Korea Institute of Oriental Medicine

Alzheimer’s disease (AD) is characterized by oxidative stress-mediated memory dysfunction and neuronal cell death. This study investigated the effects of an ethanol extract from Bauhinia coccinea (EEBC) on memory impairment and neuronal damage in a memory deficit mouse model. EEBC was administered to ICR mice at doses of 50, 100, or 200 mg/kg daily for 3 weeks. Cognitive impairment was induced via scopolamine (SCO) injection. Brain tissues were analyzed for acetylcholine (ACh) levels, acetylcholinesterase (AChE) activity, neuronal apoptosis, and antioxidant markers. Behavioral tests showed that SCO injection induced memory loss, whereas EEBC significantly ameliorated SCO-mediated memory impairment. EEBC regulated the cholinergic system by decreasing ACh levels and enhancing AChE activity. Nissl staining and immunohistochemistry for NeuN showed that EEBC exerted neuroprotective effects in SCO-injected mice brains. Moreover, EEBC significantly reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic cells increased by SCO treatment. EEBC also reversed the SCO-induced changes in apoptosis-related protein expression in brain tissues. Furthermore, EEBC significantly reduced malondialdehyde levels and activated catalase in SCO-administered brains. Quantitative RNA sequencing showed involvement of lipid metabolism in EEBC memory function regulation. Thus, EEBC is a promising candidate for attenuating AD progression as it targets the cholinergic system and neuronal apoptosis.

Following the coronavirus disease 2019 (COVID-19) pandemic, the rise of long COVID, characterized by persistent respiratory and cognitive dysfunctions, has become a significant health concern. This leads to an increased role of complementary and alternative medicine in addressing this condition. However, our comprehension of the effectiveness and safety of herbal medicines for long COVID remains limited. Here, we present a single-cell RNA sequencing (scRNA-seq) dataset of peripheral whole blood cells derived from participants in a clinical study involving three commercially available herbal medicines, targeting fatigue and brain fog in long COVID. The dataset comprises 181,205 quality control (QC)-passed cells, along with clinical metadata, enabling a comparative analysis of immune cell populations before and after treatment. To ensure the technical validity of our dataset, we implemented rigorous quality checks throughout stages of the study, including sample preparation, sequencing, and bioinformatic data analysis levels. This transcriptomic data may serve as a resource to deepen our insights into the role of herbal medicines in management of long COVID.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and excessive cytokine production. This study aimed to explore the potential of Camellia sinensis L. water extract (CSE) as a treatment for AD by the impact of CSE on inflammatory responses in keratinocytes, particularly concerning the production of inflammatory cytokines and the modulation of signaling pathways relevant to AD pathogenesis. CSE was obtained via hot water extraction from Camellia sinensis L. Ultra-high-performance liquid chromatography (UPLC) analyzed catechin and caffeine content. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), polyphenol and flavonoid content were determined. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay measured antioxidant activity. Enzyme-Linked Immunosorbent Assay (ELISA), western blotting, and Immunofluorescence (IF) assays examined cytokines, pathways, and protein localization, respectively. Molecular docking assessed compound binding with inflammation-related proteins. UPLC identified six CSE components including epigallocatechin (EGC) epicatechin (EC), caffeine (CF), catechin (C), epigallocatechin gallate (EGCG), and epicatechin gallate (ECG). CSE demonstrated a significant reduction in the production of inflammatory cytokines interleukin (IL)-2 and IL-6 in TNF-α/IFN-γ activated keratinocytes. Treatment with CSE inhibited the mitogen-activated protein kinase (MAPK) pathway, which resulted in decreased phosphorylation of p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Exposure of TNF-α/IFN-γ- stimulated human keratinocytes (HaCaT) cells to CSE resulted in a 200 µg/mL dependent inhibition of p65 and signal transducer and activator of transcription 1 (STAT-1) translocation from the cytosol to the nucleus, as confirmed through immunofluorescence (IF) staining. Molecular docking simulations provided insights into the underlying mechanisms of CSE action, which supported its potential as a therapeutic agent for AD. CSE might be a potential candidate for its therapeutic efficacy for inflammatory skin conditions like AD. Thus, based on this evidence, the authors suggest that CSE should be studied further for its anti-inflammatory activities and topical application in the treatment of AD.

Caesalpinia sappan L. has exhibited various pharmacological effects, yet its anticancer activities against colorectal cancer (CRC) and underlying molecular mechanisms remain unclear. This study investigated the anticancer properties of an ethanol extract of C. sappan L. (CSE) against CRC cells, focusing on the identification of bioactive compounds and their mechanisms of action. A network pharmacology analysis was conducted to identify potential CRC targets and bioactive compounds of CSE, using LC-MS for compound identification. The anticancer effects of CSE were then validated through in vitro and in vivo models of CRC. The network pharmacological approach identified 87 overlapping genes between CSE targets and CRC-related genes, with protein–protein interaction analysis highlighting 33 key target genes. CSE inhibited cell proliferation in human CRC cell lines, including HCT 116, KM12SM, HT-29, and COLO 205, and induced apoptosis via caspase 3/7 activation. Western blot analyses confirmed the modulation of critical signaling pathways, including STAT3, AKT, and mitogen-activated protein kinases. Furthermore, CSE significantly suppressed tumor growth in MC38 CRC-bearing mice. These findings suggest that CSE possesses substantial potential as a natural anticancer agent for CRC treatment, highlighting the need for further exploration in therapeutic development.

In this study, we investigated the synergistic effect of co-administration of osimertinib and HAD-B1 using gefitinib-resistant non-small cell lung cancer cells, HCC827-GR. HAD-B1 is composed of 4 natural drugs, Panax Notoginseng Radix, Panax ginseng C. A. Meyer, Cordyceps militaris, and Boswellia carterii Birdwood, and has been reported to have therapeutic effects on patients with advanced non-small cell lung cancer in several studies. Resistance to gefitinib in HCC827 cells was acquired through MET activity. Co-treatment with osimertinib and HAD-B1 reduced the cell viability of HCC827-GR cells. In addition, phosphorylation of MET and ERK were effectively suppressed for HCC827-GR cells. And, compared to when osimertinib and HAD-B1 were administered alone, cell proliferation was significantly inhibited and apoptosis was effectively induced when osimertinib and HAD-B1 were co-administered to HCC827-GR cells. We found that the synergistic effect of osimertinib and HAD-B1 combination therapy resulted in cancer cell death and cell cycle arrest by targeting the ERK and mTOR signaling pathways. In conclusion, this study confirmed that the combination of osimertinib, a third-generation anticancer drug, and HAD-B1, a natural anticancer drug, had a potentially synergistic effect on non-small cell lung cancer resistant to EGFR-targeted anticancer drugs.

Objective Hypertension, a common chronic disease, often leads to serious complications. While conventional management relies on antihypertensive drugs, which can cause side effects and adherence issues, alternative treatments like herbal medicine are gaining attention. This study examines the efficacy and safety of modified Saengmaeksan, an East Asian herbal remedy, in treating hypertension. Methods This single-arm, prospective, observational study will be conducted at Kyunghee Bichedam Korean Medicine Clinic from October 23, 2023 to August 30, 2024, enrolling 30 hypertensive patients. Over 12 weeks, participants will undergo 4 visits, receiving modified Saengmaeksan twice daily for 8 weeks, with a subsequent 4-week follow-up. Primary outcome is the change in systolic blood pressure from the baseline to week 8. Secondary outcomes include diastolic blood pressure changes, radial artery tonometry, and quality of life evaluations. Safety assessments will include monitoring hematologic parameters and adverse events. Data will be analyzed using an ANCOVA model for adjusting confounders. Discussion Modified Saengmaeksan has shown potential for lowering blood pressure in clinical settings, supported by animal and cell studies. However, human studies are scarce. This research will employ radial artery tonometry to analyze blood pressure comprehensively, exploring Saengmaeksan’s hemodynamic effects. The study’s goal is to support the approval of modified Saengmaeksan as a hypertension treatment by the South Korean Food and Drug Administration and to promote the industrialization of traditional herbal medicine in managing hypertension. The findings will provide essential data for future clinical research, aiding in feasibility assessments and sample size determinations for randomized controlled trials.

Samul-tang (SM) is a traditional multi-ingredient herbal formula that is widely used in clinical practice for treating female infertility. Despite its known therapeutic benefits, the complexity of its action mechanisms owing to the combination of multiple compounds has limited its research and integration into modern pharmacological science. To address this challenge, we identified 38 herbal compounds as the major ingredients in SM and generated their transcriptome data from aged-mice ovaries by administering these individual compounds. This dataset provides a resource for investigating the action mechanisms of SM and assist in identifying effective combinations of ingredients that can reproduce the therapeutic effects of SM.

Background The demand for health management services has grown among individuals with physical disabilities. It is noteworthy that a significant proportion of this demographic has sought the services of traditional Korean medicine (TKM). Nevertheless, there is a lack of research on the characteristics of TKM utilization within this population. Therefore, this study aims to explore the characteristics of individuals with physical disabilities who utilize TKM services, to support future policy development in TKM for enhancing the health and quality of life for individuals with physical disabilities. Methods The study utilized a dataset from the Korea Health Panel (KHP) version 1.7, from the years 2008 to 2018. A panel analysis was conducted to analyze the correlation between the characteristics of participants and their influence of the TKM utilization. Results Based on the panel logistic regression analysis, the probability of TKM utilization was higher for individuals with physical disabilities who were female (p < 0.001), had a chronic musculoskeletal disorder (p < 0.001), Charlson Comorbidity Index of 1 (p = 0.025), and multiple chronic conditions (p = 0.025). Based on the panel hybrid regression analysis, those covered with Medical Aid spent less on TKM than those covered with National Health Insurance (p < 0.001), while those who were female (p < 0.001), had chronic musculoskeletal disorders (p = 0.007), or multiple chronic conditions (p = 0.007) had higher medical expenses for TKM utilization. Conclusions Individuals with physical disabilities accompanying nonfatal chronic musculoskeletal disorders or other chronic conditions frequently utilized TKM services. Those covered by Medical Aid spent less on TKM, while females and individuals with chronic musculoskeletal disorders or multiple chronic conditions incurred higher medical expenses for TKM. These results suggest the need for targeted interventions and policy changes to improve TKM access and address financial burdens for people with disabilities.

To combat influenza A virus (IAV) infection, it is vital to develop effective therapeutic strategies, including immunomodulators. In this study, we examined the antiviral effects of Hovenia dulcis Thunb. honey (HDH) against IAV using RAW 264.7 cells. HDH treatment significantly reduced IAV infection and viral protein expression. Moreover, it enhanced the production of interferon (IFN)-β, activated the innate immune response through the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, and upregulated IFN signaling through signal transducer and activator of transcription (STAT)1/2 phosphorylation and interferon-stimulated gene (ISG) expression. In addition, HDH decreased IAV-induced intracellular and mitochondrial reactive oxygen species (ROS) production by upregulating the expression of antioxidant proteins, such as Sirt3 and SOD2. The results suggest that HDH is a potential therapeutic agent inhibiting viral replication and boosting host antiviral immunity.

Purpose This study aimed to evaluate the effectiveness and safety of combination treatment with thread-embedding acupuncture (TEA) and electroacupuncture (EA) in patients with persistent knee pain after arthroscopic surgery, autologous chondrocyte implantation, or autologous osteochondral transplantation. Patients and Methods Twelve patients with knee osteoarthritis (KOA) who experienced postoperative pain were randomized to either the treatment group (TG) or control group (CG) in a 1:1 ratio. The TG received TEA once a week for four sessions and EA twice a week for eight sessions while continuing usual care, defined as standard conventional treatments. The CG received only usual care for four weeks. The primary outcome was the visual analogue scale (VAS) score at week 4 compared with the baseline. The secondary outcomes were the VAS scores at weeks 2, 6, and 8, the Korean version of the Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC), the EuroQol 5-Dimension 5-Level (EQ-5D-5L), and rescue medication consumption at weeks 2, 4, 6, and 8. Adverse events were assessed at each visit. Results The TG showed significant improvement in the VAS scores at weeks 4, 6, and 8 compared with the CG (week 4: −24.5; p = 0.0106, week 6: −19.667; p = 0.0228, week 8: −28.667; p = 0.0036). In the TG, significant differences were observed in K-WOMAC total scores at weeks 2, 4, 6, and 8 (week 2: 17.167; p = 0.0083, week 4: 23; p = 0.0018, week 6: 29.833; p = 0.0009, week 8: 30.5; p = 0.0006); however, there were no differences between the two groups. The two groups had no significant differences in the EQ-5D-5L and rescue medication consumption. No adverse events were observed in either groups during the study period. Conclusion This feasibility study suggests that adding combination treatment with TEA and EA to usual care might relieve pain in patients with KOA. Large-scale clinical trials are needed to confirm the long-term effects of combination treatment.

The worldwide obesity prevalence is increasing, affecting around 4 million individuals annually. This research critically evaluated the anti-obesity efficacy of the Korean mudflat halophyte herb Suaeda japonica (Suaeda japonica Makino). In the obese mice model, the administration of 200 mg/kg b.w. of S. japonica extract (SJE) significantly mitigated obesity by modulating body and organ weight, food efficiency ratio, energy expenditure, multiple blood chemistry parameters, lipid accumulation, adipose tissue hypertrophy, and various gene expressions associated with lipogenesis and thermogenesis. The significant obesity control (80%) of the aforementioned concentration of SJE treatment in mice mimics the plant-derived commercial anti-obesity drug Garcinia cambogia (Garcinia gummi-gutta) (80%, 245 mg/kg) b.w. Since SJE has not been extensively studied for obesity management, this study demonstrated that it might influence physiological, biochemical, and molecular pathways to combat obesity and related metabolic illnesses. Graphical Abstract

The Traditional Formula (TF), a combination of herbs prepared in accordance with traditional medicine principles, is increasingly garnering global attention as an alternative to modern medicine. Specifically, there is growing interest in exploring TF’s therapeutic effects across various diseases. A significant portion of the state-of-the-art knowledge regarding the relationship between TF and disease is found in scientific publications, where manual knowledge extraction is impractical. Thus, Natural Language Processing (NLP) is being employed to efficiently and accurately search and extract crucial knowledge from unstructured literatures. However, the absence of a high-quality manually annotated corpus focusing on TF-disease relationships hampers the use of NLP in the fields of traditional medicine and modern biomedical science. This article introduces the Traditional Formula-Disease Relationship (TFDR) corpus, a manually annotated corpus designed to facilitate the automatic extraction of TF-disease relationships from biomedical literatures. The TFDR corpus includes information gleaned from 740 PubMed abstracts, encompassing a total of 6,211 TF mentions, 7,166 disease mentions, and 1,109 relationships between them encapsulated within 744 key-sentences.

The natural world is a vast reservoir of exceptionally varied and inventive chemical compositions. Natural products are used as initial compounds to create combinatorial libraries by targeted modifications and then by analyzing their structure-activity connections. This stage is regarded as a crucial milestone in drug discovery and development. Bergenin, a naturally occurring secondary metabolite, has been extracted from several plant components. It is a constituent found in herbal and Ayurvedic preparations. It demonstrates antiviral, antifungal, antitussive, antiplasmodial, anti-inflammatory, antihepatotoxic, antiarrhythmic, antitumor, antiulcerogenic, antidiabetic, and wound healing activities. Bergenin efficiently inhibited the proliferation of human cancer cells by stimulating the production of intracellular reactive oxygen species (ROS), causing DNA damage and leading to cell cycle arrest in the G1/G2 phases by blocking cell signaling pathways. More comprehensive reviews are needed on the anticancer properties of bergenin. Therefore, our review aimed to update the multifaceted benefits of bergenin to the future scientists and researchers, which can be leveraged to formulate safer and novel cancer therapies, while also establishing a robust framework for future investigations into bergenin in cancer treatment. More preclinical and clinical investigations are needed to validate the candidature of bergenin as a potent anticancer agent.

Nuclear factor-κB (NF-κB) cell signaling pathway is essential for the progression and development of numerous human disorders, including cancer. NF-κB signaling pathway regulates a wide range of physiological processes, such as cell survival, growth, and migration. Deregulated NF-kB signaling resulted in unregulated cell proliferation, viability, movement, and invasion, thus promoting tumor development. Recent findings have increasingly shown that plant derived phytochemicals that inhibit NF-κB signaling have the potential to be employed in cancer therapeutics. Flavonoids are a group of polyphenolic natural compounds present in various plants and their fruits, vegetables, and leaves. These compounds have numerous medicinal properties owing to their antioxidant, anti-inflammatory, antiviral, and antitumor characteristics. The main mechanism by which these flavonoids exhibit their anticancer potential is via potent antioxidative and immunomodulatory actions. Current research reports have demonstrated that these flavonoids exhibited their anticancer effects via suppressing the NF-κB signaling. Based on these facts, we have comprehensively outlined the cancer promoting role of NF-κB pathway in various processes including tumor progression, drug resistance, angiogenesis and metastasis. In addition to these, we also summarize the anticancer potential of flavonoids by specifically targeting the NF-κB pathway in various types of cancers.

Background Gastric cancer (GC) is the second most prevalent cancer in Korea, and is associated with significant morbidity and mortality. Although advancements in early detection and treatment have improved survival rates, management of postsurgical recovery remains vital. Herbal medicine (HM) has emerged as a potential adjunct therapy for enhancing the recovery and quality of life (QoL) of patients post-GC surgery. Methods This systematic review and meta-analysis evaluated the efficacy and safety of HM in the postsurgical recovery of patients with GC. We searched both Korean and international databases and identified 16 randomized controlled trials that met our inclusion criteria. We assessed the study quality using the Cochrane Risk of Bias tool and analyzed the data using the Review Manager Software (RevMan). Results Our analysis included 1546 patients from selected studies, demonstrating that HM significantly improved gastrointestinal recovery times, including the time to first flatus, bowel movement, and return of bowel sounds. Significant improvements were also observed in nutritional markers, such as albumin and prealbumin, along with beneficial effects on immune markers, such as CD3 ⁺ and CD4 ⁺ levels. QoL assessments using the WHOQOL-BREF and QLQ-C30 indicated substantial improvements. HM had a favorable safety profile, showing a reduced incidence of adverse effects compared to the controls. Conclusion The findings suggest that HM can significantly enhance recovery and improve quality of life following GC surgery, with a favorable safety profile. However, due to the considerable heterogeneity in study results, extended clinical trials and rigorous follow-ups are recommended to comprehensively assess long-term effects and side effects.

Background Neck pain is a common condition across various populations, with a substantial impact on daily life and quality of life. Forward head posture is frequently observed in individuals with neck pain and is closely associated with lifestyle factors. This study aimed to examine the relationship between lifestyle factors and forward head posture in young adults with neck pain and determine the optimal cutoff value for assessing the risk of forward head posture. Methods In total, 200 men and women aged 35–44 years with persistent or recurrent neck pain with a numeric rating scale score of ≥ 3 in the previous week were included in the study. The participants’ sex, age, medical history, anthropometric parameters, posture- and activity-related lifestyle, pain, radiographs, and the craniovertebral angle were obtained. The associations between lifestyle factors and forward head posture were analyzed using logistic regression. The cutoff values for risk prediction were analyzed using receiver operating characteristic curves. The impact of lifestyle factors on changes in craniovertebral angle at the 6-month follow-up was analyzed using multiple linear regression and analysis of covariance. Results After adjusting for covariates, there were significant differences in lying time (odds ratio = 3.342, 95% confidence interval = 1.607–6.952) and physical activity level index (odds ratio = 0.404, 95% confidence interval = 0.210–0.775) between the forward and non-forward head posture groups. The cutoff values for detecting forward head posture were 6.50 h of lying time and a physical activity level score of 2.88. At the 6-month follow-up, the craniovertebral angle was closer to the diagnosis of forward head posture, with increasing lying time and lower physical activity level score; however, the association was not statistically significant. Conclusions The findings indicate that lying time and physical activity level scores are important lifestyle-related predictors of forward head posture. Thus, lying time and physical activity level should be addressed to predict and prevent forward head posture.