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The Role of Epigenetics in Traditional Chinese Medicine

Traditional Chinese medicine (TCM) has been around for thousands of years, and for good reason. It’s a holistic approach to health that can help you feel your best, both physically and mentally. But it wasn’t until recently that scientists started to uncover some of the underlying mechanisms behind its effectiveness.

One such mechanism is epigenetics, which refers to changes in gene expression that can occur without alterations to the DNA sequence itself. Epigenetic changes can be influenced by a variety of factors, including the environment and lifestyle choices. Interestingly, research has also shown that TCM can have an impact on epigenetics, making it a promising avenue for investigation.

What is Traditional Chinese Medicine (TCM)

Traditional Chinese Medicine (TCM) is an alternative medicine system that has been used in China for thousands of years. It is based on the belief that the body is a complex system of energy (called qi) and that health is maintained when this energy flows smoothly along meridians (channels). TCM practitioners use a variety of techniques to help restore the flow of energy and promote healing. These techniques include acupuncture, herbal medicine, dietary therapy, and exercise.

There is growing evidence that TCM can be effective in treating a variety of health conditions. For example, acupuncture has been found to be effective in reducing pain and improving function in people with arthritis. As well, herbal medicines are often used as an alternative for treating anxiety and depression.

However, TCM does not follow the conventional Western medical system, which seeks to identify specific pathogens or disease-causing agents and treat them with targeted therapies. As a result, health practitioners are cautious about suggesting TCM as a sole treatment method. Additionally, there may be concerns about the safety and regulation of TCM practices and products.

To validate the efficacy of TCM, more scientific evidence and clinical trials are needed. This is where epigenetic studies can help, as it has been found that epigenetic alterations can be mediated by natural compounds, as well as exercise and other non-drug-type therapies. Therefore, clearly describing these underlying mechanisms of TCM will no doubt benefit the search for novel agents in preventing and treating various diseases.

Epigenetic Studies and TCM

Several studies have investigated the effects of TCM on various epigenetic processes, such as DNA methylation, histone modification, and m6A RNA methylation. Many have shown that TCM can regulate gene expression to inhibit tumor growth, protect against cell damage, reduce inflammation, and improve cognitive function. While most of the studies are preliminary, understanding how TCM influences epigenetic mechanisms provides insight into how TCM promotes health and wellness. Below are some highlighted areas of study with specific research examples that have found a connection between TCM, epigenetics, and health benefits.

DNA Methylation Studies

DNA methylation is a well-researched epigenetic modification that involves adding a 5-carbon to DNA’s cytosine ring via DNA methyltransferases. It’s vital for gene expression and regulation, and faulty methylation can cause severe medical conditions like cancer, diabetes, and cardiovascular diseases. Scientists are exploring ways to either maintain or reverse DNA methylation as a new strategy for treating these diseases.

Natural compounds derived from TCMs, like curcumin and resveratrol, have been shown in studies to decrease levels of enzymes involved in DNA methylation, which can activate certain genes that help fight cancer. Additionally, green tea, commonly used in TCM, contains epigallocatechin gallate (EGCG), a potent phytochemical with anti-inflammatory and antibacterial properties. EGCG has been found to inhibit DNA methyltransferases, which can lead to changes in DNA methylation patterns and affect gene expression

In a study published in the Chinese Journal of Integrative Medicine, researchers explored the efficacy of TCM herbs, including Astragalus membranaceus, Ligustrum lucidum, Panax ginseng, Rehmannia glutinosa, Scutellaria baicalensis, Trichosanthes kirilowii, and Zingiber officinale, for cancer treatment. The study demonstrated that these herbs induced DNA demethylation in cancer cells, leading to cell death. Moreover, they were found to modulate DNA methylation by inhibiting DNMTs and activating DNA demethylases. The researchers also suggested that combining these herbs with conventional treatments such as chemotherapy and radiation therapy could potentially enhance their effectiveness. [1]

In another study published in PLoS One, researchers found promising results regarding the effectiveness of a TCM called San-Huang-Xie-Xin-Tang (SHXXT) in treating atherosclerosis. SHXXT is a combination of three herbs: Coptidis rhizoma, Rhei rhizome, and Scutellariae radix. The study revealed the positive effects of SHXXT on specific molecules and genes associated with atherosclerosis. Notably, SHXXT increased the levels of microRNA-152, a molecule involved in gene regulation. It also reduced the activity of DNMT1, an enzyme responsible for the maintenance of DNA methylation. Moreover, SHXXT increased the expression of a gene called estrogen receptor α (ERα), known for its protective role against atherosclerosis. These findings indicate the potential of SHXXT as a treatment to counteract the negative effects of atherosclerosis.[2]

Research published in the journal Pain examined the effects of the TCM practice acupuncture in addressing chronic pain and its emotional and cognitive implications. The study utilized a mouse model of neuropathic pain and focused on the potential influence of this acupuncture on DNA methylation patterns in the prefrontal cortex. Over a 6-month duration, acupuncture effectively mitigated pain sensitivity, emotional disruptions, and cognitive deficits, leading to the restoration of DNA methylation levels. Notably, acupuncture reversed DNA methylation alterations in genes linked to pain, mitochondrial function, and neural processes, highlighting its potential positive impact through TCM-based epigenetic modifications and intricate molecular pathways.[3]

Histone Modification Studies

Histone modifications are one of the main epigenetic mechanisms that regulate gene expression. Histone proteins are found in the nucleus of cells and are wrapped around DNA to form nucleosomes. Histone modifications can affect how tightly the DNA is wrapped around the histones, which in turn can affect how easily the DNA can be transcribed into RNA.

TCMs have been shown to modulate histone modifications in a variety of ways. For example, some TCM herbs can inhibit histone deacetylases (HDACs), which are enzymes that remove acetyl groups from histones. Acetylation of histones loosens the DNA around the histones, which makes it easier for the DNA to be transcribed. Other components of TCMs can directly modify histones by adding or removing chemical groups. Evidence has shown that TCMs that modulate histones can have therapeutic effects in the treatment of arthritis, cancer, cardiovascular and cerebrovascular diseases, as well as some skin diseases.

In a PLoS One study investigating the pharmacological effects of the Chinese herb Salvia miltiorrhiza on breast cancer cells, researchers found that certain compounds in the herb, called tanshinones, could stop the growth of breast cancer. One specific tanshinone, known as T1, was particularly effective in inhibiting the growth of triple-negative breast cancer cells. The protein Aurora A, which is overexpressed in breast tumors, played a role in T1’s effects. Interestingly, the researchers found that histone acetylation influenced the overexpression of Aurora A. T1 reduced the levels of histone acetylation, which in turn inhibited the growth of breast cancer cells. The findings suggest that T1 could be a promising treatment option for breast cancer. [4]

In another article published in BioMed Research International, researchers screened the world’s largest database of TCM for natural compounds that could be used to develop inhibitors of HDAC2, an enzyme that has been linked to Alzheimer’s disease. Utilizing a technique called molecular docking, they identified the top ten TCM candidates capable of interacting with HDAC2. Then, they used different prediction models to determine the potential effectiveness of these compounds. Through molecular dynamics simulations, they further examined how the compounds interacted with HDAC2. The results indicated that (-)-Bontl ferulate, monomethylcurcumin, and ningposides C had the highest potential for inhibiting HDAC2. The way these substances interacted with the protein, through hydrogen bonds and hydrophobic interactions, suggested that they could effectively inhibit the enzyme’s activity and thus could possibly be a promising source of new treatments for Alzheimer’s disease.[5]

RNA methylation Studies

RNA methylation is a modification of RNA molecules that plays a crucial role in gene expression and various cellular processes. It has been implicated in several diseases, including cancer, neurodegenerative disorders, and metabolic disorders. The most well-known form of RNA methylation is N6-methyladenosine (m6A, which occurs predominantly on adenosine residues in mRNA molecules and is dynamically regulated by enzymes known as “writers,” “erasers,” and “readers.” These enzymes add, remove, and interpret the m6A modification, influencing mRNA stability, splicing, transport, and translation efficiency. RNA methylation has also been observed on other nucleotides, such as cytosine (m5C) and uridine (m5U), although their functions are not yet fully understood.

In recent years, there’s been growing interest in how TCM could influence RNA methylation. Some studies suggest that TCM herbs might adjust RNA methylation levels, either increasing or decreasing them, depending on the specific herb and disease being targeted. This opens up intriguing opportunities for exploring new therapeutic approaches.

In a mouse study done in 2022, researchers explored the effects of the TCM, Hua Tuo Zai Zao Wan (HTZZW), on atherosclerosis (AS) treatment. Their research showed that mice fed a high-fat diet and given HTZZW had smaller plaque areas in their arteries, improved blood lipid levels, and reduced inflammation compared to the control group. HTZZW influenced the expression of certain enzymes involved in RNA methylation (METTL14, METTL3), affecting the stability of a specific mRNA molecule (NF-κB), leading to reduced inflammation and ultimately improving AS progression.[6]

In a study published in Biomedicine & Pharmacotherapy, researchers investigated the therapeutic potential of the ling-gui-zhu-gan (LGZG) decoction, a classic formula in traditional Chinese medicine (TCM), for alleviating hepatic steatosis induced by a high-fat diet. The study aimed to uncover the mechanisms underlying the LGZG decoction’s effects in the context of nonalcoholic fatty liver disease (NAFLD). The results demonstrated that the LGZG decoction effectively reduced hepatic steatosis and m6A levels, with a specific focus on the coding sequence domain as a critical site of m6A methylation. Furthermore, the study identified differentially methylated genes (DMGs) associated with important functions such as insulin-like growth factor receptor binding, fatty acid metabolism, and degradation. In addition, the LGZG decoction was observed to regulate the m6A methylation levels of suppressor of cytokine signaling 2 (SOCS2), indicating a plausible mechanistic route underlying its therapeutic impact on NAFLD. [7]

In Summary

Understanding the connection between Traditional Chinese Medicine (TCM) and epigenetics opens a captivating realm of exploration. This promising avenue allows us to uncover how TCM practices, like acupuncture and herbal remedies, impact gene behavior at a molecular level. While these current studies are at an early stage, they provide a glimpse into the fascinating interplay between TCM and epigenetics.

It’s worth noting that TCM should not replace conventional medicine but rather complement it. While epigenetic insights offer intriguing clues about how TCM works on a molecular level, they also underscore the importance of careful consideration. Further research will be essential to uncover the full scope of this relationship and determine how TCM practices could contribute to overall health and wellness. As we move forward, the combination of epigenetics and TCM offers a pathway to enhance our knowledge of holistic health and promote a more personalized approach to healthcare.

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