The synergistic effects of the plant totum

The phenomenon of synergy, a fact recognized by all plant specialists, has been scientifically proven. But what are the mechanisms by which it can be explained?

The multi-target synergistic effect

The multi-target synergistic effect is due to the fact that different constituents of the plant totum will act not on a single target but on several targets, and will co-operate in a synergistic agonist pathway (an agonist pathway is one that will lead to an effect in the same vein as the expected effect) to lead to a potentiated pharmacological activity.

Included in the notion of targets are enzymes, substrates, proteins and metabolites, receptors, ion channels, transport proteins, DNA (deoxyribonucleic acid) /RNA (ribonucleic acid), ribosomes, monoclonal antibodies, physiochemical mechanisms, as well as signal cascades (1).

The example of whole extract of St John’s Wort perfectly illustrates the mechanism of the multi-target synergistic effect. The antidepressant activity of St John’s Wort is the result of relatively low synergistic actions induced by different constituents of St John’s Wort whole extract, on different targets involved in mild and transient manifestations of depression (2, 3).

The advantage of this abundance of active constituents and their complementary actions gives St John’s Wort whole extract an action that is at once gentle, deep and long-lasting, compared to a drug derived from chemical synthesis which, usually composed of a single active ingredient, will have a single, targeted and incisive action.

Synergistic effects based on increased bioavailability

Certain constituents of the plant totum do not in themselves possess their own pharmacological effects, but they enable an improvement in the bioavailability of other active components of the plant totum, thus enabling the active components to be much more effective than if they were acting in isolation. These constituents, usually polyphenols or saponins, are called co-effectors.

The role of some of these co-effectors will be, for example, to increase the water solubility of other active constituents of the plant totum, or to help their passage through cell membranes in the intestinal wall, thus facilitating their diffusion in the blood. Other co-effectors can also have a protective role with regard to the metabolic action of enzymes involved during the passage of active substances into the body before they reach their sites of action. Thus the active substances cannot be degraded and retain all of their activity.

As a result of kinetic studies, scientists have discovered that two polyphenols found in St John’s Wort whole extract, procyanidin B2 and hyperoside, enable an improvement in the bioavailability of hypericin and thus its effect on mild and transient manifestations of depression (4).

Synergistic effects based on the elimination of secondary or toxic effects

One of the constituents of the plant totum suppresses one or more of the adverse or toxic effects of another constituent. This is called “quenching”.

Quenching has been shown in Rhizoma Coptidis (Huang Lian), which is a plant used in Chinese traditional medicine to regulate blood sugar levels (5). In Rhizoma Coptidis, the cytotoxicity of berberine is reduced by the presence of other alkaloids and other constituents of the plant (6).

Through its multitude of constituents (several hundred), their corollary of combined and variable synergistic effects, their versatility of complementary activities, their effectiveness at low doses and by the coordinated and harmonious action of other constituents that accompany them (ideas of bioavailability, toxicity), the plant totum acts in a gentle, deep and lasting way and can have a regulatory effect in addition to its own symptomatic action.

Dr. Karine Ancolio Morcq

Bibliography:

(1) Imming P, Sinning C, Meyer A. Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov 2006 5(10):821-34.
(2) Simmen U, Higelin J, Berger-Büter K, Schaffner W, Lundstrom K. Neurochemical studies with St. John's wort in vitro. Pharmacopsychiatry 2001;34(Suppl 1):S137-42.
(3) Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 2009;16(2-3):97-110.
(4) Butterweck V, Liefländer-Wulf U, Winterhoff H, Nahrstedt A. Plasma levels of hypericin in presence of procyanidin B2 and hyperoside: a pharmacokinetic study in rats. Planta Med 2003;69(3):189-92.
(5) Mills S, Bone K. Principles and practice of phytotherapy – Modern Herbal Medecine – Churchill Livingstone 2000 : p. 58-62.
(6) An XP, Cui QR. Study advances on antidiabetes of Rhizoma Coptidis. Gansu J Tradit Chin Med 2008;21:57-58.