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Background: Blood stasis (BS) refers to a pattern of symptoms resulting from circulatory dysfunction or stagnation in the human body. Due to its historical origin and diverse interpretations, communication between patients and doctors of traditional Korean medicine (DKMs) presents challenges. Efforts to improve patients understanding in traditional Korean medicine (TKM) have led to the development of disease-specific standard clinical practice guidelines. However, there is a limited focus on creating clinical practice guidelines or informative leaflet specifically addressing BS, which is a frequently encountered pattern of symptoms in TKM., Methods: This study aimed to bridge the gap between patients and DKMs by developing an informative leaflet focusing on BS for metabolic diseases. We assessed its appropriateness through expert advisory meetings and the Delphi process, and evaluated its clinical effectiveness. We conducted a prospective, randomized, crossover trial to compare the clinical effectiveness of using BS leaflets in TKM treatment. The hypothesis investigated whether the leaflet group would show higher scores in satisfaction of DKMs' explanations, understanding of DKMs' explanations, improving the reliability of TKM, satisfaction with treatment time, improvement in explanations compared to previous TKM experiences, and necessity of managing BS treatment, compared to the no-leaflet group., Results: In a study involving 40 patients (mean age: 62.3 ± 7.8 years), symptoms persisted for an average of 16.75 ± 9.3 hours daily, with a severity rating of 2.53. The leaflet group exhibited significantly higher satisfaction scores than the no-leaflet group in all aspects (all P < .0001). After confirming the absence of sequence and period effects using a linear-mixed effect model, we were able to ascertain the presence of a treatment effect, as evidenced by statistically significant higher scores across all survey items in the leaflet group compared to the no-leaflet group (all P < .0001)., Conclusion: Expert consensus on symptoms aligning with the BS pattern resulted in the development of an informative leaflet. Its utilization notably improved patient satisfaction, comprehension, and trust in TKM treatment, unaffected by temporal influences, thus demonstrating its clinical effectiveness. In summary, the BS leaflet significantly enhanced patient understanding and optimized treatment procedures., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Ethnopharmacological Relevance: Larvae of the rhinoceros beetle (Allomyrina dichotoma) (ADL) are used ethnopharmacologically to treat gut-related disorders in Korea and China since 1596 and are also approved as a safe novel food with high nutritional value., Aim of the Study: We investigated the protective effects of ADL extract against leaky gut disease using a Drosophila model and sought to elucidate the underlying biological mechanisms., Materials and Methods: We examined the protective effects of ADL extract (2 mg/mL) against the leaky gut disease using a dextran sulfate sodium (DSS)-induced leaky gut Drosophila melanogaster model., Results: We found that oral administration of ADL extracts significantly increase the survival rate of DSS-fed Drosophila. Under conditions of DSS-induced gut damage, ADL extract reduced gut cell apoptosis and gut permeability, resulting in the maintenance of gut tissue homeostasis. Furthermore, we observed that oral administration of ADL extract can induce high levels of E-cadherin gene expression and also restored the original membrane localization of DSS-disrupted E-cadherin contiguous with the armadillo., Conclusion: We concluded that ADL extract plays an important role in maintaining gut homeostasis through the up-regulation of E-cadherin and that it may have a protective effect against leaky gut syndrome., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abstract: Although collaborative treatment by traditional Korean medicine doctors (KMDs) and medical doctors occurs, it is mainly done by referral. As no survey of the general public's preference for the type of collaboration has ever been conducted, we aimed to investigate Koreans' preferences for a collaborative treatment type.The responders were extracted by random digit dialing and then reextracted using the proportional quota sampling method by sex and age. From July to October 2017, telephone interviews were conducted and the participant responses regarding treatment history for spinal or joint diseases, experiences with collaborative treatment, and preferred type of collaborative treatment were recorded.Of the 1008 respondents, 44.64% reported a history of treatment for spinal or joint diseases at a medical institution. The concurrent collaborative treatment system, in which both KMDs and medical doctors are present in one location participating in the treatment concurrently, was the most preferred system among the respondents. Respondents who reported experience with traditional Korean medicine hospitals were more likely to prefer a one-stop treatment approach than those who did not have experience with traditional Korean medicine hospitals (adjusted odds ratio: 1.73; 95% confidence interval: 1.12-2.68). Respondents who were familiar with collaborative treatment but did not report any personal experience with it were more likely to prefer a one-stop treatment approach than those who were not familiar with collaborative treatment (adjusted odds ratio: 1.82; 95% confidence interval: 1.37-2.44).Koreans prefer a concurrent type of collaborative treatment system by KMDs and medical doctors. Therefore, efforts and support are needed to increase the application of the concurrent type of collaborative system., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Scoliosis is a spinal deformity and is diagnosed as Cobb angle being greater than 10°. Because it is accompanied with structural dysfunction, it can cause pain, worsen the patient's general health and quality of life. The prevalence of scoliosis has been increasing and many treatments, including surgical treatment and conservative treatment, such as observation, bracing, physiotherapy, and Chuna manual therapy (CMT), have been suggested. CMT is a manual therapy in Korean medicine that provides effective stimulation to the patient's body structure to treat structural dysfunction. After Korean national health insurance's coverage of CMT in 2019, the application of CMT for scoliosis has increased, and many studies have been reported. There have been attempts to elucidate the effectiveness of CMT on scoliosis; however, its effectiveness still remains unconfirmed. Therefore, the aim of this study is to evaluate the effectiveness and safety of CMT on scoliosis., Methods: The published randomized controlled trials that evaluated the effectiveness and safety of CMT for scoliosis will be searched for in multiple electronic databases without the limitation of country and language. Data on characteristics of studies, interventions, comparators, outcome measures, results, and information for assessment of study quality will be extracted. The primary outcome will be the Cobb angle and the secondary outcomes will be the scales of pain, function, quality of life and disability, and adverse events. Data synthesis and analysis will be conducted using the Review Manager software for Windows (RevMan ver. 5.3.; Copenhagen; The Nordic Cochrane Center, The Cochrane Collaboration, 2014). Subgroup analysis to identify the differences between different CMT maneuvers will also be performed. For risk of bias assessment, the "risk of bias" tool from Cochrane Collaboration will be used., Results: This study will present the clinical evidence on the effectiveness and safety of CMT on scoliosis., Conclusion: This study will propose useful evidence for treatment, further research, and health policies in the future., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Agastache rugosa is used as a Korean traditional medicine to treat gastric diseases. However, the active ingredients and pharmacological targets of A. rugosa are unknown. In this study, we aimed to reveal the pharmacological effects of A. rugosa on gastritis by combining a mice model and a network pharmacology method. The macrophage and gastritis-induced models were used to evaluate the pharmacological effects of A. rugosa . The results show that A. rugosa relieved mucosal damage induced by HCl/EtOH in vivo. Network analysis identified 99 components in A. rugosa ; six components were selected through systematic screening, and five components were linked to 45 gastritis-related genes. The main components were acacetin and luteolin, and the identified core genes were AKT serine/threonine kinase 1 (AKT1), nuclear factor kappa B inhibitor alpha (NFKBIA), and mitogen-activated protein kinase-3 (MAPK3) etc. in this network. The network of components, target genes, protein-protein interactions, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was closely connected with chemokines and with phosphoinositide 3-kinase-Akt (PI3K/AKT), tumor-necrosis-factor alpha (TNFα), mitogen-activated protein kinase, nuclear factor kappa B, and Toll-like receptor (TLR) pathways. In conclusion, A. rugosa exerts gastro-protective effects through a multi-compound and multi-pathway regulatory network and holds potential for treating inflammatory gastric diseases.

Introduction: Treating blood stasis is effective in treating obesity and metabolic diseases in traditional Korean medicine. The aim of this prospective observational study is to determine the effectiveness of the diagnosis index for metabolic diseases with blood stasis by analyzing clinical data and blood samples., Methods and Analysis: We will perform a prospective observational study. Participants who meet the inclusion criteria will be recruited from the Dongguk university Ilsan Oriental hospital. The outcomes are resistin, serum amyloid P component, C-reactive protein, D-dimer, and blood stasis scores. In addition, the blood pressure, ankle-brachial pressure index, brachial-ankle pulse wave velocity, body mass index, waist circumference, and levels of blood lipid will be assessed., Discussion: Through this study, we could collect specific data for diagnosing metabolic diseases with blood stasis. Therefore, the findings of this study will provide a summary of the current state of evidence regarding the effectiveness of the diagnosis index in managing metabolic disease with blood stasis., Ethics and Dissemination: The study was approved by the Institutional Review Board of the Dongguk University Ilsan Oriental Hospital (DUIOH-2018-09-001-007). The results will be published in a peer-reviewed journal and will be disseminated electronically and in print., Trial Registration Number: Clinical Research Information Service: KCT0003548.

Background: Obesity is a global health problem and its incidence is on the rise. Euiiyin-tang is an herbal medicinal formula that is often used in the clinical treatment of obesity. The purpose of the present study was to evaluate the efficacy and safety of Euiiyin-tang in obesity treatment., Methods: A randomized, double-blind, placebo-controlled, multicenter trial was conducted. Participants with obesity were randomly assigned to receive Euiiyin-tang or placebo 3 times daily for 12-weeks. The primary outcome was weight reduction between the baseline and 12 weeks. The secondary outcomes included the rate of weight loss compared to baseline, and changes in body mass index, lipid profiles, and questionnaires related to the quality of life and diet. Safety factors, such as vital signs and laboratory parameters, were also measured., Results: A total of 149 participants were randomly distributed to either the Euiiyin-tang group (n = 76) or the placebo group (n = 73). Weight reduction in the Euiiyin-tang group was significantly greater than that in the placebo group (2.50 kg in the Euiiyin-tang group vs. 0.82 kg in the placebo group). The participant response rates of ≥3% weight loss compared to baseline was 36.8 % in the Euiiyin-tang group and 17.8 % in the placebo group. Body mass index, waist circumference, and hip circumference showed a greater change in the Euiiyin-tang group than in the placebo group (1.00, 3.23, and 2.00 in the Euiiyin-tang group vs. 0.33, 1.96, and 0.86 in the placebo group). Questionnaires, lipid profiles, and safety factors did not show significant differences between groups., Conclusion: The results of this study suggest that Euiiyin-tang has beneficial effects on weight loss., Trial Registration: Clinicaltrials.gov NCT01724099., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We developed a protocol for a prospective registry to prove the effectiveness and safety of integrative Korean medicine treatment for inpatients with sciatica due to lumbar intervertebral disc herniation. We plan on recruiting 1000 inpatients receiving integrative Korean medicine treatment for lumbar intervertebral disc herniation at four spine specialized Korean medical hospitals. Patients enrolled in the registry will be evaluated at the time of hospitalization, 2 weeks after hospitalization, at discharge, and 6 months after hospitalization on predefined outcome variables such as intensity of back and leg pain, Oswestry Disability Index, quality of life, Patient Global Impression of Change, and adverse effects. The protocol of this study was registered in CRIS (KCT0003709) and Clinical trial gov (NCT03750591). This study is significant in that it cannot only be a basis for safety-related evidence of complementary alternative medicine, which has been lacking, but it also gives clear evidence on the effectiveness and validity of treatment effects such as accompaniment of stenosis, sex, age, and type of disc herniation.

Background: Cold hypersensitivity in the hands and feet (CHHF) commonly affects Asian women, especially Korean women, and it negatively impacts the quality of life of the affected individuals. One commonly used herbal prescription for treating CHHF is Onkyeong-tang (OKT). Although OKT is widely used clinically in treating CHHF, no randomized clinical trial has been performed to evaluate the efficacy and safety of OKT in the treatment of cold hypersensitivity in the feet (CHF). This clinical trial aims to provide objective evidence for the basis of using OKT in the treatment of CHF in Korean women., Methods: This trial will be a double-blind, randomized, placebo-controlled, parallel-group, multicenter pilot study. A total of 112 participants will be randomly divided into an OKT treatment group or a placebo group with a 1:1 ratio via a web-based randomization system. The OKT and placebo groups will receive prescribed medications orally three times per day (3 g each time) before or between meals for 8 weeks. The primary outcome studied will be the changes in Visual Analog Scale (VAS) scores of CHF from baseline. Secondary outcomes studied will be the VAS score changes of cold hypersensitivity in the hands, changes in the skin temperature of the hands and feet, total scores of the Korean version of the World Health Organization Quality of Life Scale-abbreviated version, and the results of the cold stress test., Discussion: This trial will be the first clinical trial to assess the efficacy and safety of OKT in the treatment of CHF. We anticipate that the findings of the study will provide evidence for the basis of using OKT in treating CHF symptoms and generate basic data for designing a further large-scale randomized clinical trial., Trial Registration: Clinical Research Information Service (CRIS): KCT0003723. Retrospectively registered on 8 April 2019.

Objective: To understand the impact and implications of cold, heat, deficiency, or excess pattern identification in relation to dysmenorrhea, comparing the prevalence of these patterns between women with and without dysmenorrhea is needed., Methods: We gathered data from the Korea Constitutional Multicenter Bank. A total of 508 patients were recruited and provided with cold, heat, deficiency, or excess pattern and dysmenorrhea questionnaires. On the basis of their responses, they were divided into the dysmenorrhea group (moderate or severe dysmenorrheic pain; n = 90) and non-dysmenorrhea group (no dysmenorrheic pain; n = 155). We analyzed the characteristics of the groups and compared the cold, heat, deficiency, or excess pattern scores. Comparisons were performed using the independent t-test. We also performed multiple comparisons of each individual symptom between the groups to explore which symptoms appear with dysmenorrhea using the Bonferroni adjustment method., Results: There was a high positive correlation between deficiency pattern scores and excess pattern scores (p < 0.001). The cold, deficiency, and excess pattern scores were significantly higher in the dysmenorrhea group than in the non-dysmenorrhea group (p < 0.001). Twenty among the 76 pattern items showed significant differences between the groups (p < 0.001). Among all items, there was a large effect size only in sleep quality (mean difference 1.07, 95% confidence interval 0.75-1.39, p < 0.001)., Conclusions: Women with dysmenorrhea have higher cold, deficiency, and excess pattern scores than those without dysmenorrhea. The longitudinal observation of these symptoms needs to be evaluated using a clinical prospective study design in accordance with pattern differentiation in the future., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Hypothyroidism, the most common endocrine disease, comprises a deficiency of thyroid hormone, causing coldness, fatigue, and dysmenorrhea. Here, we report the improvement of hypothyroidism symptoms and thyroid hormone level normalization by using Korean herbal medicine and acupuncture therapy., Patient Concerns: A 30-year-old woman (Case 1) presented at the clinic with continuous seborrheic dermatitis on the scalp, accompanied by dysmenorrhea. A 55-year-old woman (Case 2) presented with symptoms of coldness of the limbs and fatigue., Diagnosis: Both patients were diagnosed with "Yin deficiency and Yang hyperactivity" and hypothyroidism after serum thyroid function tests., Interventions: Both patients received herbal medicine decoction, acupuncture, and electroacupuncture therapy., Outcomes: Korean medicine improved the symptoms of hypothyroidism and significantly normalized thyroid-stimulating hormone and free-thyroxine levels., Conclusion: These outcomes suggest that Korean medicine may be effective for resolution of hypothyroidism; however, further research is needed to confirm these findings.

Background: Cold hypersensitivity in the hands and feet (CHHF) is a common complaint in Asian female population especially in Korea. Due to the symptoms of CHHF the quality of individual's daily life can be degraded. Ucha-Shinki-Hwan (UCHA) is widely used in the treatment of various diseases including CHHF by harmonizing Yin and Yang, and improving the vitality of whole body. However, the efficacy of UCHA as a treatment option of CHHF has not been assessed in trials. Thus, we aimed to investigate the efficacy and safety of UCHA in Korean women with CHHF through this trial., Methods: This study will be an exploratory, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Korean women aged 19 to 59 years who complaint with CHHF will be enrolled from 5 university affiliated Korean medicine hospitals. A total of 164 subjects will be randomly assigned to a treatment group (UCHA) or a placebo group at a 1:1 ratio. The subjects will receive 2.5 g of either UCHA or placebo three times a day for 8 weeks. The primary outcome will be evaluated with the visual analog scale score of CHHF. The secondary outcome measures will be changes in skin temperature in extremities as measured by using a thermometer and the Korean version of the World Health Organization Quality of Life Scale Abbreviated Version., Discussion: This study will be the first trial to explore the efficacy and safety of UCHA for CHHF patient. This will provide meaningful clinical information on herbal medicine treatment of CHHF and a clinical evidence for planning a full randomized clinical trial., Disclosures and Acknowledgments: The authors report no competing interests., Trial Registration: This study is registered at ClinicalTrials.gov, ID: NCT03790033. Registered on (31 December 2018) PROTOCOL VERSION:: The final approved version of the trial protocol is V1.3. (25 January 2019).

Korean herbal medicine treatment (KHMT) involves treating with a combination of natural products, which have been used for thousands of years. Recently, it has been reported to be effective and safe in cancer patients. This case report demonstrates the efficacy of KHMT in a 49-year-old man with malignant pleural mesothelioma (MPM), a rare and highly aggressive cancer. The patient showed recurrent pleural effusion and was diagnosed with epithelioid MPM at cT3NxM0 stage III in December 2017. The multidisciplinary care team recommended multimodal treatment based on an extrapleural pneumonectomy, but he refused this because the treatment was aggressive and the effectiveness was unclear. He decided to undergo pemetrexed plus cisplatin chemotherapy if his condition worsened. He visited the Korean Medicine Cancer Center for alternative treatment options. A KHMT regimen, consisting of twice-daily Gunchil-dan and thrice-daily Bangam-tang, was initiated in December 2017. Since commencement of KHMT, computed tomography and X-ray imaging scans have shown no significant interval changes and progression. At 21 months into treatment (September 2019), no significant adverse events have occurred. Given that the median overall survival of patients with MPM is approximately 1 year, the ongoing progression-free survival of this patient for 21 months is relatively long. This case, therefore, suggests that KHMT is a potential treatment option for MPM patients.

Background: Low back pain is a common symptom and continuous or recurrent pain results in chronic low back pain (CLBP). While many patients with CLBP have tried various treatments, complementary and alternative medicine including acupuncture and herbal medicine is one of the commonly used treatments. Palmijihwang-hwan is a herbal medicine used frequently in clinical practice but there has been no report of the efficacy, safety, or cost-effectiveness analysis of Palmijihwang-hwan for CLBP., Methods: This study is a randomized, assessor-blinded, multicenter, clinical trial with two parallel groups. Four Korean medicine hospitals will recruit 84 participants and randomly allocate them into the control or treatment group in a 1:1 ratio. The control group will receive acupuncture treatment at 11 local and 4 distal acupuncture points for 20 min twice a week for 6 weeks. The treatment group will receive the same acupuncture treatment as the control group and also take Palmijihwang-hwan for 6 weeks. The primary outcome will be the change in visual analog scale (VAS) score between baseline (visit 1) and completion of the intervention (visit 12), and secondary outcomes will be pain-related clinical relevance (minimal clinical important difference or the proportion of the participants who decrease more than 30, or 50% on VAS), disability (Roland and Morris Disability Questionnaire), quality of life (EuroQol-5D), global assessment (Patient Global Impression of Change), and economic analysis (cost-effectiveness and cost-utility analysis). Additionally, safety will be assessed., Discussion: The results of our study will provide the clinical evidence about the efficacy, safety, and cost-effectiveness analysis of Palmijihwang-hwan for CLBP. There will be a chance to provide multiple subdivided influence of this treatment with various outcome measures, but lack of placebo is our limitation., Trial Registration: Clinical Research Information Service, KCT0002998. Registered on 12 July 2018.

We aimed to develop forest therapy programs (FTPs) to prevent dementia and related health problems in the elderly population, with the assumption that health benefits are FTP-type specific and depend on the participant's psychophysiological traits. For this purpose, we developed two distinct FTPs, namely, a guided-breathing meditation program (BP) and a walking program (WP); we adopted the approach of Sasang constitutional (SC) medicine, which categorizes individuals into one of three SC types (SC1, SC2, or SC3) for medical care. The FTPs ran 11 sessions over 11 weeks. We recruited 29/31/28 participants who were 65 years of age or older for the BP/WP/control groups, respectively; obtained electrophysiological measurements via electroencephalogram (EEG), heart rate variability (HRV), and bioimpedance; and analyzed the intervention effects with analysis of covariance. Compared with the control, the BP and WP resulted in benefits for neural activity and parasympathetic nervous activity (PNA), respectively, and both FTPs yielded distinct beneficial effects on bioimpedance. Constitution-specific effects were also present. The SC1- and SC2-type participants gained positive effects in neural activity from the BP and WP, respectively. The SC3-type participants showed improvements in PNA from the WP. In conclusion, for older individuals, both programs conferred health benefits that would help prevent dementia, and the benefits were program-specific and constitution-specific.

Headache after traumatic brain injury (TBI) is a common symptom which includes moderate-to-severe pain more than 5 years after the injury and severely limits the quality of life. Some guidelines have indicated that there are several cases where headaches do not respond adequately to conventional therapies. Therefore, effective alternative approaches are needed. In this case report, we present a 74-year-old woman, who had persistent headache attributed to traumatic injury to the head and subjective cognitive impairment. By using the Korean Medical (KM) treatment blood stasis-removing therapy using Dangguixu-san and auriculotherapy, her headache improved markedly. Improvements in the cognitive function and hemorrhage were also observed. This case report suggests that KM treatments using Dangguixu-san and auriculotherapy may be an alternative therapeutic approach for headache after TBI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Many infertile patients have used Korean medicines (KMs) as a primary or adjuvant therapeutic method to improve in vitro fertilization success rates. The aim of this multicenter observational study is to investigate the effects of KMs on poor ovarian reserve (POR) in infertile patients., Methods and Analysis: We will perform a prospective multicenter observational study. This study will recruit 50 women between 25 and 44 years of age with infertility caused by POR from among patients who visit the KM clinic. All participants will visit the KM clinic on the 2nd or 3rd day of menstruation to receive the KMs. KM treatment will be delivered for 3 menstrual cycles (3 months) and will include herbal decoction, acupuncture, or moxibustion on demand. Every participant will be assessed based on KM clinical symptoms, a quality of life questionnaire, and ovarian reserve test results., Ethics and Dissemination: The study was approved by Institutional Review Board of Semyung University (SMU-IM-190501). The results will be published in a peer-reviewed journal and will be disseminated electronically and in print., Trial Registration Number: Clinical Research Information Service: KCT0004209.

While stress is known to cause many diseases, there is no established method to determine individuals vulnerable to stress. Sasang typology categorizes humans into four Sasang types (So-Eum, Tae-Eum, So-Yang, and Tae-Yang), which have unique pathophysiologies because of their differential susceptibilities to specific stimuli, including stress. The purpose of this study was to determine if Sasang typology can be used identify individuals who are vulnerable to stress by evaluation of heart rate variability (HRV).This was a cross-sectional study. A total of 399 healthy men and women aged 30 to 49 years were recruited. Physical examinations for stress included HRV measurement and blood tests. The subjects also completed questionnaires about psychological stress, self-awareness, and lifestyle. HRV was analyzed using frequency-domain analysis. Subjects were divided into So-Eum (SE) and non-So-Eum (non-SE) groups according to their diagnosis.The weight and body mass index in the SE group were significantly lower than those in the non-SE group (both, P = .000). There were no significant between-group differences in any other demographic variables. In HRV analysis, the normalized high frequency (nHF) was higher (P = .008) while the normalized low frequency (nLF; P = .008) and LF:HF ratio (LF/HF; P = .002) were lower in the SE group than in the non-SE group.Although there was no difference in variables affecting HRV, HRV values were significantly different between groups. The LF/HF value for the SE group was at the lower limit of the normal range, although there were no associated clinical problems. These findings suggest that individuals with the SE type are more susceptible to stress than those with the other types. Thus, middle-aged individuals who are vulnerable to stress can be identified using Sasang typology.

Madi-Ryuk (MDR) is a traditional Korean medicine and it has been widely used in Korea to treat arthritis and we previously reported the anti-allergic inflammatory effect of MDR in vitro model. However, therapeutic evidence of MDR on in vivo model of allergic inflammatory reaction has not yet been demonstrated. The research purpose was to investigate the efficacy of MDR and its active ingredient tannic acid (TA) in ovalbumin (OVA)-induced AR mice model. OVA-challenged AR mice orally medicated MDR or its active ingredient TA daily for ten days. In mice having a AR, MDR and TA prominently diminished number of rubs and levels of histamine, IgE, thymic stromal lymphopoietin, interleukin (IL)-1β, IL-4, IL-5, IL-13, IL-33, and tumor necrosis factor-α. In addition, protein expression levels and activities of caspase-1 were declined by oral medication of MDR and TA. Decline in levels of macrophage inflammatory protein-2 and intercellular adhesion molecules-1 and reduction in penetrations of inflammatory cells into inflamed tissue were also noted in MDR and TA groups. Taken together, identification of MDR effect in preclinical models suggests that MDR may be a therapeutic drug for the treatment and prevention of AR., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: So-Cheong-Ryong-Tang (SCRT), also known as Xiao-Qing-Long-Tang or Sho-seiryo-to, is a mixed herbal formula that is used to treat allergic rhinitis, bronchitis, allergic asthma, and common cold in traditional Korean medicine., Objective: To assess the efficacy and safety of the SCRT for the treatment of allergic rhinitis., Methods: We conducted a double-blind, randomized, placebo-controlled, parallel-group, multicenter study of Korean adults with perennial allergic rhinitis. The trial consisted of a 4-week oral administration of SCRT or placebo, with two visits at 2-week intervals, and an 8-week follow-up period, with two visits at 4-week intervals. The primary outcome was a change in the total nasal symptoms score. The secondary outcomes included changes in the Rhinoconjunctivitis Quality of Life Questionnaire score, total serum immunoglobulin E (IgE), cytokines levels, and nasal endoscopy index., Results: SCRT improved nasal symptoms and quality of life in patients with PAR after 4 weeks medication, and these effects did not last 8 weeks after the end of medication. The level of serum IgE, eosinophil counts, and cytokines did not alter after medication. Nasal endoscopy index did not show significant difference. No serious AEs and safety assessment changes were observed in this trial., Conclusion: SCRT is an effective and safe medication for patients with chronic, perennial, and moderate to severe AR. A clinical study with a >4-week period of medication use, and more participants for immune material test is needed to investigate the long-term efficacy of SCRT in relieving the symptoms of nasal obstruction and identifying the underlying mechanisms of action and indications for traditional Korean medicine., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rationale: Hormone imbalance and menstrual irregularities are normal for postpill women. Pharmacopuncture and moxibustion can stimulate acupoints with herbal extract and heat, respectively, to regulate the function of qi and blood, expel pathogens, and support health., Patient Concerns: A 39-year-old female patient presented with amenorrhea, >6 months after she had stopped taking the oral contraceptive pill, which she had taken for more than 10 years, and possible associated infertility. Additionally, she reported sudden weight gain of approximately 12 kg in 1 year., Diagnoses: In this study, we examined the amenorrhea lasted more than 6 months for postpill patient., Interventions: She refused a strong acupuncture stimulus; she underwent lower abdomen pharmacopuncture with wild ginseng complex (WGC) and moxibustion at CV4, 5 times during 1 month. As a secondary treatment, 1 g Geoseub-hwan pills were prescribed for overeating and during social events. After 5 weekly primary treatments, Geoseub-hwan was prescribed intermittently., Outcome: After 3 primary treatments, she began menstruation without menstrual cramps or discomfort. After 5 treatments, she exhibited improvement of body weight and body composition. At 1- and 3-month follow-up examinations, she confirmed regular menstruation without discomfort., Lessons: Pharmacopuncture with WGC and moxibustion may be effective for the treatment of postpill amenorrhea with abdominal obesity and can be used for patients with fear of a strong acupuncture stimulus.

Background: Knee osteoarthritis (KOA) is a common disease in elderly individuals. Many medications for KOA have the potential to cause side effects. We used Juglandis semen complex extract (JCE) consisting of 4 herbs derived from Cheong-A-Won, which has been commonly used for KOA treatment. In this study, we will evaluate whether JCE improves symptoms in patients with KOA and will identify the changes in the inflammation factor., Methods: This study will be a single-center, randomized, double-blind, and placebo-controlled trial. Three groups, JCE 1000 mg, 2000 mg, and placebo, will be randomly allocated. Total duration of the clinical trial will be 12 to 14 weeks. Study participants will be followed up every 6 weeks and the effect and safety will be assessed at the 2, 3, and 4 visit. All participants were asked to maintain a dosage schedule for this protocol. The primary outcomes will be measured using Korean Western Ontario and McMaster Universities Questionnaire and the secondary outcomes will include pain Visual analog scale score, EuroQol Five Dimensions questionnaire, Patient Global Impression of Change, and the changes in the laboratory test parameters of inflammation. Repeated-measure analysis will be used to measure primary efficacy based on full analysis set., Discussion: This study has limited inclusion and exclusion criteria and a well-controlled intervention, and it will be the first randomized controlled trial to assess the efficacy and safety of JCE in patients with KOA. This study provides insights into the mechanisms that explain the therapeutic effects of JCE in KOA and will lay the groundwork for further studies.

Introduction: In Korea, low back pain (LBP) which is occupation-related symptom is one of the major health issues owing to rapid industrialization. Even traditional Korean medicine has the long history in pain treatment, there still has been lack of supporting evidence on herbal prescription itself. Sogyeonghwalhyeol-tang, a Korean herbal medicine prescription, has been suggested as a medication for treating chronic LBP as well as work-related pains., Objective: This study aims to evaluate the clinical efficacy and safety of herbal medicine, Sogyeonghwalhyeol-tang on work-related chronic LBP patients., Method: This trial is designed as a multicenter, randomized, controlled, clinical trial. Seventy-two participants who have chief complaint of LBP in Korean medicine rehabilitation center will be randomly assigned to ether Sogyeonghwalhyeol-tang group or placebo group with a ratio of 1:1. They will receive assigned drugs in 4 weeks and follow-up for 2 weeks., Discussion: The result of this study will provide the valuable information for efficacy and safety of Sogyeonghwalhyeol-tang for patients with work-related chronic LBP.

We examined the effects and safety of Korean herbal medicine (MYOMI-14) to treat infertile men with low semen quality. This study included 17 patients who received MYOMI-14 for 10 weeks. The primary outcomes were the mean differences between sperm test values. The secondary outcomes were changes in the Fertility Quality of Life and the difference in skin temperature between the thigh and scrotum. Adverse events were also monitored. The average values of sperm concentration, sperm progressive motility and total motile sperm count significantly improved after MYOMI-14 treatment (36.2%, 51.7% and 55.5%, respectively; p < 0.05). The core Fertility Quality of Life and the difference in skin temperature between the thigh and scrotum did not change significantly. No adverse events were observed. MYOMI-14 improved the semen quality of infertile men without adverse effects. Additional studies in a larger population and longer prospective randomised clinical trials are needed to confirm these results., (© 2019 Blackwell Verlag GmbH.)

Objectives: Blood stasis is an important pathophysiologic concept in Traditional East Asian Medicine. It has been considered to be a pathogenic factor in chronic and incurable conditions such as pain, infertility, cancer, coronary heart disease, and others. The aim of this study was to investigate the effects of pain reduction by blood stasis treatment for blood stasis syndromes with traumatic injury., Methods: A single-center prospective pretest-post-test pilot study included 73 patients with a trauma that occurred within the past 2 weeks who were admitted into Jaseng Hospital of Korean Medicine from August 2015 through December 2015. Of the 50 patients analyzed in this study, 42 were women (mean age, 33.52). Triple Energizer-reinforcing Saam acupuncture set, herbal medicine (Dangkwisoo-san), and wet cupping on tender point, which are Korean medical therapies generally executed to treat post-traumatic pain, were performed. The patients had to receive at least six sessions of treatment during the 2 weeks, with subsequent treatment being performed within 3 ± 1 days after the previous treatment. Numeric rating scale (NRS) score and general pain severity indicator was measured as a primary outcome measure. The blood stasis questionnaire, oximetry, and patient's satisfaction were also measured., Results: The mean size of subcutaneous bleeding (width and length) and NRS score as a general pain indicator significantly decreased over the visits (all p < 0.01, visit 1 vs. visit 6). Among the blood stasis symptoms in the questionnaire, 11 blood stasis indicators significantly decreased (all p < 0.05). The patients showed significant improvement in the minimum and maximum value of peripheral perfusion index after the treatment (p = 0.011 and p = 0.15, respectively)., Conclusions: This study reveals that blood stasis treatment may help improve the pain of patients with traumatic injury by enhancing the peripheral blood flow. The significant results observed in this study support some evidence of the theories of diagnosing blood stasis pattern and treatments of that pattern in Korean Medicine.

Cervus nippon mantchuricus extract, known as nok‑gol (NGE) in Korean, is useful for the treatment of various inflammatory diseases, including bone resorption and neutropenia. However, NGE has not been widely investigated, and its efficacy and safety remain to be fully elucidated. In the present study, histological analysis, blood analysis, reverse transcription‑semi-quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assays were performed to verify the inhibitory effect of NGE on atopic dermatitis (AD) in BALB/c mice and on inflammatory effects in HMC‑1 human mast cells. NGE suppressed the development of AD in mice, and decreased the infiltration of inflammatory cells, mast cells and CD4+ T cells into AD skin lesions. NGE also decreased leukocyte levels induced by 2,4‑dinitrochlorobenzene (DNCB). NGE alleviated AD‑like inflammatory symptoms in mice by suppressing the production of CD4+ T cells. NGE downregulated the mRNA expression of inflammatory cytokines induced by DNCB. It also decreased the serum immunoglobulin E concentration and inflammatory cytokine levels in DNCB‑treated BALB/c mice. The in vitro experiments demonstrated that NGE reduced the phorbol 12‑myristate 13‑acetate + ionomycin‑induced expression of pro‑inflammatory cytokines interleukin (IL)‑4, IL‑13, tumor necrosis factor‑α, and IL‑6 in HMC‑1 cells. Taken together, the results of the present study indicated that NGE suppressed the progression of DNCB‑induced AD in BALB/c mice and reduced inflammatory effects in HMC‑1 cells. This suggests that NGE may be a useful drug for the treatment of AD.

In recent decades, various bioactive compounds from plants have been investigated for their potential use in the treatment of diseases in humans. Aster incisus extract (AIE) is the extract of a common plant that is mostly found in Asia. It has traditionally been used for medicinal purposes in South Korea. In this study, we evaluated the potential anticancer effects of a methanolic extract of Aster incisus in a normal human cell line (HaCaT keratinocytes) and in 4 different types of human cancer cell lines (A549, lung cancer; Hep3B, liver cancer; MDA‑MB‑231, breast cancer; and AGS, gastric cancer). The HaCaT, A549, Hep3B, MDA‑MB‑231 and AGS cells were treated with various concentrations of AIE and following treatment, cell survival was evaluated. Additional analyses, such as WST-1 assay, western blot analysis, DAPI staining, flow cytometry, immunofluorescence staining and wound healing assay were performed to elucidate the mechanisms and pathways involved in the cell death induced by AIE. Treatment with AIE induced morphological changes and considerably reduced the viability of the both normal and cancer cell lines. Further analysis of the AGS gastric cancer cells revealed that AIE led to the induction of apoptosis and a high accumulation of cells in the G1 cell phase following treatment with AIE in a dose-dependent manner. The results also revealed that AIE successfully suppressed the migration of the AIE-treated AGS cells. The results of western blot analysis indicated that AIE increased the expression of pro-apoptotic proteins, particularly Bid, Bad, Bak, cytochrome c, apoptosis inducing factor (AIF), cleaved caspase‑3, -8 and -9 and cleaved poly(ADP-ribose) polymerase (PARP). Additionally, AIE decreased the expression of the anti-apoptotic proteins, Bcl-2 and Bcl-xL. On the whole, the findings of this study demonstrate that AIE induces apoptosis through the activation of the caspase‑dependent pathway mediated by the mitochondrial pathway and by arresting the cell cycle in AGS cells.

Background: This study aims to evaluate the efficacy, safety, and appropriate dose of Hanslim, a Korean traditional herbal medicine, for obese patients, when compared to a placebo., Methods/design: This study is a randomized, double-blinded, multicenter, multidose, placebo-controlled, phase IIb clinical trial. A total of 165 obese patients with a body mass index (BMI) of more than 30 kg/m or obese patients with a BMI of 27 to 29.9 kg/m and one or more risk factors such as hypertension, diabetes, or hyperlipidemia will be enrolled. Participants will be randomly assigned to 1 of 3 groups (high-dose, low-dose, or placebo) with a 1:1:1 allocation ratio and will have 4 scheduled visits during the 12-week treatment period. The participants will be administered 2 tablets of Hanslim or placebo, 2 times per day. The difference in the proportion of participants who lost weight by more than 5% from their baseline at 12 weeks compared to the placebo group will be examined as the primary efficacy outcome. Secondary efficacy outcomes include differences in body weight, BMI, body-fat percentage, fat mass, skeletal-muscle mass, edema index, waist circumference, hip circumference, waist-hip ratio, serum lipid, blood glucose, C-reactive protein, and total score of Korean version of obesity-related quality of life after 12 weeks of treatment. Adverse events, laboratory test results, vital sings, and electrocardiography will be recorded to evaluate safety., Discussion: This is the first prospective clinical trial to explore the efficacy and safety of Hanslim for obese patients. If the results provide the appropriate dosage of Hanslim, this study would contribute to the confirmatory evidence for the use of Hanslim as a treatment for obesity needed to conduct a large-scale, phase III clinical trial. The results will be published in a peer-reviewed journal., Trial Registration: Clinical Research Information Service, ID: KCT0002193. Registered on January 6, 2017. https://cris.nih.go.kr/cris/search/search&#95;result&#95;st01&#95;en.jsp?seq=7468.

Objectives: Traditional medicine has been used worldwide in recent decades. The aim of this study was to determine the incidence of adverse events (AEs) in traditional medicine hospitals and investigate patient and health-care utilization factors associated with AE occurrence., Methods: A 2-stage review of 1152 randomly sampled charts in 2 teaching Korean traditional medicine hospitals was conducted. Three physicians and a quality improvement specialist identified AE occurrence, severity, and preventability using the Global Trigger Tool (Appendix 1, Supplemental Digital Content, http://links.lww.com/JPS/A19). Two traditional Korean medicine professors validated the findings. Logistic regression analysis was performed to determine factors associated with AE occurrence., Results: One hundred twenty-two admissions (10.6%) had at least one AE (7.39 events per 1000 patient days and 14.5 events per 100 admissions). Among 167 AEs, 73.7% were mild and 70.7% were judged preventable. Procedure-related AEs were most common. After considering other patient and health-care utilization characteristics, factors associated with AE occurrence were altered mental status on admission (OR, 3.86; 95% confidence interval [CI], 1.20-12.44), use of various traditional medicine therapies (OR, 1.69; 95% CI, 1.32-2.15), length of stay (OR, 1.02; 95% CI, 1.01-1.03), and number of unique triggers (OR, 6.35; 95% CI, 4.54-8.89)., Conclusions: Approximately 11% of inpatients in traditional medicine hospitals experienced AEs. Because patients have a higher risk of AEs, special attention should be paid to those with altered mental status on admission, receiving various traditional medicine therapies, staying for a longer period, and having various positive triggers.

Background: South Korea has a dual medical system comprising conventional Western medicine (WM) and traditional Korean medicine (KM), which has yielded both positive results (increased opportunity to choose medical care) and negative results (increased medical costs). Thus, the Ministry of Health and Welfare has been performing a pilot project to evaluate this collaborative system in the real clinical situation. As treatment of dementia requires a social approach, the Korean government aims to strengthen the role of the national health care system to reduce the burden of dementia. The aim of this study was to evaluate the clinical - and cost-effectiveness of collaborative KM and WM treatment in patients with dementia or mild cognitive impairment (MCI) in Korea., Method/design: In total, 180 patients with dementia or MCI will be recruited and will undergo monthly check-up for 12 weeks. Information regarding demographic characteristics, baseline disease-related data, and outcomes related to cognitive function and quality of life will be obtained. For data analysis, the patients will be classified into 2 groups using a comparative observational study design: the sole treatment group, which will receive either WM or KM alone, and the collaborative treatment group, which will receive both WM and KM., Discussion: The treatment of dementia/MCI in South Korea will be studied in the real world during the pilot project. There will be no limitations on the type of treatment or the specific treatment method. Examining the clinical- and cost- effectiveness of the different methods will supply information for building an optimal medical system for the treatment of dementia/MCI., Trial Registration: The protocol for this study has been registered at the clinical research information service (CRIS: KCT0002868).

Objectives: This study aimed to identify the relationship between health-related quality of life (HRQoL) measured by the Functional Assessment Cancer Therapy-General (FACT-G) and survival in metastatic colorectal cancer (mCRC) patients., Methods: The clinical characteristics and FACT-G scores were retrospectively reviewed in mCRC patients who visited the Cancer Center of Korean Medicine. The overall survival (OS) was calculated and compared using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were performed based on clinical characteristics and FACT-G scores. To identify significant differences in answer frequency, χ 2 tests and Fisher's exact tests were used., Results: A total of 58 patients were reviewed. The proportion of patients who had an Eastern Cooperative Oncology Group-Performance Status ≥ 2 was 43.1%, multiple distant metastatic sites was 77.6%, liver metastases was 43.1%, been previously treated was 89.7%, and received more than the second-line chemotherapy was 75.5%. The mean total FACT-G score was 65.3 (median 65.6). The median OS was 7 months. There was no significant difference in OS between the 2 groups divided by the median values of FACT-G total and subscores. In univariate analyses, functional well-being (FWB) score had a significant impact on survival. In multivariate analyses, presence of liver metastasis, FACT-G total score, and FWB score were significant prognostic predictors of survival. No statistically different answer frequency was observed for any question regarding FWB., Conclusions: This study found that FACT-G total and FWB scores were potential prognostic factors for predicting OS in relapsed or refractory mCRC patients treated with Korean Medicine.

Male factor subfertility has increasingly been considered the cause of infertility in couples. Many men with male infertility have sperm problems such as oligozoospermia, asthenozoospermia, or teratozoospermia. Because abnormal semen parameters are idiopathic to some extent, no standard therapy has been established to date. Herbal medicine has been reported to have beneficial properties in the treatment of subfertility, especially in improving semen quality both in vivo and in human studies. Therefore, we intend to investigate the effectiveness and safety of treatment using Korean medicine (KM) for infertile male patients with poor semen quality.This will be a single-center, prospective, case-only observational pilot study. About 20 male patients with infertility who visit Conmaul Hospital of Korean Medicine will be recruited. We will follow the standard treatment protocol, which has shown good results in the treatment of male infertility. The protocol is composed mainly of a 10-week herbal decoction treatment; acupuncture and/or pharmacopuncture are added when needed. Semen samples, quality of life, and the scrotal temperatures of infertile men will be observed before and after the 10-week treatment with KM.The study has received ethical approval from the Public Institutional Review Board (approval number: P01-201708-21-008). The findings will be disseminated to appropriate audiences via peer-reviewed publication and conference presentations., Trial Registration: Korean Clinical Trial Registry (CRIS), Republic of Korea: KCT0002611.

Infertility is a condition in which a woman has not been pregnant despite having had normal intercourse for 1 year. The number of unexplained infertile females is increasing because of late marriage customs, as well as environmental and lifestyle habits. In Korea, infertile females have been treated with Korean medicine (KM). However, these effects have not been objectively confirmed through clinical trials. Therefore, this study was conducted to demonstrate the effectiveness of herbal medicine treatment in infertile patients and to demonstrate the economic feasibility through economical evaluation with assisted reproductive technology.This study is designed as a multicenter, single-arm clinical trial. All participants included will be from 3 Korean Medicine hospitals in Korea and will voluntarily sign an informed consent agreement. All recruited patients will conduct related surveys and tests, and be provided with treatment according to their menstrual cycle. Patients will take herbal medicines for 4 menstruation cycles and receive acupuncture and moxibustion treatment at 3 times (menstrual cycle day 3, 8, 14) during 4 menstruation cycles. They will also undergo an approximately 4 menstrual cycle treatment period, and 3 menstrual cycle observation period. If pregnant during the study, participants will take the herbal medicine for implantation for about 15 days. In this study, the primary outcome will be the clinical pregnancy rate, whereas the secondary outcome will include the implantation rate, ongoing pregnancy rate, and live birth rate.Ultimately, this study will provide clinical data regarding the effectiveness and safety of KM treatment for females with unexplained infertility and important evidence for establishing standard KM treatments for unexplained infertility. Moreover, we will identify the most cost-effective way to treat unexplained infertility., Trial Registration Identifier: Korean Clinical Trial Registry (CRIS), Republic of Korea: KCT0002235. Date: February 21, 2017 (retrospectively registered)., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Chemotherapeutics are often used to inhibit the proliferation of cancer cells. However, they can also harm healthy cells and cause side effects such as immunosuppression. Especially traditional oriental medicines long used in Asia, may be beneficial candidates for the alleviation of immune diseases. Cervus nippon mantchuricus extract (NGE) is currently sold in the market as coffee and health drinks. However, NGE was not widely investigated and efficacy remain unclear and essentially nothing is known about their potential immune-regulatory properties. As a result, NGE induced the differentiation of RAW264.7 macrophage cells. NGE-stimulated RAW264.7 macrophage cells elevated cytokines levels and NO production. NGE-stimulated RAW264.7 macrophage cells activated MAPKs and NF-κB signaling pathways. NGE encouraged the immuno-enhancing effects in immunosuppressed short-term treated with NGE mice model. NGE or Red ginseng encouraged the immuno-enhancing effects in immunosuppressed long-term treated with NGE mice model. Our data clearly show that NGE contains immune-enhancing activity and can be used to treat immunodeficiency., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This experimental study investigated the efficacy of Korean Red Ginseng (KRG) extract in reducing the partial losses of random flaps., Method: Forty Wistar Albino rats were randomly distributed into 4 groups as (A) control group, (B) stress group, (C) oral KRG group, and (D) intraperitoneal KRG group. The modified McFarlane flap of 9 × 3 cm with a caudal pedicle was harvested from the back of the rats in all the groups. Korean Red Ginseng was administered to groups C and D at standard doses for 10 days. After 10 days, the flaps were removed in all groups and were examined macroscopically, histopathologically, histochemically, and biochemically. The results were statistically analyzed and compared among the groups., Results: The flap necrosis rates were significantly lower in groups C and D compared with groups A and B (P < 0.05). The vascular density, antioxidant activity, and hypoxia-inducible factor-1α levels were significantly higher in the groups C and D compared with the groups A and B (P < 0.05). Although vascular density, hypoxia-inducible factor-1α, and catalase levels were negatively correlated with the flap necrosis rates, there was a significantly positive correlation between malondialdehyde and necrosis rates., Conclusions: Korean Red Ginseng increases the viability of random pattern skin flaps, resulting in reduced rates of distal necrosis. Korean Red Ginseng has antioxidant activity and increases neovascularization.

Cysteine X cysteine (CXC) chemokine receptor 4 (CXCR4) and C-X-C motif chemokine 12 (CXCL12) were originally identified as chemoattractants between immune cells and sites of inflammation. Since studies have validated an increased level of CXCL12 and its receptor in patients with colorectal cancers, CXCL12/CXCR4 axis has been considered as a valuable marker of cancer metastasis. Therefore, identification of CXCR4 inhibitors has great potential to abrogate tumor metastasis. Onbaekwon (OBW) is a complex herbal formula that is derived from the literature of traditional Korean medicine Dongeuibogam. In this study, we demonstrated that OBW suppressed CXCR4 expression in various cancer cell types in a concentration- and time-dependent manner. Both proteasomal and lysosomal inhibitors had no effect to prevent the OBW-induced suppression of CXCR4, suggesting that the inhibitory effect of OBW was not due to proteolytic degradation but occurred at the transcriptional level. Electrophoretic mobility shift assay further confirmed that OBW could block endogenous activation of nuclear factor kappa B, a key transcription factor that regulates the expression of CXCR4 in colon cancer cells. Consistent with the aforementioned molecular basis, OBW abolished cell invasion induced by CXCL12 in colon cancer cells. Together, our results suggest that OBW, as a novel inhibitor of CXCR4, could be a promising therapeutic agent contributing to cancer treatment.

The methanol extract of the roots and stems of Daphne genkwa and its constituents yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating effects and neuroprotective effects in an animal model of Parkinson's disease (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2), wikstroemia factor M 1 (3), yuanhuadine (5), and yuanhuatine (6)) and two phorbol-type diterpenes (prostratin Q (4) and 12-O-n-deca-2,4,6-trienoyl-phorbol-(13)-acetate (7)) were isolated as Nurr1 activating compounds from the D. genkwa extract. Consistent with their higher Nurr1 activating activity, compounds 1, 4, 5, and 7 exhibited higher inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine microglial BV-2 cells with an IC 50 (µM) of 1-2, which was 15-30 times more potent than that of minocycline (29.9 µM), a well-known anti-neuroinflammatory agent. Additionally, these diterpenes reduced expression and transcription of LPS-induced pro-inflammatory cytokines in BV-2 cells. Thus, the daphnane-type and phorbol-type diterpenes had anti-neuroinflammatory activity with Nurr1 activation and could be responsible for the anti-PD effect of the roots and stems of D. genkwa.

Background: Evidence of ginseng for reducing blood pressure (BP) in hypertensive patients is controversial. This systematic review updated the previous reviews and evidence for it., Methods: Ten databases were searched from their inception through October 2016, without language restriction. Randomized clinical trials (RCTs) were included if any types of ginseng were tested as the sole treatment or as an adjunct to other treatments for pre-hypertension or hypertension. The risk of bias (ROB) was assessed with Cochrane ROB tools by two independent reviewers., Results: We found 528 potentially relevant articles, of which 9 RCTs met our inclusion criteria. Two studies reported positive effects of Korean red ginseng (KRG) on acute reduction of systolic BP (SBP: n=54, mean differences (MD), -6.52; P=0.0002; I2=0%) and diastolic BP DBP: MD, -5.21; P=0.0001; I2=0%), while two other trials failed to do so with north American ginseng (NAG) in both SBP and DBP. Five RCTs assessed the long-term effects of ginseng (KRG or NAG) on SBP and DBP. Two studies showed positive effects of KRG on reducing SBP and DBP compared with placebo (SBP: n = 183, MD, -2.92, P=0.04; I2 = 0%; DBP: MD, -3.19, P=0.008; I2 = 0%)., Conclusion: This systematic review provides positive evidence for the efficacy of KRG on reducing blood pressure in patients with pre-hypertension and hypertension in acute and long-term. Future RCTs appear to be warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)