Plants are better chemist than humans?

Plants have had an essential role in the folklore of ancient cultures. In addition to their use as food and spices, plants have also been utilised as medicines for over 5000 years. The traditional Chinese medicine (TMC) and Ayurveda, the traditional Indian medicine (TIM), have provided most of the current knowledge related to medicinal plants. In TCM and TIM folklore, herbal medicines were prepared as teas, tinctures, poultices, powders, and other types of formulations. The expertise to select the right plants, methods of drug concoction and their specific use has been first transferred orally from one generation to the next until set down.

It is estimated that 70-95 per cent of the population in developing countries continues to use traditional medicines. Today, medicinal herbs are defined as plants that contain valuable substance with therapeutic or beneficial effect in healing and prevention of various ailments in man and animals. Herbal products such as plant extracts, dry powders and parts of plants, fungi, and algae have been used as complementary treatments alongside conventional drugs.

Many flowering plants in nature and cultivated gardens all over the world aren’t just beautiful to be used only as ornamentals, they are also carriers of properties with powers to heal diseases and treat various ailments of humans and animals. For instance, Feverfew (Tanacetum parthenium L. family Asteraceae) is a medicinal plant traditionally used for the treatment of fevers, migraine headaches, rheumatoid arthritis, stomachaches, toothaches insect bites, infertility and problem with menstruation and labor during childbirth.

The Fever few herb has a long history of use in traditional and folk medicines, especially among Greek and early European herbalists. The first century Greek physician Dioscorides used Fever few as an antipyretic. Feverfew was also known as the medieval aspirin or the aspirin of the 18th century.

Feverfew has also been used for psoriasis, allergies, asthma, tinnitus, dizziness, nausea and vomiting. The plant contains a large number of natural products, but the active principles probably include one or more of the sesquiterpene latones known to be present, including partnenolide. Other potentially active constituents include flavoid glycosides and pinenes. It has multiple pharmacologic properties, such as anti-cancer, anti-inflammatory, carchotonic, antispasmodic, and emmenagogic, and as an enema for worms.

Feverfew, originally native to the Balkan Peninsula, is now widely cultivated to a large regions of the world. It is now found in Australia, Europe, China, Japan, N. Africa, USA, Canada, and nearly all regions of the world and its importance as a medicinal plant is growing substantially with increasing and stronger reports in support of its multifarious therapeutic uses.

Another example
Researchers have developed an anti-cancer drug based on a decade of research into the commercial applications of jasmonate, a synthetic compound derived from the flower jasmine itself. The chemical, grandifloracin found in the tropical Uvaria grand flora could help treat the deadly pancreatic cancer. Anti-cancer activities of genius such as puella, tuberrosa, brittoniana (mexcan pertunia) are alternative treatment of cervical cancer cells, and the list goes on.

A new trend, that involved the isolation of plants active compounds begun during the early nineteenth century. This tendency led to the discovery of the analgesic (painkilling) drugs, morphine and codeine, from opium (papaver somniferum L.) cocaine gotten from erythroxylum coca, the cardiac glycoside, digitoxin that was isolated from Digitalis purpurea and Digitalis lanata that has been used for cardiac conditions and as anti-cancer drug, and quinine from Cinchoma calisaya. Some of these molecules are still in use. Such natural compounds provide huge varietyies, often with strong biological activity and, therefore, play a significant role in the development of therapeutic treatments.

Discovery of plant-derived substances has evolved during the last 200 years due to the variety of experience and expertise needed to identify such compound. Initially, a plant is identified by a botanist, ethonobotanist, ethnophamacologist or plant ecologist. Next, plant extract followed by biological screening performed by a phytochemist to identity the potential therapeutic activity, and this is followed by isolation of the active compound. Finally, molecular biology studies are required to reveal the mode of action and relevant molecular targets. The combination of these fields determines an interdisciplinary approach termed pharmacognosy.

Today, it is estimated that about 25-28 per cent of all modern medicines are directly or indirectly derived from higher plants demonstrating the enormous medicinal potential of plants that has been known for thousands of years in traditional medicine.

In the last decades, more and more new materials derived from plants have been authorised and subscribed as medicines. Important examples of plant origin medicines are Artether (artmotil), a sesquiterpene lactone isolated from Artemisia annua and serves for treatment of malaria, and Galantamine, an Amaryllidaceae alkaloid from Galanthus woronowii used for Alzeheimer treatment due to its activity as a selective acetylcholinesterase inhibitor.

Apomorphine hydrochloride (apokyn), a dopamine receptor agonist produced in papaver somniferum L. is used to treat Parkinson’s disease; Tiotropium bromide isolated from atropa belladonma is used to treat COPD (chronic obstructive pulmonary disease; Nitisinone (orfadin), a modified mesotrione from callistemon citrinus inhibits the 4-hydroxypheny (pyrivate dioxygenas (HPPD) encyme and prevents accumulation of fumaryl and maleyi acetoacetate in the liver and kidneys.
Interestingly, many isolated substances against cancer are connected with interactions between plants and microbes. Such interactions are related to rhizospheric or endophytic bacteria, yeasts, and fungi.

These microorganisms penetrate and reside within plants without injuring them or causing any disease. Furthermore, such microbes serve as a barrier for colonisation by pathogenic microorganisms and participate in plant growth and defense response by production of large variety of secondary metabolites.

Since almost all plants co-exist, at least one endophyte and many molecules have been isolated from such systems. Two recent studies revealed that extracts from Chaetomium globosum and 5-methyl phenazine -1-carboxylic acid that is produced by pseudomonas putida had cytotoxic effects against cancer cell lines. The similarity of secondary metabolites produced by endophyutes and their hosts implies on gene transfer between them throughout co-evolution. Taking advantage of biotechnology, new drug from endophytes can be manufactured in faster and controlled processes

In addition to the drugs mentioned above, other plants-derived substances with anti-cancer activity such as paclitaxel (Taxol) and camptothecin have been isolated and approved for use.

Examples of Plants-Derived Substances with Anti-Cancer Activity
Cancer is among the leading causes of morbidity and mortality worldwide. In 2012, 8.2 million cancer-related deaths and approximately 14 million new cases were counted. The number of new cases is expected to rise by about 70 per cent over the next two decades. Among men, the five most common sites of cancer diagnosed in 2012 were lung, prostate, colorectum, stomach, and liver. Among women, the five most common sites diagnosed were breast, colorectum, lung, cervix, and stomach. It is expected that cancer cases will rise from 14 million in 2012 to 22illion within the next two decades

Today, solid tumors are surgically removed and patients receive adjuvant radiation treatment and chemotherapy that cause severe sides effects and dramatically reduce quality of life. In addition, the toxicity of some treatments restricts their use and effectiveness. Certain types of cancer, such as breast cancer, can be treated using biological drugs (Herceptin).

However, the cost of these drugs is very high and their effectiveness is limited in most cases to certain kinds of tumors. In many cases, the tumor develops resistances to a particular drug and the patients are transferred to a different drug. In addition, many patients are treated with a combination of several drugs. Thus, there is no doubt that there is a real need for new efficient anti-cancer drugs with reduced side effect, and plants are a promising source for such entities.

Probably the most well known plants-derived anti-cancer is Paclitaxel (Taxol). The cytotoxic activity of this taxane dipertene is found in extracts from the bark of Taxus brevifolia nutt (Western yew). Later on, other Taxus species were found to produce this molecule. Interestingly, in 1993, Taxol was also found to be produced at low levels by Taxus’ endophytic fungus, Tamomyces andreanae and later on by the endophytic fungi, allowing its possible production by future microorganism fermentation.

Other plant–derived compound such as Vinca alkaloids, Taxol, disrupts microtubule function. However, in contract to Vinca alkaloids that disrupt microtubule assembly by binding depolymerised microtubules, Taxol (essentially all taxanes) inhibits microtubules disassembly by binding the polymerised mircotubules.

Although discovered in the early 1970s of the twentieth century, it took over 25 years to bring Taxol to the market. It was approved by the Food and Drug Administration (FDA) only in 1992 for the treatment of metastatic ovarian cancer.

Clinical trials also demonstrated encouraging results for other cancer types such as head, neck, lung, and breast cancers.

This anti-cancer drug that is now produced in a semi-synthetically process reached the list of the top-selling 20 drugs and sold above $ 1 billion yearly in 1999 with a peck of $ 1.6 billion in 2000. Before generic drugs appeared in the market in 2002, sales for Taxol and camptothecin, a DNA topoisomerase I inhibitor, were more than $2.75 billion, approximately a third anti-cancer drug market. Docetaxel (Taxotere), Taxol’s analog, had sales of $3 billion in 2009. Taxol’s success serves as an example and encouraging story for discovery and bringing to market additional plant- derived substances.