Herbal Medicine: Synergy in Action

Herbal Medicine: Synergy in Action

Flora’s Burnaby, British Columbia office is located a stone’s throw right across the street from the Fraser River Foreshore Park, a large park sprawling east-west along the Fraser River. The park is home to eagles, heron, and many other types of bird, coyote, beavers, squirrels, and sometimes even seals in the river. It’s also a great place for an herb walk in spring and summer. I’ve found of course the ubiquitous plantain (mostly Plantago lanceolata, or Ribwort plantain) and dandelion (Taraxacum officinalis) but also blackberry (Rubus fruticosus), red clover (Trifolium pretense), Ginkgo biloba, rose hips (Rosa canina), horsetail (Equisetum arvense), skunk cabbage (Symplocarpus foetidus), and St. John’s Wort (Hypericum perforatum). Part of being an herbalist is to appreciate how knowing and identifying local plants enhances your sense of place and your connection to your locale.

One of the most amazing aspects about medicinal herbs is that they each usually have multiple different actions, or effects. This is because the herbs themselves contain a multitude of different plant compounds with therapeutic effects. For example, Burdock (Arctium lappa), one of the main ingredients in Flor•Essence®, can be considered a diuretic, diaphoretic, cholagogue, alterative and antioxidant. In herbal medicine, a diuretic stimulates urine production as a means to flushing the urinary system of waste products. A diaphoretic has a warming effect on circulation, stimulating mild perspiration. This is useful for supporting skin health and immune health. A cholagogue has bitter properties that stimulate the liver to release bile to aid digestion and liver health. Alteratives (yes, you’re reading correctly, not “alternatives”) are herbs that gradually restore the proper function of the body and increase health and vitality. They “alter” the body’s processes of metabolism, enhance absorption of nutrition and elimination of waste products. Many herbs with this action improve the body’s ability to eliminate waste through the kidneys, liver, lungs, or skin. Antioxidants in herbs are often different kinds of polyphenols that neutralize free radicals in the body to prevent oxidative damage to cells and tissue. And this is just for a single herb!

Plants are amazing chemical factories. A single yarrow plant (Achillea millefolium) for example contains well over 100 different compounds. They use water, CO₂ and light to produce sugar and oxygen. They absorb elements from the earth and produce a dizzying array of metabolites. Besides the primary ones of sugars, fats, starches, proteins, etc. they also produce secondary metabolites that are usually the ones thought responsible for any therapeutic effects. These include alkaloids, polyphenols, and terpenes.

Because each herb contains a multitude of different compounds, there’s the potential for synergy between them and between different herbs in a formula. Synergy in herbal medicine is an argument away from assuming just one or two active ingredients are all that’s needed and everything else is useless. With synergy across a wide spectrum of ingredients, suddenly some of those “useless” ingredients may not be so useless after all. Maybe it turns out some of them aid absorption of the active ingredients, prevent side effects, or prolong the effects of the main active ingredients.

There are already several popular herbal medicines that use more than one standardized ingredient because it’s been found to work better. St. John’s wort (Hypericum perforatum), Rhodiola rosea, and Panax ginseng are just a few examples. Finding out what’s real and actual for synergy is the hard work of science and testing, over long periods of time. The reality is that the science of it is nearly endless. How much money and time do you invest? Finding one active ingredient in one herb that proves effective in clinical trials and clinical practice is often an amazing lottery win in itself! Let alone digging deeper to explore all the other constituents that might be beneficial as well. If nothing else, we have a long history of getting better at trial and error though and it’s amazing the progress that has been made in discovering what various compounds in plants do. So, what does the science have to say so far in terms of synergy between plant compounds in phytotherapy?

Let’s start with bacteria. Antibacterial resistance has been a microscopic arms race with huge consequences for some time now.  Heliobacter pylori, a bacterium that is implicated in development of ulcers, once exposed to the antibiotic clarithromycin on 10 occasions, is able to already develop resistance. But when exposed 10 times to essential oil of lemongrass (Cymbopogon citratus), consisting of at least 23 different compounds—16 of which have known antimicrobial activity—H. pylori was unable to develop resistance.¹ In this case, the complexity and variety of compounds in the essential oil is an advantage over the single, standardized compound. Plants themselves generally have evolved with a wide variety of phytochemicals as a response to various organisms, micro or otherwise, that attack them.

Antimalarial drug resistance has also been a problem for quite a while and in 2015 a group of scientists won the Nobel Prize in Physiology/ Medicine for discovery of artemisinin from Sweet Wormwood (Artemisia annua); as a result, artemisinin combined with antimalarial drugs has helped overcome drug resistance and saved millions of lives. Pharmacological studies of Sweet Wormwood have also found other constituents that aid in more rapid absorption of artemisinin and that may act as multidrug resistance inhibitors.² This may become crucial in the coming years as resistance to pure isolated artemisinin has already been found in some cases.

Goldenseal (Hydrastis canadensis) root has been used in herbal medicine for its antimicrobial properties. Three flavonoids with no antimicrobial effects themselves have been found to enhance the effects of berberine, the main active ingredient. The flavonoids are found in the leaves, while berberine is mainly in the roots. ³

In the case of Ginkgo biloba, ginkgolides A and B have been shown to have synergistic, protective effects in the brain. Other ginkgolides and bilobalide have also been found to contribute and provide a more effective neuro-protective extract than with just ginkgolides A and B alone.^4,5

St. John’s wort  (Hypericum perforatum) is a popular herbal medicine for cognitive health and mood that originally seemed to have one main active ingredient in hypericin. Hypericin works as a monoamine oxidase (MAO) inhibitor but the effect was too small to explain the overall properties of the extracts. Further research has found that hyperforin is another important constituent that prevents synaptic re-uptake of various neurotransmitters like serotonin and dopamine and other flavonoids have been found that also contribute to the overall positive effect.⁶

Rhodiola rosea is an adaptogenic herb generally used for stress and cognitive health. Studies have found several active ingredients so far: salidroside, rosavins, triandrin, and tyrosol. Each of these has their own isolated effects and has been compared with the total effect of Rhodiola extracts standardized for all three. The active ingredients together contribute to Rhodiola’s overall effects in regulating psychological, neurological, cardiovascular, metabolic, endocrine, and gastrointestinal health.^7,8

Clinical trials in humans originally were just standardized for salidroside and then adding rosavins proved to result in superior effects.

Licorice (Glycyrrhiza glabra) has a long history of use in Traditional Chinese Medicine where it is often included in formulas for its synergistic effect in aiding absorption of other ingredients or harmonizing with their effects. One example of this is both licorice root and milk thistle (Silybum marianum) protecting and supporting liver health.⁹

Piperine, a constituent of black pepper, is another ingredient sometimes added to herbal formulations to aid absorption – especially in the case of turmeric, where it has been found to increase absorption by 20 times.¹⁰

Most of this research is still in the in vitro/cell study and animal study realm. This is where potential synergies and new active constituents are discovered. Time will tell if this informs and translates into new, broader standardized extracts used in human clinical trials. In some cases, as with St. John’s Wort and Rhodiola, it already has.

So the next time you sip some of our Flor•Essence® herbal tea, you can pause and appreciate the fact that you’re tasting and drinking 8 herbs traditionally gathered and used in Canada and the USA that each contain numerous compounds all working together to stimulate and modulate a symphony of beneficial effects for your overall health and vitality. 

References

1. Ohno T, Kita M, Yamaoka Y, Imamura S, Yamamoto T, Mitsufuji S, Kodama T, Kashima K, Imanishi J. Antimicrobial activity of essential oils against Helicobacter pylori. Helicobacter. 2003 Jun;8(3):207-15. PubMed PMID: 12752733.
2. Rasoanaivo P, Wright CW, Willcox ML, Gilbert B. Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions. Malar J. 2011 Mar 15;10 Suppl 1:S4. doi: 10.1186/1475-2875-10-S1-S4. Review. PubMed PMID: 21411015
3. Junio HA, Sy-Cordero AA, Ettefagh KA, Burns JT, Micko KT, Graf TN, Richter SJ, Cannon RE, Oberlies NH, Cech NB. Synergy-directed fractionation of botanical medicines: a case study with goldenseal (Hydrastis canadensis). J Nat Prod. 2011 Jul 22;74(7):1621-9. doi: 10.1021/np200336g. Epub 2011 Jun 10. PubMed PMID:21661731.
4. Curtis-Prior P, Vere D, Fray P. Therapeutic value of Ginkgo biloba in reducing symptoms of decline in mental function. J Pharm Pharmacol. 1999 May;51(5):535-41. Erratum in: J Pharm Pharmacol 1999 Dec;51(12):following 1466. PubMed PMID: 10411212.
5. E. M. Williamson. Synergy and other interactions in phytomedicines. Phytomedicine.2001. Vol. 8(5), pp. 401–409.
6. Oliveira AI, Pinho C, Sarmento B, Dias ACP. Neuroprotective Activity ofHypericum perforatumand Its Major Components. Frontiers in Plant Science. 2016;7:1004. doi:10.3389/fpls.2016.01004.
7. Panossian A, Hamm R, Wikman G, Efferth T. Mechanism of action of Rhodiola, salidroside, tyrosol and triandrin in isolated neuroglial cells: an interactive pathway analysis of the downstream effects using RNA microarray data. Phytomedicine. 2014 Sep 25;21(11):1325-48.
8. Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. 2010 Jun;17(7):481-93. doi: 10.1016/j.phymed.2010.02.002. Epub 2010 Apr 7. Review. PubMed PMID: 20378318.
9. Rasool M, et al. Hepatoprotective Effects of Silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: A Possible Synergy. Evid Based Complement Alternat Med. 2014;2014:641597.
10. Patil VM, Das S, Balasubramanian K. Quantum Chemical and Docking Insights into Bioavailability Enhancement of Curcumin by Piperine in Pepper. J Phys Chem A. 2016 May 26;120(20):3643-53.