The Role of Epigenetics in Traditional Chinese Medicine

Exploring the Molecular Mechanisms Behind this Alternative Health Practice

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.

Sources:

  1. Shen F, Zhao Y, Yu X, Wang B, Wu X, Lan G, Gao R. (July 9, 2021) Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies: A New Paradigm of “State-Target Medicine”. Chinese Journal of Integrative Medicine.
  2. Wang Y-S, Chou W-W, Chen K-C, Cheng H-Y, Lin R-T, Juo S-HH (January 25, 2012) microRNA-152 Mediates DNMT1-Regulated DNA Methylation in the Estrogen Receptor α Gene. PLoS One.
  3. Jang JH, Song EM, Do YH, Ahn S, Oh JY, Hwang TY, Ryu Y, Jeon S, Song MY, Park HJ. (Feb 1, 2021) Acupuncture alleviates chronic pain and comorbid conditions in a mouse model of neuropathic pain: the involvement of DNA methylation in the prefrontal cortex. Pain.
  4. Yi Gong 1, Yanli Li, Hamid M Abdolmaleky, Linglin Li, Jin-Rong Zhou. (April 2, 2012) Tanshinones inhibit the growth of breast cancer cells through epigenetic modification of Aurora A expression and function. PLoS One.
  5. Hung TC, Lee WY, Chen KB, Chan YC, Lee CC, Chen CY. (June 23, 2014) In silico investigation of traditional Chinese medicine compounds to inhibit human histone deacetylase 2 for patients with Alzheimer’s disease. BioMed Research International.
  6. Zhihua Yu, Xuanlu Zheng, Chenghui Wang, Chuan Chen, Na Ning, Danting Peng, Te Liu, Weidong Pan. (March 28, 2022) The Traditional Chinese Medicine Hua Tuo Zai Zao Wan Alleviates Atherosclerosis by Deactivation of Inflammatory Macrophages. Evidence-Based Complementary and Alternative Medicine.
  7. Dang Y, Xu J, Yang Y, Li C, Zhang Q, Zhou W, Zhang L, Ji G. (May 20, 2020) Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine. Biomedicine & Pharmacotherapy.

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