It is reported that there are 396,000 higher plant taxa (the smallest classification unit used for species with different characteristics) identified so far on the earth. There are hundreds of compounds in every plant. Among these, the basic elements found in every plant and necessary for the development of the plant, such as carbohydrates, proteic components, and fixed oils, which determine the nutritional properties of the plant, are called "Primary metabolites". Components such as alkaloids, phenolic compounds, and terpenic compounds that differ from plant to plant and are generally responsible for their biological effects are called "Secondary metabolites". However, each plant organ differs in terms of both chemical content and biological activity. Phytotherapy, on the other hand, can be simply defined as “utilizing the holistic effect of the components in a plant organ without separating them from each other.”

On the other hand, secondary metabolites are often used as a model for the development of new drugs by separating and identifying them. However, this group of drugs is no longer included in the scope of phytotherapy.

Are Phytotherapy Experiences Merely Observations? Are Laboratory or Clinical Studies Conducted as in Pharmaceuticals?

Phytotherapy literally means "Treatment with Plants". However, today it should be evaluated with two different dimensions.

• Applications developed with the effect of European Phytotherapy in general.
• Applications that are used by people in the world or developed with the effect of Traditional Treatment Systems (Chinese Medicine, Ayurvedic Medicine)

 For both groups, the beginning is undoubtedly based on experience.

Unani Medicine, which developed as a result of the translation of works reflecting the experiences of ancient Greek and Roman physicians (Hippocrates, Dioscorids, etc.) into Arabic and the contribution of Islamic physicians (Ibni Sina, etc.), continued its influence in Europe and the Middle East until the 1700s and formed the basis of today's phytotherapy.

The inclusion of herbal medicines in the second group (b) into common phytotherapy applications has been due to the effects of scientific research results that have increased recently. As a matter of fact, some plants that are widely known in today's phytotherapy originate from traditional treatment systems. “Ginkgo biloba” (Tebokan etc.) used in the treatment of dementia; “turmeric” (Curcuma longa) Devil's Claw (Harpagophyllum procumbens) herbal medicines developed with modern methods from Traditional Chinese Medicine Ayurvedic Medicine (the Indian Therapeutic System) and South African Tribes’ treatments, respectively.

 Long and expensive clinical studies (phase studies) are not required by the International Health Authorities (WHO, EMA, etc.) in phytotherapy products, as in chemical drugs, to demonstrate and prove their efficacy and safety, if they are used as traditional folk medicine for a long time. However, it definitely must be analyzed whether it contains sufficient “active substance”.

Since Phytotherapy is Based on Hundreds or Even Thousands of Years of Traditional Knowledge, Could it Find a Place Among Modern Medical Practices?

The main reason why phytotherapy has attracted increasing attention today, especially after the 2000s, is thanks to the developing modern chemical and biological methods, the efficacy and safety of herbal medicines have been proven, the pharmacological mechanisms of action have been elucidated, and the pharmacokinetic and pharmacodynamic parameters have begun to be analyzed to a large extent.

These defined features are indispensable elements of today's drug concept. What I particularly want to emphasize is the synergistic and antagonistic interactions of the multiple components present in herbal medicines. Today, research on the etiology of diseases reveals that each disease develops due to various factors. For example, in the treatment of microbial infection, to what extent would it be correct to kill the microorganism/stop the development by only giving antibiotics? Because in this way, the inflammatory pathway is triggered in the body against the lipopolysaccharides that form the cell structure of the microorganism, and a group of signaling molecules (interleukins, TNF-alpha, IFN-gamma) are synthesized.

These endogenous molecules synthesized against the threat of microorganisms, on the other hand, act as free radicals and cause oxidative damage in the body, and as a result of this vicious circle, pathogenicity can be observed in body cells. There are components in the combined structure of herbal medicines, that can fight different phases of diseases, and, some of them are effective against microorganisms, some of them ensure the balancing of signal molecules in the body, and some of them prevent oxidative damage in organs. As a matter of fact, it is now seen in the modern drug concept that multiple drugs have been developed that can be effective over this basic approach in treatment.

Of course, it is not logically and scientifically possible to expect every plant to be effective on every disease. Studies show that inflammation and oxidative damage are involved in the etiology of almost every disease. Studies show that almost all plants contain anti-inflammatory and antioxidant-effective components. Surely, the activities of the plants may differ according to the proportions of these components in the plants. I would like to give the following example, perhaps to be more explanatory in this regard; only 9 different anthocyanidin structures provide the color riot of flowers in nature. When these are mixed in different proportions, the colors of the flowers emerge. Just like in color printers, any color can be obtained with 3-4 color cartridges. Likewise, the presence of terpenic components in different proportions in the composition of essential oils provides very different fragrances.

Phytotherapy is a Science. However, Many Unrelated People Suggest That They Do Herbal Treatments. To What Extent Is This True? What are the Drawbacks?

Phytotherapy Training is given scientifically only by the Pharmacognosy Departments of Pharmacy Faculties. In other words, only pharmacists receive this training. Because in order to make a scientific evaluation, it is necessary to know plants (Botany), to know their chemical contents (Phytochemistry), and to interpret their biological effects (Pharmacology). As can be seen, in order to make an evaluation on a scientific scale, information from many different disciplines must be correctly blended. The suggestions made by a person who knows only one of these sciences, seeing himself as an "expert" can be very dangerous. Of course, the most important danger is the suggestions made by people who "feel themselves experts", who do not have any scientific knowledge, with great pedantry in the written and visual media.

There are Abuses in Some Areas Like In Oncology. What is Your Opinion on These Abuses? In Which Areas Does It Happen Most Often?

The proverb "a dworning man clutch a straw", which is widely known among the people, describes this situation the best. In some areas where modern medicine has had limited success, hope merchants, who carelessly make "definitive treatment" recommendations, unfortunately, sell products at high prices. Cancer is the most abused area in this regard. After a lack of conscience, what can be done against those who gamble so easily with human life? This is one of the issues that I am sensitive about.

If physicians ignore current scientific developments about phytotherapy and other possible treatment options in their fields of expertise and give negative messages to patients on these issues, they cannot prevent their patients from shifting to treatments beyond their control. In this case, the patient falls prey to charlatans, who claim "definitive treatment". The physician loses control over his patient and cannot know the real reasons for the success or failure of his treatment. For this reason, physicians' knowledge of phytotherapy and other complementary treatment options, at least in their field, and integrating them into their own treatment practices as much as possible will increase the patient's belief in the physician and the treatment. I consider this as a social responsibility of physicians toward their patients and I care about it. 

There are many Books Published on Herbal Therapies in the Market. How Reliable Are the Recommendations in These Books?

I have a collection of books in my library, written on phytotherapy in the market, the authors of which include lawyers, farmers, housewives, and beauticians other than health professionals. The false treatment recommendations or information in these books are truly alarming. Some are funny! A comedy show can be made using the information in these books.

I tell examples to my students once in a while and it is very entertaining. People generally think that they are writing books by buying and translating foreign-sourced books. However, there is a similar situation abroad. In other words, the book you are trying to translate may have been written by someone who is not an expert. For this reason, the books to be used as a source should be chosen well. There are also some news and articles published in newspapers and magazines. There are also some news and articles published in newspapers and magazines.  For example, after observing that a plant extract kills cancer cells due to the content of high fever in in vitro conditions, we often witness it creates an agenda in newspapers like; "Turkish scientist discovered and patented a drug against cancer". The reason for this is that these people are unaware of the pharmacokinetic and pharmacodynamic changes in the body when the plant components are used orally. Of course, some scientific resources can be used. However, whether these sources are reliable or not should be evaluated according to the quality of the scientific literature, the institution that prepared it, the authors, and the experts. The history of knowledge is also important. Because phytotherapy is a branch of science that is open to improvement. Information from a few years ago may lose its validity with constantly renewed findings.

What Do You Think About Treatment Recommendations And Product Sales Through Herbalists, the Internet, Grocery Stores, or Television Sales Channels?

When herbal medicine is mentioned, herbalists/spice sellers come to mind immediately. Undoubtedly, herbalists have been an address where herbal healing products are provided for hundreds of years in the entire Islamic world. However, today, there is no healthy environment as it used to be. That is, toxins such as industrial wastes, agricultural and veterinary drugs, radiation, heavy metals, and microbiological endo/exotoxins can contaminate all sources around us. In this respect, it is necessary to control whether herbal products carry these toxic risks. Why are there so many liver and kidney patients? In my opinion, the contribution of aflatoxin, heavy metal, etc. intoxication is great! Unfortunately, it is unclear to what extent these risks can be controlled in channels such as Akhtar or Spice Shop. I think it would be right for them to limit their sales and suggestions to "spices" that are also beneficial for our health, rather than endangering human health in this way, of course on the condition of paying attention to the quality of the products they sell and not making exaggerated health recommendations...

We occasionally conduct analysis studies in our laboratories regarding the products sold in the market and sales channels. The results are truly deplorable. For example, none of the 25 different May daisy samples we received from herbalists turned out to be real daisies. There was no active substance. Again, despite its high price, we could not find any effective substance in an artichoke capsule imported from America, which we bought from a beautifully decorated modern spice shop in a shopping mall. We have detected high levels of sibutramine, which can cause death, in herbal slimming products sold on the market and on the internet. And we detected sildenafil and its derivatives in all herbal aphrodisiac products sold on the internet. It is possible to multiply these examples. I think that people who buy this type of health products online like to play "Russian Roulette".

Some Physicians are very Skeptical about These Treatments. In fact, They Hardly Believe in Them at all. Some are More Moderate. Do You Think to What Extent the Medical World Knows About Phytotherapy?

Unfortunately, since the subject of phytotherapy is not included in the basic training of physicians, they cannot make effective comments on this subject. Because without knowing the plant and its chemical content, it is not possible to make an accurate assessment based only on the biological effect. Since they do not have time to learn new information in their busy work tempo, they give false information such as "ineffective" or "harmful". In this case, they push patients into the arms of hope merchants. Physicians, who love their profession and give importance to human health, learn basic information in order to make accurate scientific evaluations by taking education in our post-graduate programs. However, the number of these physicians needs to increase rapidly. Physicians can work as "Phytotherapy Specialist" after 280 hours of training, within the scope of the "Regulations on Traditional and Complementary Medicine Practices" that came into force in 2014. However, I think that this period is not enough to gain sufficient knowledge about phytotherapy. Still, I consider it an important development. According to my observations, this situation leads to different risks in my opinion. Physicians who have completed their training as Phytotherapy Specialists within the scope of this regulation suddenly see themselves as “Phytotherapy Masters” and make wrong evaluations and directions. As in any profession, mastery is gained only with long-term experience; “Nobody is born as a master.”

What Should Be Considered While Purchasing Herbal Products?

The most important parameter of the current drug therapy concept is "standardization". In other words, each dose should reach the same level in body fluids in order to achieve the desired treatment response. The same is true for herbal medicines. In this regard, it is recommended to buy "Herbal Medicine" (phytotherapeutic, phytopharmaceutical) and Nutritional Supplement (nutraceutical) group products preferably from pharmacies, and to buy herbal teas from pharmacies or markets with packaged products of reliable brands. Speculative claims about filtered tea bags are unfounded. The filtering bags are made from banana leaf fibers. It is the healthiest form of herbal tea as the herbs can be dosed appropriately in filter bags. Since there are no controls on products sold online, buying these products means risking our health while trying to protect them. Some nutritional supplements such as Omega-3 are sold very cheaply in some discount markets. The product, which is 70-90 liras in pharmacies, is sold for 15-20 liras. Cheap products are made with the lowest quality and cheapest raw materials found on internet sites in China. This does more harm than good to health. It can even trigger cancer. In fact, I know that the cheap markets are not aware of this situation. Some greedy people abuse an innocent act to provide cheap goods to the public.

On the other hand, current developments in pharmaceutical technology are also applied in the field of herbal medicine. Techniques such as nanoparticles and phytosomes are used to increase bioavailability beyond standardization. Therefore, current phytotherapy meets all contemporary requirements beyond boiling and drinking the herbal plant. In this regard, quality reliability should be considered. For example, the absorption of curcuminoids from turmeric root taken from herbalists is only 1%. This amount is sufficient when used as a spice. However, in order to get a treatment response in a wide-ranging pathology such as cancer, or osteoarthritis, continuous and high absorption is required. Adding "black pepper", one of the suggestions made for this purpose, increases the absorption by 1 time, that is, it is absorbed by 2%. Again, an insufficient level. While turmeric oil formulas provide 7 times (700%) absorption, the developed phytosome formulas provide 29 times (2900%) high absorption.

Does Being Herbal Mean Being Innocent?

 It should not be forgotten that; The strongest poisons are herbal. The important thing is to use appropriate quality, appropriate quantity, and appropriate time. Like water. We cannot live without water, but too much water will kill us. Knowledge is extremely important in phytotherapy applications. Because herbal medicines also show pharmacological effects. Therefore, herbal medicines used unconsciously with the thought of "helping the treatment" may strengthen the effect of the applied allopathic treatment, leading to side effects / adverse effects, or may antagonize the effect of the applied treatment, leading to the weakening/ineffectiveness of the applied treatment. For example, St. John's Wort (Hypericum perforatum) is a very important herbal medicine. However, it causes rapid elimination of some drugs from the body due to P-glycoprotein induction and/or hepatic enzyme induction. Risks can be seen due to the inability of vital drugs such as digoxin and cyclosporine, which are among these drugs, to reach a sufficient concentration in the body.

Do Herbal Products Change the Effects of Some Medications Used?

This is a separate topic in itself. It definitely must be evaluated scientifically. Herbal products also act on some biological systems in the body like drugs. Therefore, herbal products that are used unconsciously to support the synthetic medicine taken can pose a life risk. For example, when some herbal products are taken together with diabetes medications, the patient may enter a diabetic coma. Likewise, blood pressure medications and plants that have a blood pressure-lowering effect may pose a risk. The blood-thinning effect is very common in plants, including nutrients. In this regard, the risk of bleeding increases with antiplatelet and antithrombotic treatments. I would like to draw attention to an important point here. Components beneficial in helping regulate the health values such as blood sugar, blood pressure, blood thrombin level, etc., are commonly found in plants. However, when these are used in healthy individuals, they never cause a health risk beyond normal blood values. They do not cause risks such as hypoglycemia shock, low blood pressure, or increased risk of bleeding. When used together with allopathic drugs, they may increase the effect of the drugs and lead to risk.

When to Use Phytotherapy, When to Use Pharmacological Medicine?

Scientific research reveals that natural components of plant or animal origin, unlike chemical drugs, are recognized by the physiological systems in our body and processed into active metabolites. In particular, the rich enzyme diversity of probiotic bacteria plays an extremely active role. For example, glycyrrhizin, the active ingredient of licorice root, has a weak antiviral effect, while the antiviral and antiallergic effect is strengthened by the compound (18-glycyrrhizic acid-3-O-monoglucuronide) that occurs when the terminal one of the two glucuronic acid molecules attached to the triterpene ring is removed by the specific enzyme found in probiotic bacteria. In this regard, intestinal flora plays an important role in the effectiveness of herbal medicines.

My treatment philosophy is “herbal medicine first, pharmacotherapy second, knife last.” This order is the current version of the suggestion made by Asclepius, who was called the God of Health in Ancient Aegean civilizations, 3000 years ago. I am trying to implement this order. In my opinion, therapy is engineering; “Health Engineering.” System crashes when not well-directed!

Prof. Dr. Erdem YEŞİLADA

Yeditepe University Faculty of Pharmacy
Department of Pharmacognosy and Phytotherapy