After reading this essay we will discuss about:- 1. History of Medicinal Plants 2. Source of Active Principles 3. Plant Drug with Proven Pharmacological and Therapeutic Efficacy 4. Autonomic Indigenous Drugs 5. Anthelmintics of Herbal Origin 6. Anti-Microbial Agent 7. Plants Possessing Unique Pharmacological Actions.
Essay # History of Medicinal Plants:
The use of medicinal plants for the prevention and treatment of various diseases is an age-old practice. The first written record regarding the use of medicinal plants appeared from Sumerian and Babylonian physicians around 3000 BC. The Chinese herbal Materia medica Pen-Tsao having been compiled during the region of Emperor Shen-Nung (2.735-2700 BC).
The Ebers papyrus (1500 BC) mentioned several herbs used by the ancient Egyptians. The ancient Hindu literature, the Rig-Veda (3000-2500 BC), recommended the medicinal values of herbs. Ayurveda, the traditional system of Indian medicine, described herbal remedies for various ailments.
The Ayurveda is a sub-section of the Atharva Veda. The Susruta Samhita was written during 1000 BC and contains a comprehensive chapter on herbal therapeutics. Charak Smhita, written about the same period, gives a remarkable description of the materia medica as it was known to ancient Hindus. Later during the Buddhist period, considerable progress was made and medicinal plants were cultivated under the direction of highly qualified specialists.
Essay # Source of Active Principles:
The medicinal values or active principle of plants reside in different parts of a plant Viz. seeds, roots, stems, flowers, leaves, rhizomes, barks and bulbs.
The pharmacologically active principles obtained from plants are as follows:
A. Alkaloids:
These are basic nitrogenous compounds which are insoluble in water but soluble in alcohol and some other organic solvents. Oxygen containing alkaloids (atropine, morphine etc.) exist as solid, while that devoid of oxygen molecule (nicotine) exist in liquid form.
Alkaloids are obtained from different parts of plants like:
Seeds-physostigmine, arecoline
fruits-conine
leaves-cocaine
roots-atropine
barks-quinine
rhizomes-emetine
These are having immense pharmacological activity.
B. Glycosides:
These are sugar ethers. The compounds contain at-least one sugar (glycone) and one non-sugar (aglycone) moiety, linked with ether linkage. These are soluble in alcohol but not in water. Medicinal properties of glycosides reside in their aglycone part. The sugar moiety influences their solubility and tissue permeability.
Examples:
Digitalis-used as cardio-stimulant
Aloe compounds-used as cathartic and vulnerary agent.
C. Saponines:
These are sub-class of glycoside and yield both sugar and non- sugar upon hydrolysis. They produce foam when shaken with water.
Examples:
Glycyrrhiza glabra contains glycyrrhizine that possesses demulscent and expectorant properties. This is also used to treat dermatological inflammations, peptic ulcer and Addison’s disease (chronic adrenocortical insufficiency). Saponins obtained from Panex ginseng are widely used as revitalizers.
There are some other pharmacologically active sub-classes of glycosides, like-
Flavones:
Their aglycone part is called flavonoids e.g. Ginkolide from Ginko biloba (a potent platelet activating factor antagonist) Rutin from Ruta graveolens (used to arrest capillary bleeding).
Lactones:
The examples are coumarin (anti-coagulant), cantharidine (counter irritant), santonine (anthelmintic) etc.
Phenols:
Aglycone are phenolic in nature: example-Uva ursi (bearberry).
D. Tanins:
Chemically these are mixture of polyphenols. They are having astringent action on mucosa by virtue of their protein precipitating effect. These are used as anti-diarrhoeal (catechu), topical astringent (tannic acid).
E. Resins:
These are amorphous solids that are fused readily when heated. Example-Jalap obtained from the root of Exogonium purga is used as a strong cathartic, eriodictyol obtained from Eriodictyon californicum is used to disguise the bitterness of certain preparations like quinine.
F. Oils:
These are of two types:
Fixed oil:
These are mixture of long chain fatty acids of glycerol. These are mainly of nutritional/food value. The fruits of Olea europea yield olive oil which is used as soothing emolient in skin preparations. It has also mild laxative effect.
Volatile oil:
These are odorous principles found in various plant parts. They evaporate when exposed to ordinary temperature. They are also called essential oil as they represent essence or odoriferous constituents of the plants.
Examples:
Peppermint oil form Mentha piperita and cinnamon oil from Cinnamomun zeylanicum are used as carminative and flavouring agent. Camphor obtained from Cinnamornus camphora is used as topical antipruritic, rubifacient and anti-infective. Clove oil from Eugenia carryophyllus, is used as dental analgesic, Eucalyptus oil is used as antiseptic, diaphoretic and expectorant.
G. Gums:
These are plant hydrocolloids, classified as anionic or non-ionic polysaccharide or salts of polysaccharides. These are translucent, amorphous substances. Example-Tragacanth, acacia etc. These are used as pharmaceutical vehicles in skin preparations.
Essay # Plant Drug with Proven Pharmacological and Therapeutic Efficacy:
i. Anti-Inflammatory:
The active principle isolated from willow bark salicin is metabolised to salicylic acid which is having other pharmacological actions like uricosuric and anti-platelet activity is still one of the most widely used analgesic and anti-inflammatory agent. Other important plant products of this group are-curcumin from Curcuma longa, berberine from Berberis aristata, cedrus deodara, root oil of Cyperus spp. etc.
They all possess significant anti-inflammatory activity. Curcumin has been reported to inhibit activated proteases responsible for acute inflammatory process. A compound derived from the rhizomes of ginger has been shown to inhibit prostaglandin synthesis, even better than indomethacin.
ii. Anti-Ulcerogenic:
The most potent in this group is Musa paradisica. It possess PGI2 like action on gastric mucosa. Curcuma longa and Brassica oleracia have anti-ulcerogenic action by virtue of their mucus secreting effect on stomach mucosae. Glycyrrhiza glabra enhances the muscosal barrier to diffusion of acid and thereby produces anti-ulcerogenic effect.
iii. Purgative:
Castor oil obtained from Ricinus cumunis seed, emodin alkaloid from Aloe berbadensis, isapgul (Plantago ovata) husk, Jalap obtained from Exogonum purga are very common and potent purgative.
iv. Diuretic:
Xanthine containing plants (Camelia sinensis), Borrhavia diffusa, Dolichos biflorus etc. possess profound diuretic effect.
v. Anti-Urolithiatic:
Lupeol derivatives obtained form Crateva nurvala and leaf- extract of Didymocarpus pedicellate have reported to possess excellent urinary stone dissolving action.
vi. Galactagogue:
Leptadenia reticulata has significant lactogenic property, while Nigella sativa and Cuminum cyminum are potent galactopoietic herbs. On the other hand Jasminum multiflorum flowers suppress milk production and lead to involution of mammary glands.
vii. Cardio Tonic:
Digitalis purpurea and D.lanata are still the most potent cardio-stimulants. They act through inhibition of Na-K ATPase. Bark of Terminalia arjuna possesses powerful cardio- stimulant action.
viii. Hypotensive Agents:
The anti-hypertensive action of reserpine, an alkaloid from Rawulfia serpentina, is based on its ability to deplete noradrenaline stores from peripheral adrenergic nerves. The veratrum alkaloids lowers blood pressure by eliciting a depressor reflex. They stimulate vagal sensory nerve ending in the carotid sinus and heart, which in turn diminishes tonic impulses from the vasomotor centre in the brain leading to reduced blood pressure.
Claviceps purpurea yields an alkaloid, di-hydro-ergotamine which has alpha-adrenoceptor blocking activity. Its main effect is to induce relaxation of precapillary arterioles. It also causes a central reduction of sympathetic tone.
ix. Expectorant:
A large number of herbs produce expectoration. Vasicine of Adhatoda vasica, glycyrrhizic acid of Glycyrrhiza glabra are under this class. Emetin of Ipecac acts as nauseant expectorant while, comphorated tincture of opium acts as an anodyne expectorant. Vapour of Eucalyptus oil is used to combat affection of respiratory passage.
x. Emetics and Anti-Emetics:
Mustard Seeds and Ipecac are potent emetic. Emetin, an alkaloid of Ipecac acts both centrally and peripherally, Belladona alkaloid (hyoscine) and ginger are effective anti-emetic.
xi. Anti-Diarrhoeals:
Seeds of Holarrhena antidysentrica has shown promising activity against amoebic dysentery. Catechu is widely used as intestinal astringent. Spasmolytic action of morphine restricts bowel movement and acts as a strong anti-diarrhoeal.
xii. Appetizer and Digestive Tonic:
Vegetable bitters are used to promote appetite of farm animals. Trachyspermum ammi (Ajowan) and ginger are important constituents of appetizer mixture. They are used to promote the activity of various digestive enzymes.
xiii. Carminative/Anti-Bloat:
Ginger, ajwan, capsicum, peppermint oil, anise oil, eucalyptus oil, linseed oil etc. are used in different carminative formulations.
xiv. Hepato-Protective Agents:
There is a long list of hepato-protective plants: Andrographis paniculata, Picrorrhiza kurroa, silybum marianum, Eclipta alba, Phyllanthus niruri, Tephrosia purpurea etc. have shown definite hepato- stimulant actions against various pathological conditions in experimental and clinical hepatitis, viral hepatitis and related conditions.
xv. Hypolipidaemic Agents:
Guggul sterone (active principle of Comiphora mukul) is a very potent hypolipidaemic agent. It lowers total and LDL cholesterol and increase HDL cholesterol level of blood. Another example of this group is Allium sativum. Na-curcuminate obtained from Curcuma longa acts as cholagogue and cholera etic and helps in secretion and flow of bile. Anti atherogenic action of Terminalia arjuna is widely reported.
xvi. Hypoglycaemic Agents:
These are used to treat Diabetes mellitus. The fresh juice of Momordica charantia promotes peripheral utilization of glucose. It potentiates the action of tolbutamide. Peripheral utilization of glucose is also improved by Casearia esculenta. The seeds of Eugenia jambolina and Trigonella foenum-graecum exert strong anti-hyperglycaemic response.
Epicatechnic obtained from Pterocarpus marsupium reduces blood sugar, hampers glucose absorption from gut and promotes regeneration of the β- cell of pancreatic islets. The sap of banyan (Ficus bengalensis) showed pancreatotropic effect. Gymnemic acid from Gymnea sylvestra have reported to exert beneficial effect against maturity onset diabetes.
xvii. Anti Fertility and Abortifacient:
There are a series of herbs reported to produce anti-fertility and abortifacient activity in ayurvedic literature. Vasicine holds the promise of an ideal abortifacient by acting through the promotion of synthesis and or release of prostaglandins.
It is effective in parenteral route only. Vasicine when given orally is converted to oxidative products vasicinone and deoxyvasicine and does not produce any oxytocic effect. Ergot alkaloids are used as abortifacient and uterotonic agent.
Powerful spermicidal activity was noted in Na-nimbidate and Na- nimbinate derived from Azadirachta indica(Neem). Gossypol, a phenolic compound from cotton seed oil, can produce near aspermia and hinder sperm motility. Extracts of Aristolochia indica, Vitex negundo, Randia dumertorium, impair development of fertilized ovum through anti-oestrogenic activity.
Albizzia lebbeck inhibits ovulation through central neurohumoral mechanism. Embelia ribes and Mentha avensis showed anti- implantation activity through their anti-prostaglandin activity. Centchroman, a research product of CDRI, now in the market, is derived from the rhizomes of Curcuma longa. It hampers reception of the fertilized ovum by endometrium.
xviii. Anti-Stress/Adaptogen:
These are used to cope against various stressors viz. social, climatic, nutritional, transportation, vaccination and handling (in case of poultry) etc. They preserve health rather than cure disease. Panex ginseng, Ginko biloba, Ocimum sanctum, Withania sominifera, Tinospora cordifolia, Emblica officinale etc. are under this group. They improve endurance against stress, increase non- specific resistance against infections and retard aging process.
xix. Plasma Volume Expanders:
These are frequently used to treat hypovolaemia and shock. Hydroxy ethyl starch (Hetastarch) with an average MW of 450000, a 6% solution has nearly the same colloidal osmotic pressure as human plasma. Fermentation of cane sugar yields glucose polymers called dextran.
Low mol. wt. dextran (MW 40,000) improves micro circulation by plasma volume expansion. High mol. wt. dextran (MW 70000 and 110000) at 6% concentration are used for plasma volume expansion and prevent post-operative thromboembolic disorders.
Drugs Affecting CNS Function:
(a) Cerebral Stimulant:
They have ability to induce wakefulness, mental alertness and increased motor activity; examples are-ephedrine from Ephedra sinica possesses action similar to sympathomimetic amine, xanthine containing plants like caffeine. It inhibits phosphodiesterase with consequent increase in tissue CAMP level.
(b) Brain Stem Stimulant:
This group is often referred to as respiratory stumulant or analeptics; examples are -camphor from Cinnamomum camphora, picrotoxin from Anamirta cocculas.
(c) Spinal Cord Stimulant:
They have the characteristic of producing tonic convulsion; alkaloids of Strychnos nux vomica (strychnine and brucine) causes spinal cord stimulation.
(d) Medullary Reflex Stimulants:
They stimulate medullary respiratory centre through the carotid sinus, e.g. nicotine from Nicotiana tabacum, lobeline from Lobelia inflata.
Narcotic Analgesics:
These are used as potent analgesic as well as sedatives and for relief of anxiety; e.g. morphine obtained from poppy seed (Papaver sominiferum).
Antidepressant:
Hypericin obtained from Hypericum perforatum leaves are potent inhibitor of MAO enzyme. Their antidepressant action has been explored and reported widely.
Antiparkinson Drug:
Mucuna prurience contains α-dopa, which is available to CNS at therapeutic concentrations and used to treat parkinson’s disease.
Essay # Autonomic Indigenous Drugs:
Cholinergic Agents:
(a) Muscarine:
It is an alkaloid from Amanita muscaria. Its curious effect was described as muscarinic effect. It stimulates postganglionic parasympathetic nerves. It has little therapeutic value.
(b) Pilocarpine:
It is a tertiary amine alkaloid compound isolated from Pilocarpus jaborandi. It produces strong postganglionic stimulation. The major use has been for the treatment of open or wide angle glaucoma to facilitate the drainage of aqueous humor from the anterior chamber of the eye via the canal of schlemn.
(c) Physostigmine:
It is an alkaloid obtained from the seed of calaber bean, Physostigma venenosum. It inhibits the enzyme acetylcholine esterase and thereby enhances the availability of acetylcholine to post ganglionic nerve endings.
Chloinergic Blocking Agents:
The alkaloids found in Atropa belladona, Datura stramonium, and Hyoscyamus niger (atropine, scopolamine and hyoscyamine) block post ganglionic receptors and prevent their access to acetylcholine. Atropine is widely used as anti-secretory and antispasmodic. It is also used to treat organophosphate poisoning in animals.
Ganglionic Blocking Agents:
Nicotine and lobeline obtained from Nicotiana tabacum and Lobelia inflata have been shown to paralyse autonomic ganglia and produce persistant depolarization.
Neuro-muscular blocking agent:
The classical example is curare or d-tubocurarine isolated from chondodendron tomentosum. It produces its paralytic effect by competing with and raising the threshold for acetylcholine at the myoneural receptors of the striated muscles.
Essay # Anthelmintics of Herbal Origin:
Herbal anthelmintics are used since long. Extracts of pumkin (cucurbita maxima) seeds were found to possess anti- trematodal action. The active component in this seed is cucurbitine. Kymographic studies revealed that it produces an excitatory response followed by inhibitory effect. Extract of the berries of Embelia ribes yields a quinone derivative, embelin which was found very effective in treatment of ascarides.
Aspidium oleoresin obtained from the powdered rhizome of the male fern (Dryopteris felix mas) yield filicic acid acts as a taeniafuge. It causes temporary relaxation of the worms. A purge is necessary to ensure passage of the worms.
(i) Palasonin, an active principle isolated from Butea frondosa, seeds exhibits good anthelmintic activity against ascarides.
(ii) The glands and fruits of Mallotus philippensis yield kamala, once considered the drug of choice for cat cestodes. It acts as a stimulant and then paralyses the cestodes.
(iii) Melia azedarach leaves extract shows significant anthelmintic activity against tapeworm and hookworm.
(iv) Earlier nicotine sulphate was used in combination with copper sulphate against ruminant tapeworms.
(v) Extract of Punica granatum possesses anthelmintic activity as revealed by dose-dependent inhibition of transformation of eggs to filariform larvae.
Arecoline is an alkaloid isolated from Areca catechu (betel nut palm) is still used as an anti-cestodal. The anti-cestodal action is appeared to be due to paralyzing effect on the worms. The worms get loosened from intestinal mucosa and expelled out with purgation produced by the cholinomimetic action of the same alkaloid.
Essay # Anti-Microbial Agent:
Berberine obtained from Berberis aristata and Hydrastis canadensis is a potent antiprotozoal agent and active against cholera toxin. It produces anti-secretory activity against cholera toxin induced secretion. An alkaloid conessine is isolated from the bark of Holarrhena antidysentrica which possesses powerful anti-amoebic action against Ent. histolytica.
Karanjin, the furano-flavonoid active principle of Pongamia pinnata, exerts strong anti-bacterial effect against both Gram positive and negative organisms, Alkaloids obtained from Curcuma longa and Azadirachta indica are very potent anti-bacterial agents. Hemidesmus indicus (leave) and Cassia fistula (stem) extracts inhibit the replication and cytopathic activity of Ranikhet disease virus and vaccinia virus.
Their anti-viral activity may be due to the presence of interferon like factor in these plants. Root extract of H. indicus show anti-bacterial activity against Staph. aureus, Staph, albus, Salmonella typhae, E. coli, shigella sp.
Oil of Ocimum sanctum, O. basilicum, O. gratissimum possess antifungal activity. Extract of O. sanctum leaves showed anti-bacterial activity. Euphorbia sp. inhibit the growth of pathogenic fungi.
Extracts of Annona squamosa seeds and alkaloids obtained from Azadirachta indica were found to be very potent insecticides. Other botanical insecticides are rotenoids, pyrethrum, nicotine etc. The tuber root of Derris elliptica yields rotenone, which is very effective against head lice, scabies and other ectoparasites. Pyrethrum is one of the oldest insecticides known and the active principle of the pyrethrum flowers are pyethrin- I and II and cinerin-I and II.
Essay # Antiseptic:
Oil obtained from Azadirachta indica and Allium sativum possess strong antiseptic property.
Essay # Anti-Cancer Agents:
Plants hold great promise of therapeutic property to fight cancer. Catharanthus roseus yields vinca alkaloids, vinblastine and vincristine which are powerful cytotoxic agents. They bind to tubulin proteins, inhibit mitotic spindle formation of dividing cells at metaphase. They are used to treat Hodgkin’s and non-Hodgkin’s lymphomas, lymphocytic leukaemia, neuroblastoma, rhabdomyo- sarcoma and carcinoma of breast, bladder and gonads.
Etoposide and teniposide, two glycosidic derivatives of Podophyllum peltatum shows anti-neoplastic activity against Hodgkin’s disease, bronchogenic carcinoma and testicular cancers.
Taxol is the most promising of newer anti-neoplastic agents with a broad spectrum of activity. It is isolated from the bark of Taxus brevifolia, T. baccata, T. cuspidata. It has shown to bind preferentially to malignant cell microtubules. Microtubule mediated interruption of mitosis is induced in cancer cells, the cell cycle being disrupted at the G2 or the M phase.
This has proved beneficial against ovarian, breast and lung carcinoma. Besides, the beneficial effect of taxol have been reported against malignant melanoma, squamous cell carcinoma, Hodgkin’s disease, colonic cancer, leucocytic and myelocytic leukaemias etc.
Homoharringtonine is obtained from the bark of Caphalotaxus harringtonia. This cytotoxic alkaloid inhibits protein synthesis by detaching the ribosomes from endoplasmic reticulum. The effect is cell cycle specific, the time of interference being G1 phase. It has been shown to be effective against acute myeloid leukaemia.
Campothecin is isolated from Campotheca acuminata. It interferes with microtubule function, mitosis and DNA synthesis in malignant cells. It is effective against colorectal adenocarcinoma, malignant melanoma and pulmonary adenocarcinoma.
Other plant principles which are in various stages of clinical trials include:
Dimeric benzylisoquinoline alkaloids from Cyclea peltata and Thalictrum species benzophenanthridine from Zanthoxylum nitidum and Fagara macrophylla ; triptolides isolated from Tripterygium wilfordi, etc.
Essay # Plants Possessing Unique Pharmacological Actions:
A. Forskolin isolated from Coelus forskohli is an exogenous stimulator of cAMP synthesis. It is having immense experimental importance.
B. Piperine (1-piperonyl piperidine) is a major alkaloid isolated from Piper species. It has been reported to enhance the bio-availability of different drugs and xenobiotics. Piperine inhibits a number of hepatic and extra-hepatic drug metabolising enzyme reactions: viz. aryl hydrocarbon hydroxylation, de-methylation and 7-ethoxy coumarine-o-dethylation along with UDP- glucuronyl transferase activity.
C. Ginger increases the bio-availability of drugs by promoting their absorption and protecting their destruction as they pass through the liver.