There is a tree, or perhaps a large shrub, that grows commonly in the Middle East and North Africa, often known as the “desert date”, “island tree”, or “soapberry”. It is Balanites aegyptiaca, a close relative of chaparral (Larrea tridentata). In Egyptian legend it is said that at dawn Osiris, the lord of the underworld, opens a gate to allow Ra, the sun lord, to ascend into the sky. He is carried upward as a scarab by Thoth, the messenger of the gods, through the roots of the Balanites tree. As he moves up the trunk he ignites into a brilliant flame, is reborn as the Sun, and sets the tree on fire. Every morning this journey takes place in the East, yet the tree endures, for it is sacred to Thoth who protects it so it can continue to serve as a channel for the sun’s fire.
This myth has echoes in the cult of the phoenix, who rises reborn from the flames of its own death, and may also be the foundation for the biblical story of Moses and the burning bush. Regardless, it couches the daily dawn in terms of fire: brilliant destruction, but also birth and renewal. And it features a mercurial figure, Thoth, as the facilitator and “overseer” of this fire-born process. A diplomatic messenger, it seems, is required to ensure that the tree burns but does not perish, and that life is renewed at just the right moment. If we are going to play with fire, a subtle conversationalist might be required – someone who can balance night and day, mediate life and death, and communicate like no other.
In the human body, the expression of fire is visible in the inflammatory response. Mediated both by immune cells and by a range of chemical factors at the cellular and genetic level, we rely on it for protection, repair and renewal. But it also underpins almost every disease process, and has been the obsession of medicine for a very long time. We’ve wanted to whisper to it, to enchant it, to bend it to our will yet, like a desperate parent of an unruly teenager, so often we resort to screaming, suppressing, or sheltering. Using steroids, anti-inflammatory drugs, or broad-spectrum antiseptic agents may be useful at times; but they can also be excessive, unsustainable, and perhaps even harmful strategies. Certainly not the subtle tools of a master conversationalist.
So if we are going to start talking to the inflammatory fire within us, we need a different set of tools. The first step is to understand the language. Molecular “words”, often made up of sugar chains or combinations of sugars and proteins (polysaccharides and proteoglycans), are found on the surfaces of viruses, bacteria, and fungi. They are also on the surfaces of our own cells, as well as in connective tissue. Here they act as unique identifiers that help our immune system differentiate friend from foe, or become active in the case of trauma or damage. Sometimes, as with the wheat proteins gluten and gliadin, these molecular words can trigger unnecessary damage. But in all these cases, the conversation is carried by words made from an alphabet of sugars and proteins.
Many of the chemicals found in certain plants also have sugar- and protein-based structures, and can participate in this conversation with the immune system. Both pure polysaccharides and molecules such as saponins (sugar chains, usually attached to a large ring-based backbone, with a soap-like texture) have a huge influence on our immune system. Researchers have known about these molecules for a long time. Bacterial polysaccharides are used to activate immune cells in experimental models[i]. Saponins from the bark of Quillaja species are used as aids to elicit a stronger immune response as part of vaccination[ii].
When we look deeper into the inflammatory response, we see a cocktail of chemicals in the blood, intracellular fluid, and even all the way in the nucleus of our cells. These substances serve as mediators of the immune system’s signals: as we gain meaning from the words we perceive as we breathe, touch, eat, and drink, these chemicals interpret this meaning and help carry out consequences in our physiologies. Genetic switches are turned on or off. Secondary messengers erupt into a cascade of signals. Blood proteins and hormones amplify the message and coordinate the response. Polyphenolic compounds from medicinal plants and mushrooms intersect beautifully with this complex dance. Substances such as bioflavonoids, triterpenoids from resins and saponins, and pungent polyphenols like those found in the Zingiberaceae (the ginger and turmeric family) have profound long-term effects on the inflammatory fire – but only if consumed habitually[iii]!
So it would seem that our immune system responds to the messages it hears from the outer and inner world of our bodies, coordinates with our nervous and endocrine systems, and helps guide the inflammatory response into clear, effective, and balanced expression. But if the words that the immune system is used to hearing are silenced, the conversation ceases, and balanced expression is lost. It is like trying to eat food blindfolded and with your nose plugged: it’s hard to understand what’s happening and participate in the meal. The repeated suppression of inflammatory fire with drugs like ibuprofen and aspirin are leading to immune weakness when we need it most: severe skin infections, for example, can affect children who are given anti-inflammatories for chicken pox[iv]. And our over-emphasis on sterility (and the consequent obliteration of our immune system’s vocabulary training) has led to increased rates of asthma, allergies, and auto-immune disease[v].
The central therapeutic principle in working with immunity and inflammation is to follow the lead of Thoth, the messenger-god who balances the ebb and flow of Ra and Osiris. Talking to fire requires a bit of diplomacy: the conversation has to have enough challenge in it to be lively, but it also has to keep a clear focus on a constructive outcome. Saying “no” to everything is a great way to shut things down. But getting bored can be even more dangerous – think of a preschooler here. So from an herbalist’s perspective, employing plants and mushrooms that carry meaning to the immune system and are capable of interacting with the chemical dance of inflammation can be a great way to inject interesting topics into the conversation. Judiciously timed, these interventions can return our fire to that place of clear, effective, and balanced expression.
In seeking to identify and differentiate botanical immunomodulators I’ve found a traditional classification can be useful. It’s useful to note that taste, “temperature”, and chemistry often follow broadly similar patterns in plants; but it’s even more interesting to see how disease expression in humans seems to incorporate those patterns, too. In some folks, fire seems to be missing: redness is absent, and though infections are frequent, they rarely elicit strong responses. In others, fire is a bit out of control: there may be visible redness, pain, or swelling as with allergies or autoimmune connective tissue diseases. Many can be somewhere in between, or show signs of both patterns.
Plant preparations that contain straight polysaccharides and proteoglycans tend to be sweet, and they feel warm and nourishing. They start with simple convalescence foods, like rice congee or super-cooked oatmeal, given to rebuild strength after protracted illness. As you might guess, these can (very, very gently) stoke the fire. You may also notice that, if there is a lot of heat in the system (from a very hot day, or from a fever), these foods become much less appetizing – which makes sense.
Roots that are polysaccharide-rich, like astragalus[vi] (A. membranaceus) or mushrooms such as maitake[vii] (Grifola frondosa) and reishi [viii] (Ganoderma tsugae and others) have a more tempered sweetness, but are still warm and nourishing. Even echinacea (E. purpurea and others) has a good quantity of sweet polysaccharides[ix] that speak to immune cells, getting them more involved and interested[x].
Polysaccharides can interact with our physiologies by meeting immune cells in the lympatic tissue that lines the digestive tract[xi]. Here they provide an alternative to a bacterial or viral signal: they have molecular profiles that looks similar enough to be meaningful messengers to our immune systems. You might be concerned that there would be cases where these chemicals might be contraindicated – and you’d be right. In general, lots of warm, sweet, polysaccharide-rich plants might not be the best choice for hot, inflamed, fiery and feverish states. But even astragalus, which we often withhold during fever, seems helpful for allergies[xii] and asthma[xiii]. As is the case in many negotiations, if you can just get everyone talking, you can usually find a mutually agreeable balance point.
Part of the reason astragalus and the medicinal mushrooms can work in warm as well as deficient, depleted conditions is that their chemistry is not simply limited to polysaccharides. They are also rich in the polyphenols so useful in cooling an out-of-control blaze. These polyphenols, mostly of the flavonoid, steroidal, and general triterpenoid class[xiv], are often bitter or sour tasting, and cool in temperature. They interact at multiple levels with the cascade of inflammatory signals[xv]: from genetic switches such as nuclear-factor-kappa-B[xvi], to pro-inflammatory enzymes such as endothelial nitric oxide synthase[xvii], and blood-borne factors such as prostaglandins[xviii]. None of these polyphenols will ever have the immediate, powerful effects of a corticosteroid, not the anti-inflammatory action of ibuprofen. But in terms of conversations, plants are gentle but firm negotiators, while steroids and NSAIDs are bullies. Different short-term effects, of course – but different long-term effects, too.
Some of the more bitter, sour, and cool botanicals that appear in this category are species such as Baikal scullcap (Scutellaria baicalensis)[xix], goldenrod (Solidago canadensis and others)[xx], berries (Vaccinium species)[xxi], chocolate (Theobroma cacao)[xxii], tea (Camellia sinensis)[xxiii], holy basil (Ocimum sanctum)[xxiv] and many, many more. They have all found traditional uses as fire-modulators, protecting the heart and vessels from inflammation while also controlling allergies and hypersensitivities[xxv], autoimmune disease, and cancer. Try these plants in situations where there is visible heat and fire, either in connective tissue, on the skin, or in more subtle areas such as the tongue or the radial pulse.
There is a third type of chemical class, usually found in bittersweet plants. The temperature of these botanicals is somewhat neutral, though some are considered slightly warming and others slightly cooling. A unifying feature is that they produce soapy, slimy extracts that leave a persistent head of foam when shaken[xxvi]. The chemicals responsible are saponins and they have the most balanced effect of all on our internal fire. This is because a saponin is a combination of a sugar chain (like a polysaccharide) and a polyphenol (or triterpene) backbone. When saponins from plants such as American ginseng (Panax quinquefolius)[xxvii], licorice (Glycyrrhiza glabra)[xxviii], horsechestnut (Aesculus hippocastanum)[xxix], or fenugreek (Trigonella foenum-graecum)[xxx] get into our digestive tract, they form stable “bubbles” around fat droplets, encircling them with their sugar chains sticking out. To the immune system, these look a lot like little bacteria or viruses: the fire is stoked. But as they are metabolized, the polyphenolic backbones are absorbed and exert an anti-inflammatory activity. The fire is contained and directed.
Very often, herbal antibacterial approaches fail. We try garlic (Allium sativum) or mugwort (Artemisia vulgaris), thyme (Thymus vulgaris) or rosemary (Rosmarinus officinalis), but the infection persists or returns. Other times, herbal anti-inflammatory approaches don’t provide relief. I have found that adding in a saponin-rich herb that is neutral in energy, even as a small (10%-25%) fraction of the formula, can make an incredible difference. I believe this is because the saponins are great conversation starters, and they provide the necessary context for our immune systems much as Thoth provides the context and guidance for the healthy expression of solar energy. Saponin-rich plants can also be useful in managing the relapsing-remitting autoimmune diseases such as lupus, rheumatoid arthritis, even multiple sclerosis. Using a three-part formula (such as astragalus, horse chestnut, and Baikal scullcap), you can increase the proportion of Baikal scullcap during a hot flare-up to buffer symptoms, and focus more on astragalus and horsechestnut during more “quiet” periods to try re-training the immune system.
It is interesting to note that the Balanites tree has traditional uses as a soap plant, an anti-inflammatory, and a digestive aid[xxxi]. It is extremely rich in saponins. The burning bush that serves as a vehicle for the rebirth of the sun, and which is sacred to the god of balance and communication, provides us with the chemistry necessary to talk to our own internal fire. And if we re-enter into a conversation with our sacred flame, rather than attempting to stamp it out or do its work for it, we may yet see a new day dawn for the treatment of chronic inflammation, autoimmune disease, and cancer. Consider adding some saponin- and polysaccharide-rich plants and mushrooms to your anti-inflammatory blends. Talk to fire on its own terms, for it deserves a seat at the table. Your results will improve.
[i] Alexander, Christian, and Ernst Th Rietschel. “Invited review: Bacterial lipopolysaccharides and innate immunity.” Journal of endotoxin research 7.3 (2001): 167-202.
[ii] Vaccination itself is an attempt to talk to the immune system. Medicine is still working on exactly how to do this most effectively, but it seem clear that adjuvants, or “helpers”, are required to get the immune system listening. They are mixed in with the piece(s) of microbe specific to the vaccine in question. See, for instance: Cox JC et al (1998). “ISCOMs and other saponin-based adjuvants.” Adv Drug Deliv Rev 32 (3).
[iii] For an excellent review see: Santangelo, Carmela, et al. “Polyphenols, intracellular signalling and inflammation.” ANNALI-ISTITUTO SUPERIORE DI SANITA 43.4 (2007): 394.
[iv] Mikaeloff, Yann, Abbas Kezouh, and Samy Suissa. “Nonsteroidal anti?inflammatory drug use and the risk of severe skin and soft tissue complications in patients with varicella or zoster disease.” British journal of clinical pharmacology 65.2 (2008): 203-209.
[v] See for instance Folkerts, Gert, Gerhard Walzl, and Peter JM Openshaw. “Do common childhood infections teach’the immune system not to be allergic?.” Immunology Today 21.3 (2000): 118-120. And relating to the connection between farm life, bacterial exposure, and its effects on asthma rates: von Mutius, Erika, and Donata Vercelli. “Farm living: effects on childhood asthma and allergy.” Nature Reviews Immunology 10.12 (2010): 861-868.
[vi] Li, Rui, et al. “Extraction, characterization of Astragalus polysaccharides and its immune modulating activities in rats with gastric cancer.” Carbohydrate Polymers 78.4 (2009): 738-742.
[vii] Mizuno, Takashi, et al. “Fractionation and Characterization of Antitumor Polysaccharides from Maitake, Grifola frondoscfi.” Agric. Biol. Chem 50.7 (1986): 1679-1688.
[viii] Wang, Yuan-Yuan, et al. “Studies on the immuno-Modulating and antitumor activities of< i> Ganoderma lucidum</i>(Reishi) polysaccharides: functional and proteomic analyses of a fucose-Containing glycoprotein fraction responsible for the activities.” Bioorganic & medicinal chemistry 10.4 (2002): 1057-1062.
[ix] Barnes, Joanne, et al. “Echinacea species (Echinacea angustifolia (DC.) Hell., Echinacea pallida (Nutt.) Nutt., Echinacea purpurea (L.) Moench): a review of their chemistry, pharmacology and clinical properties.” Journal of Pharmacy and Pharmacology 57.8 (2010): 929-954.
[x] Rice, Peter J., et al. “Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge.” Journal of Pharmacology and Experimental Therapeutics 314.3 (2005): 1079-1086.
[xi] Volman, Julia J., Julian D. Ramakers, and Jogchum Plat. “Dietary modulation of immune function by ?-glucans.” Physiology & behavior 94.2 (2008): 276-284.
[xii] Matkovic, Zinka, et al. “Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis.” Phytotherapy Research 24.2 (2010): 175-181.
[xiii] Wang, Gang, et al. “Effects of Astragalus membranaceus in promoting T-helper cell type 1 polarization and interferon-? production by up-regulating T-bet expression in patients with asthma.” Chinese journal of integrative medicine 12.4 (2006): 262-267.
[xiv] Not all steroidal and triterpene backbones are also polyphenols, but many are. Regardless, they still possess substantial anti-inflammatory activity.
[xv] Bravo, Laura. “Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance.” Nutrition reviews 56.11 (2009): 317-333.
[xvi] Nam, Nguyen-Hai. “Naturally occurring NF-kappaB inhibitors.” Mini reviews in medicinal chemistry 6.8 (2006): 945.
[xvii] Borchard, Jillian, Lily Mazzarella, and Kevin Spelman. “A review of medicinal plants that modulate nitric oxide activity.” Alternative Medicine Studies 2.1 (2012): e6.
[xviii] Yoon, Joo-Heon, and Seung Joon Baek. “Molecular targets of dietary polyphenols with anti-inflammatory properties.” Yonsei medical journal 46.5 (2005): 585-596.
[xix] Chirikova, N. K., D. N. Olennikov, and L. M. Tankhaeva. “Pharmacognostic study of aerial parts of Baikal skullcap (Scutellaria baicalensis Georgi).” Russian Journal of Bioorganic Chemistry 36.7 (2010): 909-914.
[xx] Apati, P., et al. “HPLC analysis of the flavonoids in pharmaceutical preparations from Canadian goldenrod (Solidago canadensis).” Chromatographia 56.1 (2002): 65-68.
[xxi] Giovanelli, Gabriella, and Susanna Buratti. “Comparison of polyphenolic composition and antioxidant activity of wild Italian blueberries and some cultivated varieties.” Food chemistry 112.4 (2009): 903-908.
[xxii] Natsume, Midori, et al. “Analyses of polyphenols in cacao liquor, cocoa, and chocolate by normal-phase and reversed-phase HPLC.” Bioscience, biotechnology, and biochemistry 64.12 (2000): 2581-2587.
[xxiii] Lin, Yung-Sheng, Sang-Shung Wu, and Jen-Kun Lin. “Determination of tea polyphenols and caffeine in tea flowers (Camellia sinensis) and their hydroxyl radical scavenging and nitric oxide suppressing effects.” Journal of agricultural and food chemistry 51.4 (2003): 975-980.
[xxiv] Hakkim, F. Lukmanul, C. Gowri Shankar, and S. Girija. “Chemical composition and antioxidant property of holy basil (Ocimum sanctum L.) leaves, stems, and inflorescence and their in vitro callus cultures.” Journal of agricultural and food chemistry 55.22 (2007): 9109-9117.
[xxv] Take green tea, for instance: Maeda-Yamamoto, Mari, et al. “The efficacy of early treatment of seasonal allergic rhinitis with benifuuki green tea containing O-methylated catechin before pollen exposure: an open randomized study.” Allergology International 58.3 (2009): 437-444.
[xxvi] Cheeke, P. R. “Nutritional and physiological implications of saponins: a review.” Canadian Journal of Animal Science 51.3 (1971): 621-632.
[xxvii] Assinewe, Valerie A., et al. “Phytochemistry of wild populations of Panax quinquefolius L.(North American ginseng).” Journal of agricultural and food chemistry 51.16 (2003): 4549-4553.
[xxviii] Fenwick, G. R., J. Lutomski, and C. Nieman. “Liquorice, Glycyrrhiza glabra L.-Composition, uses and analysis.” Food Chemistry 38.2 (1990): 119-143.
[xxix] Sirtori, Cesare R. “Aescin: pharmacology, pharmacokinetics and therapeutic profile.” Pharmacological Research 44.3 (2001): 183-193.
[xxx] Taylor, Wesley G., et al. “Analysis of steroidal sapogenins from amber fenugreek (Trigonella foenum-graecum) by capillary gas chromatography and combined gas chromatography/mass spectrometry.” Journal of agricultural and food chemistry 45.3 (1997): 753-759.
[xxxi] Speroni, E., et al. “Anti-inflammatory, anti-nociceptive and antioxidant activities of Balanites aegyptiaca (L.) Delile.” Journal of ethnopharmacology 98.1 (2005): 117-125.
Image by burnetbuddy, courtesy of Creative Commons license.