Therapeutic Potential of Combined Herbal Medicine and Electroacupuncture in Mild Cognitive Impairment Through Cytokine Modulation: An Observational Study.

Purpose: We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action. Patients and Methods: This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively. Results: The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], p < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas. Conclusion: Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.

This was a single-centered study focusing on the therapeutic effect of combined herbal medicine and electroacupuncture in patients with mild cognitive impairment, including a small number of participants, a relatively long treatment intervention of 12 weeks, and a follow-up assessment of 24 weeks. The intervention was a combination of a herbal formula and electroacupuncture treatment customized for each participant. The blood cytokine analyses of the participants were compared with the network analysis of the predicted target organs and pathways for the herbal formulas administered. Because each participant was not given the exact same intervention, we were unable to identify the specific treatment that produced the predicted effect. The observational study design of the study limited the ability to accurately assess causation between intervention and outcome. However, combined traditional medicine has potential therapeutic application in preventing mild cognitive impairment progression to dementia.

Establishment of a Dataset for the Traditional Korean Medicine Examination in Healthy Adults.

We established a protocol for the traditional Korean medicine examination (KME) and methodically gathered data following this protocol. Potential indicators for KME were extracted through a literature review; the first KME protocol was developed based on three rounds of expert opinions. The first KME protocol's feasibility was confirmed, and data were collected over four years from traditional Korean medicine (KM) hospitals, focusing on healthy adults, using the final KME protocol. A literature review identified 175 potential core indicators, condensed into 73 indicators after three rounds of expert consultation. The first KME protocol, which was categorized under questionnaires and medical examinations, was developed after the third round of expert opinions. A pilot study using the first KME protocol was conducted to ensure its validity, leading to modifications resulting in the development of the final KME protocol. Over four years, data were collected from six KM hospitals, focusing on healthy adults; we obtained a dataset comprising 11,036 healthy adults. This is the first protocol incorporating core indicators of KME in a quantitative form and systematically collecting data. Our protocol holds potential merit in evaluating predisposition to diseases or predicting diseases.

Identifying target organ location of Radix Achyranthis Bidentatae: a bioinformatics approach on active compounds and genes.

Background: Herbal medicines traditionally target organs for treatment based on medicinal properties, and this theory is widely used for prescriptions. However, the scientific evidence explaining how herbs act on specific organs by biological methods has been still limited. This study used bioinformatic tools to identify the target organ locations of Radix Achyranthis Bidentatae (RAB), a blood-activating herb that nourishes the liver and kidney, strengthens bones, and directs prescription to the lower body. Methods: RAB's active compounds and targets were collected and predicted using databases such as TCMSP, HIT2.0, and BATMAN-TCM. Next, the RAB's target list was analyzed based on two approaches to obtain target organ locations. DAVID and Gene ORGANizer enrichment-based approaches were used to enrich an entire gene list, and the BioGPS and HPA gene expression-based approaches were used to analyze the expression of core genes. Results: RAB's targets were found to be involved in whole blood, blood components, and lymphatic organs across all four tools. Each tool indicated a particular aspect of RAB's target organ locations: DAVID-enriched genes showed a predominance in blood, liver, and kidneys; Gene ORGANizer showed the effect on low body parts as well as bones and joints; BioGPS and HPA showed high gene expression in bone marrow, lymphoid tissue, and smooth muscle. Conclusion: Our bioinformatics-based target organ location prediction can serve as a modern interpretation tool for the target organ location theory of traditional medicine. Future studies should predict therapeutic target organ locations in complex prescriptions rather than single herbs and conduct experiments to verify predictions.

The Survival Benefit of Combination Therapy With Mild Temperature Hyperthermia and an Herbal Prescription of Gun-Chil-Jung in 54 Cancer Patients Treated With Chemotherapy or Radiation Therapy: A Retrospective Study.

Background: The combination of herbal medicine with conventional treatment increases the survival rate of cancer patients, but the effect is not great. Hyperthermia may have a synergistic effect with herbal medicine alongside conventional medicine. Objective: To monitor the efficacy of hyperthermia together with Gun-Chil-Jung (GCJ) capsule for event-free survival (EFS) and overall survival (OS) for the treatment of various cancers. Methods: We collected data retrospectively on 54 cancer patients of all stages. They were divided into 4 groups according to each hyperthermia or GCJ treatment period. Hyperthermia with 0.46 MHz radiofrequency wave was applied a power of 50 to 100 W for 70 minutes. GCJ capsules were administered orally 3 times a day. Results: The median follow-up was 13.4 months, and 25 (55.6%) patients showed disease-related events. Hyperthermia with GCJ treatment was administered in combination group (n = 36, 66.7%) and traditional Korean medicine-only group (n = 17, 31.5%). The median EFS was 190 days, and the median OS was 390 days. The group of hyperthermia 7 times or fewer and GCJ more than 28 days showed longer EFS and OS. The analysis of superiority between hyperthermia and GCJ showed no significant difference (EFS, P = .55; OS, P = .364). Conclusions: The combination of hyperthermia 1 to 2 times a week with GCJ treatment may improve survival of cancer patients treated or being treated with conventional cancer therapies.

Efficacy and safety of Yukgunja-Tang for treating anorexia in patients with cancer: The protocol for a pilot, randomized, controlled trial.

BACKGROUND: Anorexia is a common cause of malnutrition and is associated with negative effects on the quality of life (QOL) for patients with cancer. Management of appetite is the key to improving both the QOL and the prognosis for such patients. Yukgunja-tang (YGJT) is a traditional herbal medicine extensively prescribed in Korea as a remedy for various gastrointestinal syndromes. Currently, no standardized herbal medicine treatment exists for patients with cancer who are suffering from anorexia after surgery, chemotherapy, and/or radiotherapy. For that reason, this study aims to examine the efficacy and the safety of using YGJT to treat anorexia in such patients and to establish whether or not YGJT can be recommended as the primary therapy. METHODS: We will enroll 52 cancer patients diagnosed with anorexia. The enrolled participants will be randomly allocated to 2 groups: The control group will receive nutrition counseling, and the YGJT group will receive nutrition counseling and be administered YGJT at a dose of 3 g twice a day for 4 weeks (a total of 56 doses of 3.0 g per dose). The primary outcome of this study is the change in the score on the anorexia/cachexia subscale (A/CS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes are the changes in the FAACT score with the A/CS score excluded, the score on the Visual Analogue Scale (VAS) for appetite, the weight and the body mass index (BMI), and laboratory tests for compounds such as leptin, tumor necrosis factor-α (TNF-α), ghrelin, and IL-6. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (CBC, chemistry, urine test), and adverse events, will be documented on the case report form (CRF) at every visit. CONCLUSION: This study is the first randomized controlled trial to investigate the efficacy and the safety of using YGJT for treating patients with cancer-related anorexia in Korea. We designed this study based on previous research about YGJT. This study will serve as a pilot and provide data for planning further clinical trials on herbal medicine and cancer-related anorexia. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0002847. Registered retrospectively on 3 April 2018.

Integrative cancer treatment may have a survival benefit in patients with lung cancer: A retrospective cohort study from an integrative cancer center in Korea.

Integrative oncology is being increasingly adopted in mainstream cancer care to strengthen anticancer effects and to control cancer-related symptoms.The objective of this study is to identify the characteristics of patients with lung cancer treated at an integrative cancer center in Korea and to determine the effects of integrative cancer treatment (ICT) on survival outcome in traditional Korean medicine (TKM).We reviewed medical records for lung cancer patients who visited a single integrative clinical setting, East-West Cancer Center, between January 2014 and December 2015. We classified the patients into groups according to their ICT and whether or not they underwent anticancer traditional Korean Medicine treatment with a multiherbal formula containing Panax notoginseng Radix, Cordyceps militaris, P ginseng C.A.Mey., and Boswellia carterii BIRDWOOD (HangAmDan-B), with a herbal formula containing Rhus verniciflua Stoke, or with cultivated wild ginseng pharmacopuncture. A descriptive analysis of the characteristics and a survival analysis using the Kaplan-Meier curves with log rank test and a Cox proportional hazard model were performed.A total of 91 patients were included, and the majority had advanced-stage cancer. Of those patients, 45.1% were in the mono-TKM group and 39.6% were integrative group. Patients with advanced stage had significantly higher mortality than patients with early stage (crude hazard ratio [HR]: 4.41, 95% confidence interval [CI]: 1.56-12.5; adjusted HR: 6.31, 95% CI: 1.24-32.1). In the unadjusted model, for patients in the integrative group, the mortality rate was reduced by 50% compared to mono-TKM group with statistical significance. After adjusting confounders, the mortality rate of integrative group was reduced by 6% compared to mono-TKM group, suggesting positive effect on survival probability of integrative group.The results suggest that integration of TKM and conventional cancer treatment may have survival benefits in patients with lung cancer. Even though this study has limitations including heterogeneity between treatment groups, the study results suggest that ICT has positive effect on survival probability. To clarify the impacts of ICT for lung cancer and other cancers on survival outcome, further prospective study with a rigorous study design is required in multiclinical setting.