Systems Biology and TCM

I was reading The End of Illness the other day by Dr. Agus (I know I'm a sucker for anything featured on the Daily Show). He gets into explaining the role that proteomics can have and will have in the future of medical diagnosis. Proteomics is a systems biology approach to lab analysis that takes a snapshot of the various peptides present in a tissue sample and thereby quantifies and qualifies the relative strength of inflammatory, homeostatic, and other processes in the body to arrive at a richer and more nuanced view of health. Sounds an awful lot like some good old bian zheng (or pattern differentiation) to me. Nobody tell them they can do it without all that expensive machinery, our economy needs those purchases.

Well, I dove a bit deeper and found that a lot of research has been done, looking at systems biology approaches such as proteomics, transcriptomics and metabolomics and how well it correlates across patients with the same TCM diagnosis, and the answer is, wait for it....pretty darn well. There is some really interesting stuff out there on this subject. We know that multiple Western Medical diagnosis can have the same TCM diagnosis. If they also have the same proteomic profile, then Western Medicine may finally have a tool that puts them at least in the same ballpark as TCM in terms of overall diagnostic ability. Granted their diagnostic accuracy with this technique is pretty crude still and it'll take a pretty long time before this sort of diagnostic approach really reaps gains for them. But, the value to me is in having anther peg to hang a hat on when I think of what exactly is happening in the body when I think of kidney yang deficiency, or spleen qi deficiency, or liver qi stagnation. Before I outrage my chinese medicine brethren, I am in no way suggesting that this sort of understanding is any more "real" or "true" than our own understanding of them or that any blood test can replace our unique diagnostic skills and approach. Truly complete understanding of the patient's health I think is like the Tao in that understanding it in abstractions is possible but when grasping for a concrete and objective finality inspection will always yield a deeper level of murkiness. So...so to the fun part! The studies!

In one study, in the American Journal of Chinese Medicine, they looked at "heat" type asthma in a group of patients and sought a systems biology style correlate of this TCM term. They found that those diagnosed with a "heat" pattern demonstrated an increase in eosinophil cationic protein, which according to wikipedia is released during degranulation of eosinophils...ie inflammatory process and in our medicine, a very simplistic, and potentially unreliable indicator of heat patterns. I know I would trust my 4 examinations long before the ECP count in my patients serum as an indicator of their pattern, but you gotta give it to them for trying.

Another article, in the Journal of Pharmaceutical and Biomedical Analysis (sorry no free full text). Looked at multiple studies on this subject and the authors wrote about various zheng and their relevant systems biology style biomarkers:

Investigations into the characters of the ‘Kidney-Yang Deficiency syndrome’ induced by high dose of hydrocortisone and the therapeutic effects of Rhizoma Drynariae, classic TCM in treating the syndrome, have been performed by robust metabolomics method based on UPLC/MS [44]. It was found that significant difference in metabolic profiling was observed from hydrocortisone-induced group compared with the pre-dose group by using PCA. The time-dependent regression tendency in Rhizoma Drynariae treatment group was obtained, and the major metabolic alterations responsible for group separation were linked to some significantly changed metabolites like phenylalanine, N(2)-succinyl-L-ornithine, phenylacetylglycine, creatinine, hippurate, L-proline, and citrate. Biochemical changes were related to the disturbance of amino acid metabolism, energy metabolism and gut microflora, which are helpful to further understand the ‘Kidney-Yang Deficiency syndrome’ and the therapeutic mechanism of Rhizoma Drynariae. Therefore, metabolomics not only opens out mechanism of classical TCM theory on syndrome but also enriches current research on complex diseases [45].

So in plain english that means they induced kidney yang deficiency in these rats by giving them hydrocortisone then compared the metabolites present in their blood with those in other rats with their kidney yang intact. They found changes consistent across the study group in terms of the amino acid building blocks present. They attributed the changes in the biochemical profiles of these rats to not only this difference in the metabolites, but also the energy metabolism that resulted from it as well as changes in gut flora. I really appreciate their recognition of the gut flora (other systems biology folks also ascribe huge importance to these bacteria). I think the gut flora should be considered its own discrete organ from the western sense and I consider it to occupy a pretty large part of what we recognize as the spleen zang in Chinese Medicine.

I try not to jump up and down too much when a new testing method comes out. I don't, for instance, see this new approach as a reliable diagnostic for autism. (check out this great blog post on this subject by Paul Whiteley.) What I do think, is that this is an exciting new way to look at the body. A way that allows for gray areas and very subtly nuanced differences. This type of investigational approach serves due respect to the organism whose true nature often defies clear distinction.

Wound Healing and Chinese Herbs

I get cuts, scraps bumps, bruises and so do my patients. Some of them heal quickly, while others seem to remain at a standstill for months, oozing red tissue angrily and present weeks after the offending impact. Proper healing of wounds is dependent upon numerous factors and as such is a reflection of overall health. 

But first here's a great resource, does everybody know about this nutritional information database?

Luckily, we have lots of options in Chinese Medicine to speed healing. First, from a Chinese Medicine perspective...

Just a quick heads up for those out there who aren't versed in Chinese Medical theory, the references to organs in this paragraph relate to their function within Chinese Medicine, which is distinct from their physiological function recognized by western medicine. We know that the spleen is the organ most closely associated with flesh, and also that the lungs regulate the skin. Sufficient function is required in both in order to have appropriate healing. The kidneys also play a role as the foundational yang substrate for the transformation and transportation of the spleen. The lungs also rely on healthy kidney function as the ability to properly effuse lung qi and moisture throughout the body, moistening the cou li requires unrestricted ventilation of the lungs, which pivots on sufficient grasping of the lung qi by the kidneys. The kidneys lastly play a pivotal role in healing by maintaining appropriate yin and yang balance in the body as a whole. For instance the decreased healing we see in Cushing's syndrome or menopause seems to have a basis in what our medicine would call kidney qi and yin deficiency respectively. Western medical recognizes the intricate work that the white blood cells do and makes clear the reliance on a healthy wei qi. The spleen in a western sense stores monocytes and deploys them when a wound requires more immune cells, a healthy healing process relies on sufficient stores of monocytes in the spleen whether you can relate this to the chinese medicine spleen or not seems murky. 

Western Medicine wise...Healing of wounds passes through 4 main stages beginning with homeostatic (where the immediate danger of bleeding is addressed), then inflammatory (where numerous immune cells and inflammatory mediators cooperate to guide the initial patch work), then proliferative (where progressively more permanent materials are laid down) and finally the remodeling phase, where the wound is prettied up; fibrin that was laid down haphazardly is made to point the right direction. 

A lot of the information about wound healing comes from the full text of this article, and good ol' wikipedia: here. 


The inflammatory phase is the phase where most of our patients are going to be able to benefit from our help. It's the most complex in terms of the interaction of various cell types. It's arguably where our herbal interventions can have the most influence. 


The inflammatory phase involves the immediate constriction of local vasculature mediated by prostaglandins and thromboxanes, which is followed shortly by vasodialation, mediated largely by histamine, which enhances the aggregation of immune cells both by increasing local perfusion and creating porous vessel walls. 


Neutrophils are the initial responders, arriving on the scene within the first 24 hours. They are responsible for cleaning up foreign and damaged tissue at the sight of injury. Their function is important and it was found through rat experimentation that the lack of sufficient neutrophil presence resulted in poor debridement of the site and decreased fibrinoplasia. 


The macrophages move in next and are key. They proliferate in the second to third day (48-96 hours) and carry out multiple functions: detecting the low levels of oxygen in the local tissue they are triggered to induce angiogenesis (the laying down of new blood vessels, and lymph vessels.) The presence of new vessels is key to the continued healing of the wound. They also coordinate the recruitment and aggregation of other cells at appropriate times through the secretion of cytokines and growth factors, thereby conducting the transition from step to step along the healing process. They "express inducible nitric oxide synthase, and are a source of nitric oxide production in the early phase of wound healing." Nitric oxide, besides having antimicrobial actions, also facilitates reepitheliazation, collagen deposition, and speeds the rate of wound closure. So numerous steps in the healing process are carried out by the macrophages, and numerous steps in the healing process are carried out by other cells, which are orchestrated by the macrophages. Wow, those macrophages are busy little blobs.


T-lymphocytes, moving in next, have actions in would healing that are not yet fully clear. Experiments done on rats showed that eradication of certain types of T cells (CD8) increase the strength of a healed wound, whereas eradication of all types of T cells results in a decreased strength of a healed wound. Lau and friends concluded that they "...may bracket control of the proliferation phase of wound healing." In other words they tell when to start and stop laying down fibrin and collagen. Too much fibrin and collagen and there is a big lumpy scar, too little and there is a weak closure that may open again. The T cells maintain moderation in this process. 


What can't be overstated is just how crucial the immune cells are in this process. They are doing much more than just attacking invaders, but supervising and directing every stage of the healing process. We can see right away why conditions like diabetes that decrease immune function also affect wound healing. Also, knowledge about the cells active in each phase of wound healing can give us useful clues in how to best help our clients heal. We can look at the place where the healing process is going awry and stimulate specific components of the immune system. Such as the macrophages if the issue is presenting during the inflammatory phase, and specific immunity if it's the proliferation phase that is buggered up.

When it comes to stimulating wound healing there are a number of herbs that I remember from school stimulating healing: huang qi, hua shi, mo yao, ru xiang, and others. When we look at the classifications at the end of the Chen book "Chinese Medical Herblogy and Pharmacology" we find just 5 herbs listed as stimulating the generation of flesh: di yu, gu sui bu, lu hui, lu lu tong, and shan yao. And a trip through the medical literature reveals still a different list that includes: san qi, dan shen, shu di huang, sha ji, and huang qi.

This is a great study from Poland, looking at the proangiogenic actions of a handful of herbs and their application in wound healing. By proangiogenic they mean "making new blood vessels" this is what the macrophages do during the inflammatory phase to speed healing and bring more tissue to the site. It is crucial in the healing process. Anyway, this article is great, it is chalk full of little nuggets of scientific minutiae that bring a bit more clarity to our understanding of these herbs. First, they looked at ginseng (including ren shen, xi yang shen, and san qi.) Then, as western medicine loves to, they got all microscopic and looked at the chemical nature. What they found is that there are multiple ginsenosides (over 40) present in various types of ginseng and the types present and the quantities of each dictate the actions. In the author's words:

The ginseng root contains 2–3 % ginsenosides

of which Rb1 and Rg1 are the most abundant (Sengupta

et al., 2004). The mass-spectroscopic compositional analysis

performed by Sengupta et al. has revealed that Rg1

and Rb1 are present in all investigated extracts, however,

each extract displays distinct ginsenoside composition,

especially in the ratio between the two.

It is the ratio between the two types that seems to have the real action on angiogenesis. A predominance of Rg1 lends to more angiogenesis actions while a predominance of Rb1 seems to limit angiogenesis. San Qi is predominantly Rg1, while ren shen and xi yang shen are both predominantly Rb1. This proangiogenic action of san qi might go a long way towards explaining it's apparently contradictory actions of stopping bleeding while invigorating blood. More blood vessels means holding that blood in the body, while also carrying it away from the site.

The study also looked at aloe vera. It wasn't clear whether they looked at Aloe Vera gel, or at what we know as Lu Hui, which are quite different. Lu Hui is the dark resinous material removed from the fiberous outer rind of the aloe plant, then dried, or charred. Aloe Vera gel on the other hand is the gelatinous material removed from the inner compartments of the stalks of the aloe plant. The chemical constituents are different, but one chemical that they both contain (and many wound healing herbs do) is sitosterol (in Lu Hui it's Beta sitosterol). This chemical has pretty strong actions on increasing angiogenesis and it's where this study put most of its money on why aloe works.

Sea buckthorn, or sha ji, has also demonstrated results in accelerating wound healing. It also contains large amounts of sitosterol (57-76 and 61-83% of the seed and peel respectively) as well as a high oil content, and a number of flavonoids. It has the special application in TCM of being used to treat hematomas, and Bensky also notes it can be applied topically to treat burns.

Sea Buckthorn, Aloe Vera, and Curcuma Longa (jiang huang) were tested together as a topical treatment for slow healing wounds by Gupta and friends. In Gupta's words: "treatment increased cellular proliferation and collagen synthesis at the wound site." He found benefit in both diabetic and normal rats. He used a water extraction of the first two ingredients and an alcohol extraction of the third, combined in a specific ratio (1:7:1) for best results. Sounds like a good thing to have on hand in the clinic.

Astragalus was investigated and found in some studies to contain the ingredients that should speed healing, but was found in another study that topical application did not speed healing of diabetic ulcers, until it was given combined with rehmanniae at a 2:1 ratio. Enter the synergistic actions of herb combining. This is an exciting new arena of research where they are attempting to examine how herbs interact. It's wicked complicated though, and the nice thing is we don't really need to know the why to continue prescribing our herbs in traditional combinations. For me this gives me more reason to respect the formulas created over the centuries. Besides being well balanced in their actions, the formulas that have persisted all these years likely have synergistic actions that go beyond their cumulative effects. It is also a  good reason to try to always use herbal mixtures that are extracted or decocted together unless the classics specified another method. So for all the granule people out there, that means just pouring the 4 ingredient powders together to make si wu tang is different than buying the formula decocted together and granulated. You may be losing actions, or introducing other actions that weren't part of the traditionally recognized actions. I'd love to do a post someday on what science knows so far about herb combining. Anyway, back to wound healing...

I found it interesting that Huang Qi contains phytoestrogens that are able to bind to and stimulate estrogen receptors. Here's a nice study showing that. (the others that they looked at that also had estrogen activity, so you don't have to go look up the botanical names were: ge gen, yin yang huo, suo yang, she gan, huang qin, jue ming zi, bu gu zhi, hu zhang, he shou wu, and da huang, they didn't look at shan yao sorry.) As we know estrogen has a proliferative and protective effect when it comes to flesh; mucosa thin and skin thins in menopause and this seems a likely mechanism by which astragalus operates (when taken internally). Astragalus also has actions on increasing wbc count (specifically in regards to macrophages) and macrophages have so much going on in the process of wound healing it seems a no brainer to get our poor healers on huang qi (and our diabetics for that matter.)

So in conclusion there are numerous ways to improve wound healing from directly stimulating new tissue growth via topical application of powdered herbs or extractions with angiogenic actions (san qi, lu hui, sha ji, dan shen, etc.) if you use huang qi topically to improve healing you need to include shu di huang in a 1:2 ratio (huang qi : shu di). Giving herbs internally that regulate and support healthy immune function and improve white blood cell production such as adaptogenic herbs (huang qi, ren shen, san qi, dong chong xia cao, bu zhong yi qi, si jum zi tang etc) will support wound healing by making sure that the cells that are active in wound healing are available to complete the tasks. I know most people in this healing trade always look to treat the root as well as the branch and this area is no exception. Dab a bit of that 2:1 huang qi shu di juice on that thing, or better yet follow Gupta's lead and make your very own 1:7:1 mixture of sha ji, aloe gel and jiang huang but after you've addressed it on the surface, get that patient on some qi tonics as well.

Sorry there was so much mumbo jumbo from the science side in this post, I'll keep the next post a little more Chinese Mediciney.

All the best

Welcome to my first blog post!

Hello! Welcome to my blog! (if indeed anybody out there is actually reading it!) 


What's if for? This blog is intended as a resource for acupuncturists, herbalists and medical doctors to learn about new research in the application of science based herbs to patient care. It'll also be useful to those laypeople out there who want to have a more involved hand in your care (and by the way kudos to you!). I'll go through recent studies both from Chinese and English sources that offer useful clinical nuggets, and investigate them in light of the classical wisdom on those herbs and formulas. I recognize and value the empirical wisdom of the thousands of years of knowledge in Chinese Medicine, but also recognize that modern experiments are valuable in understanding the nuances of the application of these herbs. 


I guess a brief introduction is in order. I'm Kieran Jones. I'm an acupuncturist practicing in Washington State near Seattle. I attended Five Branches University in Santa Cruz, Ca, graduating in 2009. I'm currently applying to attend a Doctoral Program at Oregon College of Oriental Medicine. 


Anyway, enough about me, lets get to the studies. To kick it off lets look at a promising herb called dan shen and it's use in the treatment of something we didn't hear about using it for in Chinese Medicine School.


Hopefully most of us know about the spontaneous fractures that occur as a result of taking the Biophosphonate drug Fosomax, and many of us probably know patients still taking Fosomax. I just saw one a few weeks ago. It leaves us wondering, how we can best treat these patients for their risk of fractures, without (hard to say this with a straight face) increasing their risk of fractures. 


Well, enter the chinese herb Dan Shen. Categorized as a regulate blood herb in the Chinese Pharmacopeia, Dan Shen invigorates the blood, tonifies the blood and calms irritability due to blood heat. (source Materia Medica 3rd edition) Dan Shen has been long used to treat pain associated with what Chinese Medicine calls blood stagnation, and has a particular affinity (tropism we say in the herb nerdery) for the heart.


An exciting study came out back in 2004 looking at this amazing little herb's action in the treatment of Osteoporosis with pretty encouraging results. In this study by Liao et. al., rats were ovariectomized (ovaries removed) leaving them without the glands that make their estrogen. Without the protective effects of estrogen they began a made dash for osteoporosis, their bones thinning like pre weigh-in high school wrestlers. They were treated variously with estrogen, the dan shen extract (tanishonine) or a control injection of deionized water.


The results were that dan shen protected against bone loss almost as well as the estrogen did. Also the dan shen didn't have any significant effects on increasing the weight of the uterus as the estrogen did. (meaning the dan shen was not stimulating the estrogen receptors, but was working through another mechanism. This is important because as we know the use of Hormone Replacement Therapy can increase the risk of cancer, heart attack and stroke, so we want to avoid stimulating those receptors in this patient population.) 


Note that this was a fat soluble extraction of Dan Shen, which is traditionally extracted in a water based decoction. This is key. The active ingredients in various dan shen preparations varies widely so the safest bet is to get the raw herb for your patients and either extract it yourself or send them home to decoct it. It isn't immediately clear to me how many of the fat soluble components are retained in the water decoction. If anybody has seen a detailed analysis of the constituents in a water extraction of dan shen, I'd love to see it. 


The authors stated Dan Shen's ability to decrease the loss of bone mass as a result of its action on decreasing the actions of the osteoclasts, however, unlike estrogen it does this without decreasing the action of the osteoblasts. The constant back and forth action of the osteoblasts and osteoclasts ensure the bones remain both dense (enough material) and structurally strong (properly placed material). After all, anybody can carry a stack of two by fours into your living room, but unless they are placed strategically in the walls at the correct locations they won't increase the strength of your house. Here are the authors:

Unlike well-known antiresorptive agents estrogen, as shown in this study, which inhibit bone resorption accompanying with a subsequent decrease of bone formation through coupling mechanism^[16], tanshinone treatment only decreased mineral apposition rate but not mineralizing surface at the PTM of OVX rats. In addition, all bone formation indices such as mineralizing surface, mineral apposition rate, and bone formation rates were not altered by tanshinone treatment at the LV in OVX rats. Furthermore, tanshinone also thickened the trabecula whereas estrogen did not have such effect as shown in the current study. These results indicate that tanshinone does not inhibit osteoblast bone formation occurred on bone surface while inhibiting bone resorption thus causes a positive bone balance resulting in bone gain.

Add to that the benefits Dan Shen shows in preventing cardiac ischemia and it's a bit of a no brainer getting your elderly patients on this as a regular piece of their herbal supplementation!


Later till next time!