Lisa Ganora - synergy in botanical medicines

From the AHG Symposium

The scientific research process makes it difficult to research more than a small handful of chemicals at a time. Considering that, by some estimates, botanicals contain up to 10,000 active constituents, scientific research runs up against a limit very quickly. Fortunately, we have a practical use history to turn to: we've been eating these plants for a long time with no harm.

Polymolecular approaches, which rely on synergy, have a unique ability to interface with the complex biological system of the human being. Plants provide this. Huge difference compared to pharmaceutical agents. Additionally, pharmaceuticals are very new on the scene. And most aren't cheap (whereas plants...)

Vitalism: boiled down by Paul Bergner, "Nature is Smarter". Case in point: digoxin in foxglove. When consumed alongside other foxglove chemicals, overdoses cause nausea and vomiting. When digoxin is purified, it loses that "warning sign". Molecules are like people: we behave differently in different situations. You're not going to behave in the same way at church with grandma as you do at the corner bar. Another example: "when embedded in a phytochemical matrix with companion molecules, ascorbic acid can behave differently ... this is antioxidant synergy". Ascorbic acid + Iron, on the other hand, is a strong oxidative agent.

Plants are chemistry's dynamic matrix. Dynamic is key. Always changing, always adapting, always efficient! This variability can seem to be a source of difficulty, of confusion. But herbalists can get a handle on the overall balance of botanical chemistry through organoleptic (sense-based) assays. [Guido's note: I really feel that human intuition is an expression of an interaction between complex living systems. That is to say, when we intuit that a plant is ready to harvest and will be useful, we are drawing on the sum total of our organoleptic assay, environmental awareness, memory, and need and coming up with a synthesis that determines usefulness. Our physiology (brain included) is a great pattern-recognition system that can be drawn upon to do complex, "fuzzy" calculations in near-real time... but only if we let the rational side go].

Co-evolutionary theory underlies the development of complex phytochemical matrices - and extends to humans as well. As people develop relationships with plants, we select for each other.

Types of synergy: potentiating (enhanced activity), stabilization (protect certain constituents), modification (attenuation of toxicity). Side note - "just because there's a known toxic constituent in a plant doesn't mean that plant will be toxic. I ate comfrey as a vegetable when I was pregnant. Modification synergy at work".

St. Johnswort is a great example of a plant that only works through potentiating synergy. Isolation of an active ingredient has consistently failed. Hyperforin, hypericin, xanthones, hyperoside, melationin and more all work together [Guido's note: Ginseng is another great example. We still can't point out an active constituent].
Clinical note: consider mixing your concentrated extract (St. Johnswort, Ginkgo, Milk Thistle, Turmeric, etc...) with a little powdered whole herb, tea, tincture or other crude prep. Take advatage of synergy.

Potentiating synergy types: affecting stability / reactivity of different constituents; increasing bioavailability; chemicals can be co-ligands of a receptor; one compound might inhibit enzymatic breakdown of another chemical.

An example of stabilizing synergy is the process of "redox cycling": botanical antioxidants re-activate one another and prevent pro-oxidant activity. Way more effective than eating isolated, single antioxidants (vitamin c, or quercetin, e.g.). There are well over 60 types of citrus bioflavonoids in a fruit, along with carotenoids or vitamin c.
This might underlie an interesting observation about carotenoids: 20mg/day trans-beta-carotene over 5-8 years to 29K smokers / drinkers actually led to 18% more lung cancer. When taken with Vit. E, no change in lung cancer rates. If they simply ate a high-carotenoid diet, there was less lung cancer (NEJM 1994; 330:1029-35).

Dandelion flowers are a great example of phytochemical synergy. They contain a cocktail of carotenes (beta and other). Also xanthophylls (lutein, cryptoxanthin). Flavonoids (luteolin, quercetin and their glycosides). Phenylpropanoids  - simple plant acids such as caffeic and chlorogenic acids. Triterpenes such as taraxasterol. Bitter sesquiterpene lactones. Some are oily, some watery. Taken together, they are anti-cancer, antioxidant, anti-inflammatory, and neuroprotective - but only when eaten as WHOLE dandelion flowers.

Black pepper (and its alkaloid piperine) is another example of synergy, but one where synergy relies on affecting endogenous (inside us) processes and thereby potentiating the activity of other phytochemicals. Piperine increases absorption and delays breakdown of many oil-based plant constituents. This has long been known in Ayurveda, where Trikatu is added to lots of formulas.

Oregon grape root is a great story of synergy. Its root contains lots of berberine, which is antibacterial and strongly inhibits Staph aureus. However, Staph uses a multi-drug-resistance pump (P-glycoprotein) that ejects the berberine to try to counteract its toxicity. But in the leaf of Oregon grape has 5'-MHC-D and pheophorbide-A which inhibit the multi-drug-resistance pump. Moral of the story: great synergy, but take a whole-plant preparation! (Stermitz, 1999)

Attenuation of toxicity is often seen in traditional polyherbal preparations. For example, Licorice markedly buffers the toxicity of prepared Aconite (monkshood) root.