Scientific evidence for synergy in a botanical product

So, you’re curious about herbal medicine. Is there any truth to this stuff?

Uncle Howie tells you that he read in the National Enquirer about an herb that has better antibacterial effects on cuts and scrapes than Neosporin ointment — never mind that Neosporin is composed of three different antibiotics that come originally from bacteria themselves.

So you set out on a quest to purchase some of this herb, known colloquially as goldenseal. When you go to your local Whole Hippie Dump-a-Load-of-Cash Emporium you find goldenseal alright, in about twenty different forms. On one side of the aisle are containers with loose, crushed up leaves and roots that look like medical marijuana. On a shelf, you find see-through capsules that seem to contain a powdered version of the herb. Down the aisle a bit you find boxes of blister-packs containing a proprietary extract of free-range goldenseal from the Appalachians harvested under moonlight by bare-breasted virgins. The same company also makes an ointment, allegedly procured the same way.

A scraggly young man with a rainbow-colored Whole Hippie tam comes by and says, “Dude, can I help you?” As you wave away the cloud of patchouli oil and three days of body odor, you ask him, “So, this goldenseal — which one should I buy?”

Hippie Boy looks both ways down the aisle and motions with his finger to come close.

“Dude, all this expensive stuff is just a ploy by The Man trying to make a buck with their fancy scientific words and processes. What you want is the whole herb, man — the stuff given to us by the sprites and spirits. Those capsules miss the point. Part of the magic is missing. You pay extra to get less.”

“But, dude,” you say. “I want to try the ointment, you know, for cuts and scrapes. How do I use this herb?”

The fine young man then explains how to make a poultice, an old-fashioned decoction of plant material that one wraps on a cut — sort of like collard greens.

This really seems like more trouble than it’s worth. You’re about a millisecond away from just heading down to the Done-Rite Drugs, Liquor, and Tobacco to buy a simple tube of Neosporin. But hey, it’s an experiment and you’re curious.

While you’re checking out from the health food store, a local scientist friend is in line at the next register, checking out your stash of goldenseal.

“You know, you should really go read Science-Based Medicine to get the straight dope on that stuff.”

And so, here you are. And I’m here for you.

[Note to readers: Apologies to my hippie friends. I love you all. No hippies were harmed in the drafting of this blogpost.]

Is there any scientific evidence to support a common herbalist claim that whole plant materials are “better” than semi-purified extracts or pure, individual chemicals made by the plant?

And I can tell you this — it depends.

ResearchBlogging.orgBut as long as the National Center for Complementary and Alternative Medicine (NCCAM) is in existence, this is the exactly the kind of work that should be supported by this arm of the US National Institutes of Health. In a recent paper to appear in the Journal of Natural Products, Dr. Nadja Cech and colleagues from the University of North Carolina at Greensboro, Dept. of Chemistry & Biochemistry, used traditional separation chemistry and cutting-edge analytical chemistry techniques to address this very question.

[Update: I neglected to note at the time of posting that Catherine M. Cooney wrote a nice article on this work at the online site for Chemical & Engineering News.]

The medicinal use of goldenseal (Hydrastis canadensis L. (Ranunculaceae)) dates back to Native Americans of the Cherokee and Iroquois tribes. Goldenseal was used externally for skin and eye infections and internally for relief from gastrointestinal symptoms. Today, goldenseal ranks among the 20 top-selling herbal products in the US.

In her group’s paper, Cech demonstrates the cooperative action in goldenseal between berberine, a weak, naturally-occurring antibacterial compound in the plant, and other chemicals that make the berberine more active. Even more fascinating is that these berberine-enhancing chemicals have no antibacterial activity on their own. In other words, these other chemicals potentiate the bacteria-killing effects of berberine. This potentiation is a form of synergy, a process where the combined action of two or more chemicals is greater than the sum of the parts.

(Disclosure: I have a NIH-funded collaboration with co-authors on Dr. Cech’s paper but not with her laboratory.)

Cech and her co-workers had already known that berberine killed Staphylococcus aureus bacteria at relatively high concentrations. Microbiologists use a term called, “minimum inhibitory concentration,” or MIC, to describe the minimum concentration of a drug required to kill a population of bacteria. But Cech had also observed that some parts of the goldenseal plant could increase the action of berberine.

To find out what these chemicals were, Cech’s lab purchased whole goldenseal plants, crushed them up in a series of alcohols and solvents, and separated out the constituents using a process called flash chromatography. Picture a tube filled with a specialized type of sand, silica gel. When you pour a gimmish on top of this column of separation material, some chemicals stick to it and flow through the bottom of the tube rather slowly while others wash past the silica quickly. Other chemicals bind somewhere in between, allowing this complex plant extract to be separated into smaller groups of chemicals.

Each fraction of these chemicals were then tested in multiple combinations alone and together with pure berberine. The research team observed that some of these fractions could increase the antibacterial action of berberine by a factor of 16. This synergistic action was not due to berberine in the plant extract of other related antibacterial alkaloid compounds.

After repeating the separation and antibacterial assay several times, Cech used a molecular sizing technique called mass spectrometry to identify two compounds whose size had not been previously known to occur in goldenseal. The group then used nuclear magnetic resonance spectroscopy to determine the strengths of bonds between individual atoms in the chemicals.

This combination of techniques led to the identification of three flavonoid compounds responsible for this synergy. One of the goldenseal chemicals is called sideroxylin. The other compound turned out to be two isomers that share the same molecular size, 8-desmethyl-sideroxylin and 6-desmethyl-sideroxylin. But how do these chemicals work?

Staphylococcus aureus has a protein that pumps toxic compounds out of the cell. This pump called NorA considers the plant chemical berberine to be toxic to its survival. The siderloxylin compounds block the action of the NorA pump and allow berberine to accumulate in the S. aureus cells to cytotoxic levels. Cech demonstrated that in S. aureus cells lacking the NorA pump, these chemicals could no longer potentiate berberine’s antibacterial action.

Cech’s team then went back to the original plant material to investigate where these synergistic compounds were present. Interestingly, the sideroxylin compounds were up to 50-fold more concentrated in the leaves relative to the root and rhizomes. In contrast, berberine was 5-fold more prevalent in the roots. Cech writes,

The finding that goldenseal leaf extracts have higher levels of synergists while root extracts contain higher levels of alkaloids suggests the potential benefit of using a mixture of root and leaf material in the production of dietary supplements from goldenseal. Further studies would, however, be needed to evaluate the safety and efficacy of goldenseal leaf extracts in vivo.

Indeed, goldenseal still needs to be studied in living models of bacterial infections rather than on laboratory dishes containing an optimal growth medium. Nevertheless, the traditional use of goldenseal alone has caused the plant to be endangered due to overharvesting in the wild. The plants used for this study were instead cultivated in their native environment of hardwood forest understory. Cech’s work provides a strong argument for herbalists and herbal compounds to be more responsible in sourcing their products and use cultivated plants.

But the primary significance of this work is that substantiation of common claims for combined or synergistic action in herbal products requires intensive chemical and biological investigation by a multidisciplinary research team. In this one case of goldenseal, synergy does indeed exist. This synergy-directed fractionation research strategy should be applied to other natural products where similar cooperative activity is suspected.


Junio HA, Sy-Cordero AA, Ettefagh KA, Burns JT, Micko KT, Graf TN, Richter SJ, Cannon RE, Oberlies NH, & Cech NB (2011). Synergy-Directed Fractionation of Botanical Medicines: A Case Study with Goldenseal (Hydrastis canadensis). Journal of Natural Products PMID: 21661731

Posted in: Basic Science, Herbs & Supplements

Leave a Comment (46) ↓

46 thoughts on “Scientific evidence for synergy in a botanical product

  1. windriven says:

    “[T]his is the exactly the kind of work that should be supported by [NCCAM].”


    One suspects that the scientific interest here lies in the action of the siderloxylin compounds attenuating NorA pump activity rather than the relatively weak antibacterial properties of berberine unless berberine appears to be effective against MRSA. Does anyone know if this claim has been made? Substantiated?

    Goldenseal for golden (aureus) staph; nice.

    Thanks for an amusing start to my day.

  2. Hey! I really appreciated that write up. I so rarely find satisfying articles about herbal medicine and I’m glad to see that you guys occasionally put out a pro alt-med article if it holds up to scientific scrutiny.

    I’d definitely like to see someone do an in-vivo study comparing homemade goldenseal, neosporin, manufactured goldenseal extract cream, and placebo. Also, it might be interesting to further test that conclusion that a mixture of leaf and root compared to just leaf or just root would be more effective. Lastly, I wonder if different strains of goldenseal have different concentrations of those compounds and if they could be bred to be more effective and grown, rather than harvested in the wild. Maybe even compare wild crafted with grown…the possibilities are endless with these herb studies. Admittedly I don’t know anything about the politics of harvesting goldenseal.

    Lastly, I found your opening paragraphs to be offensive towards dirty hippies like myself who also like science. Actually, no, I’m not really offended. =)


  3. Scott says:


    The trouble is that this doesn’t support use of the actual herb. Extracting the active ingredients and using them in whatever combined dosages are (empirically) determined to be the optimum ratio, sure. But it doesn’t at all change the fact that an herb is always going to be inferior to a purified, known concentration preparation of the active ingredient (or in this case, active ingredientS).

    Especially so since, as windriven implies, it may well turn out that the best approach will be to take the siderloxylin compounds and combine them with a *different* antibiotic.

    For that matter, goldenseal may not turn out to be the best source of the compounds, or that related synthetic compounds would do even better, etc.

    Taking this as a pro-herbal-medicine result rather misses the point.

  4. @nobodyyouknowon
    “I’m glad to see that you guys occasionally put out a pro alt-med article if it holds up to scientific scrutiny.”

    But this isn’t alt med. When herbs are studied scientifically, it’s scientific medicine, specifically pharmacognosy.

    Medicinal herbs != CAM.

  5. daedalus2u says:

    So which is the better smoke? The leaves or the roots? ;)

  6. David Gorski says:

    What I’d be curious about is whether the synergy detected is actually clinically relevant. I’d actually tend to doubt that it is. Scientists find effects in cell culture and animal models all the time. These can point the way to clinical trials, but that doesn’t mean the effects are clinically superior in a meaningful way. One also notes that this study doesn’t necessarily demonstrate that the compounds within the goldenseal “poultice” actually behave synergistically when used on a wound, only that they might. After all, what these researchers did was to fractionate the active compounds and then recombine them.

  7. David Gorski says:

    Medicinal herbs != CAM.

    Indeed. This study doesn’t support CAM. It’s just another example of pharmacognosy doing what pharmacognosy does and trying to identify natural compounds or combinations of natural compounds with medicinal purposes. Unlike the herbalism that is part of CAM, these investigators did it rigorously and scientifically.

  8. cervantes says:

    No, it doesn’t support CAM, it only reminds us that there may be some empirical basis for some traditional medicine, so it’s a place to look for leads. Which is in fact going on all the time. Even the evil drug companies pursue the strategy. So this is not anything unusual.

    Aspirin, anyone?

  9. Harriet Hall says:

    For every study like this that found evidence of synergy, how many other studies are there that tested for synergy and failed to find it? Isn’t it common for a study to show that the whole plant extract is no more effective than the isolated active ingredient? My impression is that synergy is frequently claimed by herbalists but seldom verified by science.

    Another thing to keep in mind is that the plant extract might have other ingredients that worked against the desired effect or that could cause unwanted side effects.

  10. JPZ says:

    So, if the scientists find clinical trial efficacy of a whole herb leaf/root/etc., then it is herbal medicine and thus CAM? I am not sure when you see a field of study crossing over from pharmacognosy to herbal medicine and then over the cliff into the CAM-yon (OK maybe that pun didn’t work).

  11. WilliamLawrenceUtridge says:


    I’m glad to see that you guys occasionally put out a pro alt-med article if it holds up to scientific scrutiny.

    Question – assuming this triple (quadruple?)-molecule combination is indeed clinically effective either as a topical or ingested preparation, if it is synthesized by bacteria in vats, extracted and purified, then packaged into a variety of ointments and gel caps and sold as either an over-the-counter or prescription preparation, is it still alternative medicine? If so, how is it different from either other botanically-derived medications or completely synthetic medications that do not exist outside of a pharmaceutical setting?

    Have you ever heard the joke, what do they call alternative medicine that has been proven effective beyond reasonable doubt?

    They call it medicine.

    Implicit in your comment is that science, doctors and medicine “hate” or reject alternative medicine outright and a priori. They do not. They merely ask that in order for something to be called “medicine” it must be demonstrated effective, not simply asserted that it is effective. If a molecule genuinely works to heal infections or gastrointestinal complaints, it doesn’t matter if it’s administered by a Native American who manually extracts and prepares it directly from a plant or a grown in a vat and sold at a pharmacy. A genuinely effective molecule will have an effect no matter what it’s source. That’s the overall point of medicine and science – prove it, and if you can’t prove it, stop talking about it.

  12. windriven says:


    “So, if the scientists find clinical trial efficacy of a whole herb leaf/root/etc., then it is herbal medicine and thus CAM? I am not sure when you see a field of study crossing over from pharmacognosy to herbal medicine and then over the cliff into the CAM-yon (OK maybe that pun didn’t work).”

    Medicine is medicine anything else is not medicine. If it is not medicine and it is purported to be medicine it is quackery – not complementary, not alternative, not holistic, or any other sorta-kinda medicine.

    To rehash an overused example – willow bark was known as a folk remedy for a long time but that did not make it medicine. When willow bark was scientifically studied and salicylic acid isolated it became medicine.

  13. windriven says:

    BTW, the pun worked well :-)

  14. JPZ says:

    @Harriet Hall

    Perhaps I haven’t been reading the right journals, but I don’t think there are all that many studies of natural compound synergy. Pharmacognosy seems to focus on finding the most potent natural compound so that the chemists can modify the molecule to make it even more potent as well as patentable.

    It is time consuming to mix and match different isolated bioactives at different concentrations to test for synergy. Trust me, I had 3 FTEs doing this for 8 months with hops compounds. In a pharmaceutical company, this exercise wouldn’t have much bang for its buck.

    As for anti-bioactives and toxic compounds, you are right. It is also true that chemical modification of natural compounds can introduce additional toxicity. Careful safety and efficacy testing are the only solution.

  15. Scott says:

    So, if the scientists find clinical trial efficacy of a whole herb leaf/root/etc., then it is herbal medicine and thus CAM? I am not sure when you see a field of study crossing over from pharmacognosy to herbal medicine and then over the cliff into the CAM-yon (OK maybe that pun didn’t work).

    As long as it’s scientifically supported, then it’s not CAM. I’d say it would qualify as scientific herbal medicine (though also still pharmacognosy) if there were some demonstration that the most effective formulation was the actual herb itself, and that this could not be improved upon (e.g. by purification and dose control). I can’t conceive of any mechanism by which that would be the case, but in principle if there were one then it would constitute scientific herbal medicine.

    Yes, this does mean that the set of “scientific herbal medicine” is now, and probably will remain in the future, empty. This is because it’s effectively always possible to improve on nature, by means of purity and controlled dosage if nothing else.

    It becomes CAM when claims are made which are not supported by proper scientific evidence. Other characteristics would need to be there to deserve the label, as well, but that’s the key one.

  16. rork says:

    Nice work, nice article.

    I like the story of one-eyed lambs leading to finding corn lily (Veratrum californicum) leading to purifying Cyclopamine, figuring out it inhibits SHH pathway, working out that whole pathway, then Genetech and maybe some other companies making inhibitors that might be good against cancers benefiting from that pathway (some skin and brain cancers particularly). The little I know is from Frederic de Sauvage talking in Ann Arbor. No, I do not have a crush on him.

  17. Josie says:

    Interesting. I had not heard of goldenseal as an anti-biotic, all I knew was that it us supposed to help you pass a drug test for marijuana. I’ve never had need of it in that context but now I’m curious to go look up the straight dope on THAT dope.

  18. If the compounds did prove effective in vivo (and that’s a big if), it’s very likely that the safest and most effective use of these compounds would be in purified form (a pharmaceutical preparation) to ensure consistent, safe and effective concentrations of the drugs. Direct use of the herb is not likely to contain consistent amounts of the active substances from source to source or even plant to plant. It is likely that straight herb would vary from too little to too much active ingredient as well as have inconsistent relative proportions of the compounds for proper synergy and could also contain undesirable contaminants, toxins, or counter-agents.

  19. overshoot says:

    Given that goldenseal is not a particularly benign herb, at least taken internally, purification is a Real Good Idea. At least, assuming that the antibacterial fractions are not the ones with the adverse effects.

    On the other hand, discovering a modulator for one of s. aureus‘ defensive mechanisms has interesting possibilities itself.

  20. Mark P says:

    The research team observed that some of these fractions could increase the antibacterial action of berberine by a factor of 16.

    So it will be outperformed by berberine at 20x the strength in a conventional ointment?

    Unless it is actually killing a greater range of infectious agents, what do I gain by getting a synergistic effect that I would not gain by merely increasing dosage?

    When I put on a topical antibiotic I want to:

    1) be able to do it immediately. Not have to go out and buy some fresh herbs to crush to make a poultice.

    2) know that it is at effective strength. Not have to guess whether my leaves have enough active compound and that I am applying them correctly.

    3) it will have limited side-effects, and a minimised chance of allergic reaction.

  21. CC says:

    JPZ: “so that the chemists can modify the molecule to make it even more potent as well as patentable.”

    Patents are better applied to the processes, in my opinion. (I know this isn’t the case in practice.) Aspirin synthesis from phenols, instead of willow trees, was patented, as were process modifications to make it more efficient over the years, and those are entirely reasonable.

    I recently wrote (from an engineering point of view, not a medicine POV) about a synthesis process for conolidine, a plant-derived painkiller candidate which is entirely impractical to purify from the plant. I have no doubt that if that’s translated into a commercial painkiller the commercial scale process will be patented, and so will the process improvements.

    And since I make my living on a patented process (though not a medicinal one) I’m in favour of patenting processes that are novel and useful. Not so much in favour of patenting items that already exist, like naturally occurring biological molecules, however. I think it’s unfortunate that it’s been allowed.

  22. pmoran says:

    Apart from with burns, is there any evidence that topical antibiotics of any kind reduce infection rates or hasten healing? This was considered very dubious on the available evidence, back when I was up to date on such questions. A moist protective environment was coponsidered optimal.

    I agree that this is a rather banal finding — that two chemicals within the same plant might possess combined toxicity against bacteria.

    It may not be an evolutionary accident, but it represent a response to threatening microorganisms unconnected to the needs of humans.

    The chemical that poisons the bug’s “poison pump” may be of particular interest, if of low human toxicity.

  23. Okay okay okay! I stand corrected. Geez. Do you know how many people corrected me on the exact same point?

    That herbal medicine is not alt med if it’s rigorously tested, then it’s just medicine. Yeah, okay. Sorry. I kind of figured a bunch of people would jump down my throat just after I posted that comment but I figured I couldn’t go back and edit after that. Oh well. Sorry.

    I guess I’m not saying YAY NATURAL MEDICINE. Because I’m not. Let me make that clear. I do understand that this study didn’t really explain much about how goldenseal would treat a wound. Which is why I suggested all of those other research questions. Yes, I’m not a researcher. I’m not even a student (anymore). Someday someone will let me into grad school and I can get better at assessing the quality of research and improve my critical thinking. In the meantime, I suppose all you real scientists will have to put up with my wide eyed interest in your writing and a bunch of newbie mistakes.

    Thank you in advance for your patience. =)

  24. Diomedes says:

    “It may not be an evolutionary accident, but it represent a response to threatening microorganisms unconnected to the needs of humans.”

    Indeed, that’s what most interesting about it (apologies to fans of medicine)! What a fascinating evolutionary event– I wonder if anyone has worked out the gene network involved in response to micro-organisms in goldenseal?

  25. daedalus2u says:

    If it is a new compound, with low systemic toxicity that inhibits the NorA pump, it is too valuable to waste in a topical OTC generic antimicrobial which will likely lead to rapid evolution of resistance.

    I think Dr Crislip would give a lot for something that made MRSA susceptible to Cipro. It is NorA that makes it resistant.

  26. WilliamLawrenceUtridge says:

    nobodyyouknow, if you’re interested in improving your research, and in particular critical thinking skills (in general and for science specifically) you should definitely read through at least a couple more posts on this blog. Its two main thrusts are to criticize flawed research and flawed conclusions and to highlight good research that actually increases and improves the medical knowledge base.

    And yeah, you did hit a nerve, and the very fact that you admitted there replies you received had a point means you took some strong criticism far, far better than many other people in the same situation. Admitting the “other side” might have a point, even in potential, is a pretty huge step because it means you may change your mind based on evidence rather than ideology. Kudos, and good luck getting into grad school.

  27. GLaDOS says:

    That was a genius troll, nobodyyouknow, even if unintentional.

    If you go to a skeptics meeting, you can try it out again for the lulz.

  28. woo-fu says:

    Nice breakdown of the experimental process! And there are plenty of good points for additional consideration in the comments, too.

    I was introduced to herbalism from studying colonial times. I was impressed with the medicinal gardens that folk maintained. However, I also recognized that as important as these gardens may have been, the quality of life and the lifespan itself were still rather poor by modern standards.

    Once I was stuck camping when I managed to suddenly develop a bladder infection, a bad one. Unfortunately we were far from any doctors. One of our companions was a wildcrafter and traditional herbalist who ground up some plantain and goldenseal into a dark green slime, asked if I was pregnant, a big no, and proceeded to make an awful-tasting tea out of the concoction.

    “Drink,” she said after taking the time to describe why she used what she used and even some of the risks. I have to say I was pretty desperate, so I took it. Meanwhile, we started to pack up and head home.

    After some time she asked me how I felt, “Not much better, really,” I said.

    “Well, we do what we do with what we have,” she replied. “Just make sure you get to the doctor ASAP!”

    That encounter reminded me of the colonists who made do with what they had available. This doesn’t mean they wouldn’t have appreciated the benefits of modern medicine.

    Side note: My memory of animal behavior 201 is rather hazy, but I think I remember the usage of the word medicine when bears, and other animals, used certain leaves; etc. to rub on sore spots. I think they called it self-medicating, even though experiments had not actually been run to determine efficacy.

    Is this still true? If so, it might open the definition to herbalism in general as medicine, but it doesn’t necessarily mean it’s good medicine.

    I’m not trying to define medicine here, but I am looking for feedback on this specific circumstance. Maybe there is a difference between medical science and behavioral science in terms of word usage?

  29. JPZ says:


    If I had to choose one word that creates the most visceral, passionate replies on SBM, it is “medicine.” The very term “alternative medicine” is anathema to some (and based on their own personal definition of “medicine” I can see why). For example (and I personally haven’t come to a rigid definition of “medicine” – so this is not my own), a CAM treatment proven to work by modern science but not taught as medical school curriculum or used in medical practice might be called by some “alternative medicine.” Others will say, “It works, its medicine, end of story.” Unfortunately, I don’t see a lot of interest in common understanding of terminology (on the SBM or CAM side).

    If I had to pick the words with the greatest variation in definitions on SBM, it would be CAM. That seems to be a source of a lot of misunderstanding in the discussions I join – on the other hand, I could be the unknowing catalyst for some of the misunderstanding. I always hope that my belief in science-based efficacy gives us enough common ground.

  30. Anthro says:


    They are very attack-oriented here. I knew what you meant and also realized that they were going to jump on your inexact wording. I’m glad you responded in your own defense, but now get ready for them to call you a “concern troll”.

    I wish they’d save their invective for the real trolls and dunces and be a little more lenient for those who are truly interested but maybe don’t have a PhD in a hard science.

  31. Ben Kavoussi says:

    Nothing in biology makes sense except in the light of evolution

    — Theodosius Dobzhansky

    The raison d’être of naturally-occurring antibacterial compounds in goldenseal or any other plant is EVOLUTION.

    It is the natural selection resulting from the 24/7 arms race between plants and pathogens that is at the origin of such compounds.

  32. jtfische says:

    I am a natural product chemist working in the field of pharmacognosy. Thanks for writing this article it was very refreshing to see how you present the scientific angle of medicinal plant research. I often try to explain this concept to people when I discuss my research and this paper is a great example of synergy research. Look forward to reading the full study.

    Too often when I tell people I study the chemistry of medicinal plants, I get 1 of 2 uninformed responses. Either I get “oh so you study all that alternative medicine nonsense” or “oh so you study herbalism, cool dude”. Both sides are misinformed about this kind of research. Its estimated that half of all drugs come from natural product scaffolds. Meaning chemicals that either are natural products or that are designed based on ideas that came from natural products.

    Furthermore from an evolutionary perspective it makes sense that plants would take the strategy of using multiple compounds to reach multiple kinds of biological effects. A plant has no way of knowing if a compound it produces will be biologically active or useful for defense. If a plant can make a complex mixture of biologically active compounds while at the same time minimizing the allocation of its resources towards producing those compounds because of synergy it can provide a significant evolutionary advantage.

    For these reasons I get a bit saddened both when “hippie” types over sensationalize herbal medicine and when medical doctors knock it down. Both sides have a lot to learn from natures chemical warfare! Medicine can and will come up with new approaches and effective drug combinations by studying how compounds interact with organisms in this manner. The analytical technology and data analysis advancements in systems biology, metabolomics, proteonomics, and genomics make this area even more exciting and ripe for renewed investigation.

  33. woo-fu says:


    I always hope that my belief in science-based efficacy gives us enough common ground.

    I do relate! I had apparently been misunderstanding the uses of these terms in a big way. And sometimes it seemed that different contributors either had different personal definitions for these terms, CAM, SCAM and medicine, or they were in agreement (more or less) and just the particular wording threw me off.

    I’ve made more than a couple of charges of “foul play,” simply because I was reacting, rather than taking the time for a proper response, to a phrase or passage that I took entirely the wrong way. Then, once the less than pleasant exchange was over, I was able to look back through the thread and, “Doh!” I was wrong. That’s more than a tad embarrassing, but still a learning experience all the same.


    Back to herbals: I know it has been mentioned before about the risks of taking non-regulated herbal remedies including variations in potency and contamination of remedies with other substances, but in case it hasn’t been mentioned I’d like to add mold to the list.

    This is especially true for herbs collected and dried at home or by individual wildcrafters. I’ve walked into homes where bunches of herbs were suspended from the ceiling rafters to dry. On at least one occasion mold was actually visible. I asked the woman whose home it was if she planned to throw the bunch out. “There’s always a little mold,” she said.

    For one who is allergic to mold, that’s a big deal, and I told her so. When herbs are bunched, mold grows easily since the air flow around each stem is minimized. Other methods of drying can greatly reduce the mold growth but may be too hot, rendering the active ingredient useless. In any case, this is something to consider before buying or trying!

  34. daedalus2u says:

    There has been the suggestion that consuming nitrate could be an effective treatment for bladder infections. Virtually all plants accumulate nitrate, especially in the green leafy parts. Lettuce and spinach have a few tenths of a percent (depending on soil fertility).

    Nitrate is well absorbed and excreted in the urine. Some bacteria (such as E coli) reduce that nitrate to nitrite. If the urine is then acidified and/or made reducing by taking vitamin C, the nitrite can be reduced to NO and acidified nitrite is quite a good antimicrobial. NO inhibits quorum sensing and causes many bacteria in biofilms to switch to a planktonic form.

    Nitrite in urine is often used as a test for a UTI.

  35. GLaDOS says:

    The study of biologically active compounds in plants has always been part of science based medicine.

    CAM herbalism is different in one important way: non-study.

    On the CAM side, if a plant seems to have some effect in humans, you dry it and sell it without figuring out what’s in the plant, how much, receptor binding, metabolism, etc.

    Why on earth should 21st century humans favor non-study over study?

  36. Tell it like it is says:


    Alternative medicine is like alternative comedy. Neither bring joy.

    Its either medicine or it isn’t – its either comedy or it isn’t.

  37. woo-fu says:


    Interesting! I have to admit there were plenty of dark leafy greens in that concoction. And I cannot judge from one dose what effect it could have had, if I had continued on that course of treatment. However, I was told the herbal treatment would have to be taken several times a day for at least a week.

    Yuk! I gagged the first time I tasted it and had a hard time imagining taking it for the recommended time. If I were stuck there longer without any medical access, sure I probably would have gone through with it. But, as soon as I had the opportunity, I got what I needed from my doc and was feeling better in short order.

  38. TsuDhoNimh says:

    @josie Interesting. I had not heard of goldenseal as an anti-biotic, all I knew was that it us supposed to help you pass a drug test for marijuana. It doesn’t work any more. It used to, because it interfered with the most common analysis, but labs wen on to better and more specific testing.

    Berberine – from goldenseal or barberry – is absorbed in the intestine and excreted through the mucus membranes. It was widely used for pneumonia because it gets dumped right where the bacteria are.

    It can also chew the heck out of your intestinal tract if you take it for more than a couple of weeks – it starts killing off the mucosa.

  39. Nikola says:


    Excellent accidental trolling, indeed.
    I appreciated your comment and was immediately worried you’d get trampled by a herd of passing skeptics who didn’t give time for your actual point to sink in:P

  40. hippiehunter says:

    I have found that the back half of the bullet works in synergy with the front.

  41. ImperfectlyInformed says:

    Interesting neutrally-worded, science-focused article – the addition of David Kroll is indeed welcome. This is a post that I don’t think any of the other contributors could have come up with.

  42. Calli Arcale says:

    Mark PL

    Unless it is actually killing a greater range of infectious agents, what do I gain by getting a synergistic effect that I would not gain by merely increasing dosage?

    Not needing to increase dosage, for one thing. All antibiotics have side effects. Being able to reduce the effective dose also means reducing the side effects. Of course, the synergistic chemicals might also have adverse side effects, but perhaps the very reason the plant makes them is because the total side effects of all of them together is less than if it just made a whopping huge dose of antibiotic. They all stay under the toxic threshold.

    Also, as pointed out after your comment, this particular pump within the cell is part of how MRSA evades many of our common antibiotics. Being able to shut that pump down could help a great deal in treating these infections, even if the other chemicals are being aligned with ciprofloxacin rather than berberine.

    I completely agree about the downsides of using a poultice. Purified compounds put into a convenient preparation are vastly preferable, in my book. I don’t think the post was intended to promote the use of poultices; it was to show that sometimes synergy does happen, and we can learn useful things from studying it.

  43. We have to be careful what we throw out when we look for these secret ingredients. An apple a day may keep the doctor away. But if we try to isolate the active ingredient, we won’t find it – the active ingredients may have been roughage and water.

  44. Apologies to all for not jumping into the comments last week as i got tied up with travel and the day job.

    Many thanks to ImperfectlyInformed for the vote of confidence. I was delighted that Dr. Gorski and the others invited me to write here back in 2008 and I really wish I could do more (I have two other blogs where I write regularly: Terra Sigillata and Take As Directed). I think that I just come at this field a little differently than the others and am actively engaged in natural products research. I’ve been funded to work both on single-agent anticancer natural products and complex herbal extracts so, to me, it’s just science that uses the same techniques.

    @jtfische – Yes, I know exactly what you are saying about the perception of natural products research, much less trying to explain what pharmacognosy is relative to pharmacy and pharmacology. “Natural products” as a branch of biological chemistry is often mistaken for retial products that are sourced from nature. The “products” word of natural products refers to the chemical compounds made by plants, microorganisms, marine creatures, etc. in the way that chemical reactions are said to have reactants that give rise to products. All we can do is to keep active in promoting our field!

    Gorski and others raise the very good point as to whether the synergistic compounds would have systemic bioavailability – more of an issue if the herb or compounds were ingested orally and subject to hepatic metabolism. I suspect that this is the next line of work by the research team.

    Indeed, this work is neither pro- or anti-alternative medicine. It is simply solid science and leads us to develop new hypotheses on how other natural products might have benefit. At this point, we don’t know just how many specie of plants have these synergistic compounds primarily because people in the field have not been systematically looking for them. (There are exceptions, such as a related berberine synergistic compound from Berberis fremontii the group of Frank Stermitz in a 2000 PNAS paper, but this was also a NorA inhibitor that potentiated the antibiotic activity of berberine.)

    We’ll see just how common or rare this theme is in medicinal plants. Chemists and biologists sometimes observe that biological activity in a plant extract is sometimes lost upon chemical fractionation. More often than not, this loss is attributed to chemical instability of the active compound(s). Perhaps this is due to previously unappreciated loss of these potentiating compounds upon separation.

    Therefore, the major contribution of the work of Cech et al. is the demonstration of a process by which chemical fractionation and bioassay can be used to detect synergistic compounds. This systematic examination for synergistic compounds is, again, exactly the kind of work that should be done with medicinal plants.

  45. JPZ says:

    @David J Kroll

    Thank you for a thoughtful reply and thoughtful review!

    As a nutritional products scientist who runs GCP/ICH compliant trials on efficacy, I have been surprised at how many of the commentators on SBM dismiss scientifically-valid, empirical evidence of a natural product’s efficacy when the active component is unknown, pharmacology has not been established, and a chemically modified form of an active ingredient (for company patents of course) is not available in their formulary. There are also many who have said, “if it works, it is medicine” which by extension might indicate acceptance of empirical evidence.

    As an example, I cite the use of ginger in post-operative emesis and pregnancy-related nausea ( In general, studies have found it is equally effective to other treatments and superior to placebo. The active component is not known thus there is no pharmacology other than gingerols, and it has only been tested as a complete extract/powder. Does this discredit its efficacy? In my opinion, it does not. Does this mean that bottles of ginger extract on the shelves can claim what is proven? Based on my read of the regulations, it does not. Is it safe? In addition to extensive history of use, there is no significantly higher reporting of AEs or SAEs for ginger in the published clinical trials.

    One can call something medicine if it works and demand regulation, but if the layman can hand some peeled ginger to his wife every morning when she is “worshipping the porcelain god” during pregnancy, perhaps that is where some see an alternative to medicine (dimenhydrinate).

    As long as it is science-based evidence, I am good with that. ;)

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