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 Since time immemorial, natural products have been the backbone of

traditional system of healing throughout the globe, and have also been an
integral part of history and culture. Although the use of bioactive natural
products as herbal drug preparations dates back hundreds, even thousands,
of years ago, their application as isolated and characterized compounds to
modern drug discovery and development started only in the 19th century. It
has been well documented that natural products played critical roles in
modern drug development, especially for antibacterial and antitumor agents.
Even though popularity of the synthetic products increased due to its
production cost, time effectiveness, easy quality control, stringent regulation
and quick effects, but their safety and efficacy was always remained
questionable, resulting in the dependence on the natural products by more
than 80% of the total population in the developing world, because of its time
tested safety and efficacy. A huge number of natural product-derived
compounds in various stages of clinical development highlighted the existing
viability and significance of the use of natural products as sources of new
drug candidates.
 Plants have been used in the treatment of various diseases from time
immemorial. The traditional Indian system of medicine, Ayurveda,
Siddha and Unani systems, are based on the use of plants and other
natural substances. There are 200,000 to 250,000 species of flowering
plants growing on earth which belongs to 10,500 genera and about 300
families.
 Scrutiny of the drugs obtained from plants reveals that the majority of
the drugs are derived from seed bearing plants (Spermatophytes).
Among these the flowering plants (angiosperms) have yielded a good
number of useful medicinal plants than the non-flowering plants
(Gymnosperms). The gymnosperms are useful source of oils, resins
and the alkaloids such as ephedrine.
 Drugs consisting of entire plant or some part of it are often designated
as crude drugs. Examples are seed, fruits, leaves, flowers, roots,
barks etc. Many of the plant products are important therapeutic
agents, eg; alkaloids, cardiac glycosides, flavonoids, mucilages etc.
 Eg, of drugs from plant sources: Myrobalan, isapgol, catechu, agar
etc.
 Certain animal parts and animal products are used as drugs in
therapeutics. The major groups of animal products used in medicine are
hormones, enzymes, animal extractives, organs and bile acids.
 Hormones:
• Hormones are mammalian products that are secreted by endocrine or
ductless glands of animals and released directly into the blood. eg:
thyroid, thyroxine, insulin, epinephrine etc.
 Enzymes:
• Pancreatin, trypsin, pepsin etc
 Animal extractives and organ
• Eg; Liver & stomach preparations and bile.
 Other useful animal drugs:
• Carmine : a colouring principle obtained from cochineal insects.
• Cod-liver oil
• Shark-liver oil
• Cantharidin : an irritant constituent of cantharide insects
• heparin
 Oceans and seas, rich in fauna and flora covers about 70% of
earth surface. But it has not been properly explored for the
search of biomedicals. The active constituents obtained from
marine organisms such as algae, sea weeds etc. are used to
cure various human ailments.
 Examples of conventionally used drugs obtained from
marine organisms are:
• Shark and cod-liver oil, Sodium alginate, Agar, Chitin etc.

 About 5 Lakhs species of marine organisms have been


reported from the oceans and seas from various parts of the
world. Some of these organisms are antimicrobial, antiviral,
antibiotic, anticancer, antiinflammatory etc.
 Many of these species contain toxic compounds.
No: Class Examples
1. Antibiotic compounds Cycloeudesmol, variabilin, ircinin-1
2. Anti-inflammatory & Manoalide, tetrado toxin
antispasmodic agents

3. Antimicrobial compounds Holotoxin ABC, tholepin


4. Cardiovascular active Anthopleurins, Laminine, Saxitoxin,
substances spogosine

5. Cytotoxic compounds Ara-C, crassin acetate, simularin


6. Marine toxins Ciguatoxin, palytoxin, saxitoxin
7. Miscellaneous compounds Kainic acid, domoic acid
 Even though, majority of natural drugs are derived from plant and
animal origins, a few of them obtained from mineral sources are of
paramount significance as pharmaceutical aids.
 The drugs of herbo-mineral origin like shilajith is very effective
tonic and stimulant.
 Clays: clays are product of decomposition of rocks rich in
aluminium silicate. They possess characteristic plasticity and can
be easily molded into any shape. Clays are made up of mineral
grains, some of which are very small in size. They are classified as
• Kaolin group:
 They are hydrated aluminium silicate
 Includes kaolinite, nacrite etc.
• Montmorillonite group:
• Alkali bearing clay minerals
No: Name Main constituents Uses
1. Kaolin (China clay) Hydrated aluminium Adsorbent, filter aid
silicate
2. Kieselguhr Aluminium silicate Filter aid for
(Diatomeceous clarifying liquids
earth)
3. Mica Aluminium silicate Insulation, refractory
bricks
4. Paraffins Saturated Ointment bases
hydrocarbons
5. shilajith Herbomineral General tonic,
aphrodisiac
6. Talc Hydrated magnesium Lubricant, dusting
silicate powder, filter aid
 Tissue culture is an experimental technique through which mass of cells
(callus) is produced from an explant tissue, and the callus produced could be
used directly either to:
• Regenerate plantlets
• Produce primary/secondary metabolites
• Manipulation of primary and secondary metabolites, for increasing the
production through genetic engineering

 In the recent scenario, tissue culture technique or asceptic method of micro


propagation is recognized duly to be a novel method for the meaningful
propagation of medicinal plants.

 Under asceptic condition, plant tissue culture is utilized for:


• Protoplast culture (culture of plant protoplast; ie., cells devoid of their cell
wall)
• Cell culture
• Tissue culture
• Organ culture
 The exploration of biosynthetic capabilities of cell cultures derived from
different higher plants has been systemically investigated in the last two
decades by scientists all over the world. In many cases the desired compounds
are not produced, while in others only low amount could be detected.
 To avoid these problem of poor yield of secondary metabolites, development
of hairy root cultures, immobilized cell systems and techniques to encourage
excretion of desired product into the medium are attempted. On the other
hand, there are examples which show that callus and suspension cultures are
capable of synthesizing secondary metabolites with yields comparable to the
intact plant.
 Plant cells grown in culture have potential to produce and accumulate
chemicals similar to the parent plant from which they were derived.
 To date, over 30 classes of compounds have been produced in appreciable
quantities by plant cell cultures. These include digitalis glycosides, rosmarinic
acid, opium alkaloids (cedeine, morphine), ginsenosides, ajmalicine and other
indole alkaloids (vincristine and vinblastine) and complex mixtures such as
rose and jasmine oil.
 Several pharmacologically active novel compounds are extracted from
plants. In plant systems, they accumulate in
• leaves (nicotine in Nicotiana)
• roots (ajmalicine in Catharanthus roseus)
• bark (quinine in Cinchona) or
• in the whole plant (ephedrine in Ephedra).
 Sometimes these products are produced in specialized differentiated
tissues such as resin in resin ducts and latex in laticifers.
 Except the herbaceous cultivated plants (e.g., Papaver somniferum), most
of the secondary metabolites are accumulated after a certain age or
maturity of the plant. In the case of tree or shrub species, e.g., Cinchona,
Rauwolfia etc., plants attain maturity in a few years before they
accumulate the active principle in high amounts. It is difficult to increase
the area under plantation for a particular species and growth of plants
takes it own time. To meet the ever-increasing demand (e.g., vincristine)
the natural resources are not sufficient.
 To overcome all these hurdles, the industry requires alternative methods of assured
supply of uniform material throughout the year. Harvesting of plants (except
cultivated species) from natural forest resources is not only difficult, but also makes
them endangered species; e.g., Ephedra gerardiana and several other Himalayan
plants.

 When plant material is not available throughout the year in a quantity sufficient for
industrial production and chemical synthesis is not possible, particularly for large
complex molecules, biotechnological methods offer an excellent alternative. But
before implementing this approach, cost of the product and its demand should justify
production by biotechnological means.
 Tissue culture techniques have made in the study of fundamental problems of
• plant physiology and cytology
• Genetics
• Plant breeding
• Viral, bacteria & nematode plant relationships
 Some of the medicinal compounds localized in morphologically specialized organs or
tissues have been produced in culture system.
COMPOUNDS SPECIES YIELD (% DRY
WEIGHT)
Ajmalicine Catharanthus roseus 1.8
Anthraquinone Morinda citrifolia 18.0
Diosgenin Dioscorea deltoidea 7.8
Ginsenosides Panax ginseng 17.0
Nicotine Nicotiana tabaccum 5.0
Rosmarinic acid Coleus blumei 21.4
 Tissue or cell of an interesting plant is selected and
sterilized (disinfected) by mercuric chloride or alcohol.
 Sterilization of cells: The cells taken for tissue culture are to be
surface sterilized. This helps the cell wall and tissue surfaces to be
free from any bacterial or fungal infections. Care should be taken
during their handling, transfer etc. to keep them free from infection.
 Then tissue is placed in media and incubated with proper oxygen
supply and right temperature.
 Oxygen supply: Since tissue has no direct mechanism to take up
oxygen, oxygen supply has to be provided. The gas should be free
from contamination and also aseptic. The rate and pressure of flow of
gas into the chamber of tissue culture should be optimal.
 The tissue or cell multiplies and then forms plant-lets.
 This can be transplanted to green house. Tissue culture plants are
highly sensitive to tolerate natural environment conditions. They
have to be slowly adopted to normal atmosphere. So first they are to
be grown in green houses.
1. Natural products can be produced under controlled environmental
conditions.
2. Studying biogenesis of secondary metabolites
3. Used for synthesis of medicinal compounds which are too difficult to
synthesize chemically.
4. Possible to attempt biotrasformation reactions in plant cell cultures.
5. Cells of any plant is multiplied to yield specific metabolites.
6. Cultured cells could be maintained free from any microbial
contamination and insect attack.
7. Create a large number of clones from a single seed/explant.
8. For species that have long generation time (eg, taxol), low levels of seed
production or seeds that do not readily germinate, rapid propagation is
possible.
9. It allows for the internal exchange of sterilized plant materials.
10. Elimination of plant disease through careful stock selection and sterile
techniques.
11. Enables the cold storage of a large number of viable plants in a small
place.
 Costly technique.
 require high skilled personnel.
 Ability to grow off the plantlets will limits
the production.
 Care and handling of plantlets is
required prior to their