Traditional East Asian Medicine Research Articles

Modified Gwakjeongtang for Diarrhea-Predominant Irritable Bowel Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Pilot Clinical Trial.

Irritable bowel syndrome (IBS) is a chronic condition characterized by recurrent abdominal pain associated with bowel movements. Modified Gwakjeongtang (MGT), an herbal prescription rooted in traditional East Asian medicine, consists of thirteen botanical drugs known for their potential to enhance intestinal barrier function, regulate gastrointestinal motility, and exhibit anti-inflammatory and antioxidant properties. Despite a few previous clinical trials highlighting MGT's potential for IBS symptom management, limited evidence exists with placebo control. In this pilot randomized clinical trial protocol, we aim to exploratively evaluate the efficacy and safety of MGT in patients with diarrhea-predominant IBS (IBS-D) by comparing it with a placebo. A total of 60 IBS-D patients will be enrolled, and eligible participants will be randomly allocated to either the MGT or placebo groups. Over a 4-week period, they will receive MGT or placebo granules three times a day. The primary endpoint will be the overall response rate post-treatment, determined through daily assessments of abdominal pain intensity and stool consistency. This clinical trial protocol has received approval from the Korean Ministry of Food and Drug Safety for an investigational new drug application and Institutional Review Board of the Kyung Hee University Korean Medicine Hospital. The research findings will be submitted and published in international peer-reviewed journal. Clinical research information service (registration number: KCT0008523).

Collaborative Design of a Chinese Herbal Medicine Case Report Guideline (CHM-CARE)

IntroductionCase reports have a long history in Chinese herbal medicine (CHM), and even into the modern day, case reports are still a preferred format for traditional East Asian medicine (TEAM) practitioners. However, the tradition of case reports in teaching and research is not nearly as common in the English-speaking world as in China, possibly due to the lack of a specific case report guideline. This study aimed to co-design a CHM guideline (CHM-CARE) to assist practitioners in compiling structured and comprehensive case reports. MethodsA two-phased mixed approach was used to develop the case report guideline. In phase one, focus groups of TEAM practitioners were used to determine what components of existing guidelines (e.g., Case Report (CARE) and Case Report in Chinese Medicine (CARC)) were relevant to include, along with any additions or changes. Content analysis of phase 1 provided the checklist items for a two-round Delphi process (Phase 2). All checklist items from the first Delphi round with a median of three or higher were included in the second round, with consensus set at >70% for inclusion in the final guideline. ResultsA total of 18 CHM practitioners from four countries joined five separate focus group discussions. Focus group discussions led to 98 checklist items being used in the first round of the Delphi process. 15 international experts on case reports participated in two rounds of Delphi. 69 checklist items moved forward into the second round where 61 items (88%) reached consensus and formed the final CHM-CARE guideline. ConclusionKey elements of a herbal medicine case report checklist were identified, and a 61-item case report guideline (CHM-CARE) was produced, providing clear guidelines for case reports to TEAM practitioners operating in private practice.

Visualizing a Cold Stress-Specific Pulse Wave in Traditional Pulse Diagnosis ('Tight Pulse') Correlated with Vascular Changes in the Radial Artery Induced by a Cold Pressor Trial.

Radial pulse diagnosis is the most common method to examine the human health state in Traditional East Asian Medicine (TEAM). A cold stress-related suboptimal health state (subhealth) is often undetectable during routine medical examinations, however, it can be detected through the palpation of specific pulse waves, particularly a 'tight pulse', in TEAM. Therefore, this study examined a correlation between 'tight pulse' and vascular changes in the radial artery (RA) induced by a cold pressor trial (CPT). Twenty healthy subjects underwent sequentially control trial and CPT with room-temperature and ice-cold water, respectively, on the right forearm. The radial pulse and vascular changes were then examined on the left arm. The radial pulse scores for frequencies of 'tight pulse' with strong arterial tension increased after the CPT compared with the control trial. The pulse scores were reversely correlated with the RA thickness and volumes in ultrasonography, but not with changes in the systolic/diastolic blood pressure. The RA thickness-based vascular surface and three-dimensional images visualized a 'tight pulse' showing the vasoconstriction and bumpy-/rope-shaped vascular changes in the radial pulse diagnostic region after the CPT. These findings provide valuable insights into the potential integration of clinical radial pulse diagnosis with ultrasonography for cold-related subhealth.

A Herbal Prescription of Insamyangyeongtang as a Therapeutic Agent for Frailty in Elderly: A Narrative Review.

Frailty is a major geriatric syndrome with a multifactorial etiology that induces a decline in multiple physiological and psychological functions. In traditional East Asian medicine (TEAM), qi and blood deficiency clinically represent as fatigue, anemia, anorexia, decreased strength after illness, and weakness, commonly interpretated as frailty. An herbal prescription of Insamyangyeongtang (IYT, Ninjin'yoeito in Japanese, Ren-Shen-Yang-Rong-Tang in Chinese) tonifies qi and blood and has the potential to treat multiple targets caused by qi and blood deficiency. As the population ages and frailty increases, there is an increase in the potential effectiveness of IYT in frailty. This study reviewed relevant clinical trials to provide an updated view on the effect of IYT on frailty. IYT has therapeutic effects on frailty associated with chronic respiratory diseases (e.g., chronic obstructive pulmonary disease) and cognitive impairments (e.g., Alzheimer's disease) and improves respiratory symptoms and cognition. IYT also has therapeutic effects on weight gain, muscle mass, and strength, and improves nutritional status in frail elderly individuals who have decreased muscle mass and strength, loss of appetite, and weight loss. The same effect has been shown in frailty in elderly individuals with rehabilitation treatment and chronic diseases. IYT also improves frailty associated with symptoms such as intractable dizziness and genitourinary symptoms. The beneficial effects of IYT in several diseases could be important for medication replacement, reduction, and prevention of polypharmacy. Based on the results of this review, we suggest that IYT has the potential to be a therapeutic agent against frailty.

Comparative Analysis of Hindgut Microbiota Variation in Protaetia brevitarsis Larvae across Diverse Farms.

Protaetia brevitarsis larvae are farm-raised for food, are used in traditional East Asian medicine, and convert organic waste into biofertilizers. Here, the comparative analysis of the gut microbiota of third-instar larvae obtained from five different farms was investigated using 16S rRNA microbial profiling. Species richness, evenness, and diversity results using α-diversity analysis (observed species, Chao1, Shannon, Simpson) were similar between farms, except for those between the TO and KO farms. β-diversity was significantly different in distribution and relative abundance between farms (PERMANOVA, pseudo-F = 13.20, p = 0.001). At the phylum level, Bacillota, Bacteroidota, Actinomycetota, and Pseudomonadota were the most dominant, accounting for 73-88% of the hindgut microbial community. At the genus level, Tuberibacillus, Proteiniphilum, Desulfovibrio, Luoshenia, and Thermoactinomyces were the most abundant. Although oak sawdust was the main feed component, there were large variations in distribution and relative abundance across farms at the phylum and genus levels. Venn diagram and linear discriminant analysis effect size analyses revealed large variations in the hindgut microbial communities of P. brevitarsis larvae between farms. These results suggest environmental factors were more important than feed ingredients or genetic predisposition for the establishment of the intestinal microbiota of P. brevitarsis larvae. These findings serve as reference data to understand the intestinal microbiota of P. brevitarsis larvae.

A Modern Interpretation of Cold-Heat Pattern in Traditional Medicine with a Focus on Thermo-Regulation

Cold-heat patterns (C-HPs) in Traditional East Asian Medicine are essential for individually diagnosing and treating patients. However, the concept of C-HPs and their biological mechanisms (thermoregulation) remains unclear. C-HPs studies published between January 2000 and May 2023 were retrieved from 5 databases (PubMed, Google Scholar, OASIS, Korean studies Information Service System, and Research Information Sharing Service). Among the 8,373 articles screened, 132 were included in the review and categorized. Nineteen articles were clinical studies related to traditional concept of C-HP identification, 14 studies investigated diseases affecting thermosensation or thermoregulation, and 99 studies identified candidate genes as potential markers for C-HP identification. Further analysis, including gene ontology, and gene set enrichment analysis of the candidate genes, revealed 3 primary biological processes closely associated with thermoregulation-related genes, including localization, responses to stimuli, and homeostatic processes. Notably there was a significant association between the candidate genes and inflammatory mediator regulation of transient receptor potential channels (<i>p</i> < 0.001). A significant association between C-HPs and inflammation-related pathways across thermosensation-related and thermoregulation-related clinical and preclinical studies was observed, suggesting that the traditional concept of C-HPs should be studied further from an immunological perspective.

The Modernization of Oriental Music Therapy: Five-Element Music Therapy Combined with Artificial Intelligence

In recent years, music has been regarded as a promising non-pharmacological intervention for a number of physical and mental conditions. Five-elements music therapy—based on the five-element theory—is a unique non-pharmacological therapy of East Asian traditional medicine. It has the potential to effectively provide individualized music therapy to individuals with illness. However, one limitation of this music therapy is that the classification of the five elements and its application is mainly based on subjective judgment. The development of artificial intelligence (AI) has enabled the acoustic analysis of multi-factor sound sources. This can develop five-element music therapy. Here, we discussed the challenges proposed by the future combination of five-element music therapy and AI. Further, we hypothesized that AI may promote its use in the medical field.

Feasibility of Applying the OMOP Common Data Model to Traditional Eastern Asian Medicine Dataset.

To evaluate the feasibility of applying the Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) to databases of traditional East Asian medicine (TEAM), we composed a TEAM dataset and transformed it to the OMOP CDM. We found that some important TEAM information entities could not be transformed to the OMOP CDM (version 6.0) data fields. We suggest to develop data fields and guideline for transforming TEAM data to the OMOP CDM.

Current Research Status and Implication for Further Study of Real-World Data on East Asian Traditional Medicine for Heart Failure: A Scoping Review.

This study used real-world data (RWD) to explore the long-term effects of East Asian traditional medicine (EATM) on heart failure (HF). A comprehensive search was conducted across five databases to identify relevant studies, which were then reviewed using the Arksey and O'Malley scoping review framework. The analysis focused on a descriptive examination of the long-term outcomes associated with EATM intervention. Methodologically, the study explored various aspects, including study subjects, interventions, applied clinical outcomes, and statistical methods. Out of 258 studies, 12 were selected. Eight studies involved patients with HF, while the others used HF as an outcome. Datasets from the National Health Insurance Research Database were used in Taiwan, while electronic medical record data were used in China and Japan. EATM interventions have been found to be associated with lower mortality and readmission rates. One study indicated that an increased dose of Fuzi, a botanical drug, or prompt use of Fuzi after diagnosis led to a decreased mortality hazard ratio. In two studies examining readmission rates, a significant increase was observed in the non-exposed group, with odds ratios of 1.28 and 1.18. Additionally, in patients with breast cancer, the subdistribution hazard ratio for the occurrence of doxorubicin-induced HF was reduced to 0.69. Although cohort studies with survival analysis were common, methodological flaws, such as issues with statistical methods and HF diagnosis, were identified. Despite these challenges, the study observed an association between EATM and improved clinical outcomes in patients with HF, emphasizing the potential of RWD studies to complement randomized controlled trials, especially for longer-term follow-ups. These results provide foundational data for future RWD research.

Anti-Inflammatory Effects of Alphitolic Acid Isolated from Agrimonia coreana Nakai Extracts Are Mediated via the Inhibition of ICRAC Activity in T Cells.

Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai-a naturally growing species in South Korea-and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases.

Cold sensitivity classification using facial image based on convolutional neural network

Objectives: Facial diagnosis is an important part of clinical diagnosis in traditional East Asian Medicine. In this paper, we proposed a model to quantitatively classify cold sensitivity using a fully automated facial image analysis system.Methods: We investigated cold sensitivity in 452 subjects. Cold sensitivity was determined using a questionnaire and the Cold Pattern Score (CPS) was used for analysis. Subjects with a CPS score below the first quartile (low CPS group) belonged to the cold non-sensitivity group, and subjects with a CPS score above the third quartile (high CPS group) belonged to the cold sensitivity group. After splitting the facial images into train/validation/test sets, the train and validation set were input into a convolutional neural network to learn the model, and then the classification accuracy was calculated for the test set.Results: The classification accuracy of the low CPS group and high CPS group using facial images in all subjects was 76.17%. The classification accuracy by sex was 69.91% for female and 62.86% for male. It is presumed that the deep learning model used facial color or facial shape to classify the low CPS group and the high CPS group, but it is difficult to specifically determine which feature was more important.Conclusions: The experimental results of this study showed that the low CPS group and the high CPS group can be classified with a modest level of accuracy using only facial images. There was a need to develop more advanced models to increase classification accuracy.

The Effects of Natural Product-Derived Extracts for Longitudinal Bone Growth: An Overview of In Vivo Experiments

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children’s height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies.

Variability in Phytochemical Contents and Biological Activities among Adenophora triphylla Genotypes

Genetic diversity can remarkably impact the quality of derived products. This study focused on Adenophora triphylla, an herbaceous perennial used in East Asian traditional medicine. It is known for its diverse therapeutic effects that are attributed to phytochemicals. However, despite its therapeutic potential, a comprehensive exploration of the influence of genetic diversity on the pharmaceutical properties of various A. triphylla genotypes remains unknown. To address this knowledge gap, we employed DNA barcoding regions (ITS2, matK, and psbA-trnH) to elucidate the genetic diversity among the collected genotypes. The combined application of these barcoding regions is a robust method to identify A. triphylla genotypes. In addition, leaf extracts consistently exhibited higher antioxidant potential than root extracts. Nitric oxide production was strongly inhibited by the leaf extracts of the BG genotype (IC50 = 124.52 ± 12.97 µg/mL), and the leaf extracts (200 µg/mL) of the BT genotype contained significant antimelanogenic properties (IC50 = 181.56 ± 16.17 µg/mL). Various genotypes displayed diverse levels of phytochemical content, and the total saponin content exhibited a strong correlation with various biological activities of A. triphylla, suggesting a genetic influence on their pharmaceutical attributes. These findings highlight the significance of genotype selection for optimizing health benefits and promoting the potential utilization of specific genotypes in various industries, such as cosmetics and pharmaceuticals.

Acupotomy in Korean Medicine Doctors: A Preliminary Survey on Experiences, Perceptions, and Clinical Usage Status.

Acupotomy is a widely used medical intervention in traditional East Asian medicine, and efforts are being made to improve its effectiveness and safety. As a first step toward establishing more standardized procedural guidelines, a survey was conducted to explore the current clinical practice status and perceived adverse events (AEs) by Korean Medicine (KM) practitioners. The survey was developed via expert consensus and included information on clinical usage, perception, and the AEs experienced. The largest acupotomy society in Korea, which consists of 185 KM doctors, participated in an online survey conducted in September 2021. Of the 185 KM doctors, 107 (57.8%) responded. Musculoskeletal and connective tissue diseases accounted for 80.8% of suggested indications by KM doctors. Regarding the detailed procedure, there were considerable discrepancies between KM doctors. The most frequent acupotomy-related AEs observed by KM practitioners were bruises (77.3%), fatigue (57.7%), pain (51.8%), and hematoma (51.8%). Only 1.8% of the respondents answered that they had experienced severe AEs. Survey respondents answered that the use of imaging devices during acupotomy and the development of clinical practice guidelines are the most necessary policy requirements for promoting the use and ensuring the safety of acupotomy. To the best of our knowledge, this study marks the initial exploration into the KM physicians' clinical usage status, AEs experienced, and their requests for standardized guidelines and expanded health insurance coverage concerning acupotomy. Further research should include qualitative studies to assess patient experience and prospective observational studies to examine the effects of operator skills and treatment modalities on AEs and adherence.

Suicidal use of East Asian traditional herbal medicine: A systematic review of observational studies and implications for regulation

Suicidal use of East Asian traditional herbal medicine: A systematic review of observational studies and implications for regulation

길랑바레증후군에 대한 ‘의학적 상상’

Guillan-Barré Syndrome (GBS) is a rare neuropathic disease characterized by the monophasic progression of paralysis, affecting the limbs and the trunk, and by the high rate of recovery. The condition is frequently preceded by intestinal infection caused by Campylobacter jejuni, on the basis of which it is believed that the destruction of the myelin sheath covering the peripheral nerve is triggered by a mechanism called ‘molecular mimicry.’ This process occurs when antibodies created by previously generated bacterial infection mistakenly attack the nerve tissues by the misrecognition of molecular markers. This article engages with this interesting condition philosophically through the concept of ‘imaginary’ based on the author’s role as a physician of Korean medicine, the mainstream medical profession in South Korea associated with the practice of traditional East Asian medicine (EAM). With some epistemic freedom from the constraining ‘embrace’ of biomedical principles granted by that positionality, the author offers two imaginaries concerning GBS: one linguistic, the other EAM-based. For the linguistic interpretation, the author argues, based on studies on walking that illustrate the shared properties between walking and speech (having rhythm and cadence, as well as the intent to engage with the outside world), the paralysis of GBS can be analogous to that of speech, i.e. mutism or aphasia, in that those shared properties disintegrate. For the EAM-based interpretation, the author argues that given the non-musculoskeletal characteristics manifested in GBS, the condition can be considered as ‘the cold-damp disorder’(寒濕病), or diarrheal disease, in the imaginaries of EAM. These deliberations open the door for philosophical engagement with medical conditions for improving the clinical management of GBS.

In Vitro Inhibition of Xanthine Oxidase Purified from Arthritis Serum Patients by Nanocurcumin and Artemisinin Active Compounds.

Curcumin and artemisinin are commonly used in traditional East Asian medicine. In this study, we investigated the inhibitory effects of these active compounds on xanthine oxidase (XO) using allopurinol as a control. XO was purified from the serum of arthritis patients through ammonium sulfate precipitation (65%) and ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose. The specific activity of the purified enzyme was 32.5 U/mg protein, resulting in a 7-fold purification with a yield of 66.8%. Molecular docking analysis revealed that curcumin had the strongest interaction energy with XO, with a binding energy of -9.28 kcal/mol. The amino acid residues Thr1077, Gln762, Phe914, Ala1078, Val1011, Glu1194, and Ala1079 were located closer to the binding site of curcumin than artemisinin, which had a binding energy of -7.2 kcal/mol. In vitro inhibition assays were performed using nanocurcumin and artemisinin at concentrations of 5, 10, 15, 20, and 25 µg/mL. Curcumin inhibited enzyme activity by 67-91%, while artemisinin had a lower inhibition ratio, which ranged from 40-70% compared to allopurinol as a control.

Cytotoxic and anti-metastatic action mediates the anti-proliferative activity of Rhazya stricta Decne inducing apoptotic cell death in human cancer cells: Implication in chemopreventive mechanism

Cancer is associated with a high rate of pre-mature mortality worldwide and serves as a significant impediment to extended life expectancy, leading to undesirable long-term effects on the quality of life of the patients. Bioactive chemical products derived from natural sources have an important place in the well-being of the human population since ancient times. Compounds derived from natural sources have dominated the drug discovery programs in the last five decades and comprise a substantial proportion of current-day pharmaceutical agents. Rhazya stricta, an evergreen shrub, it belongs to family Apocynaceae of order Gentianales, and the Rhazya stricta is known to have certain medicinal properties, as the Middle East and South Asian traditional medicine employed this plant as a cure for different diseases. Herein, the hydro-methanolic extract of Rhazya stricta Decne has been studied for its effect on spectrum of cancer cells, including LNCaP, C4-2B, PC-3 prostate cancer cells, MDA-MB-231, MCF-7, SKBR3 breast cancer cells, A-549 lung cancer cells and BxPC-3, MiaPaCa-2 pancreatic cancer. Hydro-methanolic extract of Rhazya stricta Decne in a dose-dependent manner, showed progressive inhibition of cell growth by induction of cell death in the treated human cancer cells. The IC value range for different breast cancer cell lines was 142-178 µg/ml; for prostate cancer cell lines, it was 90-148 µg/ml; for pancreatic cancer cell lines 116-166 µg/ml and for the lung cancer cells, it was reported to be 180 µg/ml. The anti-metastatic potential of extract was indicated by the notable reduction in invasiveness and cell migration. Moreover, the structurally diverse phytochemical rich extract, also downregulates the signaling of NF-kB and the NF-kB downstream target cytokine VEGF, providing an insight into the anticancer action mechanism.Keywords: Cell biology; Cancer chemoprevention; Anticancer drugs; Cell signaling; Natural compounds

Experience of traditional East Asian medicine treatment in patients with chronic obstructive pulmonary disease: A qualitative study protocol

Experience of traditional East Asian medicine treatment in patients with chronic obstructive pulmonary disease: A qualitative study protocol

Herbal Medicine Yukgunja-Tang for Functional Dyspepsia: A Protocol for a Randomized, Controlled, Multicenter Clinical Trial.

The herbal medicine Yukgunja-tang has been widely used for the treatment of functional dyspepsia (FD) in the clinical setting of East Asian traditional medicine. This paper presents a protocol for a randomized, assessor-blind, controlled, multicenter, three-arm parallel clinical trial comparing the effectiveness, safety, and cost-effectiveness of Yukgunja-tang with Pyeongwi-san and usual care. A total of 140 participants with Rome IV-diagnosed FD will be randomly assigned to either the Yukgunja-tang (n = 56), Pyeongwi-san (n = 56), or usual care (n = 28) groups. All participants will be educated on dietary guidelines for FD patients. Participants in the Yukgunja-tang and Pyeongwi-san groups will take investigational products for 6 weeks. All participants will be assessed for clinical parameters at weeks 0, 3, 6, 9, and 24. The primary outcome will be measured on the total dyspepsia symptom scale, and the secondary outcome will include the single dyspepsia symptom scale, overall treatment effect, the visual analog scale for dyspepsia, FD-related quality of life, hospital anxiety and depression scale, EuroQol-5 dimension, pattern identification, and serum levels of acyl-ghrelin and deacyl-ghrelin. Adverse events and laboratory tests will be monitored for safety assessment. The results will provide evidence of the effectiveness, safety, and cost-effectiveness of Yukgunja-tang in the treatment of FD.