Monday, November 19, 2012

The Synergy of Chinese Herbs

Herbal prescription in Chinese Medicine follows advanced and sophisticated dosage and combining protocols. For example an herb may have a specific action like raising prolapsed organs (for instance the herb sheng ma), however that action may only come out when that herb is prescribed with other herbs with similar actions. An herb might treat a particular symptom, but when prescribed with a guiding herb is capable of treating a related but different symptom in a different part of the body. In short, herbal medicine combining, or Dui Yao is not a additive, cumulative science, but a complicated science of synergy and complex interaction.

(entirely off topic, here's a really great video for any adrenalin junkies out there, if you haven't seen this nut, you should.)

Anyway, this is a pretty fascinating topic. We have a sense of how these things operate from a Chinese Medical Paradigm. Within our strange and interesting Chinese Medicine brains, acupuncturists really get these relationships, they make sense and are intuitive, because we have taken the time to build the rules and thought processes for how this world operates. Within the framework of western sciences these relationships are much more difficult to identify. In truth, like a lot of what happens in Chinese Medicine, western science just hasn't caught up yet. But there are some promising approaches developing out there, and I found one particularly interesting study.

"Synergistic therapeutic actions of herbal ingredients and their mechanisms from molecular interaction and network perspectives." (sorry no full text, but I'll try to give you all the juicy details.)

What this paper sought to do, was to elucidate the mechanisms by which herbs interact. (one example of this is Jiao Tai Wan. Huang lian and rou gui interact synergistically to improve symptoms of xin shen bu jiao (noninteraction of heart and kidney)). Chinese Medicine is rife with these sorts of combinations: nu zhen zi and han lian cao; gan cao, sheng jiang and da zao; sheng ma and huang qi; huang lian, huang bai, and huang qin; ma huang and gui zhi; bao shao and gan cao...and so on. We identify each of these combinations as embodying powers beyond the contributions of each individual herb. In some cases entirely new functions are created that are not found, even in lesser power, in the constituent ingredients.

Often one herb alters the ADME (absorption, distribution, metabolism and excretion) of the other. This is suspected to be the case in Jiao Tai Wan, and particularly with regard to absorption. As this study shows, the specific ratio of huang lian to rou gui enhances the absorption of huang lian across the intestinal membrane, thereby increasing the activity of huang lian without increasing its dose.

Constituents also act as teams to influence change in the body. This sounds oddly reminiscent of our understanding of how to build a formula with chief, deputy, assistant, and envoy.
a. Anti-Counteractive: reduce a network's counteractive activities against a constituent's effect. 
b. Complementary: actions positively regulate a target or negatively regulate a competing target. 
c. Facilitating: secondary actions of one constituent in enhancing the activity level of another. 
d. Potentiative modulation: affecting things like cell transports, permeability, delaying or reducing first pass excretion, or metabolism, all of which enhance the activity of the first constituent. 
 The paper gave some examples of studies that have been done into single herb synergism (multiple constituents in one herb act together to have effects larger than the effects of the individual constituents added together), as well as synergism from multiple ingredients.

Berberis:  Plants of this family contain the two key ingredients berberine and 5' methyoyhydnocarpin (5 MHC). What's interesting about these two ingredients is that while berberine has pretty good antibacterial actions, it is much more potent when in the presence of 5 MHC. In order to see why think about a bacteria. Bacterial cell walls have special little pumps on them that work to pump out synthetic and natural antibacterial agents, and keep them from killing the bacteria. These pumps are called multi drug resistant pumps. 5MHC inhibits the activity of these pumps allowing berberine to accumulate inside the bacteria and result in much more effective treatment. I'm not sure whether our big berberine herbs (huang lian, and huang bai) contain 5MHC. A quick glance at Chen didn't answer that question. If anybody out there knows let me know. (here's a link to the full text of this interaction.)

Onions and Garlic: Ancient food pairing. Goes together like acupuncture and flutes, especially in the presence of rich or fatty foods. Conveniently enough when together onions and garlic act in a synergistic manner to inhibit the peroxidation of lipids. You heard me right, go big on the onions and garlic to keep those newly absorbed triglycerides and free fatty acids from turning into little artery cloggers. This one is pretty tangled and complicated...what they found is that they could feed someone 100 grams of butter (sounds like a dare I responded to as a teenager), and onions and garlic limited the increase in serum cholesterol and plasma fibrinogen, and increased fibrinogen activity and clotting time.    Onions contain quercitin, myricetin, and kaempferol all of which inhibit various enzymes involved in splitting fats (lipoxygenase 5, 16, and phospholipase A2). Garlic contains sulfurous substances (diallyl disulfide, diallyl disulfide, allicin, alliin, ajoene, N-acetyl cysteine, S-allyl cysteine, S-ethyl cysteine, S-methyl cysteine, S-propyl cysteine) all of which inhibit the mechanisms that the body uses to upregulate those now-downregulated lipase enzymes, allowing the onions to have a stronger effect than they would otherwise. This is an example of an anti-counteractive effect.

Gou Teng and Tian Ma: These two herbs are found in the formula Tian Ma Gou Teng Yin, used for wind due to rising liver yang. This study looked at these two herbs and their actions on decreasing convulsions. Gou teng contains Hirsuteine, which decreases the incidence of seizures by blocking nicotinic receptor ion channel complexes. Tian Ma contains vanilline which inhibits acetylcholinesterase and butyrlcholinesterase, which results in decreased seizures caused by acetylcholine. But unfortunately this decreases acetylcholine degradation, which increases the activity of nicotinic acetylcholine receptor, which would lead to more seizures, if it wasn't for the actions of Gou Teng and that Hirsuteine, blocking nicotinic receptor channels. An example of what the study called an "anti-negatie effect."

Ren Shen and Zhi Gan Cao: The formula ban xia xie xin tang, among others, utilizes this combination. This combination was investigated in ulcerative colitis.  The authors used the entire formula, as well as individual isolates and those isolates in combination. The combination of ginsenoside saponins (GS) and glycyrrhizin (GZ) was effective beyond the effect of both used alone. GS is effective in decreasing the activation of defective Th1 response, while GZ is effective in suppressing defective Th2 response. Together they cover both divisions of aberrant immune response, resulting in benefit beyond either alone. I wasn't aware before reading this paper that this division existed in between these two herbs. That makes these two herbs a handy herb pair that I am likely to employ in my auto-immune formulas in the future, as long as the pattern fits.

It's nice to have western science backing us up for a change, but I'm not convinced of the power of these sorts of methods to really offer a whole lot to our understanding of Dui Yao at the moment. I for one will continue to trust the time honored classics in my herb pairing over the pages of "Bioinformatics and Drug Design." I think that most herbalists out there feel the same way. Studies can provide us with the nitty gritty molecular interaction details about why what we've been doing for thousands of years works so well, but at this point the main things they are likely to add are improvements on delivery methods and small tweaks on use. But the real gems are still to be found in the pages of the Shang Han Lun, Jin Gui and, for me the Pi Wei Lun. It doesn't mean that the information about absorption, distribution, metabolism and excretion isn't important. We are likely to need to know more and more of this in order to stay current in this field. Now excuse me while I go get some onions and garlic chopped for dinner.