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Objectives: Objectives: In this study, we define a medical service type that combines Western medicine, Korean medicine, and complementary and alternative medicine (CAM) as an integrated medical service. This study, as part of tertiary hospital-based integrated medical service model and clinical field application, aims to collect status and opinions on integrated medical service for medical staff in the field.Methods: This is a survey study, and was conducted on doctors from Kyung Hee University Hospital and Korean medicine doctors from Kyung Hee University Korean Medicine Hospital. Respondents were recruited on a first-come, first-served basis until the number of respondents reached 120. The investigation was conducted for a total of 16 days from October 4, 2021 to October 19, 2021 by e-mail.Results: Recognition of integrated medical services was confirmed to be 45.8%, and 49.2% responded positively to the necessity of it. As a group of diseases that require the establishment of integrated medical services in the future, 'disorders of musculoskeletal systems and connective tissues' was the highest. The most expected advantages of providing integrated medical services were 'increased satisfaction of patients and guardians' and 'increased treatment effects.’Conclusions: In this study, we investigated the perception of doctors and Korean medicine doctors on integrated medical services that combine Western medicine, Korean medicine, and CAM. It has been confirmed that medical staff generally have a positive perception of integrated medical services, and if the scientific basis for the effect of integrated medical services is supported, the rate of positive perception is expected to increase.

Objectives: This study aimed to explore the short-term effects of bilateral masticatory training using an intraoral device on memory and concentration, which is an advanced form of Gochi, compared to the unilateral form with gum.Methods: Thirty young healthy participants (age, 16–30 years) were screened and randomly assigned to one of two sequences in a crossover design. The participants assigned to sequence A (n=15) performed bilateral mastication using an intraoral device with a total of 300 taps, followed by unilateral mastication using gum with the same number of repetitions and frequency, separated by a 7-day washout period. A reverse order was used for sequence B. The primary and secondary outcomes were the digit span test result and the symbol digit modality test and the word list recallresults, respectively, which were conducted before and after each intervention.Results: Symbol digit modality test scores increased by 12.03±8.33 with bilateral mastication, which was significantly higher than that obtained with chewing gum (5.17 points;95% confidence interval: 0.99, 9.34; p

Objectives: Currently, Korea’s medical services are divided into Western medicine and Korean medicine, and people who are not satisfied with the existing treatments are looking for complementary and alternative medicine(CAM). Therefore, this study attempted to confirm patients' perception of the ongoing collaborative treatment and integrated medical service that added CAM to collaborative treatment based on tertiary hospital users. So that we can confirm the expected advantage and disadvantage of integrated medical service system and the necessity of supporting medical expenses for it.Methods: The survey was conducted on 100 people who experienced tertiary hospital treatment and other 100 people who experienced both tertiary hospital treatment and Korean medicine treatment at the same period. The survey was conducted until the number of respondents in both group reached 100. The survey was conducted through e-mail and was conducted from September 27, 2021 to October 8, 2021.Results: For the advantages of collaborative treatment ‘increased in psychological stability,’ and for disadvantages ‘longer time spent for treatment’ were the most common. If integrated medical services are implemented in the future, expected advantages include ‘consideration of various treatments.’ and expected disadvantages include ‘increased medical cost.’ The needs to expand support for health insurance for integrated medical services were 75.5% among responders.Conclusions: We were able to find out the (expected) advantages and disadvantages of the collaborative medical care and the integrated medical system that medical users experienced or expected, also confirmed positive answers to the expansion of health insurance support for the integrated medical system.

Inflammation causes a protective immune response, which can be observed by examining the inflammatory responses of macrophages. Macrophages release various immunostimulatory factors when destroying external pathogens. We induced lipopolysaccharides (LPS) in RAW 264.7 cells, a macrophage cell line, to determine whether Helixor-M can cause immuno-suppression. Helixor-M is known to have anticancer and immune effects. However, an indicator that regulates immunity has not been clearly confirmed. To this end, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to confirm Helixor-M was not cytotoxic. Western blotting and real-time polymerase chain reaction (RT-PCR) confirmed the anti-inflammatory effects. Additionally, immunofluorescence assay confirmed the translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, a representative inflammatory pathway. Helixor-M was found to be non-cytotoxic, induce the NF-κB pathway, and reduce the levels of pro-inflammatory cytokine and mitogen-activated protein kinase (MAPK). We found Helixor-M affected the PI3K/AKT/JNK pathway. Therefore, we confirmed Helixor-M acts as an anti-inflammatory agent through NF-κB, TLR4 and PI3K inhibition and that it could be an effective immunosuppressive drug.

Lifestyle and physical characteristics affect body weight, and understanding these factors improves the precision of weight loss treatment. Many obese patients in Korea are receiving Korean medicine (KM) treatment, including herbal medicine and acupuncture, for weight loss. However, the real-world data (RWD) are insufficient in terms of being longitudinal and diverse. Weight Control Registry using KM is a prospective registry study that enrolls patients receiving KM treatment for weight loss and collects RWD from multiple clinics. The patients who are eligible for this study are aged 19–65 years, receive KM weight loss treatment, understand the study objectives, and consent voluntarily. Clinical data of patient characteristics and KM treatment patterns will be regularly collected until 2026. The longitudinal accumulation of various RWD will establish a high-quality study database for KM weight loss treatment. With this study, we expect to contribute to understanding the current trend of weight loss treatment with KM and solve further questions regarding this treatment.

Herein, a heterogeneous polymer micro valve and pump with a polypropylene (PP) membrane was developed in a low-cost manner via UV/ozone-assisted thermal fusion bonding. The proposed fabrication technique allowed for a geometrically selective bonding; consequently, the membrane was prevented from bonding with the valve seat of the diaphragm micro-valve, without patterning a protection layer or introducing an additional structure. The developed device withstands 480 kPa of static pressure and up to 350 kPa of a vibration pressure, providing sufficient bonding strength for microfluidic actuations. The fabricated micro valve and pump are fully characterized and compared with a poly(dimethylsiloxane) (PDMS) membrane glass device, showing comparable valving and pumping performance. As a result, the robust PP membrane micro valve and pump are simply implemented in a facile manner, and demonstrated excellent performance, which is highly desirable for mass production of disposable lab-on-a-chip (LOC) devices.

Background. Chinese herbal medicines (CHMs) have been widely used in the treatment of cervicogenic dizziness (CGD) based on their empirical effectiveness and safety. Herein, we reviewed and evaluated the clinical evidence of the efficacy and safety of CHMs for CGD. Methods. Among the relevant studies published in 11 electronic databases up to December 2021, only randomised controlled trials were included. Methodological quality was assessed using the revised Cochrane risk-of-bias tool for randomised trials, and the strength of evidence for the main outcomes was evaluated using the grading of recommendations assessment, development, and evaluation system. Results. All 35 included randomised controlled trials with 3,862 participants were conducted with six types of modified CHM and four types of active controls. More than half of the included studies were of low quality because of the high risk of bias due to deviations from intended interventions. CHM plus active control was more effective in the treatment of CGD than active control alone. CHM plus anti-vertigo drugs, CHM plus manual therapy, CHM plus acupuncture therapy, and CHM plus manual and acupuncture therapy were all effective in treating CGD, with CHM plus manual and acupuncture therapy showing the most reliable effect. All CHMs were effective for specific patterns of CGD when administered with active controls, with Dingxuan Tang and Yiqi Congming Tang demonstrating the most reliable effects. No serious adverse events were reported in any of the included studies. Conclusion. The current evidence suggests that CHM may enhance the treatment of CGD when combined with other treatments without serious adverse events. Further high-quality evidence is needed to draw definitive conclusions.

Background: Memory is an important part of the mental activity. Chattering teeth training practiced in Korean Medicine (known as gochi in Korean), which is a practice of making a sound by touching the upper and the lower teeth, has been accepted as a modality for the dental health. The purpose of this study is to confirm the effect of a specially designed intraoral appliance, the No-Sick Exerciser, on working memory improvement in healthy participants. Methods: Thirty healthy participants aged between 16 and 30 years will be recruited and randomized into sequence A and B of 15 each, as in a cross-over design (sequence A: chattering teeth training oral appliance)-chewing the gum; sequence B: chewing the gum—chattering teeth training oral appliance with a washout period of one week. The primary outcome will be assessed by the digit span test and secondary outcomes by the symbol digit modality test and the word list recall, which will be conducted before and after each intervention, four times on each participant. Discussion: This protocol proposes the rationale and method for the use of an intraoral appliance for working memory improvement. If the oral appliance demonstrates better feasibility for working memory improvement compared with chewing gum, a large scale study will be needed to investigate the effectiveness of the device on populations who require memory improvement. Keywords: Working memory, Intraoral appliance, Cross-over design, Gum

BACKGROUND The frequency of patients undergoing musculoskeletal surgery has been increasing with the increase in average life expectancy of the population. An aging population with sustained musculoskeletal pain and disability is the main complaint of Korean medical institutions. Recently, Korean medicine clinicians have addressed the collection and analysis of the medical utilization pattern of patients with musculoskeletal discomfort after surgery, to identify the current demographics of patients and to provide empirical evidence for Korean medicine postoperative rehabilitation strategies as well as political decisions on the healthcare coverage of Korean medicine. OBJECTIVE Overall, the aims of Korean Medicine Patient Registry of Postoperative Therapy for Musculoskeletal Disorders (KPOP-MD) are to (1) explore the general characteristics of postoperative patients with musculoskeletal discomfort and (2) evaluate the overall improvement after performing various Korean medicine treatment regimens for musculoskeletal disorders, based on a process involving the collection of nationwide registry outcomes. METHODS KPOP-MD will collaborate with 17 traditional Korean medical institutions and register postoperative patients with musculoskeletal discomfort. A total of 150 patients who meet the eligibility criteria will be registered in the study. After registration, we will collect personal health information from each patient, such as general socio-demographics, surgical site discomfort, anthropometrics, and health-related quality of life (HRQoL) at each assessment. The primary endpoint will be a change in the numeric rating scale for pain at the surgical location. The additional evaluation variables will be a change in the site-specific patient-reported questionnaires, recovery status questionnaires, other discomfort assessments, and cost data. RESULTS not applicable CONCLUSIONS This is the first prospective, multicenter, patient-based registry of postoperative patients with musculoskeletal disorders in various traditional Korean medical institutions. The results of this registry will provide valuable information on the current status of postoperative patients who receive Korean medicine treatments and evidence for reasonable decision-making in the Korean medicine healthcare system in the future. CLINICALTRIAL ClinicalTrials.gov Identifier: NCT03842098.

The aim of this study was to analyze published papers on the use of herbal medicine in obesity research over the past 20 years using bibliometric methods and present an overview of global research trends.English articles on herbal medicine for obesity published from 2001 to 2020 were retrieved from the Web of Science Core Collection database using the search terms "herbal" AND "obesity". Microsoft Office Excel was used to sort and analyze the statistical data. Bibliographic analysis and data visualization were performed using visualization of similarities viewer based on publication year, country of publication, journal, research area, author, affiliated institution, and keywords.A total of 463 English articles were retrieved, and we observed a trend in which the number of publications on herbal medicine for obesity has gradually increased over the past 20 years. The most productive countries and research organizations in this field were Korea and Kyunghee University, respectively. Many papers have been published in research areas, such as pharmacology pharmacy and integrative complementary medicine, and the journals with the most published articles in this field were Journal of Ethnopharmacology and Evidence-Based Complementary and Alternative Medicine. The main research keywords formed 3 clusters, and keywords with the most occurrences were "obesity," "adipose-tissue," and "insulin resistance."This study presents an overview of the global research trend of herbal medicine for obesity from the bibliographic analysis. An increased understanding of the recently changing research topics provides a new perspective on future research directions. This study may help guide the research in the field of obesity in the future.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, which is well known for its poor symptoms, and the incidence is increasing worldwide. Although conventional medicines are practiced initially, patients often move or accompany to complementary and alternative medicines for better outcomes. Herbal medications, one of traditional medicinal approach, are widely used in clinical conditions. However, no research has broadly reviewed the current research trends regarding the scope of herbal medicines in RA. The aim of this study was to conduct a bibliometric analysis of applications of herbal medicine for RA from 1991 to the present.We retrieved literature on herbal medicine for RA from the Web of Science database from 1991 to 2021. The VOSviewer program was used to analyze keywords, authors, countries, and organizations through visual knowledge mapping to assess the research hotspots and trends.A total of 516 articles were included in the analysis, which showed an increasing trend in the number of publications over time. Four clusters were identified from the keyword analysis: complementary and alternative medicine cluster, mechanism of the pain cluster, control for the pain cluster, and recent research trend cluster. People's Republic of China published 250 articles, which was the greatest number of publications, followed by the United States of America (82 articles) and South Korea (52 articles). Furthermore, Moudgil, KD of the University of Maryland published 15 articles about the mechanism of herbal medicine on autoimmune arthritis and their interaction with various drugs. Lu, AP of the Hong Kong Baptist University published 14 articles about herbal medicine interactions. On an institutional level, the China Academy of Chinese Medical Science published 33 articles, followed by the Hong Kong Baptist University and the University of Maryland with 27 and 20 articles, respectively. Clusters of organizations from the People's Republic of China and the United States of America revealed higher average citations for earlier average publication years.This bibliometric study identified trends in herbal medicine for RA from 1991 to 2021, which may guide the hot topics and future directions in this research field.

Introduction Chuna manual therapy (CMT), one of the therapeutic modalities of Korean Medicine which is a kind of manual therapies, is well known among Korean Medicine doctors for the treatment of TMD but the evidence for the effect of CMT is insufficient. Therefore, this trial is designed to propose a protocol to investigate the efficacy and economic efficiency of CMT on TMD, compared to usual care (UC). Methods This trial is a prospective, assessor-blinded, two-arm parallel multicenter randomized controlled trial. Eighty patients with temporomandibular disorder, with numeric rating scale (NRS) above 4, will be randomly assigned to either the CMT or the UC group, with a 1:1 ratio. Participants will be recruited by five Korean Medicine hospitals. Participants will be treated eight times for 4 weeks, and will be assessed for pain, range of motion, depressive symptoms, and quality of life. Adverse events will also be reported. To evaluate the cost-effectiveness, medical consumption data (quality of life questionnaire) will be used to assess indices such as the Quality Adjusted Life Year. Discussion There were randomized controlled trials (RCTs) investigating the effect of CMT for TMD, however, evidence is evaluated as “Low”. For this reason, this trial was designed as a high-quality RCT protocol. Conclusion We expect that this trial will contribute new knowledge on the effects of CMT for TMD, so that an economically efficient way of treatment could be developed and standardized, providing more populations with the benefits of an effective and economic treatment for TMD.

Background: Herbal medicines (HMs) have been widely used in the treatment of cervicogenic dizziness (CGD) based on their empirical effectiveness and safety. Herein, we reviewed and evaluated the clinical evidence on the efficacy and safety of HM for CGD. Methods: Among the relevant studies published up to December 2019 in 11 electronic databases, only randomised controlled trials (RCTs) were included. The studies’ methodological quality was assessed using the revised Cochrane risk-of-bias tool for randomised trials, and the strength of evidence for the main findings was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: All 17 included RCTs with 1,797 participants were conducted with six types of modified HM prescriptions and three types of active controls. More than half of the included studies were of low quality because of the high risk of bias due to deviations from the intended intervention. HMs plus active controls were more effective in CGD treatment than active controls alone. HMs plus antivertigo drugs, HMs plus manual therapy, and HMs plus acupuncture therapy were all effective in CGD treatment, with HMs plus antivertigo drugs showing the most reliable effect. All HM prescriptions were effective for specific patterns of CGD when administered with active controls, with Banxia Baizhu Tianma tang and Dingxuan tang demonstrating the most reliable effect. No serious adverse events were reported in all included studies. Conclusions: The current evidence suggests that HMs may enhance the treatment effect on CGD when combined with other treatments without serious adverse events. Further high-quality evidence is needed to draw a definite conclusion.Systematic review registration: PROSPERO (registration number: CRD42020199222), and the Research Registry (Review Registry Unique Identifying Number: reviewregistry1036)

The objective of this study is to investigate the role of paraspinal muscles in the progression of different types of spondylolisthesis by examining the correlation between cross-sectional area (CSA) of lumbar paraspinal muscle and slip percentage (SP) in degenerative spondylolisthesis and isthmic spondylolisthesis. A multicenter retrospective analysis was carried out including 219 subjects diagnosed with lumbar spondylolisthesis. Using T2-weighted axial magnetic resonance imgaging, CSAs of the psoas major (PM), multifidus (MU), and erector spinae were measured and divided by L5 vertebral body (VB) CSA. SP was measured using sagittal T2-weighted images. Correlations between muscle CSA ratio and SP were calculated in each group. Regression analysis was performed to predict the influence of each muscle CSA/VB CSA ratio on SP. No significant correlation was found in the degenerative spondylolisthesis group between any of the muscle CSA ratios and SP. Both PM/VB ratio (r = −0.24, P = .021) and MU/VB ratio (r = −0.26, P = .012) were negatively correlated with SP in the isthmic spondylolisthesis group. MU had more influence on SP than PM in the isthmic spondylolisthesis group (regression coefficient MU/VB: −8.08, PM/VB: −4.34). Both PM and MU muscle CSA ratios were negatively correlated with SP in the isthmic group. MU had more influence on SP than PM. No muscles had any correlations with SP in the degenerative group. This discrepancy between the two groups suggests that exercise programs or interventions regarding the segmental stability of isthmic spondylolisthesis and degenerative spondylolisthesis should be distinguished in clinical practice. Clinical Research Information Service of Korea Centers for Disease control and Prevention, KCT0002588. Registered on 12 December 2017, https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=10702

Allergies occur when immunoglobulin E (IgE), which is part of the body’s immune system, binds to molecules. A protein in the foods, plants or pollen is usually the problem. This causes the release of inflammatory chemicals such as histamine. There are a few cases where allergies are cause by proteins derived from herbal medicine, but we do not know yet what protein causes the immune react to IgE. Here, we demonstrate to confirm if the Pueraria Radix at the proteomic level triggers IgE immunoreactivity. Finally, we present the molecules of the Pueraria Radix-derived protein that trigger the IgE immune response. To prove our hypothesis, we used proteomic tools and SDS-PAGE stained with Coomassie blue and identified proteins using LC-MS/ MS. Proteins were separated from Pueraria Radix and allergic reaction sera were selected. We found three positive sera that showed an immune response to Pueraria Radix protein. Positive sera demonstrated a similar pattern of IgE reactivity and mostly restricted to a 50-70 kDa band. Therefore, we have identified number of different IgE binding proteins. Therefore, IgE binding proteins were identified such as enolase, hypothetical protein, DING protein and glycosyl transferase. The results imply that Pueraria Radix can act as an allergen given the identification of IgE binding proteins among the isolated proteins of Pueraria Radix.

Obesity is a chronic disease associated with lethal health conditions. Moxibustion, a frequently used treatment in traditional Chinese medicine, is effective and safe for the treatment of obesity. However, the evidence has not been systematically collected and combined to date. This systematic review and meta-analysis will analyze the effects of moxibustion on obesity.The following databases will be searched: Cochrane Central Register of Controlled Trials, MEDLINE/PubMed, EMBASE, 1 Chinese database (Chinese National Knowledge Infrastructure), 1 Japanese database (Citation Information by the National Institute of Informatics), and 3 Korean databases (Oriental Medicine Advanced Searching Integrated System, ScienceON, and KoreaMed). The quality of the included studies will be assessed according to the Cochrane Assessment Tool for Risk of Bias. Data from the included studies will be synthesized for meta-analysis. The primary outcome will be body weight, and the secondary outcomes will be body mass index, waist-hip ratio, waist circumference, hip circumference, and effective rate.Ethical approval is not necessary for this study because it will not include any patient information. The results of this systematic review and meta-analysis will be publicly available and published in a peer-reviewed journal.DOI 10.17605/OSF.IO/NTKDF (https://osf.io/ntkdf).

As a plant medicine, Oxalidaceae has been used to treat various diseases in Korea. However, there is little data on the anti-cancer efficacy of Oxalidaceae, particularly O. obtriangulata. This study aimed to investigate the anti-cancer effect of O. obtriangulata methanol extract (OOE) and its regulatory actions on pancreatic carcinoma. OOE showed anti-proliferative effects and induced cell death in the colony formation and cell viability assays, respectively. The Fluorescence-activated cell sorting (FACS) data confirmed that OOE significantly induced cell cycle accumulation at the G2/M phase and apoptotic effects. Additionally, OOE inhibited the activated ERK (extracellular-signal-regulated kinase)/Src (Proto-oncogene tyrosine-protein kinase Src)/STAT3 (signal transducers and activators of transcription 3) pathways including nuclear translocation of STAT3. Furthermore, suppression of Ki67, PARP(Poly ADP-ribose polymerase), caspase-3, P27(Cyclin-dependent kinase inhibitor 1B), and c-Myc as well as the STAT3 target genes CDK(cyclin-dependent kinase)1, CDK2, Cyclin B1, VEGF-1(vascular endothelial growth factor-1), MMP-9(Matrix metallopeptidase 9), and Survivin by OOE was observed in BxPC3. We speculate that these molecular actions might support an anti-cancer effect of OOE. In this study, we demonstrated that OOE may be a promising anti-cancer material and may serve as a natural therapy and alternative remedy for pancreatic cancer treatment.

Objective. To determine the antiobesity effects of Panax ginseng in animals. Methods. We conducted a systematic search for all controlled trials (up to March 2017) that assessed the antiobesity effects of P. ginseng in animal obesity models in the PubMed, EMBASE, Cochrane library, Web of Science, and Scopus databases. The primary outcome was final body weight measured at the longest follow-up time after administration of the intervention. The secondary outcome was the lipid profile. We assessed methodological quality using the SYRCLE risk of bias tool, and RevMan 5.3 was used to perform a meta-analysis. Finally, a subgroup analysis of parameters including intervention duration, animal models, and type of ginseng was performed. Result. We identified 16 studies that met the inclusion criteria. Data from the meta-analysis indicated that the intervention group had a significantly lower body weight than the control group (SMD: −1.50, 95% CI: −1.90 to −1.11, χ2: 78.14, P<0.0001, I2 = 58%). Final body weight was lower in an animal obesity model induced by high-fat diet than in genetic models. Also the intervention group had a significantly higher serum HDL level and lower serum LDL, TG, and TC level than the control group. Conclusion. Our meta-analysis indicated that oral administration of P. ginseng significantly inhibits weight gain and improves serum lipid profiles in animal obesity models. However, causes of obesity and type of ginseng may affect treatment effects.

Facilitation of the wound healing process is important because a prolonged wound site increases pain and the risk of infection. In oriental medicine, an extract of Morus alba root (MA) has usually been prescribed as traditional treatment for accelerating wound healing, and it has been proven to be safe for centuries. To study the molecular mechanism of MA-mediated skin wound healing, we performed a primary cell culture and a skin explant culture and observed significant difference between the groups with and without MA extract. In the cellular system, a real-time cell analysis and real-time quantitative PCR were performed. It was found that MA extract enhanced proliferation in a dose-dependent manner on Kera-308 cell line, and up-regulated keratin expression including wound-induced Krt6a. In skin explant culture, the mRNA level derived from cell outgrowth displayed a tendency toward more up-regulated mRNA associated keratin filaments and toward a more up-regulated mRNA level of C-X-C motif chemokine 12 (CXCL12) and a chemokine receptor 4 (CXCR4) axis signaling pathway downstream. In this process, we concluded that MA extract had a scientific possibility of wound repair by increasing intracellular and extracellular supports and by inducing a CXCL12/CXCR4 signaling pathway. Copyright © 2015 John Wiley & Sons, Ltd.

Cinobufagin (CBG) is a cardiotoxic bufanolide steroid secreted by the skin and parotid venom glands of the Asiatic toad Bufo bufo gargarizans (called Chan-Su). Although CBG is known to exhibit anti-cancer activities, very little is known about its potential mechanism(s) of action. In this study, we investigated whether CBG mediates its effect through the modulation of the mitogen-activated protein kinases (MAPKs) signaling pathway in human multiple myeloma (MM) U266 cells. We found that CBG caused the significant activation of ERK, JNK and p38 MAPK in U266 cells. CBG showed much higher cytotoxicity against U266 cells as compared to peripheral blood mononuclear cells (PBMC). Induction of CBG increased reactive oxygen species (ROS) generation from mitochondria, which is associated with the induction of apoptosis as characterized by increased sub-G1 DNA contents of cell cycle, positive Annexin V binding, activation of caspase-3 and cleavage of PARP. Inhibition of ROS generation by N-acetyl-l-cysteine (NAC) significantly prevented CBG-induced ERK, JNK and p38 MAPK activation and apoptosis. CBG also down-regulated the expression of various downstream gene products that mediate cell proliferation, survival, angiogenesis and metastasis. Interestingly, ERK, JNK and p38MAPK pharmacological inhibitors blocked CBG-induced MAPKs activation and ERK inhibitor (PD98059) also prevented the CBG-induced caspase-3 activation and PARP cleavage in U266 cells. Taken together, these findings suggest that CBG can act as a potent anticancer agent against MM and possibly exerts its effects through the ROS-mediated activation of ERK, JNK and p38 MAPK leading to the activation of caspase-3 in U266 cells.

The hepatoprotective effects of fermented black rice bran extracts (FF1 and FF2: black rice bran fermented by Lentinus edodes derived from mycelium supplemented with soybean or Hovenia dulcis) and their associated mechanisms were evaluated. In an in vitro experiment, FFs caused significant amelioration of the metabolic function of rat hepatocytes treated with NH4Cl. In addition, administration of FFs to rats with chronic liver injury induced by 12-week continual alcohol consumption resulted in significant restoration of body weight shrinkage, notable attenuation of excessive aspartate aminotransferase, alkaline phosphatase and endotoxin in serum, malondialdehyde in liver and the lactulose/mannitol ratio in urine. Furthermore, FF1 or FF2 also caused significant downregulation of gene expression of several critical inflammatory mediators (interleukin-6, tumor necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase). Histopathological findings also indicated that FFs reduced inflammation, necrosis and fatty infiltration in liver tissue. Taken together, FFs exert hepatoprotective effects through anti-inflammatory and anti-lipid peroxidative properties and regulation of intestinal permeability. Practical Applications In this study, mycelia fermentation was utilized as a feasible strategy for enhancing the hepatotherapeutic effect of black rice and herbs. The findings demonstrated that Hovenia dulcis exerts a synergistic protective effect on an alcoholic liver disease animal model and could provide a new effective potential approach to alleviate alcoholic liver diseases.

The protective and therapeutic mechanism of bee venom acupuncture (BVA) in neurodegenerative disorders is not clear. We investigated whether treatment with BVA (0.25 and 0.8 mg/kg) at the Zusanli (ST36) acupoints, located lateral from the anterior border of the tibia, has a beneficial effect in a myelin basic protein (MBP)(68-82)-induced acute experimental autoimmune encephalomyelitis (EAE) rat model. Pretreatment (every 3 days from 1 h before immunization) with BVA was more effective than posttreatment (daily after immunization) with BVA with respect to clinical signs (neurological impairment and loss of body weight) of acute EAE rats. Treatment with BVA at the ST36 acupoint in normal rats did not induce the clinical signs. Pretreatment with BVA suppressed demyelination, glial activation, expression of cytokines [interferon (IFN)-γ, IL-17, IL-17A, tumor necrosis factor-alpha (TNF-α), and IL-1β], chemokines [RANTES, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein (MIP)-1α], and inducible nitric oxide synthase (iNOS), and activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB (p65 and phospho-IκBα) signaling pathways in the spinal cord of acute EAE rats. Pretreatment with BVA decreased the number of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells, but increased the number of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of acute EAE rats. Treatment with BVA at six placebo acupoints (SP9, GB39, and four non-acupoints) did not have a positive effect in acute EAE rats. Interestingly, onset and posttreatment with BVA at the ST36 acupoint markedly attenuated neurological impairment in myelin oligodendrocyte glycoprotein (MOG)(35-55)-induced chronic EAE mice compared to treatment with BVA at six placebo acupoints. Our findings strongly suggest that treatment with BVA with ST36 acupoint could delay or attenuate the development and progression of EAE by upregulating regulatory T cells and suppressing T-helper (Th) 17 and Th1 responses. These results warrant further investigation of BVA as a treatment for autoimmune disorders of the central nervous system.

Several studies have demonstrated that deregulated activation of signal transducer and activator of transcription 3 (STAT3) has been associated with survival, proliferation, chemoresistance and angiogenesis of tumour cells. Thus, inhibition of STAT3 expression could be a potent therapeutic approach for cancer treatment. Using several leukaemia cell lines, the effect of the hydrolysed-catalpol (H-catalpol) and hydrolysed-aucubin (H-aucubin) products on the STAT3 signalling pathway, inhibition of BCR-ABL activation, cellular proliferation and potentiation of imatinib mesylate-induced apoptosis was investigated. We found that iridoid glycosides (catalpol and aucubin) did not exert any cytotoxicity in the tumour cells, whereas both H-catalpol and H-aucubin exhibited significant cytotoxic effects on K562 human myeloid leukaemia cells. Indeed, H-catalpol and H-aucubin down-regulated BCR-ABL phosphorylation and inhibited constitutive STAT3 activation through abrogating upstream JAK2 and c-Src and constitutive STAT5 activation leading to apoptosis through caspase-3 activation. Hydrolysed-catalpol enhanced the apoptosis induced by imatinib mesylate and this correlated with down-regulation of gene products that mediate cell proliferation (cyclin D1), and cell survival (Bcl-2, Bcl-xL and survivin); all known to be regulated by the STAT3. Overall, our results provide novel insight into the role of hydrolysed iridoids in potentially treating leukaemia through the modulation of STAT3 signalling pathway.

As a treatment for allergic asthma, inhaled treatments such as bronchodilators that contain β2-agonists have an immediate effect, which attenuates airway obstructions and decreases airway hypersensitivity. However, bronchodilators only perform on a one off basis, but not consistently. Asthma is defined as a chronic inflammatory disease of the airways accompanying the overproduction of mucus, airway wall remodeling, bronchial hyperreactivity and airway obstruction. Liriope platyphylla radix extract (LPP), a traditional Korean medicine, has been thoroughly studied and found to be an effective anti-inflammatory medicine. Here, we demonstrate that an inhaled treatment of LPP can attenuate airway hyperresponsiveness (AHR) in an ovalbumin-induced asthmatic mouse model, compared to the saline-treated group (p < 0.01). Moreover, LPP decreases inflammatory cytokine levels, such as eotaxin (p < 0.05), IL-5 (p < 0.05), IL-13 (p < 0.001), RANTES (p < 0.01), and TNF-α (p < 0.05) in the bronchoalveolar lavage (BAL) fluid of asthmatic mice. A histopathological study was carried out to determine the effects of LPP inhalation on mice lung tissue. We performed UPLC/ESI-QTOF-MS, LC/MS, and GC/MS analyses to analyze the chemical constituents of LPP, finding that these are ophiopogonin D, spicatoside A, spicatoside B, benzyl alcohol, and 5-hydroxymethylfurfural. This study demonstrates the effect of an inhaled LPP treatment both on airway AHR and on the inflammatory response in an asthmatic mouse model. Hence, LPP holds significant promise as a nasal inhalant for the treatment of asthmatic airway disease.

Although anti-inflammatory activity of guava leaves (GLE) and fruits of Citrus hassaku Hort ex Tanaka (phalsak, PSE) has been demonstrated in cell culture system, the combination therapy of GLE and PSE with better anti-inflammatory activity and the exact mechanism remains unclear. In the present study, we set out to determine whether the anti-inflammatory effects of optimal mixture (OM) are mediated to suppress mitogen-activated protein kinases (MAPKs), nuclear factor-κB (NF-κB), and activated protein-1 (AP-1) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. We found that OM significantly suppressed LPS-stimulated NO production without a cytotoxic effect on RAW 264.7 cells. OM inhibited the expression of LPS-induced iNOS and COX-2 protein and their mRNA expression. Also, TNF-α, IL-6, and PGE2 secretion were decreased by OM in LPS-stimulated macrophages. As a result, OM inhibited pro-inflammatory markers such as TNF-α, IL-6, and PGE2, which is hypothesized as being due to the suppression of LPS-induced ERK, p38, and JNK signaling pathway, but not NF-κB and AP-1. Moreover, OM improved the survival rate during lethal endotoxemia by inhibiting the production of TNF-α and IL-6 in an animal model.

AIM : Although numerous animal studies suggest that probiotic therapy has beneficial effects in various liver diseases, the evidence for beneficial effects in human liver disease is controversial. This study was carried out to investigate the efficacy of probiotic therapy in alleviating small intestinal bacterial overgrowth (SIBO) and permeability in chronic liver disease. METHODS Fifty-three patients with chronic liver disease were randomized to either probiotic therapy or placebo. Six bacterial species were used: Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. After 4 weeks, changes in the composition of fecal bacteria, SIBO, intestinal permeability, and clinical symptoms were examined. RESULTS Three of the six probiotic species, B. lactis, L. rhamnosus, and L. acidophilus, increased in the feces of the probiotic therapy group (P

Kyungheechunggan-tang (KHCGT), a mixture of 9 herbal aqueous extracts, is known in traditional Korean hepatoprotective medicine. To investigate the anti-fibrotic effect of KHCGT and its herbal ingredients, hepatic stellate cells (HSC) were activated by transforming growth factor-β (TGF-β), and the mRNA and protein expression levels of collagen type-1 (collagen-1) and α-smooth muscle actin (α-SMA) were measured. KHCGT and its 7 herbal ingredient among 9 herbal ingredients had an anti-fibrotic effect on activated HSC. Among the herbal samples, Artemisia capillaris, Salvia miltiorrhiza, Curcuma wenyujin showed the highest down-regulatory effect on α-SMA and collagen-1 mRNA expression. The liver tissues of dimethylnitrosamine (DMN)-induced rats were isolated to investigate the anti-fibrotic effect of KHCGT. This study provides understandings the effect of KHCGT and its ingredient herbal medicines on the activated HSC, and suggests herbal ingredient that plays a major role in anti-fibrotic effect of the KHCGT.

Objective To determine the antiobesity effects of Panax ginseng in animals. Methods We conducted a systematic search for all controlled trials (up to March 2017) that assessed the antiobesity effects of P. ginseng in animal obesity models in the PubMed, EMBASE, Cochrane library, Web of Science, and Scopus databases. The primary outcome was final body weight measured at the longest follow-up time after administration of the intervention. The secondary outcome was the lipid profile. We assessed methodological quality using the SYRCLE risk of bias tool, and RevMan 5.3 was used to perform a meta-analysis. Finally, a subgroup analysis of parameters including intervention duration, animal models, and type of ginseng was performed. Result We identified 16 studies that met the inclusion criteria. Data from the meta-analysis indicated that the intervention group had a significantly lower body weight than the control group (SMD: −1.50, 95% CI: −1.90 to −1.11, χ2: 78.14, P < 0.0001, I2 = 58%). Final body weight was lower in an animal obesity model induced by high-fat diet than in genetic models. Also the intervention group had a significantly higher serum HDL level and lower serum LDL, TG, and TC level than the control group. Conclusion Our meta-analysis indicated that oral administration of P. ginseng significantly inhibits weight gain and improves serum lipid profiles in animal obesity models. However, causes of obesity and type of ginseng may affect treatment effects.

Persistent activation of signal transducers and activator of transcription 3 (STAT3) has been closely related to growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells, and thus its inhibition can be considered a potential therapeutic strategy. In this study, we investigated the role of bergamottin (BGM) obtained from grapefruit juice in abrogating the constitutive STAT3 activation in multiple myeloma (MM) cells. This suppression was mediated through the inhibition of phosphorylation of Janus-activated kinase (JAK) 1/2 and c-Src. Pervanadate reversed the BGM induced down-regulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase (PTP). Furthermore, BGM induced the expression of the tyrosine phosphatase SHP-1, and gene silencing of the SHP-1 by small interfering RNA abolished the ability of BGM to inhibit STAT3 activation, suggesting a critical role for SHP-1 in the action of BGM. BGM also downregulated the expression of STAT3-regulated gene products such as COX-2, VEGF, cyclin D1, survivin, IAP-1, Bcl-2, and Bcl-xl in MM cells. This correlated with induction of substantial apoptosis as indicated by an increase in the sub-G1 cell population and caspase-3 induced PARP cleavage. Also, this agent significantly potentiated the apoptotic effects of bortezomib and thalidomide in MM cells. Overall, these results suggest that BGM is a novel blocker of STAT3 activation pathway thus may have a potential in therapy of MM and other cancers.