ALKALOIDS PHARMACOGNOSY NOTES

AKALOIDS

Ø  An alkaloid is a nitrogenous organic molecule that has a pharmacological effect on humans and animals.

Ø  First synthesized alkaloid was connine.

Ø  The term alkaloids are given by MEISSNER.

Ø  A class of compounds which typically contain nitrogen and have complex ring structures.

Ø  Alkaloids are found as secondary metabolites in plants (e.g.in Vinca and

 Datura ),animals (e.g. in shellfish) and fungi.

Ø  alkaloids are derivatives from amino acids

Ø  many alkaloids are poisonous (e.g. strychnine or coniine)

Ø  some are used in medicine as analgesics (pain relievers) or anaesthetics, particularly morphine and codeine.

Ø  Most alkaloids have a very bitter taste.

Ø  Alkaloids defined as those derived from plants source, basic in nature, containing one or more nitrogen atom and they usually have a marked physiological action.

CLASSIFICATION OF ALKALOIDS

·         TRUE ALKALOIDS  - Nitrogen founds in the hetrocyclic ring and originates from amino acids.

·         PROTO – ALKALOIDS  - These are also called amino alkaloids , these are the compounds that lack one or more of the properties of typical alkaloids . Mainly nitrogen not found in the ring system. E.g. Hordenine , ephedrine , colchicines .

·         PSEUDO-ALKALOIDS – Do not originate from amino acids. E.g. Purine alkaloid – coffee

PROPERTIES OF ALKALOIDS

·         They are usually secondary metabolites.

·         These are usually crystalline in nature and exist as salts or as X-oxides in plants exception in of coniine from hemlock and nicotine from tobacco which are liquids.

·         With respect to the elemental composition, theses contain C, H, N and O. Exception is of coniine from hemlock and nicotine from tobacco which are oxygen free.

·         They are usually colourless . Exception is of betadine ( red ) , tylophorine and berberine ( yellow ) and salts of sanguinarine ( copper red in colour ).

·         The isolation procedure of alkaloids from plants is on the basis of difference in solubility of alkaloids and  its salts.

·         Alkaloids bases are sparingly soluble in water where as its salts have greater solubility in water. Exception is caffeine which has ready solubility in water and colchicines being soluble at all conditions of pH in water.

·         Liquid alkaloids are connine, quinine and nicotine.

CHEMICAL PROPERTIES OF ALKALOIDS

·         Basic in nature and ther have similar properties similar to ammonia.

·         ALKALOIDS     +        Aq. Mineral acids ( HCL )       =     SALTS

           SALTS        +        OH         =         FREE AMINE FOR IS LIBRATE

·         Nitrogen  can be usually present in primary, secondary, tertiary, and quartonary amines.

·         Alkaloids form double salts with compound such as platinum, gold and heavy metals.

·         Optically inactive but exception are atropine ( recimic mixture ) and papaverine.

CHEMICAL TESTS OF ALKALOIDS

The chemical tests are performed from neutral or slightly acidic solution of drug.

Dragendorff’s Test

Drug solution + Dragendroff ’s reagent (Potassium Bismuth Iodide), formation of Orangish red colour.

Mayer’s Test

Drug solution + few drops of Mayer’s reagent (potassium mercuric iodide), formation of creamy-white precipitant.

Hager’s Test

Drug solution + few drops of Hagers reagent (Saturated aq. Solution of Picric acid), formation of crystalline yellow precipitate.

Wagner’s Test

Drug solution + few drops of Wagner’s reagent (dilute Iodine solution), formulation of reddish-brown precipitate.

Tannic Acid Test

Drug solution + few drops of tannic acid solution, formation of buff coloured precipitate.

Ammonia Reineckate Test

Drug solution + slightly acidified (HCl) saturated solution of ammonia reineckate, formation of pink flocculent precipitate.

* PELLETRINE  -  Derived from the name of discoverer of alkaloid and obtain from pomegranate

1) PYRIDINE­­ – PIPERIDINE

·         Pyridine, also called azabenzene and azine.

·         It is a heterocyclic aromatic tertiary amine characterized by a six-membered ring structure composed of five carbon atoms and nitrogen which replace one carbon–hydrogen unit in the benzene ring (C5H5N).

·         It is colourless, flammable, toxic liquid with unpleasant odor, miscible with water and with most organic solvents, boils at 115°C.

·         Its aqueous solution is slightly alkaline.

·         Pyridine is a base with chemical properties similar to tertiary amines.

·         Piperidine derivative compounds are used as intermediate to make crystal derivative of aromatic nitrogen compounds containing nuclear atoms.

·         They are used in manufacturing pharmaceuticals.

TOBACCO

Synonyms

Tobacco, Tabaci Folia.

Biological Source

It consists of dried leaves of Nicotiana tobaccum, belonging to family Solanaceae.

Geographical Source

It is mainly found in India, United States, China, Brazil, Russia, Turkey and Italy.

Cultivation and Collection

·         Cultivation is done by sowing seeds.

·         Warm climate and well drained fertile land is required for good growth.

·         Transplantation is done when the seedlings are 12 weeks old.

·         Flowering tops are cut in order to enhance growth of foliage.

·         After 70–90 days of transplantation leaves are collected.

Characteristics

Colour - Green or slightly brown

Odour - Characteristic to Nicotine

Taste - Bitter

Shape - Ovate, elliptic or lanceolate

Size - 60–80 cm in length 35–45 cm in width

Chemical Constituents

·         The most important constituent is the alkaloids nicotine, nicotianin, nicotinine, nicoteine, nicoteline.

·         After leaves are smoked the nicotine decomposes into pyridine, furfurol, collidine, hydrocyanic acid, carbon monoxide, etc.

·         Thepoisonous effects of Tobacco smoke are due to these substances of decomposed nicotine.

Uses

·         Nicotine is very like coniine and lobeline in its pharmacological action, and the pyridines in the smoke modify very slightly its action.

·         It is used as a sedative, diuretic,expectorant, discutient and sialagogue.

·         The leaves in combination with the leaves of belladonna or stramonium make an excellent application for obstinate ulcers, painful tremors and spasmodic affections.

·         Tobacco leaves are made wet and applied for piles.

·         Externally nicotine is an antiseptic.

·         Nicotine exerts stimulant effects on heart and nervous system.

ARECA

Synonyms

Betal nuts; Pinang; Semina Areacae, Supari (Hindi).

Biological Source

Areca nuts are the seeds of Areca catechu Linn., belongingto family Palmaceae.

Geographical Source

·         The tree is cultivated in tropical India, Sri Lanka, Malay States, South China, East Indies, Philippine Islands and parts of East Africa (including Zanzibar and Tanzania).

·         In India it is cultivated in the coastal regions of southern Maharashtra,Tamil Nadu, Karnataka, Bengal and Assam.

Cultivation and Collection

·         Areca palm is mostly propagated by seeds.

·         The palm requires a moist tropical climate for luxuriant growth; it is very sensitive to drought.

·         It grows in areas with heavy rainfall in between temperature of 15–38°C.

·         It is cultivated in plains, hill slopes and low lying valleys.

·         The seeds are collected from 25–50 years old trees.

·         Each tree contains about 100 fruits per year which are detached by means of bamboo poles and the seeds extracted.

·         The pericarp is fibrous and surrounds a single seed which is easily separated.

·         The seeds are usually boiled in water with the addition of a little lime and dried.

Chemical Constituents

·         Areca nut contains a number of alkaloids of a piperidine series, such as arecoline (methyl ester of arecanine), arecaine (N-methyl guvacine), guvacine (tetrahydronicitinic acid), arecaidine, guvacoline, arecolidine, leucocyanidine,(+)-catechin, phthalic, lauric, myristic, palmitic and stearic acids, sitosterol and choline.

·         Arecoline is present in about 0.1–0.5% yield and is medicinally important. In addition to alkaloids, areca nuts contain fat (14%) and amorphous red tannin (15%) known as areca red of phlobaphene nature.

·         The fat consists mainly of the glycerides of lauric, myristic and oleic acids.

Uses

·         Powdered Areca is used as anthelmintic, taenifuge and vermifuge for dogs.

·         It has aphrodisiac action and useful in urinary disorders, as nervine tonic and emmenagogue.

·         The chewing of Areca nut may cause mouth cancer.

Substituents and Adulterants

Nuts from other plants, such as, Areca caliso, A. concinna, A. ipot, A. laxa, A. nagensis, A. triandra, Caryota cumingii and Heterospathe elata are used as substituents for Areca nuts.

Sago palm nuts (Metroxylon species), dried tapioca (Manihot esculenta), and slices of sweet potato (Ipomoea batatas) form cheap adulterants that are mixed with slices of Areca nuts and prove a serious menace affecting the industry.

Nuts of Caryota urens, cut to various shapes and sizes resembling genuine Areca nuts, and coated with concentrated Areca nut extract kali, form the principal adulterant. Adulteration above 10% significantly increases the fibre content of the sample, which can be used as a measure of detecting

Adulteration.

Marketed Products

It is one of the ingredients of the preparations known as Himplasia (Himalaya Drug Company), Khadiradi bati and Pigmento.

2) TROPANE

·         The tropane alkaloids, which have the 8-azabicyclo octane nucleus, are commonly found in plants of three families, the Solanaceae, Erythroxylaceae and Convolvulaceae families.

·         They are esters combined with acids. These esters of tropic acid could be detected by vitalimorin reaction. Other organic acids like tiglic acid, acetic acid,isobutyric acid and isovaleric acid are also present.

·         Ornithine is the precursor for biosynthesis of tropane.

·         These are found as the salts of tropic acid which gives vitali morin reaction.

           

TROPANE IS A FUSSION OF TWO RINGS ARE PYRROLIDINR AND PIPERIDINE.

TROPIC ACID             +                TROPINE

                                                ( TROPINE DERIVED FROM FENYL ANILINE ACID )

                                         

              

                        L – hyoscyamine  ( Scopoline )

              ( ester of tropane and tropic acid )

 

                           Its resimmic mixture is ATROPINE

·         If there is epoxide linkage then it is hyoscine.

                                        

                                                 Hyoscine   ( Scopokmine )

BELLADONNA

Synonyms

Belladonna herb; Belladonna leaf; Deadly night shade leaves; Banewort; Death’s herb, Dwale; Poison black cherry; Folia belladonnae.

Biological Source

Belladonna consists of dried leaves and flowering tops of Atropa belladonna Linn. (European Belladonna), Atropa Acuminata  ( Indian ) , belonging to family Solanaceae.

It contains about 0.35% of total alkaloids calculated as hyoscyamine.

Geographical Source

A. belladonna is cultivated in United States, Canada, UK, Germany and India.

Cultivation and Collection

·         Plants are cultivated by sowing seeds in nurseries and seedlings are transplanted in April to moist, calcareous and loamy soil.

·         Weeds are removed and manure is applied for proper growth of the crop.

·         During flowering session leaves and flowering tops are cut at least three times in a year at an interval of two months from one to three years old plants.

·         When the plant is four years old, roots are dug out. The collected drug is dried at 40–50°C.

·         Un-dried leaves deteriorate and give off ammonia.

Macroscopical characters:

Leaves:

(i) Type- Simple;

(ii) Form-Broadly ovate;

(iii) Color- yellowish-green;

(iv) Arrangement – alternate, arranged in pairs on the upper stems, each pair with a large and a small leaf;

(v) Size- 5-25 cm length, 2, 5-12 cm broad;

(vi) Margin- acuminate;

(vii) Surface- slightly hairy; Petiolate, petiole 4cm length

Flower:

(i) Colour- purple;

(ii) Size- 2.5 cm length, 1.2 cm wide;;

(iii) Arrangement of flower- born singly upon short, drooping pedicels arising in

(iv) the axils of the pairs of leaves;

(v) Corolla- campanilate;

(vi) Calyx- 5 lobed, stemns-5, epipetalous;

(vii) Ovary- superior, bilocular with numerous ovules and axile Placentation

Fruits:

(i) Colour- green to dark purplish black,

(ii) Type- berry.

Microscopical characters of belladonna root:

 

Stomata =  Anisocytic ( mmajor ) and Anomocytic ( minor )

Periderm:

Periderm is distinguishable into Phellem and Phellodenn.

Cork:

Cork few layers, cells tangentially elongated and arranged in radial rows.

Phellogen:

Phellogen is not distinguishable through a faint layer can be made out.

Phelloderm:

Phelloderm few layers, cells tangentially elongated and contain starch and yellowish matter.

Secondary Phloem:

Several layers of starch bearing parenchyma with groups of sieve elements. Phloem fibres absent. Numerous sandy bails, a characteristics feature of belladonna root and leaf, are seen scattered throughout in the phloem tissue.

Cambium:

It is represented in the form of a ring containing 4 to 5 layers of rectangular cells arranged in radial rows.

Secondary xylem:

Secondary xylem forms the bulk of the root and occupied a large area. Secondary xylem consists of largely starch bearing parenchyma with several scattered groups of vessels (3 to 10), associated with tracheids, fibres and Cellulosic parenchyma. The groups of vessels are more towards the cambium. Primary xylem forming the central mass shows distinct diarch nature.

 

Chemical constituents:

1. Tropane alkaloids (0.2-0.5%):

i. L-hyoscyamine (90%),

ii.D, L- hyoscyamine(Atropine) . Atropine is not naturally present but occur during the extraction process.

·         Flouroscence substance Scopoletin present.

iii. Scopolamine (10%),

iv. Apoatropine,

Uses:

i. Mydriatic (dilation of the pupil).

ii. Antispasmodic (a drug that counteracts a sudden, violent, involuntary muscular contraction)

iii. Antimuscarinic effect (acts peripherally to produce parasympathetic inhibition).

iv. Antisialagogue (a drug that arrest the flow of excess of saliva)

v. Cerebral sedative (reduce excitement)

6. Use as antidotes in chlorohydrate and opiu poisioning.

Chemical Test:

 

Vitali Test:

A drop of fuming HNO₃ is added it a small portion of a extract of any Solanaceous drug like species of Atropa, Hyoscyamus and Datura or the Tropane alkaloids themselves and then evaporated to dryness on a water bath. Thereafter it is cooled and on addition of 2 drops of 5% alcoholic potassium hydroxide solution, purple colour is formed indicating the presence of Tropane alkaloids.

Substitute and adulterants:

Belladonna is compared along with two common adulterants.

DATURA

Synonyms – Angle’s trumphet , Indian strammonium

Botanical source:

It consists of dried leaves and flowering tops of Datura metal Linn. And Datura innoxia

Family:

Solanaceae

Geological source:

India

Macroscopical characters:

Datura metal:

Leaves:

(i) Sub glabrous spreading herb with cylindrical stem.

(ii) Shape single triangular ovate.

(iii) Base unequal

(iv) Margin toothed.

Flower:

(i) Solitary, funnel shaped large and tubular, 7.5 to 9 cm length.

(ii) Corolla 15 to 18 cm length, 10-12.5 cm across at the mouth.

Fruit:

Sub-globose capsule covered with short and blunt spines, 2.5 to 3.2 cm diameter nodding or sub erect.

Microscopical characters:

Lamina:

Upper epidermis:

They are single layered, cells rectangular with cuticularized outer walls. Trichomes, both covering and glandular are seen. Covering trichomes are uniseriate, multicellular, warty and blunt at the apex.

Mesophyll:

It is differentiated into palisade and spongy parenchyma.

Palisade:

It is a single layered, compact and cells radially elongated

Spongy parenchyma:

They are many layered, loosely arranged with intercellular spaces. Sphaeraphides, microsphenoidal crystals and vascular strands are found in the upper layers of spongy parenchyma.

Lower epidermis:

It is identical to upper epidermis. Stomata and numerous trichomes are seen on the lower epidermis.

Midrib:

The epidermis layers of lamina are continuous in the midrib region also. Strips of collenchymas appear below the upper and above the lower epidermis. This is followed by cortical parenchyma containing prisms of calcium oxalate and microsphenoidal crystals. Embedded in the central region of the cortical parenchyma is a bicollateral bundle.

Chemical constituents:

1. Tropane alkaloids-

a. Hyoscyamine

b. Scopolamine (hyoscine)

2. Fastudine and fastunine,

3. Fastusic acid, alantoin.

4. Ascorbic acid, etc.

 Uses:

1. Mydriatic (dilation of the pupil).

2. Antispasmodic (a drug that counteracts a sudden, violent, involuntary muscular contraction)

3. Antimuscarinic effect (acts peripherally to produce parasympathetic inhibition).

4. Antisialagogue (a drug that arrest the flow of excess of saliva)

5. Cerebral sedative (reduce excitement)

 Chemical Test:

1. Vitali- Morin reactions:

The drug is treated concentrated nitric acid, filtered and solution is evaporated to dryness. To the residue, add acetone and methanolic potassium hydroxide solution, violet colour is produced due to Tropane derivative.

 
WITHANIA

Synonyms

Withania root. Ashwagandha, Clustered Wintercherry.

Biological Source

It consists of the dried roots and stem bases of Withania somnifera  Dunal, belonging to family Solanaceae.

Geographical Source

Withania is widely distributed from southern Europe to India and Africa.

Cultivation and Collection

·         Withania somnifera are propagated by division, cuttings or seed.

·         Seed is the best way to propagate them.

·         Seed sown on moist sand will germinate in 14–21 days at 20°C.

·         Withania somnifera need full sun to partial shade with a well-drained slightly alkaline soil mix.

·         Plants do best when the soil Ph is 7.5–8.0.

·          Soil mix consisting of two parts sandy loam to one part sand will to better. The plants are allowed to dry thoroughly in between waterings.

Characteristics

·         A low lying plant, often reaching only 1–2 ft, but occasionally 6 ft.

·         It is a perennial, but can be grown as an annual.

·         Plant and fruits resemble its relatives the ground cherry and Chinese lantern.

·         Young roots are straight, unbranched and conical and in pieces of different lengths.

·         Root thickness varies according to age and usually it is 5–12 mm below crown.

·          Outer surface is buff to yellow and longitudinally wrinkled. Taste is bitter and mucilaginous.

Microscopy

·         Transverse section of root shows cork exfoliated or crushed; when present isodiamatric and nonlignified; cork cambium of two to four diffused rows of cells; secondary cortex about twenty layers of compact parenchymatous cells; phloem consists of sieve tubes, phloem parenchyma, companion cells, cambium shows four to five rows of tangentially

elongated cells; secondary xylem hard forming a closed vascular ring separated by multiseriate medullary rays and a few xylem parenchyma.

Chemical Constituents

·         The plants contain the alkaloid withanine as the main constituent and somniferine, pseudowithanine, tropine and pseudotropine, hygrine, isopellederine, anaferine,anahygrine and steroid lactones.

·         The leaves contain steroid lactone, commonly known as withanolides.

Uses

·         All plant parts are used including the roots, bark, leaves, fruit and seed are used to treat nervous disorders, intestinal infections and leprosy.

·         Ashwagandha is one of the most widespread tranquillizers used in India, where it holds a position of importance similar to ginseng in China.

·         It acts mainly on the reproductive and nervous systems, having a rejuvenative effect on the body, and is used to improve vitality and aid recovery after chronic illness.

·         It is also used to treat nervous exhaustion, debility, insomnia, wasting diseases, failure to thrive in children, impotence, infertility; multiple sclerosis, etc.

·         Externally it has been applied as a poultice to boils, swellings and other painful parts.

·         Withania is considered as an adaptogen and so is used in number of diseases.

·          

Marketed Products

·         It is one of the ingredients of the preparations known as Abana, Geriforte, Mentat, Mentat syrup, Reosto, Tentex forte, AntiStress Massage Oil, Nourishing Baby Oil, Nourishing Skin Cream, Anxocare, Galactin Vet, Geriforte Aqua, Geriforte Vet, Immunol, Speman forte Vet, Tentex forte Vet, Ashvagandha tablet (Himalaya Drug Company), Balarishta

·         (Baidyanath), Aswagandha tablet

QUINOLINE AND ISOQUINOLINE

·         Quinoline is a double carbon ring containing one nitrogen atom. The alkaloid quinine is toxic to Plasmodium vivax and three additional species, the onecelled organisms (protozoans) that cause malaria.

·         Isoquinoline is a double carbon ring containing one nitrogen atom.

·         Isoquinoline alkaloids are found in varying quantities in the prickly poppy, bloodroot and celandine poppy.

·         They also cause vasodilation. the isoquinolines have proven to be more poisonous to domestic livestock than to humans.

CINCHONA

Synonyms

Cortex Cinchonae, Countess, Peruvian or Jesuit’s bark , Cinchona

Biological Source

Cinchona is the dried bark of the stem or of the root of Cinchona calisaya  Wedd., Cinchona ledgeriana Moens.,  Cinchona officinalis Linn., and Cinchona succirubra Pavon., or hybrids of any of the first two species with any of the last two species,belonging to family Rubiaceae.

Geographical Source

Tropical valleys of the Andes. Bolivia and Southern Peru. Cinchona is a native of South America, occurring wild there. At present, it is mainly cultivated in Indonesia (Java),

Zaire, India, Guatemala, Bolivia, Ceylon etc.

Cultivation and Collection

·         Cinchona is propogated by seed sowing method.

·         The seeds with approximately 3 mm long and flat are picked and are used for cultivation.

·         The seeds are sown in boxes and the seedlings are transplanted to nurseries when they reach a height of 5 cm, the nurseries are covered by a roof so as to protect the seedlings from direct sunlight.

·         The seedlings grown in shade till they attain a height of about 25 cm and in between this period they are at least transplanted twice.The plant is allowed to grow till six years.

·         first crop is collected by coppicing, uprooting or by felling method.

·         The bark is collected till the plant is 9 years old because the alkaloid content in the bark decreases thereafter.

·         Rainy season is considered suitable for the collection of the bark. The trunks and the branches are beaten to loose the periderm and the bark is removed into small pieces of 45  cm long and 12 cm in width.

·         They are then dried under sun or by artificial heating by providing gentle heat.

·          During drying the barks attain quill shape and the colour changes to red or brownish red.

Characteristics

Colour - The outer surface is yellowish to brown, with short fractures and the inner surface varies in all the four species; like Cinchona calisaya and Cinchona ledgeriana is yellowish, Cinchona offi cinalis is slightly brown and Cinchona succimbra is reddish brown

Odour – Distinctive

Taste - Highly bitter and astringent.

Shape - Curved, quill or double quill.

Extra features - The outer surface consist of longitudinal and transverse cracks,       fissures, ridges

Microscopic Characters

·         Transverse section of bark shows cork composed of uniformly arranged several layers of thin-walled cells, containing amorphous reddish-brown matter.

·         Below cork is a redion of cortex, composed of tangentially elongated parenchymatous cells with red-brown and thin walls, containing small starch grains. Idioblasts, containing microcrystals of calcium oxalate (2–6 long), and secretion cells are scattered in the cortex.

·         Phloem consists of compressed and collapsed sieve tubes, phloem parenchyma similar to cortex, and irregularly arranged, large spindle-shaped lignified fibres. Medullary rays are narrow, two to three cells wide and almost straight.

·         Longitudinal section of bark shows brick-shaped cells of medullary rays, longitudinally elongated cells of phloem parenchyma, and fibres with conspicuous pits.

Chemical Constituents

·         More than 30 alkaloids have been reported in cinchona.

·         The chiefly identified alkaloids are quinidine ( 8R, 9S ) , quinine ( 8S, 9R ) , cinchonine and cinchonidine.

·         These constituents are the stereoisomers of each other like quinine is stereoisomer of quinidine and cinchonine is stereoisomer of cinchonidine.

·         The other constituents available are quiniarnine, cinchotine, hydroquinine, hydrocinchonidine, cinchotannic acid, etc.

·         Quinine and quinidine has a methoxy group in it but cinchonine and cinchonidine do not have a methoxy group.

·          Other than these it also consist of bitter glycoside, quinovin, starch grains, calcium oxalate crystals and crystalline acid like quinic acid.

·         Tannins  like  Phlobatannins

 

                                     Cinchotannic acid

 

                                                     Degradation

                                      Cinchona red

·         IN LEAVES        the indole alkaloids are present ( Cincophylline )

Chemical Test

1. Thalleioquin test: To the extract of cinchona powder add one drop of dilute sulphuric acid and 1 ml of water. Add bromine water drop wise till the solution acquires permanent

yellow colour and add 1 ml of dilute ammonia solution, emerald green colour is produced.

2. The powdered drug when heated with glacial acetic acid in dry test tube, evolves red fumes, which condense in the top portion of the tube.

3. Cinchona bark, when moistened with sulphuric acid and observed under ultraviolet light shows a blue fluorescence due to the methoxy group of Quinine and quinidine.

Uses

It is mainly employed as antimalarial drug, but it is also used as analgesic, antipyretic, protoplasmic, bitter stomachic and tonic. Quinidine is cardiac depressant and Cinchonidine is used in rheumatism and neuralgia.

Substitutes

Cuprea Bark (Remijia pedupiculato); Family: Rubiaceae, it differs in its morphological character with cinchona but consist of constituents like Quinine, quinidine, cinchonine, cinchonamine, etc., the other species of Remijia, that is, R. purdieana (false Cuprea bark) does not contain quinine.

Adultrant are R. Purdenia , in this the cusconidine present only.

Marketed Products

It is one of the ingredients of the preparations known as Herbipyrin tablet, M.P. 6 Capsules (Vasu Healthcare).

IPECAC

Synonyms

Ipecacuanha; Brazilian or Johore Ipecac; Hippo; Ipecacuanha root; Radix ipecacuanhae.

Biological Source

Ipecac consists of the dried root or rhizome of Cephaelis ipecacuanha (Brot.) A. Rich. (Rio or Brazilian Ipecac) or of Cephaelis acuminata  Karst. (Cartagena, Nicaragua or Panama Ipecac), belonging to family Rubiaceae.

It should contain about 2% of ether soluble alkaloids calculated as emetine.

Geographical Source

The plant is indigenous to Brazil and also found in Colombia, Cartagena, Nicaragua, Savantilla, Malaya, Burma, Panama and West Bengal. In India it is cultivated at Mungpoo (Darjeeling), in Nilgiris near Collar and in Sikkim.

Cultivation and Collection

·         The plant is a low, straggling shrub containing slender rhizome with annulated wiry roots.

·         The roots are smooth, slender and whitish when young, develop on maturation a thick brownish bark with numerous closely placed transverse furrows.

·         The plant is unusually slow growing. It thrives best in forest areas on sandy loams in humus, pot ash, magnesia and lime.

·         A maximum rainfall of 90 inch is required throughout the year. A temperature between 15 and 40°C and shaded situations are essen tial for successful cultivation.

·         Temperature fluctuations should be narrow and the soil should be well drained.

·          Propagation is by stem or root cuttings planted about a foot apart each way.

·          Roots are harvested when the plants are about 2.5 years old and the alkaloid content exceeds 20%.

·         The plant may be dug up at any time of the year; the roots are washed and dried in shade.

Characteristics

·         The rhizome is thin or sometimes thick and annulated.

·          Rhio Ipecac is 5–15 cm long, 6 mm in diameter,

·          shape is cylindrical, slightly, tortuous,

·          external surface is broadlyannulated, brick red to brown in colour, the ridges are rounded and encircle the root,

·          fracture of root is short and shows a thick, greyish bark and small dense wood.

·          Odouris slight and taste is bitter and acrid.

·         The colour of the outer surface varies from a deep brick-red to a very dark brown; the colour is dependent on the type of soil in which the plant has been grown.

·         The rhizomes have a much thinner bark and definite pith.

Microscopy

·         A transverse section of the root shows a thin, brown cork, the cells of which contain brown, granular material.

·         There is wide, secondary cortexes (phelloderm), the cells of which are parenchymatous and contain starch in compound grains with from two to eight components, or raphides of calcium oxalate.

·         The individual starch grains are muller-shaped.

·         The phloem is parenchymatous, containing no sclerenchymatous cells or fibres.

·         The compact central mass of xylem is composed of small tracheidal vessels, tracheids, substitute fibres, xylem fibres and xylem parenchyma.

·         Starch is present in the xylem parenchyma and in substitute fibres.

·         The transverse section of ipecacuanha rhizome shows a ring of xylem and large pith. The pericycle contains characteristic sclerenchymatous cells.

·         The pith is composed of pitted lignified parenchyma.

Chemical Constituents

·         Ipecac root contains 2–3% of total alkaloids.

·         These include emetine, cephaeline, psychotrine and psychotrine methyl ether.

·         All the alkaloids have isoquinoline ring system and, are present in the bark.

·          Emetine is the active alkaloid and as it does not contain a free phenolic group it is called nonphenolic alkaloid.

·         In Cartagena ipecac, alkaloids are up to 2.2% and emetine is about one-third and cephaeline two-thirds. The other alkaloids are in traces.

Chemical Test of Emetine

1. Powdered drug (0.5 g) is mixed with HCl (20 ml) and water (5 ml), filtered and to the filtrate (2 ml) potassium chloride (0.01) is added. If emetine is present, a yellow colour develops which on standing for 1 hour gradually changes to red.

Uses

·         Ipecac is emetic and used as an expectorant and diaphoretic and in the treatment of amoebic dysentery.

·         The alkaloids have local irritant action.

·         Emetine has a more expectorant and less emetic action than cephaeline

·          Psychotrine and its methyl ether are selective inhibitors of human immunodeficiency virus.

Adulterants

·         The chief adulterant of the drug is the aerial stem of the plant. It can be distinguished from the root by the longitudinal striation, presence of distinct pith composed of cells with lignified walls and by the surface scars.

·         The drug is often substituted by stem and roots of Richardsonia scabra, Cryptocoryne spiralis, Psychotria emetica, Manettia ignita, Hybanthus ipecacuanha, Asclepias curassavica, Anodendron paniculatum, Calotropis gigantea and others. The powdered drug is often adulterated with almond meal

. OPIUM

Synonyms

Crude Opium; Raw Opium; Gum Opium; Afim; Post.

Biological Source

Opium is the air dried milky latex obtained by incision from the unripe capsules of Papaver somniferum Linn, or its variety P. album Decand., belonging to family Papaveraceae.

Opium is required to contain not less than 10% of morphine and not less than 2.0% of codeine. The thebaine content is limited to 3%.

Geographical Source

It is mainly found in Turkey, Russia, Yugoslavia, Tasmania, India, Pakistan, Iran, Afghanistan, China, Burma, Thailand and Laos. In India, Opium is cultivated in M.P. (Neemuch) and U.P. for alkaloidal extraction and seed production.

Cultivation and Collection

·         Opium is cultivated under license from the government.

·         Its seeds are sown in October or March in alluvial soil.

·         After germination of seeds snow falls. In spring the thin plant attains the height of 15 cm.

·         Fertilizers are used for better crop.

·         The poppy of first crop blossoms in April or May and the capsule mature in June or July.

Characteristics

·         Opium occurs in rounded or flattened mass which is 8–15 cm in diameter and weighing from 300 g to 2 kg each.

·         The external surface is pale or chocolate-brown, texture is uniform and slightly granular.

·         It is plastic like when fresh and turns hard and brittle after sometime.

·         Fragment of poppy leaves are present on the upper surface.

·         Internal surface is coarsely granular, reddish-brown, lustrous;

·         odour is characteristic; taste is bitter and distinct.

·         Opiumbis intended only as a starting material for the manufacture of galenical preparations and is not dispensed as such.

CHEICAL CONSTITUENTS

·         Opium contains about 35 alkaloids among which morphine (10–16%) is the most important base.

·         The alkaloids are combined with meconic acid. The other alkaloids isolated

·         from the drug are codeine (0.8–2.5%), narcotine, thebaine (0.5–2%). noscapine (4–8%), narceine and papaverine (0.5–2.5%). Morphine contains a phenanthrene nucleus.

·         The different types of alkaloids isolated are:

1. Morphine Type:

·         Morphine, codeine, neopine, pseudo or oxymorphine, thebaine and porphyroxine.

·         Morphine consists of alkaloids which has phenanthrene nucleus whereas those of the papaverine group has benzylisoquinoline structure

2. Phthalide Isoquinoline Type:

·         Hydrocotarnme, narcotoline,1-narcotine, noscapine, oxynarcotine, narceine, and 5’-O-demethyl-narcotine.

3. Benzyl Isoquinoline Type:

·         Papaverine, dl-laudanine, laudanidine, codamine and laudanosine.

4. Cryptopine Type:

·         Protopine, cryptopine.

5. Unknown Constituents:

·         Aporeine, diodeadine, meconidine, papaveramine and lanthopine.

Chemical Tests

1. Aqueous extract of Opium with FeCl3 solution gives deep reddish purple colour which persists on addition of HCl. It indicates the presence of meconic acid.

2. Morphine gives dark violet colour with conc. H2SO4 and formaldehyde.

Uses

·         Opium and morphine have narcotic, analgesic and sedative action.

·         Is used to relieve pain, diarrhoea dysentery and cough.

·         Poppy capsules are astringent, somniferous, soporific, sedative and narcotic and used as anodyne and emollient.

·         Codeine is mild sedative and is employed in cough mixtures.

·         Noscapine is not narcotic and has cough suppressant action acting as a central antitussive drug.

·         Opium, morphine and the diacetyl derivative heroin, cause drug addiction.

INDOLE ALKALOIDS

·         Indole (1-H-indole) is a benzopyrrole in which the benzene and pyrrole rings are through the 2, 3-positions of thepyrrole.

·         Indole was first obtained (and its structure elucidated)in 1866 by Adolf von Baeyer.

·         These are tryptophan and tryptamine derived alkaloids.

·         Indole is a colourless crystalline solid.

·         Indole has good solubility in a wide range of solvents including petroleum ether, benzene,chloroform and hot water.

ERGOT

Synonyms

Ergot; Rye Ergot; Secale cornutum; Spurred rye; Ergot of rye; Ergota.

Biological Source

Ergot is the dried sclerotium of a fungus, Claviceps purpurea Tulasne, belonging to family Clavicipitaceae, developing in the ovary of rye plant, Secale cereale (Family Poaceae).

Ergot should yield about 0.15% of the total alkaloids calculated as ergotoxine and water-soluble alkaloids equivalent to about 0.01% of ergonovine.

Geographical Source

It is mainly found in Czechoslovakia, Hungary, Switzerland, Germany, France, Yugoslavia, Spain, Russia and India. In India Ergot is cultivated at Kodaikanal (T.N.).

Cultivation and Collection

The life cycle of the fungus, Claviceps purpurea, which is a parasite, passes through the following characteristic stages:

1. Sphacelia or honeydew or asexual stage

2. Sclerotium or ascigerous or sexual stage and

3. Ascospore stage.

1. Sphacelia or honeydew or asexual stage

The rye plant becomes infected by the spores of the fungusin the spring session when flowers bloom for about oneweek. The spores are carried by the wind or by insects to

the flowers and collected at the base of the young ovary where moisture is present. There germination of the spores takes place. A filamentous hyphae is formed which enters

into the wall of the ovary by enzymatic action. A soft white mass over the surface of ovary is formed, which is known as Sphacelia. A sweet viscous yellowish liquid,

known as honeydew, is secreted during the Sphacelia stage which contains reducing sugars (reduce Fehling solution). From the ends of some hyphae small oval conidiospores

(asexual spore/s) are abstricted which remain suspended on honeydew. The sweet taste of honeydew attracts some insects like ants and weevils. Insects suck the sweet liquid

and carry the conidiospores to the plants and spread the fungal infection in the rye plants. Cultured conidiospores are used for the inoculum. Strains capable of producing

about 0.35% of selected alkaloids, mainly ergotamine, are now utilized.

2. Sclerotium or ascigerous or sexual stage

During the Sphacelia stage the hyphae enter only the outer wall of the ovary. On further development they penetrate into deeper parts, feed on the ovarian tissues and

replace it by a compact, dark purple hard tissue known as pseudoparenchyma. It forms the sclerotium or resting state of the fungus. During summer the sclerotium or ergot

increases in size and projects on the rye, showing sphacelial remains at its apex. It is collected at this stage by hands or machine and used as a drug. Ergot is then dried to  remove moisture. About 6 weeks after inoculation, the mature sclerotia are harvested. They may be picked up by hand or collected by machine. The number and size of the ergots

produced on each spike of cereal by C. purpurea varies, rye usually bears sclerotia, while wheat bears very few.

3. Ascospore stage

If Ergot is not collected, it falls on the ground. In the next spring session they produce stalked projections known as stromata which have globular heads. In the inner surface of the heads there are many flask-shaped pockets known

as perithecia. Each of these perithecia contains many sacs (asci) which possesses eight of the thread-like ascospores. These ascospores are carried out by insects or wind to the

flowers of the rye as described in the first stage. In this way life cycle of Ergot is completed. The ascospores may be germinated on a nutritive medium

to get conidiospore bearing cultures. The suspension of these conidiospores is usually used as a spray to infect rye plants for commercial production of Ergot.

Ergot is collected from fields of rye when the sclerotia are fully developed and projecting from the spike, or they are removed from the grain by shifting. The size of the crop varies according to weather conditions. The vegetative phase of the fungus can, like that of other moulds, be cultivated artificially. Under such conditions the typical

sclerotia do not develop.

Characteristics

·         The size of sclerotium (Ergot) is about 1–4 cm long, 2–7 mm broad.

·         Shape is fusiform, slightly curved, sub-cylindrical, tapering at both ends.

·         The outer surface is dark or violetblack in colour.

·          The fractured surface shows thin, dark outer layer, a whitish or pinkish-white central zone of pseudoparenchyma in which darker lines radiate from the centre.

·         Odour is characteristic and taste is unpleasant.

Microscopy

·         Ergot shows an outer zone of purplish-brown, obliterated rectangular cells.

·         The pseudoparenchyma consists of oval or rounded cells containing fixed oil and protein, and with highly refractive walls which give a reaction for chitin.

·         Cellulose and lignin are absent.

Chemical constituents:

1. Most important alkaloids are

Ergometrine group (Water soluble):

Ergometrine, Ergometrinine.

Ergotamine group (water -insoluble):

Ergotamine, Ergotaminine, Ergosine., Ergosinine.

Ergotoxine group (Water-insoluble):

Ergocristine, Ergocristinine, Ergocryptine, Ergocryptinine, Ergocornine, Ergocorninine.

2. Alkaloids obtained from lysergic acid are physiological active.

3. Histamine, tyramine, and other amine,

4. Putriscine, cadaverine, agmatine, amino acids, colouring matter.

5. Sterols like ergosterol and fungisterol,

6. Elymoclavine, sclerythrin, ergonovine,

7. Clavicepsin, ergoflavin, ergotic acid betaine, alkaloid

8. Clavine, mannitol, lactic acid and succinic acid.

Chemical Tests:

Ergot under UV light shows a red-coloured fluorescence. Ergot powder is extracted with a mixture of CHCI₃ and sodium carbonate. The CHCI₃ layer is separated and a mixture of p-dimethylaminobenzaldehyde, H₂SO₄ and 5% ferric chloride solution is added. A deep blue colour is produced.

Uses:

1. Ergot is oxytocic, vasoconstrictor and abortifacient and used to assist delivery and to reduce post-partum haemorrhage.

2. Ergotamine is used to treat migraine.

3. Lysergic acid diethylamine, obtained by partial synthesis from lysergic acid is a potent specific psychotomimetic.

4. Ergometrine is oxytocic and used in delivery.

It is stimulates the tone of uterine muscles and prevent post-partum haemorrhage.

RAUWOLFIA

Synonyms

Sarpagandha, Chandrika; Chootachand; Indian snake root.

Biological Source

Rauwolfia consists of dried roots of Rauwolfia serpentine Benth., belonging to family Apocynaceae.

Geographical Source

It is an erect, evergreen, small shrub native to the Orient and occurs from India to Sumatra. It is also found in Burma, Thailand, Philippines, Vietnam, Indonesia, Malaysia, Pakistan and Java.

In India it occurs in the sub-Himalayan tracts from Sirhind eastwards to Assam, especially in Dehradun, Siwalik range, Rohelkhand, Gorakhpur ascending to 1,300

m, east and west ghats of Tamil Nadu, in Bihar (Patna and Bhagalpur), Konkan, Karnataka and Bengal.

Cultivation and Collection

·         Rauwolfia grows in tropical forests at an altitude of 1,200–1,300 m at temperature 10–40°C.

·         There should be enough rain or irrigation for its cultivation.

·         The soil should be acidic (pH 4–6), clayey and manure is applied for better crop.

·         Propagation is done by planting seeds, root cuttings or stem cuttings. Better drug is obtained when the propagation is carried out with fresh seeds.

·         The plants should be protected from nematodes, fungus and Mosaic virus. The drug is collected mainly from wild plants.

·         Roots and rhizomes are dug out in October–November when the plant roots are two to four years old.

·         The aerial parts and roots are separated. The roots are washed and dried in air. The roots containing moisture up to 12% should be protected from light.

·         Seasonal variation, genetic differences, geographic location, improper handling and drying, and other factors account for percentage differences in alkaloid amount.

·         Rauwolfia should be packaged and stored in well-closed containers in a cool, dry place that is secure against insect attack.

Characteristics

·         The roots and rhizomes are almost identical in external characters.

·         The drug occurs in cylindrical or slightly tapering, tortuous pieces, 2–10 cm long, 5–22 mm in diameter.

·         The roots are rarely branched.

·         The outer surface is greyish-yellow, lightbrown or brown.

·         The fracture is short. A narrow, yellowish-brown bark and a dense pale yellow wood are present on the smooth transverse surface at both the ends.

·         Pieces of rhizome closely resemble the root but may be identified by a small central pith.

·         They are attached to them with small pieces of aerial stem.

·         Slight odour is felt in recently dried drug which decreases with age; taste is bitter.

Microscopy

·         Transverse section of the root shows a stratified cork, which is divided, into two to eight alternating zones.

·         It consists of one to seven layers of smaller and radially narrower, suberised, nonlignified cells alternating with one to three layers of larger radially broader, lignified cells.

·         The phelloderm is composed of about ten to twelve layers of tangentially elongated to isodiametric, cellulosic parenchymatous cells.

·         Cells of secondary cortex are parenchymatous and contain starch grains, simple and compound (two to four components), spherical with a distinct hilum in the form of a split.

·         Phloem is narrow and consists of parenchyma with scattered sieve tissue; parenchyma alternate with broader medullary rays composed of large cells and usually two to four cells wide.

·         Xylem is wide, entirely lignified and usually shows two to five annual rings.

·          Medullary rays, one to five cells wide, contain starch grains and alternate with secondary xylem consisting of vessels, tracheids, fibres and parenchyma.

·         Xylem vessels have pitted thickening.

Chemical Constituents

·         Rauwolfia contains about 0.7–2.4% total alkaloidal bases from which more than 80 alkaloids have been isolated.

·         The prominent alkaloids isolated from the drug are reserpine, rescinnamine, ψ-reserpine, rescidine, raubescine and deserpidine.

·         The other alkaloidal components are ajmalinine, ajmaline, ajmalicine (8-yohimbine), serpentine, serpentinine, tettetrahydroreserpine, raubasine, reserpinine, isoajamaline and yohambinine.

·         unsaturated alcohols and sugars.

Uses

·         Rauwolfia in used as hypnotic, sedative and antihypertensive.

·         It is specific for insanity, reduces blood pressure and cures pain due to affections of the bowels.

·         It is given in labours to increase uterine contractions and in certain neuropsychiatric disorders.

·         Ajmaline, which has pharmacological properties similar to those of quinidine, is marketed in Japan for the treatment of cardiac arrhythmias.

·         Reserpine is a white or pale buff to slightly yellow, odourless, crystalline powder that darkens slowly when exposed to light and rapidly when in solution.

·         Reserpine is an antihypertensive and tranquilizer. Rescinnamine is the methyl reserpate ester of 3,4,5-trimethoxy cinnamic acid.

·         Higher doses may cause serious mental depression. Deserpidine is 11-des-methoxyreserpine. It is a wide-range tranquilizer and antihypertensive and is free from the side effects.

Marketed Products

It is one of the ingredients of the preparations known as Confido, Lukol, Serpina (Himalaya Drug Company) and Sarpagandhan bati (Baidyanath).

VINCA

Synonyms

Vinca rosea, Catharanthus, Madagascar periwinkle. Barmasi.

Biological Source

Vinca is the dried entire plant of Catharanthus roseus Linn.,belonging to family Apocynaceae.

Geographical Source

The plant is a native of Madagascar and is found in many tropical and subtropical countries especially in India, Australia, South Africa and North and South America. The plant is cultivated as garden plant in Europe and India.

Cultivation and Collection

·         The plant is perennial and retains its glossy leaves throughout the winter.

·         The plant prefers light (sandy), medium (loamy) and heavy (clay) soils and can grow in heavy clay soil.

·         The plant prefers acid, neutral and basic (alkaline) soils.

·         It can grow in full shade (deep woodland) semishade (light woodland) or no shade. It requires dry or moist soil and can tolerate drought.

·         It is cultivated either by directly sowing the seeds or sowing the seeds in nursery.

·         Nursery sowing method is found to be economical and the fresh seeds are sown in nursery in the month of February or March.

·         Proper fertilization and weeding is done timely and leaves are stripped after nine months. In order to collect the whole plant, the stems are first cut about 10 cm above the grounds and the leaves, seeds, stems are separated and dried.

·         The roots are collected by plugging which are later washed and dried under shade and packed.

Characteristics

·         The leaves are green in colour, flowers are either violet, pinkish white or carmine red and roots are pale grey in colour.

·         It has characteristic odour and bitter taste.

·         The flowers are hermaphrodite (have both male and female organs) and are pollinated by bees.

·         Leaves are petiolate, entire margin, ovate or oblong, glossy appearance and with acute apex.

·         Fruit is follicles with numerous black seeds.

Microscopy

·         Vinca has dorsiventral leaf structure.

·         Epidermis is a single layer of rectangular cells covered with thick cuticle.

·         It consists of uni-cellular covering trichome and cruciferous stomata.

·         In the midrib region two to three layers of collenchyma is present, both below the upper epidermis and above the lower epidermis.

·         Vascular bundle consisting of xylem and phloem is present in the middle of midrib region and rest of the intercellular space is covered by five to eight layers of spongy parenchyma.

·         Calcium oxalate crystals are absent.

Chemical Constituents

·         Alkaloids are present in entire shrub but leaves and roots contain more alkaloids.

·         About 90 alkaloids have been isolated from Vinca from which some like Ajmalicine, Serpentine and Tetrahydroalstonine are known and are present in other species of Apocynaceae.

·         The important alkaloids in Catharanthus are the dimer indole indoline alkaloids Vinblastine and Vincristine and they possess definite anticancer activity.

·          Vindoline and Catharanthine are indole monomeric alkaloids.

·         It also contains monoterpenes, sesquiterpene, indole and indoline glycoside.

Uses

·         Vinblastin is an antitumour alkaloid used in the treatment of Hodgkin’s disease.

·         Vincristine is a cytotoxic compound and used to treat leukaemia in children.

·          Vinca is used in herbal practice for its astringent and tonic properties in menorrhagia and in haemorrhages generally.

·         In cases of scurvy and for relaxed sore throat and inflamed tonsils, it may also be used as a gargle.

·         For bleeding piles, it may be applied externally, as well as taken internally. It is also used in the treatment of diabetes.

·         The flowers of the Periwinkle are gently purgative, but lose their effect on drying.

·         If gathered in the spring and made into a syrup, they impart all their virtues, and this, it is stated, is excellent as a gentle laxative for children and also for overcoming chronic constipation in grown persons.

Marketed Products

It is one of the ingredients of the preparation known as Cytocristin (Cipla).

IMIDAZOLES   ( Glyoxaline )

·         Imidazole is a heterocyclic aromatic organic compound.

·         This ring system is present in important biological building blocks such as histidine and histamine.

·         Imidazoles can act as bases (Pka = 7.0) and as a weak acids (pK = 14.5).

·         Imidazole exists in two tautomeric forms with a hydrogen atom moving between the two nitrogens.

·         The most important plant of this group is Pilocarpus jaborandi.

PILOCARPUS

Synonyms

Jaborandi, Arruda do Mato, Arruda brava, Jamguarandi,Juarandi.

Biological Source

The drug consists of the leaves of

Pilocarpus jaborandi ( Pernambuca )

P.Microphyllus ( Maranham )

P. Pennatifolius ( Paraguay )

P. Trachylaphylus ( Ceara )

Belonging to family Rutaceae

Geographical Source

It is indigenous to South America and especially grown in Brazil also it is found in Venenzuela, Caribbean islands and Central America.

Characteristics

·         The shrub grows from 4 to 5 feet high; the bark is smooth and grayish.

·         the flowers are thick, small and reddish-purple in colour.

·         springing from rather thick, separate stalks about 1/4 inch long.

·         The leaves are large compound, pinnate with an odd terminal leaflet, with two to four pairs of leaflets.

Chemical Constituents

·         The drug contains imidazole alkaloids among, which pilocarpine is most important.

·         Pilocarpine is a lactone . Lactones are cyclic esters.

·         Other alkaloids are isopilocarpine, pilocarpidine, pilosine, pseudopilocarpine and isopilosine.

·         The range of total alkaloids in different species is between 0.5% and 1%.

Chemical Test

1. To the drug containing pilocarpine, small quantities of dilute sulphuric acid, hydrogen peroxide solution, benzene and potassium chromate solution is added and shaken, organic layer gives bluish-violet colour and yellow colour appears in aqueous layer.

Uses

·         Pilocarpine is antagonistic to atropine, stimulating the nerve endings paralysed by that drug, and contracting the pupil of the eye.

·         Its principal use is as a powerful and rapid diaphoretic.

·         It induces also free salivation and excites most gland secretions, some regarding it as a galactagogue.

·         It is also used in ophthalmic practice in the treatment of glaucoma.

STEROIDAL ALKALOIDS

·         They are formed by the addition of nitrogen on the similar point in the steroidal molecule, for example kurchi and veratrum.

·         The active chemical principles of such drugs contain mainly steroidal (cyclopentenophenanthrene) entity, along with basic nitrogen.

·         They belong to C21 or C27 group of steroids. Either they are used as medicines or as a precursor for synthesis of various other steroids.

KURCHI BARK

Synonyms

Holarrhenna; Kurchi (Hindi).

Biological Source

Kurchi bark consists of dried stem bark of Holarrhena antidysenterica Wall, belonging to family Apocynaceae ( H. Pubescence )

Geographical Source

The plant is found throughout India, ascending up to 1,250 m in the Himalayas, especially in wet forests.

Cultivation and Collection

·         Kurchi is a deciduous laticiferous shrub or small tree, 9–10m high.

·         The bark is collected from the tree by making suitable transverse and longitudinal incisions.

·         The alkaloidal content is high soon after the rains when new shoots are produced which declines during winter months.

Characteristics

·         The pieces of Kurchi bark are small and recurved both longitudinally and transversely.

·         The size and thickness vary from piece to piece.

·         Outer surface is buff to reddish brown and bears numerous prominent circular or transversely elongated horizontal lenticels and longitudinal wrinkles.

·         The thicker pieces are rugose and show numerous yellowish warts; inner surface cinnamon-brown, longitudinally striated, frequently with portions of pale yellow wood attached; fracture is brittle and splintery.

·         The taste is acrid and bitter while the odour is not distinct.

Microscopy

·         Transverse section of bark shows cork composed of uniformly arranged several layers of tangentially elongated cells.

·         Below cork is a broad zone of cortex, composed of thin-walled, irregular, polygonal parenchymatous cells containing starch grains and prismatic calcium oxalate crystals.

·         Groups of sclereids are scattered in the cortex; individual sclereid cells are more or less rounded-oval, thick-walled with numerous pits.

·         Cortex is limited below by a zone of groups of sclereids, which alternate with parenchymatous zone.

·         Phloem consists of phloem parenchyma similar to cortex, traversed longitudinally by medullary rays at regular intervals.

·         Medullary rays are narrow, one to two cells wide and almost straight.

Chemical Constituents

·         The total alkaloidal constituents of Kurchi bark vary from 1.1% to 4.72%. The main steroidal alkaloid is conessine (20–30%).

·         The other alkaloids isolated include conarrhimine, conimine, conamine, conessimine, isoconessimine, dimethyl conkurchine and holarrhimine.

·         In addition to alkaloids the bark also contains gum, resin, tannin, lupeol and digitenol glycoside holadysone.

Uses

·         The bark is considered to be stomachic, astringent, tonic, antidysenteric, febrifuge and anthelmintic.

·         The dried bark is rubbed over the body in dropsy.

·         Kurchi bark is used to cure amoebic dysentery and diarrhoea.

Marketed Products

·         It is one of the ingredients of the preparations known as Diarex PFS, Diarex Vet. (Himalaya Drug Company), Mahamanjishthadi kwath, Mahamanjisthadyarishta (Dabur) and Amree plus granules, Purodil capsules (Aimil Pharmaceuticals)

·         Kurchi Bismuth iodide

ALKALOIDAL AMINES

·         One or more carbon rings with a nitrogen atom on a carbon side chain.

·         Mescaline has a molecular structure that is remarkably similar to the brain neurotransmitter dopamine.

·         It is also structurally similar to the neurohormone norepinephrine (noradrenalin) and to the stimulant amphetamine.

·         Dopamine and its precursor L-dopa are also derived from a tyrosine pathway, Mescaline also occurs in several other cactus species, including the commonly cultivated, night-blooming, South American San Pedro cactus.

EPHEDRA

Synonyms

Ma Huang.

Biological Source

Ephedra consists of the dried aerial parts of Ephedra gerardiana Wall, Ephedra sinica Stapf, Ephedra equisetina Bunge, Ephedra nebrodensis Tineo and other Ephedra species, belonging to family Ephadreaceae.

Geographical Source

It is mainly found in China, India, Nepal, Turkey, Pakistan and Bhutan.

Cultivation and Collection

·         It is an evergreen shrub growing to 0.6 m by 2 m.

·         The plant prefers light (sandy) and medium (loamy) soils and requires well-drained soil.

·         The plant prefers acid, neutral and basic (alkaline) soils.

·         It cannot grow in the shade. It requires dry or moist soil and can tolerate drought.

·         Seeds are sown as soon as they are ripe in the autumn in a greenhouse.

·         It can also be sown in spring in a greenhouse in sandy compost.

·         Seedlings are transferred into individual pots as soon as they are large enough to handle and grown them for at least their first winter in a greenhouse.

·         Drug is collected in autumn since it contains maximum percentage of alkaloids. Green slender twigs are collected in autumn, dried and packed loose in bags. Sometimes the twigs are pressed tightly.

Characteristics

Ephedra gerardiana:

·         It consists of cylindrical woody stem that is grey or greenish in colour.

·         Nodes, internodes, scaly leaves and terminal buds are present in the stems.

·         The distance between the internodes is 3–4 cm and the nodes bare the scaly leaves.

·          They are bitter in taste.

·         The plant has stamens and pistils on separate flowers; staminate flowers in catkins and a membraneous perianth, pistillate flowers terminal on axillary stalks, within a two-leaved involucre.

·         Fruit has two carpels with a single seed in each and is a succulent cone, branches slender and erect, small leaves, scale-like, articulated and joined at the base into a sheath.

·          

Microscopy

·         Transverse section of the stem shows epidermis, composed of thick-walled, quadrangular cells, covered by thick cuticle.

·         Sunken stomata are present between many vertical ridges.

·         Papillae are present in the ridges.

·         Cortex is composed of chlorenchyma with outer zone of radially elongated cells and inner zone of spongy parenchyma.

·         Cortex also contains few isolated fibres or groups of fibres (two to six per group), which are lignified. Pericycle is composed of groups of lignified fibres outside the phloem region.

·         Vascular bundles are 6–10 in number, radially arranged in the cortex and composed of phloem and xylem.

·         Pith is large with rounded cells, containing dark brown mucilaginous substance in pigment cells.

Chemical Constituents

·         Ephedra contains alkaloids Ephedrine (water-soluble salt of an alkaloid), Pseudoephedrine (analog of ephedrine), Norpseudoephedrine (An analog of ephedrine).

·         The leaves and stems of ephedra also contain many potentially active compounds, such as tannins, saponin, flavone and volatile oils.

Chemical Test

1. To the drug (10 mg) in water (1 ml) dilute HCl (0.2ml), copper sulphate solution (0.1 ml) and sodium hydroxide solution (2 ml) are added; the liquid turns violet. On adding solvent ether (2 ml) and shaking vigorously, the ethereal layer turns purple and the aqueous layer becomes blue.

Uses

·         Ephedrine is antiallergenic, antiasthmatic, antispasmodic,decongestant, cough suppressant, stimulant and vasoconstrictor.

·         Pseudoephedrine is decongestant, cough suppressant and norpseudoephedrine is peripheral vasodilator used to treat angina.

·          As a whole it is decongestant; it opens sinuses, increases sweating, dilates bronchioles (antiasthmatic use), diuretic, CNS stimulant, raises blood pressure, alleviates aches and rheumatism, alleviates hay fever/colds, etc.

PURINE ALKALOIDS

·         Purine contains double carbon ring containing four nitrogen atoms.

·         Purine alkaloids have a molecular structure remarkably similar to the nitrogenous purine base adenine, which is found in DNA, RNA and ATP.

·         These alkaloids are derived from adenine and guanine which are the purine base components of the nucleotides adenosine and guanosine.

·         Most notable of the purine alkaloids are the mild stimulants caffeine and the very similar theobromine.

COFFEE

Synonyms

Coffee bean, coffee seed, Arabica coffee, Arabian coffee, Abyssinian coffee, Brazilian coffee.

Biological Source

It is the dried ripe seeds of Coffea arabica Linn, belonging to family Rubiaceae.

Geographical Source

It is indigenous to Ethiopia, Brazil, India, Vietnam, Mexico, Guatemala, Indonesia and Sri Lanka.

Cultivation and Collection

·         Propagation is usually by seed; however, budding, grafting, and cuttings have been used.

·         Traditional method of plants on virgin soil is to put 20 seeds in each hole, 3.5 × 3.5 m at the beginning of rainy season.

·         Half are eliminated naturally. In Brazil, a more successful method is to raise seedlings in shaded nurseries.

·         At 6–12 months, seedlings are taken to fields, hardened, and then planted on contoured fields 2–3 m apart in 3–5 m rows. Holes are prepared 40 × 40 × 40 cm and 4 seedlings placed in each.

·         Plants may be shaded by taller trees or left unshaded.

·         Trees come into bearing three to four years after planting and are in full bearing atsix to eight years.

·         Fruits mature seven to nine months after flowering.

·         Selective picking of ripe red fruits produces highest quality.

·         Crop ripens over a period of several weeks.

·         In Brazil all berries are stripped at one time onto ground cloths, usually in April to June; in Ethiopia, harvest season is October to December after the rainy season.

·         Berries are dried in sun; in some humid areas, artificial heat is used. Depulping after picking is increasingly practiced.

Characteristics

·         Evergreen, glabrous shrub or small tree, up to 5-m tall when unpruned.

·         Leaves opposite, dark green, glossy, elliptical acuminate-tipped, short-petioled, 5–20 cm long, 1.5–7.5cm broad, usually 10–15 cm long and 6 cm broad.

·         Flowers white, fragrant, in axillary clusters, opening simultaneously 8–12 days after wetting; corolla tubular, 1 cm long, 5-lobed; calyx small, cup-shaped.

·          Fruit a drupe, about 1.5 cm long, oval-elliptic, green when immature, ripening yellow and then crimson, black upon drying, 7–9 months to maturity.

·         Seeds usually 2, ellipsoidal, 8.5–12.5 mm long, inner surface deeply grooved, consisting mainly of green corneous endosperm and small embryo.

Chemical Constituents

·         The main constituents of coffee are caffeine, tannin, fixed oil and proteins.

·         It contains 2–3% caffeine, 3–5% tannins, 13% proteins, 10–15% fixed oils.

·         In the seeds, caffeine is present as a salt of chlorogenic acid.

·         Also it contains oil and wax.

Chemical Tests

1. Caffeine and other purine alkaloids, gives murexide colour reaction. Caffeine is taken in a petridish to which hydrochloric acid and potassium chlorate crystals are added and heated to dryness. A purple colour is obtained by exposing the residue to vapours of dilute ammonia. In addition of fixed alkali the purple colour disappears.

2. Caffeine also produces white precipitate with tannic acid solution.

Uses

·         Coffee is widely used as a flavoring agent, as in ice cream, pastries, candies and liquors.

·         Source of caffeine, dried ripe seeds are used as a stimulant, nervine and diuretic, acting on CNS, kidneys, heart and muscles.

·         Very valuable in cases of snake-bite, helping to ward off the terrible coma.

·         It also exerts a soothing action on the vascular system, preventing a too rapid wasting of the tissues of the body; these effects are not only due to the volatile oil but to the caffeine it contains.

TEA

Biological Source

It contains the prepared leaves and leaf buds of Thea sinensis (Linne) kuntz., belonging to family Theaceae.

Geographical Source

It is mainly cultivated in India (Assam), Ceylon, Japan and Java.

Cultivation and Collection

·         It is an evergreen shrub growing to 4 m by 2.5 m at a slow rate. The plant prefers light (sandy) and medium (loamy) soils and requires well-drained soil.

·         The plant prefers acid and neutral soils and can grow in very acid soil. It can grow in semishade (light woodland).

·         It requires moist soil and prefers a pH between 5 and 7. Prefers the partial   shade of light woodland or a woodland clearing.

·         It is reported to tolerate an annual rainfall of 70–310 cm, an average annual temperature range of 14–27°C and a pH in the range of 4.5–7.3.

·         It prefers a wet summer and a cool but not very frosty dry winter.

·         Seed can be sown as soon as it is ripe in a green house. Stored seed should be presoaked for 24 h in warm water and the hard covering around the micropyle should be filed down to leave a thin covering.

·         It usually germinates in one to three months.

·         Prick out the seedlings into individual pots when they are large enough to handle and grow them on in light shade in the green house for at least their first winter.

·         Seedlings take 4–12 years before they start to produce seed.

Characteristics

·         Leaves are dark green in colour, lanceolate or elliptical, on short stalks, blunt at apex, base tapering, margins shortly serrate, young leaves hairy, older leaves glabrous.

Microscopy

·         The epidermal cells are made of polygonal cells which are slightly wavy walls. It consist on itself stomata and trichomes.

·         The trichomes are thick walled, uni-cellular, conical (covering) which arise on the lower surface and in large number in young leaves.

·         The mesophyll region consistof two rows of palisade parenchyma cells and large lignified sclereids which arise at some intervals and are extended across the mesophyll from one epidermis to the other.

·         Cluster crystals of calcium oxalate are scattered in phloem and in parenchyma. In the midrib area a prominent ridge is present both above and below.

·         Vascular bundle consisting of xylem and phloem are present; the entire region being covered by slightly lignified band of pericyclic fibres.

·         The pericyclic fibres are up to four fibres in width at the widest region.

·         The remaining portion is covered with spongy parenchyma with scattered lignified sclereids.

Chemical Constituents

·         The leaves are a rich source of caffeine (1–5%).

·          It also contains theobromine and theophylline in minor quantities.

·         The colour of tea leaves is due to tannin (10–20% gallotannic acid).

·         The agreeable odour is due to presence of a yellow volatile oil.

·         Tea leaves also contain protein, wax, resin and ash.

Chemical Tests

1. Caffeine and other purine alkaloids, gives murexide colour reaction. Caffeine is taken in a petridish to which hydrochloric acid and potassium chlorate are added and heated to dryness. A purple colour is obtained by exposing the residue to vapours of dilute ammonia. In addition of fixed alkali the purple colour disappears.

2. Caffeine also produces white precipitate with tannic acid solution.

Uses

It is used as stimulant, astringent and also as diuretic.

GLYCO-ALKALOIDS

·         Glycoalkaloids are a family of chemical compounds derived from alkaloids in which sugar groups are appended.

·         There are several that are potentially toxic, most notably those which are the poisons commonly found in the plant species Solanum dulcamara (bittersweet nightshade) and other plants in the genus Solanum, including potato.

·         Glycoalkaloids are typically bitter tasting, and produce a burning irritation in the back of the mouth and side of the tongue when eaten.

·         Sale of a glycoalkaloid-based treatment marketed by Lane Labs USA Inc. for prevention of skin cancer was banned by the FDA in 2004 as an unapproved drug.

SOLANUM

Biological Source

 It consist of the dried and full grown berries of Solanum khasianum CR belonging to the family Solanaceae.

Geographical Source 

The plant grows indigenously on the Khasia Mountains in Assam (India).

Preparation 

·         The plant usually grows in various climatic and agricultural conditions.

·         Almost after a duration of six months the plants are normally harvested for the collection of berries.

·         They are dried immediately either in an artificial environment at low temperature (50-60°C) or dried preferably in shade so as to bring down the initial large moisture content to enable its prolonged storage life.

·         The dried berries are powdered by mechanical grinders and the oil is removed by solvent extraction

·          

Description 

The berries have a yellowish to greenish colouration with flattened smooth brown seeds.

Chemcial Constituents 

The berries mostly comprise of the steroidal saponin Salosanine as shown below:

                         

·         Solasonine also occurs in various Solanum species namely : Solanum aviculare Forst F., Solanum sodomeum L., Solanum xanthocarpum Schrad & Wendl, m Solanum nigrum Linn., Solanum torvum Sw., and Solanum verbascifolium Linn. Besides, the berries contain a steroidal glycoalkaloid known as solasodine (Approx. 3%) and a greenish yellow fixed oil (8-10%).

Uses

 Solasodine is the hydrolysed product of solasonine which is mostly used as a starting material for the synthesis of steroidal drugs, such as: 19-NOR steroids, pregnane etc.