Incorporating Traditional Chinese Medicine (TCM) in modern day society: over-the-counter supplement and TCM formulae

Note: I did not have any formal training in TCM practices. The TCM ingredients described below are mostly plant-based. In this article, ying/yang balance or the principle of ‘jun, Chen, zuo, shi’ (arbitrarily translated as principle/auxillary) won’t be discussed.

Nowadays, various herbal extracts were available in health stores as ‘health supplements, which are not subjected to the same regulations as chemicals or formulas that are prescribed as medications. Although these health supplements were extracted from ‘natural’ sources, they may still have biologically active ingredients that can be harmful to our body if we take them in incorrect dosages, or under disease conditions. A recent report from National Institute of Health in US showed that a lot of apparently healthy adults and children are taking one or more non-vitamin health supplements. A closer look on the list will show that most of them are “natural products” or extracts from various parts of plants. In particular, ginseng and ginkgo, which are members of commonly-used medicinal ingredients in TCM, are among the top 10 supplements taken by American adults (~ 0.7% each). Therefore, increasing number of people are taking in ingredients that are considered to have medicinal values in TCM practice. But, what’s the difference between taking supplement, which usually consist of crude extracts of a medicinal ingredient, and taking TCM medications?

Medicinal ingredients used in TCM can be divided into 3 main categories: (1) plant-based, (2) animal-based and (3) mineral-based. Here, the focus of this article is mostly on plant-based ingredients and their potential role in influencing our health. Most of them modern day TCM research focused on identifying the chemically active ingredient in any particular medicinal herb or parts of a plant. Curcumin from turmeric and ginsenosides (ginseng saponins) from ginseng are two of the few examples. As of July, 2019, the number of peer-reviewed research publications listed in Pubmed database on these two ingredients reached 13,505 and 5161, respectively. In particular, there are 251 publications on the use of curcumin in diseases, such as, Inflammatory Bowel Diseases (IBD), osteoarthritis, and various cancer.  For ginsenoside,  there are a total of 76 published results of clinical trials on diseases including stroke and diabetes. The purposes of these studies include studying

(1) the safety of the active chemical ingredients (in contrast to crude extract as in health supplement) in both healthy and disease populations;

(2) pharmacokinetics (e.g. absorption and distribution) of the active chemical ingredients in our bodies,

(3) potential therapeutic effects of these active ingredients, either when taken in alone or with standard medications;

(4) investigating the potential interactions between these active ingredients and other commonly-used medications.

It should be noted that although some of these clinical trials showed promising results for the use of TCM active ingredients, due to the highly selective nature of test subjects in these studies, more clinical trials are needed to be performed. Furthermore, performing meta analyses on the results of these clinical trials are necessary to draw meaningful conclusions on the medicinal use of these ingredients.

In contrast to modern-day TCM research, traditionally, TCM practitioners prescribed TCM formulae to patients after giving diagnoses. These classical TCM formulae were often composed of several medicinal ingredients, and the patients would receive instructions for preparing them. In the past, the instructions would be, ‘boil all the herbs with medium heat in 5 bowls of water until only 1 bowl of liquid is left’. It may sound very cryptic nowadays, but this can be translated to ‘boil the herbs in medium heat for 1 hour’. From the perspective of chemical extraction, it is not difficult to see that

(1) various chemicals from different medicinal ingredients in the formulae are extracted to the boiling water under constant heat;

(2) the extraction go on for a designated time (e.g. 1 hour);

(3) these chemicals may react / interact with each other in the heat in an aqueous (water-based) environment .

Then, how much do we know about these chemicals present in the formulae after their process of preparation? Are these formulae really effective in treating diseases when we examine them under scientific standard?

One of the best studied examples of these formulae, yokukansan (YKS), come from Kampo medicine, a traditional Japanese medicine that was derived from TCM. Similar to TCM, formulae of Kampo medicine are mainly composed of herbs. At present, there are 148 Kampo medicine formulae that are approved by the Japanese Ministry of Health, Labor and Welfare to be prescribed by physicians and covered by Japanese National Insurance Program. These formulae are mostly sold in form of dried extract and their production process adheres to Japanese Good Manufacturing Practice (GMP) criteria.

A recent review paper on Pharmacology & Therapeutics^# summarized the findings of pre-clinical investigations and clinical trials of YKS, a formula that is composed of 7 dried herbs.  YKS (D07049; D07049) is prepared by heating a mixture of the 7 components at 95^°C for 1 hour and spray-dried. In clinical trials, YKS was shown to be well tolerated for patients with dementia, reduce the dose of anitpsychotics required by Dementia patients and improve the quality of life (QoL) of patients. At least 25 chemical ingredients were identified from the extract by 3-D high performance liquid chromatography. Out of these 25 chemical ingredients, geissoschizine methyl ether (GM) binds strongly to serotonin 1A (5-HT_1A) receptor and ameliorates aggressiveness in socially isolated mice after the mice were fed with GM. In addition, GM also ameliorates head-twitch response (a hallucination-like behavior) in mice by regulating the expression of serotonin 2A (5-HT_2A) receptor in prefrontal cortex in mouse brain. Other chemical ingredients identified from YKS including glycyrrhizin and 18β-glycyrrhetinic acid (GA), also improve dementia-related symptoms in mice by improving various mechanisms involved in communications between nerve cells. Importantly, researchers can detect that GM and GA in blood in rats after the rats are fed with these two chemical ingredients. Furthermore, in vitro evidence suggested that GM and GA can pass through blood-brain barrier and act on brain cells directly. To conclude, YKS has shown to effectively improve behavioral problems related dementia in clinical trials. Its active chemical ingredients were identified and their functions upon nerve cells well clearly elucidated in human and in animal models.

Supplements made from plant parts that are considered to have medicinal values in TCM are gaining popularity. This may promote the use of TCM in our everyday lives. However, without careful studies on their safety, efficacy and physiological functions in human body, the use of these TCM-associated supplements or drugs should be not recommended to general public, especially people with chronic diseases. Nowadays, researchers are advancing our knowledge on individual active ingredients extracted from TCM herbs and some standardized formulae, which will help to promote the safe use of TCM to the general public in the future.

^# Ikarashi and Mizoguchi. (2016) Pharmacology & Therapeutics. 166, 84-95