Natural Toxicants Pharmacognosy Advance.pptx

Pharmacognosy

1. Advance pharmacognosy IIB Chapter 4 Natural toxicants

2. GENERAL INTRODUCTION TO PLANT TOXICOLOGY

3. TOXICOLOGY Toxicology is derived from Greek words “toxicos” meaning poison and “logos” meaning knowledge. “It is a study of adverse effects of chemicals on living organisms, in other words it is a study of symptoms, mechanism , treatments and detection of poisoning especially the poisoning of peoples. Chief criteria regarding the toxicity of the chemicals is dose .”

4. PLANT TOXINS Plant toxins  are  toxic  secondary  plant  metabolites which naturally occur in food, feed, weeds and ornamental  plants . Toxicity Class   Major Toxicity:  These plants may cause serious illness or death. Minor Toxicity:  Ingestion of these plants may cause minor illnesses such as vomiting or diarrhea. Oxalates:  The juice or sap of these plants contains oxalate crystals. These needle-shaped crystals can irritate the skin, mouth, tongue, and throat, resulting in throat swelling, breathing difficulties, burning pain, and stomach upset.. Dermatitis:  The juice, sap, or thorns of these plants may cause a skin rash or irritation. Wash the affected area of skin with soap and water as soon as possible after contact. The rashes may be very serious and painful..

5. Poisonous plants: A poisonous plant is one which, as a whole or a part thereof; under all or certain conditions, and in a manner and in amount likely to be taken or brought into contact with an organism, will exert harmful effects or cause death either immediately or by reason of cumulative action of the toxic property, due to the presence of known or unknown chemical substances in it, and not by mechanical action. Classification of poisonous plants : Poisonous plants can be classified in a number of ways; however the most common classifications are: Based on active chemical constituents Based on physiological action Based on taxonomical system However, they can also be classified based on the poisonous parts (bark, root, leaves, seed etc.) of the plant.

6. Classification of Plant Toxins Plant toxins are classified on their structural and chemical properties as follows: a) Alkaloids : These are organic compounds containing nitrogen in heterocyclic ring, basic in nature and derived from amino acid, most of which exhibit strong physiological activity. For example, colchicines, nicotine, aconitine, taxine, cocaine and many other. Some common toxins from this class include: Indole Alkaloids, Pyrrolizidine, Tropanes, Glycoalkaloid etc.

7. b) Glycosides: Some common toxins from this class include: Cyogenic glycosides, Cardiac glycosides, Goitrogenic glycosides, Mustard seed oil glycosides etc.

8. c) Tannins : These substances have the capability to precipitate proteins. They make the skin tough by deception of the proteins in the skin. d) Proteins : A few protein toxins produced by plants enter eukaryotic cells and inhibit protein synthesis enzymatically. Examples of poisonous proteins include ricin (castor plant), abrin (rosary pea) and white acacia. Lathyrism occurs due to a toxic amino acid.

9. e) Volatile oils : Volatile oils are liquid substances formed in special oil cells, glands, hairs, or channels. They are all soluble in alcohol. At certain concentrations, some are irritant (forming blisters) and emetic. Some volatile oils are nephrotoxic. f) Oxalic acid and oxalates : These substances may be present in trichomes or in raphides (needle-like structures). They can provoke mechanical irritation. Ingested oxalate will be absorbed. Oxalate in blood binds calcium to form the insoluble calcium oxalate. Severe hypocalcaemia with tetany can occur. ( Tetany is a symptom that involves involuntary muscle contractions)

10. Plant toxicities in humans and animals 1.The seeds of certain plants like aristida may pierce the skin giving rise to subcutaneous or intramuscular abscesses. These seed have bored into the salivary ducts of the cattle and caused injury. This action is purely mechanical, so it cannot be termed as poisonous plants. Fig: Aristida plant 2. All parts of the plant may not be poisonous. Seed of family Rosacea contain dangerous amount of prussic acid but the outer fleshy portion of the fruit is eaten.

11. 3. Certain plants are poisonous to one species and the same quantity may not affect the other species. Example; Belladonna is poisonous to most species but rodents like rabbit can have it in large quantities. Fig: Belladonna Fig: Senecio 4. Some plants if eaten affect only a particular organ of the body. It does not cause serious body harm but render the organ unable to carry on their normal functions, e.g. Senecio of sunflower family causes hepatic cirrhosis in man and animals and prevent the liver from carrying out its normal functioning

12. 5. Certain plants loose their toxicity on being dried or cooked, e.g. species of Ranunculaceae is toxic in green state but can be used as food when dried. 6. Certain plants provide food but under certain conditions produce varying amount of poisonous substance, e.g. potato is a vegetable but at time of sprouting produces dangerous amount of solanine. 7. Certain plants like khesari (Lathyrus sativus) give rise to pathological conditions when fed in large doses for prolonged use. Fig: Sprouting potatoes Fig: Lathyrus sativus

13. 8. Pyrrolizidine alkaloids are among the most significant plant chemicals causing disease in animals and humans. After absorption from the gut, the compounds are converted to electrophilic pyrroles in the liver which, apart from causing damage to this organ, may escape to cause injury to extra hepatic tissues such as the lungs, heart, and kidneys. Fig: Pyrrolizidine Alkaloids

14. 9) Consumption of cycad plants by cattle may cause a neurotoxicity characterized mainly by a posterior sensory ataxia. کنگھی پام Fig: Cycad plant 10) Many legumes contain phyto-oestrogens , notably isoflavones . Consumption of these compounds at high levels by sheep can cause extensive lesions of the genitalia of females and castrated males.

15. Higher plants, Higher plants, also known as vascular plants, is a large group of plants that have vascular tissues (with veins) to distribute resources through the plant .

16. HIGHER PLANT TOXINS Essential oils Tropene Phenly propanes Monoterpenes Plant acids Glycosides Alkaloids

17. TOXICITY OF ESSENTIAL OILS TERPENE: Cineol Botanical source : Eucalyptus glublus Family : Myrtaceae Part used : Leaves Toxicity: Systemic toxicity can result from ingestion or topical application at higher than recommended doses. The probable lethal dose of pure eucalyptus oil for an adult is in the range of 0.05 mL to 0.5 mL/per kg of body weight. Severe poisoning has occurred in children after ingestion of 4 mL to 5 mL of eucalyptus oil.

18. 2: Pine oil Botanical source : Pinus sylvestris Part used: Seed Family: Pinaceae Chemical composition: The main chemical constituents of pine oil are borneol, bornyl acetate and b- phallandrene , alpha and beta - pinene and 3-carene. Toxicity: Pine oil has a relatively low human toxicity level, however, it irritates the skin and mucous membranes and has been known to cause breathing problems. Large doses may cause central nervous system depression. MONOTERPENES : 1: Thujone Botanical source : Artemisia absinthium Family: Asteraceae Part used: Leaf & flowering top constituents Borneol Bornyl acetate

19. Chemical constituents: The hydro distilled essential oil of the aerial parts mainly contain caryophyllene oxide , p-cymene,1,8-cineole and (Z)- lanceol acetate . Toxicity: Thujone is reported to be toxic to brain, kidney, and liver cells and could cause convulsions if used in too high dose. In extreme quantities, thujone is toxic and may cause hyperactivity, excitability, delirium, seizures or worse II Menthafuran Botanical source : Mentha pulegium Family: Lamiaceae Common name: Pennyroyal Part used : Leaves Common name : Pennyroyal Toxicity : Menthofuran is an organic compound found in a variety of essential oils including that of Pennyroyal. It is highly toxic and believed to be the primary toxin in Pennyroyal responsible for its potentially fatal effect. After ingestion of menthafuran,it is metabolically activated to chemically reactive intermediates that are hepatotoxic P- cyamine Menthafura n

20. PHENYL PROPANE: i: Apiol Botanical source : Petrosileum hortense Family : Apiaceae Part used: Leaves Toxic effects: The toxic dose is difficult to define, because it depends on the mode of preparation and on the association with other substances that can enhance the toxicity of the product. But the facts that patient ingests an exceedingly large dose of the drug in a short period of time may help to enhance the severity of the symptoms. Patients show a bleeding tendency associated to thrombocytopenia and an anemia, hematuria, Fatty liver and necrosis and demyelination of peripheral nerves. All the cases reported would tend to show that the process is limited to the peripheral nerves and there is no involvement of the CNS.

21. Ii : Safrol Botanical source : Pimpinella anisum Family : Umbelliferae Part used: Root bark or fruit Toxic effects: Following the ingestion of sassafras oil symptoms can include vomiting, vertigo and pallor which can appear within 10 to 90 minutes. Excessive consumption of tea prepared from the roots of the shrub sassafras has produced sweating. It was also used as a tea. But sassafras tea contains a lot of safrole , the chemical in sassafras that makes it poisonous. One cup of tea made with 2.5 grams of sassafras contains about 200 mg of safrole . That equates to a dose of about 3 mg of safrole per 1 kg of body weight. This is about 4.5 times the dose that researchers think is poisonous. So, in 1976, the US Food and Drug Administration (FDA) ruled that sassafras could no longer be sold as sassafras tea. Safrol vertigo

22. Iii: Myristicin Myristicin is found in spices and herbs such as nutmeg, black pepper, carrot, parsley Nutmeg abuse : As narcotic. tachycardia, salivation CNS excitation PLANT ACIDS : 1: Oxalic acid: The term "oxalic acid" is formed from the Latin word oxalis, which refers to plants with leaves similar to clover. It is important to note that the leaves of a plant almost always contain higher oxalate levels than the roots, stems, and stalks. Fruits - blackberries, blueberries, strawberries, kiwifruit, Oxalic acid concord (purple) grapes, figs, tangerines and plums Vegetables - spinach, Swiss chard, beets (root part), beet greens (leaf part), parsley, leeks and quinoa are among the most oxalate-dense vegetables. Nuts and seeds - almonds

23. Toxicity :It has been reported that the lethal oral dose is 15 to 30 grams. toxicity of oxalic acid is due to kidney failure caused by precipitation of solid calcium oxalate, the main component of kidney stones. Oxalic acid can also cause joint pain due to the formation of similar precipitates in the joint , there is a possible risk of congenital malformation in the fetus; may be harmful if inhaled, and is extremely destructive to tissue of mucous membranes and upper respiratory tract; harmful if swallowed; harmful to and destructive to tissue and causes burns if absorbed through skin or is in contact with the eyes Oxalic acid

24. PLANT ACIDS 2: Amino acids : Proteins are polymerized residues of amino acids The number and proportion of AA vary from protein to protein When proteins are denatured , the AA remain To study protein, you must study AA At least 30 different AA, some essential others non-essential Most AA are made using short-chain fatty acids (FA; such as acetic, proprionic or butyric acid) Naturally-occurring have L-configuration Synthetic have large proportion of D configurations

25. “ D” vs. “L” Configuration Aromatic Amino Acids Aliphatic Amino acid

26. Amino acid Quality: Amino acids divided into two groups: Essential Non-Essential AMINO ACID TOXICITY: Toxicity/antagonisms are result of dietary imbalances in EAA when one EAA is fed in excess it can also increase the requirement for another, structurally-similar EAA Toxicity overfeeding of one EAA and negative effects not mitigated by increasing other EAA Gastrointestinal distress, such as bloating Abdominal pain Diarrhea Increased risk of gout (build up of uric acid in the body, leading to joint inflammation) Unhealthy drop in blood pressure Changes in eating patterns Need for your kidneys to work harder to maintain balance ESSENTIAL AMINO ACID lysine (LYS) arginine (ARG) methionine (MET) histidine (HIS) isoleucine (ILE) leucine (LEU) threonine (THR) tryptophan (TRY) phenylalanine (PHE) valine (VAL)

27. Amino acid Antagonism 3: Resin acid Resin acid refers to mixtures of several related carboxylic acids, primarily  abietic -type acid and pimaric -type acids Toxicity : It can cause : Carcinogenicity, Reproductive developmental toxicity, Neurotoxicity, Contact dermatitis, Eye irritation Nose irritation Throat irritation Asthma Changes in lung function. Pimeric acid

28. GLYCOSIDES 1: Cardiotonic glycosides: Agents that have a strengthening effect on the heart or that can increase cardiac output. Biological source: Digitalis purpuea TOXICITY: An irregular heartbeat that causes dizziness, feeling that the heart has skipped a beat, shortness of breath, sweating or fainting. Hallucinations, confusion and mental changes like depression. Trouble with eyesight, such as blurry eye sight, double vision, seeing yellow, green or white halos around objects. A loss of appetite or an upset stomach. It frequently causes vomiting, anorexia and diarrhea . Digitalis pupurea

29. 2: Cyanogenic glycosides: Cyanogenic glycosides serve as important chemical weapons in the defence of the plant against herbivores because of the potential to generate toxic hydrogen cyanide Amygdalin is the most common of the cyanogenic glycosides Present in abundance in the seeds and kernels of fruits such as apricot, almond, apple, cherry, plum, peach and nectarine Toxicity : Occur in humans at doses between 0.5- 3.5 mg kg-1 body weight . When cyanogenic plants are ingested by humans, enzymes produced by the intestinal microflora are able to hydrolyse intact cyanogenic glycoside to produce hydrogen cyanide in vivo. Symptoms : Headache, nausea, vomiting, abdominal pain, dizziness, weakness, mental confusion, convulsions, cardiac arrest, circulatory and respiratory failure, coma and in extreme cases death

30. ALKALOIDS Alkaloids form the most important group of vegetable base. These are complex heterocyclic nitrogenous compounds having a basic nature and are mostly tertiary amines. These have profound physiological action and in many cases are of intense poisonous nature. These plants contain bitter taste and sufficient protection from being eaten by cattle. Some of the poisonous alkaloids are— aconitine from aconite root, morphine from poppy capsules, emetine from ipecachuanha root, strychnine from nux vomica seeds, nicotine from tobacco leaves, curarine from curare, etc 1: Imidazole Biological source : Jaborandi leaves ( Pilocarpus microphyllus and P. jaborandi) Toxicity high level of amino transferase enzyme and hepatocellular toxicity Renal toxicity Eye toxicity by damaging cornea and retina. Imidazole alkaloid

31. 2: Pyrrolizidine Biological source: Senecio and Crotalaria spp Pyrrolizidine alkaloids are among the most significant plant chemicals causing disease in animals and humans. After absorption from the gut, the compounds are converted to electrophilic pyrroles in the liver which, apart from causing damage to this organ, may escape to cause injury to extrahepatic tissues such as the lungs, heart, and kidneys Senecio vulgaris Crotalaria jucea

32. 3: Tropane: Biological source : Datura stramonium , Atropa belladonna Toxicity : The toxicity (anticholinergic effects) of  Solanaceae  plants can be attributed to their tropane alkaloids content and profile (i.e., the relative amount of atropine, hyoscyamine , and scopolamine), which can differ greatly between species, geographical regions, and harvesting stages . All parts of the plants are toxic, including the flowers, seeds (fruits), leaves, and stems. Tropane alkaloids compete with acetylcholine for binding sites on the muscarinic receptors, producing both peripheral (e.g., dilated pupils, blurred vision, hyperthermia, dry mouth, dry flushed skin, tachycardia, reduced bowel motility, and urinary retention) and central (e.g., hallucinations, delirium, drowsiness, amnesia, ataxia, seizures, and coma) effects. Their toxicity is dose-dependent, with more profound effects as the dose increases. Tropane skeleton Flushed skin