiting CYP A B. Selectively inhibiting monoamine oxidase C. Increasing expression of P-glycoprotein D. Inhibiting cytochrome P450 3A4, C29, and 1A2 10. Which of the following laws is correctly matched with its subject matter? A. RA 8423 - Standards of Herbal Preparations B. RA 6675 - Herbal Drug Distribution C. RA 7394 - Consumer Protection D. RA 2382 - Legal Authority on Drug Standardization ANSWER KEY 1B, 2A, 3C, 4B, 5A, 6C, 7A, 8D, 9C, 10C RATIONALE 1. B. To guide patients in making informed decisions about the use of herbal medicine. Ethnopharmacology is important since a lot of people use them and they provide low-cost alternatives compared to the drugs that are available in the market. 2. A. Traditional and Affordable Medicine Act (TAMA Law). This should be the “Traditional and Alternative Medicine Act”, which was a law enacted to develop and integrate traditional and alternative healthcare into the national health delivery system. 3. C. Digoxin: Digitalis lanata. The herbal sources of atropine and tubocurarine are Atropa belladonna and CHondrodendron tomentosum respectively. 4. B. Only statement 2 is true . A supercritical fluid is substance at a temperature and pressure above its critical point giving it properties between a gas and a liquid, not including semi-solid. 5. A. Nuts, flowers, fruits, leaves. Leaves, fruits, flowers, or nuts must be mature before harvesting 6. C. Purgative. The common usage of tsaang gubat and ampalaya is purgative. 7. A. Mentha arvensis. Mentha arvensis, otherwise known as yerba buena or peppermint, is commonly used as an analgesic for body pains. It is also used as an antispasmodic, stimulant, and sudorific agent. 8. D. Valerian : depression. Valerian is used for anxiety and insomnia. Cranberry is used for urinary disorders, diarrhea, and diabetes. Garlic is used as an antiseptic as well as for hypercholesterolemia and hypertension. Saw palmetto is used for prostate disorders, specifically benign prostatic hyperplasia. 9. C. Increasing expression of P-glycoprotein. St. John's Wort is said to increase expression of the P-glycoprotein which acts as a pump to remove drugs from cells. It also reduces concentration by inducing (rather than inhibiting) CYP450 3A4, C29, and 1A2. While it does have monoamine oxidase inhibitor activity, this does not reduce drug concentrations in cells. CYP A inhibition is an action of furanocoumarin compounds in grapefruit. 10. C. RA 7394 - Consumer Protection. RA 7394 is the Consumer Act of the Philippines. The other RAs cover: RA 8423 - TAMA Act and PITAHC Creation; RA 6675 - Generics Act of 1988; RA 2382 - Medical Act of 1959. 10 REFERENCES REQUIRED ● 📄 Online Source Lecture: ASMPH 2027. 01.24: Principles of Ethnopharmacology by Soller, P, MD-MBA SUPPLEMENTARY Concerns and Feedback form: http://bit.ly/YL6CFF2027 How’s My Transing? form: https://bit.ly/2027YL6HMT Mid-Semester Evaluation form: https://bit.ly/2027YL6MidSem End-of-Semester Evaluation form: https://bit.ly/2027YL6EndofSem Errata Points Trackers: https://bit.ly/YL62027EPT YL6 TransMap: https://bit.ly/2027YL6TransMap FREEDOM SPACE YL6:01.24 Principles of Ethnopharmacology 11 APPENDIX Table 1. Updated Numbers of Certified or Accredited Practioners at the End of Year 2017 Updated Numbers of Certified or Accredited Practitioners at the End of Year 2017 Medical Acupuncturists 131 Homotoxicologists 25 Associated Medical Acupuncturists 70 Chiropractic Practitioners 42 Acupuncturists (Filipino) 112 TAHC Organizations 9 Acupuncturists (Foreign) 164 Acupuncture Clinics 29 Associate Acupuncturists 416 Homeopathy / Homotoxicology Clinics 5 Nonmedical Naturopaths 8 Naturopath Clinic 1 Medical Naturopaths 7 Homeopathy / Homotoxicology Training Center 1 Nonmedical Homeopaths 1 Naturopath Training Centers 3 Medical Homeopaths 2 Acupuncture Training Centers 10 Source: WHO Global Report on Traditional and Complementary Medicine 2019 Table 2. Examples of Plants as Medicinal Sources Examples of Plants as Medicinal Sources Plant (Botanical Origin) Drug Derived From Plant Drug Effects Foxglove (Digitalis lanata) Digoxin ● Decreases heart rate ● Used for: ○ Atrial fibrillation ○ Atrial flutter ○ Heart failure The Deadly Nightshade (Atropa belladona) Atropine ● Used for pupillary dilation ● Very potent ● Causes death by slowing heart rate ○ Anticholinergic Chondrodendron tomentosum Tubocurarine ● Causes paralysis ○ As a result of acetylcholine inhibition ○ Anesthetic Table 3. WHO Guidelines on Herbal Preparations I. INTRODUCTION ● Correct identification of source plants species and selection of appropriate parts for use are basic and essential steps for ensuring the safety, quality, and efficacy of herbal medicines ● Quality of plants and preparation determines the safety and efficacy of herbal medicines II. POST-HARVEST PROCESSING ● To assure purity and/or quality (such as prevention of microbial and insect infection or infestation) and to alter the therapeutic properties of raw herbs (such as enhancement of effectiveness or reduction of toxicity) A. INSPECTION OR SORTING ● ● ● ● ● Remove dirt and foreign substances Discard damaged parts Peeling (to separate unwanted parts) Sieving, trimming, singeing (to remove hairs or rootlets) Removal of residues of unwanted plant parts (removing unwanted seeds from fruits and stripping leaves from stems) B. PRIMARY PROCESSING STEP 1. Washing YL6:01.24L Principles of Ethnopharmacology DESCRIPTION ● Raw herbs: esp. rhizomes, roots, and tubers 12 ○ Washing with clean water and dried soon; chlorinated water may be used ○ Scraping and brushing may be necessary ○ Not recommended to soak herbs for long periods of time 2. Leaching ● Removing impurities by placing them in running water ● Control duration to avoid excessive loss of active ingredients 3. Primary cutting ● Reduce the size before transportation; usually at the harvest site 4. Advanced cutting, sectioning, and comminution (Fragmentation) ● Cutting or sectioning into convenient or specific sizes/forms for storage or direct use 5. Aging ● ● ● ● 6. Sweating (Fermentation) ● Keeping them at a temperature of 45-65 °C, with high humidity, for an extended period (1 week-2 months) ● Considered a hydrolytic and oxidative process ● Herbal materials are usually stacked between woolen blankets/other kinds of cloth 7. Parboiling (Blanching) ● Putting herbs in boiling water for a brief period without being fully cooked ● Purpose: Improve storage life, prevent mold/insect contamination, for easy drying, destroy enzyme activity 8. Baking/Roasting ● Dry-heating using indirect, diffused heat ● Often with the use of talc powder or bran to ensure even heating ● Some are roasted/baked until color turns yellowish brown; some are heated until charred 9. Boiling/Steaming ● Involves cooking the herbal materials in water or another liquid ● Purpose: Soften plant tissues, denature enzymes Storing herbal materials for a long period May be under the sun or in the shade (depending on the type) Excess water is evaporated Enzymatic reactions like hydrolysis or oxidation may occur 10. Stir-Frying ● Stirred or tossed for a period of time under heat until color changes, charred, or carbonized 11. Fumigation ● With the use of sulfur dioxide - to preserve color, improve fresh-looking appearance, bleaching, preventing growth of insects, and inhibiting decay by molds ● Usually applied to herbal materials of light and bright colors to avoid browning 12. Irradiation ● Irradiation/UV light can be used to eliminate or reduce microbial load 13. Primary distillation ● Done to obtain crude essential oils 14. Expression ● Done to obtain fresh juice C. DRYING 1. Sun-drying 2. Shade-drying 3. Drying by artificial heat III. ADJUVANTS ● Adjunctive substances added during the processing of herbs to alter pharmacologic and therapeutic properties of the herbal materials, neutralize, or reduce toxicity, mask the taste, assist formulation into suitable herbal dosage forms, maintain stability, or extend storage time ● Examples: Water, wine, vinegar, honey, milk, clarified butter, etc. IV. HERBAL DOSAGE FORMS ● Decoctions, tea bags, granules, syrups, ointments ● Ointments, creams, and patches ● Inhalations, tablets, capsules, lozenges YL6:01.24L Principles of Ethnopharmacology 13