Phytotherapeutics & Homeopathic remedies

• Phytotherapeuticals and homeopathic remedies both utilize plants.
• Herbal remedies (phytotherapeuticals) possess active principles exerting a pharmacological effect.
• Homeopathic remedies contain herbal and active principles in immeasurable amounts, relying on a sufficient molecular memory for therapeutic effects.

Storing Raw Materials

• Processing and preserving raw medicinal plants is achieved through freezing, stabilization, dehydration via vacuum drying, and lyophilization.
• These methods maintain the chemical composition of the raw material for extended periods.

Medicinal Oil extraction

• Volatile and fixed from Crude drugs

Fixed Oil (Fatty Oil)

• Derived via Cold press or Supercritical CO2 extraction
• Examples include black cumin oil, almond oil, pomegranate seed oil, and peach kernel oil.

Volatile oils

• Derived via Distillation (water-steam)
• Aromatherapeutics utilise volatile oils
• Examples include Lavandulae aetheroleum, Melissae aetheroleum (Lemon balm oil), Mint oil (Menthae aetheroleum), and Tee tree oil (Melaleucae aetheroleum).
• Supercritical Fluid Extraction (SFE) diffuses a supercritical fluid quickly as a gas (carbon dioxide), dissolving materials as a liquid.

Complexity of Herbal Products

• The quality hinges on active principles, referred to as "secondary" plant substances or phytochemicals.
• Herbal medicines consist of other substances that impact the ingredients.
• Reproducing the effects of herbal drugs via isolated constituents can be challenging.

Complexity of Herbal Medicines

• Plant compounds like cellulose and lignin are inactive substrates.
• Bitter or aromatic substances with minimal pharmacological activity stimulate gastric and intestinal secretions, aiding dissolution and absorption of active principles.
• Tannins and saponins facilitate intestinal absorption of active plant principles via effects on intestinal motility or bile secretion.
• Mucilages and peptic substances can modify the functions of the intestine mucous membrane, impacting absorption.

Interactions between Plant Constituents

• Interactions may occur between plant constituents that are chemically and therapeutically related.
• Herbal medicines can represent a synergic complex if they are not related chemically or therapeutically
• Herbal preparations should be administered in extract form due to their complex pharmaceutical composition.

Herbal Medicine Safety

• Safety relies on using the correct part of the medicinal plant.
• Different plant parts contain different active principles
• Nettle root contains steroid isomers effective against BPH disorders, while the leaves act as a diuretic.
• Red pulps of the Rosehip fruit (Rosa canina, wild rose ) is used in cold-flu disorders during fall-winter- spring The powder of the seeds (yellow colored) is used for manufacturing capsula* against arthritis

Active Principles and Amounts

• The active components vary based on climate, soil, genetic factors, and chemical exposure.
• Quality control is crucial to avoid contaminations with heavy metals or microorganisms, and adulteration with botanicals or chemicals.
• Common herbal medicines often contain a mixture of herbal drugs
• Some are self-prescribed.

St. John's Wort

• Hypericum perforatum is an herbal antidepressant that can interact with medications

St. John's Wort Drug Interactions

• Indinavir (treats HIV)
• Digoxin
• Cyclosporine (organ rejection)
• Antidepressant medications
• Sympathomimetic amines
• Pseudoephedrine
• Yohimbine
• Cholesterol-lowering drugs (simvastatin, etc.)
• Overdose increases sensitivity to sunlight

Standardization of Herbal Medicines

• The standardization involves identification and assay of active principles, not just analytical evaluation.
• Chromatographic techniques like TLC, HPTLC, GLC, and HPLC define chemical composition of herbal drugs.
• Spectrophotometry, colorimetry, and gravimetric determinations may be necessary.

Standardized Herbal Medicines

• Standardized herbal material involves using the correct plant with good agricultural and harvesting practices.
• It also means ensuring correct active principles and amount, without contaminations.
• Good Agricultural and Harvesting Practices (GAHP) are essential.
• Standardized extracts are obtained by Good Laboratory Practices (GLP) and checked with finger print chromatograms.
• Producing herbal pharmaceutical products requires Good Manufacturing Practices (GMP).

Standardized Plant Extracts

• Standardized plant extracts have pharmacologycally active components in a same amount in a certain gram extract
• Controlled cultivation (GACP =GAHP), standardized production methods, and chemical analysis ensure homogeneity of plant extracts.
• Plant extracts are analyzed by HPLC, and a fingerprint chromatogram is obtained for each.
• This applies to raw materials (dried herbs and extracts) and the finished product.

Herbal Medicine and Scientific Research

• Ideally, botanical products should eliminate medical disorder symptoms, and alleviate suffering.
• The dosages should avoid gastro-intestinal disturbances, blood pressure changes, cutaneous reactions, and enzymatic alteration.
• Safety is more important than effectiveness
• Acute toxicity is assessed in animals via the maximal tolerated dose.

Research: Toxicity Studies

• Chronic toxicity is determined after repeated exposure: 3-10 days (subacute), 15-30 days (subchronic), or 1-2 years (chronic).

Research: Efficacy Studies

• Randomized clinical trials may report conflicting results.
• Feverfew (Tanacetum parthenium L) for headaches has varying trial outcomes.
• Systematic reviews and meta-analyses assess clinical evidence from trials to determine efficacy, and overall effect size of a particular outcome measure

Germany and Herbal Medicine

• Germany has stringent phytotherapy controls.
• The German Commission E (Komisyon E) is a special committee of the Bundesgesundheitsamt (Federal Ministry of Health), advising the German FDA equivalent.

The German Commission E

• They prepares monographs with historic information, phytochemicals, pharmacological, clinical/toxicological studies, case reports, epidemiological data, and manufacturer's data.
• Herbal products used for 15 years in the EU, and 30 years non-EU, can get production/sales permission with less clinical trials with EMA (European Medicine Agency).

Crude Drug Preservation

• Color change, leading to rapid discoloration and yellowing, results from exposure to direct or indirect light and humidity of leaves and flowers
• Light also degrades Crocus sativus (saffarin) and Cinnamomum zeylanicum (cinnamon), producing reddish marks in the latter.
• Moisture-sensitive crude drugs such as marshmallow, mullein and opium poppy are stored hermetically
• Oxygen-sensitive drugs are also stored in air-tight containers

Storage Contaminants

• Moulds and insects
• Enzymes
• Use cool, dry, well-aerated storage places
• Hyroscopic agents should be placed in containers

Storage best practices

• Following to prevent drugs alteration like, changes in color, taste, smell, consistency, or mould

Factors Affecting Smell

• Humidity and heat, like Althaea officinalis (marshmallow)
• Claviceps pupurea (ergot) ammoniacal smell
• Smell of mold

Factors Affecting Taste

• Microorganisms

Factors Affecting Humidity

• Roots, tubers, wood, rhizomes, bark, seeds, and bulbs are easily softened if not stored in dry environment

Extraction Process

• Dried drugs in extractive/tincture preparations are moistened with extractive solvents ("menstrum").
• Softening, or maceration involves being left from half an hour to days, is done at room temperature (digestion), to allow solvent to solubilize the active principles.
• Fragmentation aids ions making fragmentation easier

Extractive Solvents

• Extractive Processes and Solvents use choice for solvents, to provide efficient extraction of active ingredients and to eliminate unwanted components
• When extracting with water, remove fatty substances/waxes with hexane, petroleum ether, or dichloromethane.
• Preservatives reduce bacterial contamination and prevent mould.

Botanical Drugs and Treatment

• First, diagnose accurately.
• Combine, where appropriate, conventional and herbal medicines
• Use of a lower dose of the synthetic drug, minimizes potential for iatrogenic illness and side effects.
• They also have nutritional value (vitamins, protein, fiber, enzymes).
• Phytotherapy is complementary

Cardiac Glycosides (Digitalis Group)

• Cardiac Glycosides exist in Digitalis lanata Ehrhart (Woolly Foxglove), Digitalis purpurea Linn. (Purple foxglove), Digitalis lutea and Digitalis thapsi (scrophulariaceae family).
• Glycosides are obtained from the leaves.
• Digitalis lanata, Digitalis purpurea are part of this group

Digoxin Mechanism of Action

• Inhibits cardiac Na/K antiporter
• Causes intracellular sodium increase and potassium decrease.
• Increases sodium excretion via Na/Ca exchanger
• The excretion of sodium increases intracellular calcium levels
• Increased intracellular calcium increases inotropy.

Digoxin Uses and Effects

• Increases myocardial contraction force.
• Reduces conductivity in the atrioventricular node.
• Used mainly for Congestive Heart Failure (CHF).
• Prescribed at 62.5-250 µg daily.
• Causes a positive inotropic effect.
• Has a small therapeutic window.
• Positive inotropes make heart muscle contractions stronger, raising cardiac output to a normal level

Digitalis Toxicity

Reasons:

• Large maintenance dose
• Rapid digitalisation
• Other drugs: amiodarone, verapamil, quinidine, erythromycine
• Hypokalemia
• Hypercalcemia

Alternative Plants

• Contains steroidal cardioactive glycosides

Other Plants Containing Cardioactive Glycosides

• Some plants used for CHF offer no special advantage over digitalis.
• Adonis vernalis L. (family Ranunculaceae)
• Apocynum cannabinum L. and A. androsaemifolium L. (family Ranunculaceae)
• Helleborus niger L. (family Ranunculaceae)
• Convallaria majalis L. (family Convallariaceae)
• Nerium oleander L. (family Apocynaceae)
• Urginea maritima (L.) Bak. (family Liliaceae)
• Strophanthus kombé Oliv. or S. hispidus DC. (family Apocynaceae)

Hawthorn

• Crataegus laevigata, or C. monogyna (Rosaceae family)
• Dried leaves and blossoms/fruits treat early congestive heart failure and minor arrhythmias.
• Activity comes from oligomeric procyanidins, from catechin/epicatechin.
• Contains quercetin, rutin, hyperoside, vitexin, and vitexin rhamnoside.

Blue Berry

• The fruit contains anthocyanin glycosides.
• Treats retinopathy from diabetes/hypertension.
• Has anti-oxidant, anti-atherosclerotic, and anti-platelet properties.

Ginkgo Biloba

• Treats peripheral and cerebrovascular issues.
• Has isolated blood vessel impacts.
• Contains ginkgolides, which are specific platelet-activating factor antagonists
• Ginkgolides active principles the plant are terpene lactones type.

Horse Chestnut (Aesculus hippocastnum)

• Leaves contain saponin glycosides, with aescin as the main one.
• Contains sterols and triterpenes.
• Treats chronic venous insufficiency, bruising/sport injuries, deep vein thrombosis, varicose veins, and prevents edema.

Butcher's Broom (Ruscus aculeatus)

• The rhizome and roots treat venous disorders and varicose vein syndrome.
• Contains steroidal saponins, particularly ruscogenin and neoruscogenin.

Garlic

• Remedy for arteriosclerosis (Allium sativum)
• High in sulfur, hence its effect.
• The main compound is alliin, which inhibits oxidation
• It should be used with Caution with other cardiovascular drugs

Green Tea Extract

• Plant name - Camellia sinensis
• Can protect from cancer and cardiovascular disease, significantly decreasing plasma cholesterol and triglycerides,
• Has antioxidant polyphenols including epicatechin gallate, epigallocatechin-3-gallate (EGCG), and proanthocyanidins

Anti-Cancer Drugs

• Derived from the the Chinese tree, Camptotheca acuminata
• the alkaloid extract from it showed broad anti-cancer activity, with high toxicity
• a natural component, 10-OH campothecin, is China, is more active and treats Neck/Head Cancer

Camptothecin

• SIDE EFFECTS = Diarrhea, Anemia, hair loss, ab cramps, Vomiting.

Cont. Anti-Cancer Drugs:

• Synthetic Analogues are 9-amino-camptothecin.
• water -Soluble, derivatives - Topotecan + lrinotecan -Showed Good response on several cancers..
• for Tx of OVARIAN, AND COLORECTAL, USA uses belotecan to treat SLC. And OV CA...

Anti-Cancer Drugs continued..

• Viniceristine + Vinblastine is found in Catharanthus roseus -(a Madagascar Periwinkle Plant)..
• It folklore in Europe for Diabetes
• Now these are called Vinca Alkloids.

Taxol

• marketed by Bristol Myers Squibb to TX OVARIAN/Brease/ Small Cell Lung Cx..
• Mode of Action: Prevents mitotic Spindle - and breaks stabilized microtubules

Marine Anti cx Drugs

• aplidine -(Plitidepsin)- Trade name for colon/Lung/Bladder Cx

Marine Products:

• Dolastasin-10 : -is from Indian Seal Hare
• INHIBITS-polymerization of purified Tubulin.

Etceinascidin-743

• IS from marine invertebrate ecteinascidia turbinata
• it causes modulation of the productions of cytokines from tumors, suggesting its anti tumer acitivity