Why to go for isolation of phytochemical constituents when we know that these components act synergistically to show the enhanced efficacy?
The composition of phytochemical constituents varies with geographical locations and also with harvesting conditions. Full characterization of the crude extracts is a difficult task. The isolation and purification allows to have the phytochemicals having bioactivity and those having toxic effects separated. So in pure form the compounds showing synergistic effect can be mixed in fixed proportion to have the reproducible and accurate doses in therapeutic applications. Also the structural determination (enables production of synthetic material or chemical modification) of purified compound can be done and used to develop analytical assays which are necessary for quality control.
phytochemicals must be extracted if we are to study the composition of plant bioresources, and determine which ones have bioactivity. If they are not extracted, we may miss some important compounds and their bioactivty from plants, which may potentially be functional against a disease process. Besides, the activity of some phytochemicals may not be readily apparent if left in their original matrix perhaps due to potential inhibitors or binding to other components. If we do not extract, how then would we be able to determine which compounds were responsible for any given activity due to a plant?. There must be evidence-based justification for any activity that is claimed for a phytochemical and that includes showing a direct link between the phytochemical in question and the activity, even if it is for academic reasons. However, it is true that phytochemicals produce synergism when they are together, at least this is what our data has shown consistently. What we now try to do is to extract "rich fractions", in which a lead phytochemical is extracted together with smaller amounts of other compounds to enhance functionality. This also maximises the benefits from such plant.
Dear Bhavesh,
Mere statements does not make it Science.
If you state 'synergy in efficacy', you should first prove that the pure compounds does not have the activity or have very little activity. Then prove that once your bring them in combination, they show activity which is far more and beyond the 'additive effect'. In order to do this, one needs to isolate the compounds, study the efficacy of the mixture and the invidividual compounds and prove or disprove the statement 'synergy brings efficacy'
Good luck
If it is proven scientifically on the basis of sound research that phytochemical constituents in combination are having synergy in their efficacy with reasonable safety and in isolated forms they are showing significantly less efficacy then normally there is no need to isolate the individual compound. However there are so many practical problems in acceptance of this concept.
1. Lack of standard quality control profile is one of the major hindrances in global acceptance of phytochemical constituents in their combined forms like in form of extracts. There must be some bio-marker of the combination, on which basis the combination could be standardized. This is one thing which is required for the validity and/ or reproducibility of the therapeutic claims. If we are having combination of phytochemical constituents then again it would really be a tough job to develop standard quality control profile of the combination.
2. Once this profile is developed, again in order to generate data for claimed efficacy and safety profile of the combination or its validity pharmacokinetic parameters like Absorption, Distribution, Metabolism and Elimination (ADME) needs to be established which is again a very complex process.
3. Further, when the same combination needs to be converted in to some dosage form, there are certain parameters which can not be ignored viz. optimization of the dose of the combination to be administered at one time, type of dosage form to be converted in to, compatibility of all the phytochemical constituents with other excipients of the the dosage form, stability of the developed dosage form, standardization of developed dosage form etc.
These are some of the major issues related to development and use of phytochemical constituents in their combined forms like extract etc.
If that is the case then we might have missed the possibility of getting effective life saving drugs like Docetaxel, Paclitaxel, Vinblastine, Vincristine, Topotecan, Irinotecan as antineoplastic agents, artemisinin , arteether as antimalarial agent etc in the market now.
So it is not so...
Establishment of a lead, effective molecule as a phytochemical with lesser side effect remains important in the area of drug discovery for which standardisation in terms of quality and its pharmacokinetic profiling needs to be studied in detail and this cannot be achieved fully if it is going to be an extract or even constituent rich fraction..
Focus should be on phytochemical rather than crudes to have a clear scientific idea.
Put simply, intuitively 'knowing' multiple small molecules (phytochemicals) work together to promote some sort of biological affect is very different than demonstrating it. You must purify the individual phytochemicals from plant sources to a quantifiable level of purity, as determined by HPLC, GC, MS, NMR, IR etc - or obtain them from commercial and quality assured sources, and perform the appropriate experiments to show synergy of the components in some biological system.
Remember, synergy is defined as a biological affect which results from the combined use of multiple components, in this case phytochemicals, that results in a biological affect which is greater than the sum of the biological affect ellicited by the individual components. Simply being higher than one of the individual components does not mean it's a synergistic affect, and in fact may indicate some kind of repressive combined phenomena, depending on the total quantified affect value.
Hope this helps.
Bhavesh: There are a number of assumptions here.
You are basing your assumption on the premise that the extract is superior in effectiveness to that of the multiple phytochemical (any number of them) constituents in the matrix. Synergy in efficacy… Do you mean to say "synergistic effects'? Synergy or synergism of what parameter of the extract? In reference to what? Examples: antimicrobial activity; inhibition of release of histamine, etc. It would be fallacious to talk of synergism of a plant extract without having something to compare – two discrete and independent agents or compounds here. By, “they”, I am assuming that you are meaning crude extracts. You are alluding to synergy of the extract; in relation to what? I must hasten to add at this point that what is broadly implied in your question is interesting. However, it has to be qualified with the inclusion of two or more reference molecules, and defining what effect you are measuring (having in mind).
1. Synergism: interaction of discrete agents or conditions such that the total effect is greater than the sum of the individual effect.
2. Synergy: the increased effectiveness resulting from two or elements working together.
3. For producing synergism you need more than one agent (drug or molecule).
4. < Why to go for isolation of phytochemical constituents when we know that these components act synergistically to show the enhanced efficacy?> How do we know? What if the effect is antagonism as opposed to synergism?
5. Extracts contain complex and multiple (a panoply) components. Two or three discrete molecules in the extract, depending upon their action, may interact and produce addictive, or synergistic, or antagonistic effects. Two independent components, associated with extracts, could produce synergistic interactions but these effects may not be optimal.
6. Synergism (see above) reflects an effect that is observed.
7. Efficacy is, in general, independent of potency and affinity. It is the maximal effect that an agent is able to produce. It is related to intrinsic activity.
8. Pharmacology deals with distinct, discrete individual compounds. Science, as practiced today, is inherently Western; its approach is analytical, reduction based (reductionist), and evidence based, and related to positivity as opposed to intuitive activity.
Optimization and standardization of all the parameters involved, are very important aspects to be considered in verifying the claim of efficacy, which remains a basic shortcoming when we talk about extract as such, since it comprises of many known and unknown components. The extract may prove to be synergistic in efficacy but its ultimate destiny is to get converted to a dosage form and produce a pharmacological action. As long as efficacy is desirable, its fine. Now, from the point of view of a pharmacologist, synergy in efficacy might not always be the requirement, excessive synergistic effect is not at all desirable in almost all cases. If we are dealing with human health and talking about substantial science, the effect (pharmacological action) must be quantified and the component responsible for the effect (active pharmaceutical ingredient) must also be identified, quantified and verified. Hence, isolation of components is important.
Dear Kandaswami sir and Suchita Dubey I am thankful to you and appreciate your kind, valuable and informative suggestions.
In crude extracts we came to know partial effect, with synergistic action also we will get little more effective result but in isolation of active constituents will give 100% activity and more potential than the crude and synergistic action. Hence if you know the positiveness of the extract result then go for phytochemistry and isolate novel compound through spectral analysis.
Most times in crude extract, there are lots of phytochemicals and some of them may not be responsible for the activity of interest. Isolating them helps to determine whether each of the pure component of that extract have the activity you are interested in so that when you combine them, you can be able to demonstrate the synergysm between them.
Also toxic effects of phytochemicals can also be synergistic. so Isolating them may also reduce on toxic effects, if the toxicity is due to one of components.
The composition of phytochemical constituents varies with geographical locations and also with harvesting conditions. Full characterization of the crude extracts is a difficult task. The isolation and purification allows to have the phytochemicals having bioactivity and those having toxic effects separated. So in pure form the compounds showing synergistic effect can be mixed in fixed proportion to have the reproducible and accurate doses in therapeutic applications. Also the structural determination (enables production of synthetic material or chemical modification) of purified compound can be done and used to develop analytical assays which are necessary for quality control.
When we are using crude extracts, it will show good activity since the chemical constituents are in combined form. Each and every solvent extract has different biological activities. Identifying a active crude extract is essential. When particular solvent extract is active we should know the what are the chemical constituents in them. We should go for fractionation of the active crude extract in order to assess which fraction (single constituent or one more constituents) responsible for the activity. If the fraction has more activity and further fractionation is essential if the fraction has more than one chemical constituents using TLC. In order to eliminate the inactive constituents, we should go for isolation of single phytochemical constituent and will be mass produced using chemical synthesization. This process will enable to protect the environment by conserving the concerned plant from further exploitation if the particular plant is in serious economical threat,
It is important to isolate phytochemicals from crude extract even though some of them have synergestic effect because there could be other phytochemicals in the crude extract which do not contribute to the observed effect, and might reduce the efficacy of the extract or even cause toxic effects. However, after isolation and purification of the active principle (phytochemical), the efficacy of each phytochemical in the crude extract can be tested and those with similar properties could also be tested for synergestic effect.
Hi, Phytochemicals are chemical compounds formed during the plants normal metabolic processes. These chemicals are often referred to as “secondary metabolities” of which there are several classes including alkaloids, flavonoids, coumarins, glycosides, gums, polysaccharides, phenols, tannins, terpenes and terpenoids it is a must to isolate to verify their efficacy and usefulness, in order to know which one is good for human metabolic activity, use can check out one of my publication on the screening of phyutochemicals of Nigerian medicinal plant.
Herbal therapy is based on synergistic therapeutic action to plant or its officinal part. However the aim to isolation, characterization, structural elucidation of different types of plant secondary chemicals including steroids, alkaloids, terpenoids, polyphenols, flavonoids, glycosides, polysaccharides, terpenoids, etc to pin point the particular phytochemical responsible for specific therapeutic action. In this process some new pharmacological activities are also discovered. Furthermore, through knowing their molecular structures, attempt could be made to synthesize the desired compound. It would be worth mentioning here that with continual decline in forest cover and natural habitat of medicinal plants, a significant number of valuable MPs have become rare and endangered and some of them have become almost extinct. If this process goes on in future, the synthetic production of plant derived lead molecule would be the only option. But the fact is that a number of phytochemical could not be synthesized as yet. Therefore, use of time tested herbals in therapy is effective and safe owing to synergistic therapeutic action of compound present, their exploration through modern phytochemical, pharmacological, biotechnological approach is also warranted at the same time.
not all the components may produce synergy, some may reduce the activity of another compound by binding or forming complexes, affecting solubility, absorption rate, toxicity etc
@Godwin - It is an aspect of detailed investigation. However, non of the traditional therapeutic claims of medicinal plant have so far been denied by modern research. All traditionally known curative properties have been validated through modern phytochemical and biological studies. Yes, modern research have discovered some new bioefficacy of various medicinal plants which were not traditionally known.
It could be used as biomarker in quality control of medicinal products, knowing its structure is good for pharmaceutical evaluation in various bioactivity.It can be developed to modern medicines, planing for drug design, partial synthesis, structure related to bioactivity studies, many more benefits and lots of modern medicines can be developed froim just only one compounds.
Dear Khanittha,
Such isolations alongwith bioactivity guided fractionations will surely lead to give a chemical moiety through which new bioactive compounds can be synthesized. I appreciate the suggestions made by all.
l'isolation et la purification des composés organiques dans une herbe ne sont pas toujours facile à réaliser , mais il est important d'identifier les principes actifs, d’établir l'effet de synergie , la dose efficace et d’éviter le risque de toxicité , sachant que toutes les herbes ne sont pas sans risques ex : Salvia Officinalis , Aristolochia Longa..
de plus ces structures ainsi séparées peuvent être utilisées comme matériel de référence
You need to think that one isolated compound with significantly actitivity can be more safe to use as a drug, since it can act in a few number of receptors in human organism, than a mix of compounds that exists in a crude extract, for example.
We need to establish the bio active potency of the phytochemical constituents in isolation and in combination with one another. My experience with some plant products indicate that the environment may or may not induce synergy.Two phytochemicals may be active in isolation but when put together their potency may not be enhanced. On the other hand the biological activity of a phytochemical can be enhanced by the presence of another phytochemical. I have observed this in plant products and their isolates. Isolates from Piper guineense did not enhance activity of one another , but the crude extract shows good potency against insect pests. . The bioactive compounds from other plant products like Saccoglottis gabonensis showed synergy
It is always desirable to know the biological activity of isolated compounds from plant extract, before determining if the various compounds may work in synergy. This is because isolated bioactive compound with high potency may serve as candidate for developing a new therapeutic drug, while there may be compounds in the same plant extract which might have adverse effects on living tissues. This information can be found by isolating the active principle(s) and evaluating them individually in living organisms.
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