Drugs from plants
Created | Updated May 17, 2011
Herbal medicine has become more and more popular over the last few years but some people do ask if it really works. Many drugs that we actually use are derived from plants - Aspirin for example comes from the bark of a willow tree. Herbal medicine therefore does have a place but science is using the knowledge to refine the drugs we use and to ensure that what we take is actually safe for us. Below is a discussion of some of the ways that plants are giving us some new drugs and the science behind it.
Secondary metabolites are produced in most plants. Plants in difficult environment conditions will produce a wider spectrum of secondary metabolites. These secondary metabolites aren’t essential for growth, energy conservation or for primary metabolic pathways (the primary way that the plant makes its food and uses the energy). It's been suggested that the food specificity of insects is based largely on the presence or absence of secondary metabolites which, in contrast to most of the important nutrients in plants (proteins, vitamins, minerals, fasts, starch) possesses characteristic odours and tastes. Hence many plant secondary metabolites are insecticidal.(i.e. this is no accident).Many suggestions have been made about the use of secondary metabolites, for example, it has been suggested that alkaloids and terpenoids (2 examples of the types of chemicals they produce) have medicinal properties due to their ability to inhibit germination or growth of micro-organisms. A large proportion of existing drugs are formed from plant secondary metabolites.
Between 1983 and 1994 520 new drugs were approved. Of these 39% were or were derived from natural products. On top of this 60-80% of antibacterials and anticancer drugs are derived from natural products.
Alkaloids
Alkaloids possess a variety of structures, but all contain nitrogen usually in a heterocyclic ring (a ring of atoms which are not all the same) and most are basic (alkaline). They tend to accumulate in the vacuoles of actively growing tissues, epidermal and hypodermal cells, vascular sheaths and latex vessels of plants. Alkaloids are formed from amino acid precursors
Alkaloids are thought to act as pre-infectional compounds and can prevent infection by bacteria or fungi. Some alkaloids are therefore used in medicine. For example they are used as analgesics or pain relievers and morphine and codeine are used as anaesthetics.
The first alkaloid to be identified was morphine from the opium poppy, Papaver somniferum. This was is 1806. The use of alkaloid containing plants as medicines can be traced back to the start of civilisation.
Alkaloids are still used in modern medicine. For example a synthetic derivative of atropine is often used to dilate the eye in eye examinations. Recently tropicamide has shown useful as an early diagnostic tool for the diagnosis of Alzheimer’s disease. Also quinine, the antimalaria drug which is extracted from C. officinalis, strychnine, the rat poison, which is extracted from Strychnos nuxvomica, as well as the chemotherapeutic agents, vincristine and vinblastine which is isolated from Catharanthus roseus are still used in modern medicine.
Several alkaloids extracted from the roots of Rauwolfia serpentine have been shown to have sedative properties and can lower high blood pressure. However the most active of these alkaloids is reserpine which had an unfortunate side effect. A year after this was introduced as a drug a few patients developed Parkinson's disease symptoms. However when the drug was discontinued the symptoms disappeared. This showed that not all plant secondary metabolites are safe to use as drugs.
Terpenoids
Terpenoids are derived from the basic five carbon isopentane unit (branched 5 carbon molecule, proper name is 2-methylbutane) and the number of these units in the molecule determines its classification. Some terpenoids actually exist as glycosides (have a sugar attached), whilst others contain nitrogen and are therefore known as terpene alkaloids. Terpenoids are located in the vacuole of the leaf or root of plants while some are located outside the leaf.
The sesquiterpene ipomeamarone is produced in sweet potatoes because of its anti-fungal action against the pathogen which causes black rot. In the two lobed glands on the surface of leafs and the seeds of chrysanthemum parthenium sesquiterpene lactose parthenolide is produced. This is toxic to gram positive bacteria (named because of the way it stains, bacteria are either gram positive or gram negative) and filamentous fungi and therefore prevents microbial attack.
Sclareol and isosclareol are found on the leaf of nicotiana glutinosa. These are in high concentrations on the surface of the leaf and are visible as liquid droplets under a microscope. These are structurally similar to gibberellins (hormones produced by fungi) and interfere with normal hormone development. They therefore inhibit fungal growth.
Phytoalexins
These are formed around sites of infection in plants. Biosynthetic enzymes not normally found in the plant can be produced due to the transfer of genetic information into the plant. This can be seen in tobacco plants where the groundnut stilbene phytoalexin resveratrol is synthesised. This results in the tobacco plant having a better resistance to the established tobacco fungal parasites.
New drug sources
Many new drugs are likely to be produced by plant secondary metabolites due to their existing importance. Many laboratories around the world put a lot of time into detecting, isolating and producing pharmaceutically active secondary plant metabolites. Not all plants have been analysed. Only about 10% of the 250 000 species of plants in the world have been tested for any active molecules and less than this have been studied extensively. There are many habitats with new species in which are being discovered. It is likely that these areas could yield useful drugs.
There is also research into the possibilities of using cell cultures to produce the secondary metabolites which are or could be of use as medicines. Research has shown that for some metabolites this isn’t worthwhile but for others this may be a possibility. Tropane alkaloids are found mainly in Solanaceae plants. For example cocaine is found outside in the Erythroxylom coca. This has been used by chemists as a starting structure for modification to create an optimized drug. This can be used as a synthetic anaesthetic. Genetic engineering of these plants can create ones which have better alkaloid patterns and therefore important sources of medicines.
The technology used to create antifungal resistance in tobacco can be used to alter the secondary metabolites in plants. For flavoinoids especially, this could be important and is currently under investigation.
Many parts of the world, especially developing countries, use plants as medicines. Palestine uses medicinal herbs to cure skin diseases. Tests into these plants have shown that many plants are an important natural source of antimycotic substances. They are also an important source which is renewable, for antifungal compounds. These can be used to make antifungal drugs for humans which work against dermatophytic infections.
Conclusion
Natural products are still used to create medicines or they are used to copy the structures for drugs. Research into this field isn’t new but is continuing. We could see plants with optimized alkaloid spectra or transgenic plant cell cultures in the future. We continually need new sources of drugs as more diseases develop. Plants are very likely to continue to be important sources.
The use of plants as medicines is an established area and its use can be seen throughout history. The study of plants used by communities for medicinal use has already yielded several useful drugs. The continuing study of plants is likely to yield new drugs. However as our environment changes and as the world develops areas of high biodiversity are losing species. Two thirds of the world’s species of plants live in the rainforests which cover about 6% of the surface of the area; however this is an area of the world that is slowly being destroyed. This could have repercussions because if we don’t analyse all species in these areas we could lose sources which could have yielded useful drugs for humans.
References
Goodwin, T. W. Mercer, E. I.(1975). Introduction to plant biochemistry. A. Wheaton and co. Exeter, Great Britain.
Harvey, A. (2000) strategies for discovering drugs from previously unexplored natural products. Drug discovery today. 5:7 pp294-300
Wikipedia (2006) alkaloids <LINK HREF="http://en.wikipedia.org/wiki/Alkaloid">http://en.wikipedia.org/wiki/Alkaloid</LINK><BR/>
Secondary metabolites are produced in most plants. Plants in difficult environment conditions will produce a wider spectrum of secondary metabolites. These secondary metabolites aren’t essential for growth, energy conservation or for primary metabolic pathways (the primary way that the plant makes its food and uses the energy). It's been suggested that the food specificity of insects is based largely on the presence or absence of secondary metabolites which, in contrast to most of the important nutrients in plants (proteins, vitamins, minerals, fasts, starch) possesses characteristic odours and tastes. Hence many plant secondary metabolites are insecticidal.(i.e. this is no accident).Many suggestions have been made about the use of secondary metabolites, for example, it has been suggested that alkaloids and terpenoids (2 examples of the types of chemicals they produce) have medicinal properties due to their ability to inhibit germination or growth of micro-organisms. A large proportion of existing drugs are formed from plant secondary metabolites.
Between 1983 and 1994 520 new drugs were approved. Of these 39% were or were derived from natural products. On top of this 60-80% of antibacterials and anticancer drugs are derived from natural products.
Alkaloids
Alkaloids possess a variety of structures, but all contain nitrogen usually in a heterocyclic ring (a ring of atoms which are not all the same) and most are basic (alkaline). They tend to accumulate in the vacuoles of actively growing tissues, epidermal and hypodermal cells, vascular sheaths and latex vessels of plants. Alkaloids are formed from amino acid precursors
Alkaloids are thought to act as pre-infectional compounds and can prevent infection by bacteria or fungi. Some alkaloids are therefore used in medicine. For example they are used as analgesics or pain relievers and morphine and codeine are used as anaesthetics.
The first alkaloid to be identified was morphine from the opium poppy, Papaver somniferum. This was is 1806. The use of alkaloid containing plants as medicines can be traced back to the start of civilisation.
Alkaloids are still used in modern medicine. For example a synthetic derivative of atropine is often used to dilate the eye in eye examinations. Recently tropicamide has shown useful as an early diagnostic tool for the diagnosis of Alzheimer’s disease. Also quinine, the antimalaria drug which is extracted from C. officinalis, strychnine, the rat poison, which is extracted from Strychnos nuxvomica, as well as the chemotherapeutic agents, vincristine and vinblastine which is isolated from Catharanthus roseus are still used in modern medicine.
Several alkaloids extracted from the roots of Rauwolfia serpentine have been shown to have sedative properties and can lower high blood pressure. However the most active of these alkaloids is reserpine which had an unfortunate side effect. A year after this was introduced as a drug a few patients developed Parkinson's disease symptoms. However when the drug was discontinued the symptoms disappeared. This showed that not all plant secondary metabolites are safe to use as drugs.
Terpenoids
Terpenoids are derived from the basic five carbon isopentane unit (branched 5 carbon molecule, proper name is 2-methylbutane) and the number of these units in the molecule determines its classification. Some terpenoids actually exist as glycosides (have a sugar attached), whilst others contain nitrogen and are therefore known as terpene alkaloids. Terpenoids are located in the vacuole of the leaf or root of plants while some are located outside the leaf.
The sesquiterpene ipomeamarone is produced in sweet potatoes because of its anti-fungal action against the pathogen which causes black rot. In the two lobed glands on the surface of leafs and the seeds of chrysanthemum parthenium sesquiterpene lactose parthenolide is produced. This is toxic to gram positive bacteria (named because of the way it stains, bacteria are either gram positive or gram negative) and filamentous fungi and therefore prevents microbial attack.
Sclareol and isosclareol are found on the leaf of nicotiana glutinosa. These are in high concentrations on the surface of the leaf and are visible as liquid droplets under a microscope. These are structurally similar to gibberellins (hormones produced by fungi) and interfere with normal hormone development. They therefore inhibit fungal growth.
Phytoalexins
These are formed around sites of infection in plants. Biosynthetic enzymes not normally found in the plant can be produced due to the transfer of genetic information into the plant. This can be seen in tobacco plants where the groundnut stilbene phytoalexin resveratrol is synthesised. This results in the tobacco plant having a better resistance to the established tobacco fungal parasites.
New drug sources
Many new drugs are likely to be produced by plant secondary metabolites due to their existing importance. Many laboratories around the world put a lot of time into detecting, isolating and producing pharmaceutically active secondary plant metabolites. Not all plants have been analysed. Only about 10% of the 250 000 species of plants in the world have been tested for any active molecules and less than this have been studied extensively. There are many habitats with new species in which are being discovered. It is likely that these areas could yield useful drugs.
There is also research into the possibilities of using cell cultures to produce the secondary metabolites which are or could be of use as medicines. Research has shown that for some metabolites this isn’t worthwhile but for others this may be a possibility. Tropane alkaloids are found mainly in Solanaceae plants. For example cocaine is found outside in the Erythroxylom coca. This has been used by chemists as a starting structure for modification to create an optimized drug. This can be used as a synthetic anaesthetic. Genetic engineering of these plants can create ones which have better alkaloid patterns and therefore important sources of medicines.
The technology used to create antifungal resistance in tobacco can be used to alter the secondary metabolites in plants. For flavoinoids especially, this could be important and is currently under investigation.
Many parts of the world, especially developing countries, use plants as medicines. Palestine uses medicinal herbs to cure skin diseases. Tests into these plants have shown that many plants are an important natural source of antimycotic substances. They are also an important source which is renewable, for antifungal compounds. These can be used to make antifungal drugs for humans which work against dermatophytic infections.
Conclusion
Natural products are still used to create medicines or they are used to copy the structures for drugs. Research into this field isn’t new but is continuing. We could see plants with optimized alkaloid spectra or transgenic plant cell cultures in the future. We continually need new sources of drugs as more diseases develop. Plants are very likely to continue to be important sources.
The use of plants as medicines is an established area and its use can be seen throughout history. The study of plants used by communities for medicinal use has already yielded several useful drugs. The continuing study of plants is likely to yield new drugs. However as our environment changes and as the world develops areas of high biodiversity are losing species. Two thirds of the world’s species of plants live in the rainforests which cover about 6% of the surface of the area; however this is an area of the world that is slowly being destroyed. This could have repercussions because if we don’t analyse all species in these areas we could lose sources which could have yielded useful drugs for humans.
References
Goodwin, T. W. Mercer, E. I.(1975). Introduction to plant biochemistry. A. Wheaton and co. Exeter, Great Britain.
Harvey, A. (2000) strategies for discovering drugs from previously unexplored natural products. Drug discovery today. 5:7 pp294-300
Wikipedia (2006) alkaloids <LINK HREF="http://en.wikipedia.org/wiki/Alkaloid">http://en.wikipedia.org/wiki/Alkaloid</LINK><BR/>
