Molecular Mechanism of Cinnamomum cassia against Gastric Damage and Identification of Active Compounds.

Cinnamomum cassia is a natural product found in plants that has been used as a folk remedy for inflammation. In this study, we investigated the mechanism underlying the anti-inflammatory and antioxidant properties of C. cassia extract (ECC) in lipopolysaccharide (LPS)-induced murine RAW 264.7 cells, in comparison with 4-hydroxycinnamaldehyde, a C. cassia extract component. ECC and 4-hydroxycinnamaldehyde inhibited the production of nitrite oxide in a dose-dependent manner and did not show any change in cellular toxicity when treated with the same dose as that used in the nitrite assay. Moreover, they attenuated ROS accumulation after lipopolysaccharide (LPS) stimulation. ECC and 4-hydroxycinnamaldehyde decreased the mRNA and protein expression levels of inflammatory mediators (iNOS and COX-2) and cytokines such as TNF and IL-6. We also found that ECC and 4-hydroxycinnamaldehyde mitigated the phosphorylation of ERK, JNK, and transcription factors, such as NF-κB and STAT3, suppressing NF-κB nuclear translocation in LPS-activated macrophages. In addition, administration of ECC in a Sprague Dawley rat model of acute gastric injury caused by indomethacin significantly increased the gastric mucus volume. Analysis of serum and tissue levels of inflammatory mediators revealed a significant decrease in serum PGE2 and myeloperoxidase levels and a reduction in gastric iNOS, COX-2, and p65 protein levels. Collectively, these results suggest that ECC has antioxidant and anti-inflammatory effects and is a potential candidate for curing gastritis.

Protective Effect of Osmundacetone against Neurological Cell Death Caused by Oxidative Glutamate Toxicity.

Oxidative stress is one of the main causes of brain cell death in neurological disorders. The use of natural antioxidants to maintain redox homeostasis contributes to alleviating neurodegeneration. Glutamate is an excitatory neurotransmitter that plays a critical role in many brain functions. However, excessive glutamate release induces excitotoxicity and oxidative stress, leading to programmed cell death. Our study aimed to evaluate the effect of osmundacetone (OAC), isolated from Elsholtzia ciliata (Thunb.) Hylander, against glutamate-induced oxidative toxicity in HT22 hippocampal cells. The effect of OAC treatment on excess reactive oxygen species (ROS), intracellular calcium levels, chromatin condensation, apoptosis, and the expression level of oxidative stress-related proteins was evaluated. OAC showed a neuroprotective effect against glutamate toxicity at a concentration of 2 µM. By diminishing the accumulation of ROS, as well as stimulating the expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), OAC triggered the self-defense mechanism in neuronal cells. The anti-apoptotic effect of OAC was demonstrated through its inhibition of chromatin condensation, calcium accumulation, and reduction of apoptotic cells. OAC significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinases. Thus, OAC could be a potential agent for supportive treatment of neurodegenerative diseases.

Patterns of Integrative Korean Medicine Practice for Anxiety Disorders: A Survey among Korean Medicine Doctors (KMDs) in Korea.

Anxiety disorder is known as the most common disease among psychiatric disorders. However, many studies have not been conducted in the Korean medicine area. This study explores the current state of anxiety disorder treatments of Korean medicine through a survey research. The survey for Korean medicine doctors (KMDs) on Korean medicine (KM) diagnosis and treatments for anxiety disorder was conducted online from December 21, 2016, to December 29, 2016. The results were divided into two groups, KMDs and Korean medicine neuropsychiatric specialists (KMNPS), and comparatively analyzed. Self-evaluation and counseling were the most common in both diagnostic methods and evaluation of treatment effects, and KMNPS tended to make extensive use of objective indicators. There was no difference in the rate of psychiatric medication use among the patients between KMD and KMNPS. The main reason for patients wanting KM treatment was the tapering cessation of psychiatric medications. The most common treatments were acupuncture, herbal medicine, and moxibustion, in addition to dry cupping in KMD and psychotherapy in KMNPS. The most important factor for treatment was herbal medicine treatment, followed by rapport formation in KMD and patient's temperament in KMNPS. Opinions on various items were presented as treatment barriers, and KMNPS tended to think more importantly about the patient's family problems. For the items to be additionally trained in the future, KMD chose the diagnostic tools and KMNPS chose psychotherapies. This study is the first study to analyze the clinical patterns for anxiety disorder in KMDs. KMD and KMNPS showed similar patterns in the perception, diagnosis, and treatment of anxiety disorders, but KMNPS tended to use objective indicators and psychotherapy more actively. Further clinical studies for the development of clinical guidelines should be additionally required.

Evaluation of Anti-Colitis Effect of KM1608 and Biodistribution of Dehydrocostus Lactone in Mice Using Bioimaging Analysis.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder modulated by numerous factors. Recent failures of drugs targeting single factors suggest that multitargeting drugs could be useful for the treatment of IBD. Natural medicines may be an alternative option for the treatment of IBD, owing to the complex nature of the disease. However, most natural medicines have poor in vitro and in vivo translational potential because of inadequate pharmacokinetic study. KM1608, a mixture of the medicinal plants Aucklandia lappa, Terminalia chebula, and Zingiber officinale, was examined for its anti-colitis effects and biodistribution using bioimaging. Dehydrocostus lactone, as a marker compound, was analyzed to assess the biodistribution of KM1608. KM1608 significantly attenuated the disease activity of dextran sodium sulfate-induced colitis in mice and suppressed inflammatory mediators such as myeloperoxidase, proinflammatory cytokines (TNF-α and IL-6), and the Th2-type cytokine IL-4 in the colon. Optical fluorescence imaging revealed that KM1608 was distributed in the intestinal area as a target organ. Collectively, our findings suggest that KM1608 is a potential therapeutic formulation for IBD.

Identification and Isolation of Active Compounds from Astragalus membranaceus that Improve Insulin Secretion by Regulating Pancreatic ß-Cell Metabolism.

In type 2 diabetes (T2D), insufficient secretion of insulin from the pancreatic ß-cells contributes to high blood glucose levels, associated with metabolic dysregulation. Interest in natural products to complement or replace existing antidiabetic medications has increased. In this study, we examined the effect of Astragalus membranaceus extract (ASME) and its compounds 1-9 on glucose-stimulated insulin secretion (GSIS) from pancreatic ß-cells. ASME and compounds 1-9 isolated from A. membranaceus stimulated insulin secretion in INS-1 cells without inducing cytotoxicity. A further experiment showed that compounds 2, 3, and 5 enhanced the phosphorylation of total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, and activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), which are associated with ß-cell function and insulin secretion. The data suggest that two isoflavonoids (2 and 3) and a nucleoside (compound 5), isolated from the roots of A. membranaceus, have the potential to improve insulin secretion in ß-cells, representing the first step towards the development of potent antidiabetic drugs.

Protocol for a systematic review and meta-analysis of the efficacy of acupuncture and electroacupuncture against chemotherapy-induced peripheral neuropathy.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 30% to 40% of patients who receive chemotherapy; however, standardized treatment for CIPN has not yet been developed. Acupuncture is widely used to treat CIPN in Korea, but its efficacy has not been investigated. The purpose of this study is to review the current literature on the efficacy of acupuncture and electroacupuncture (EA) in treating CIPN. MATERIALS AND METHODS: We will perform a literature review using the relevant databases, including MEDLINE, Embase, the Allied and Complementary Medicine Databases (AMED), and China National Knowledge Infrastructure (CNKI), as well as Korean databases, including the National Digital Science Library (NDSL), Oriental Medicine Advanced Searching Integrated System (OASIS), DBpia, and Korean studies Information Service System (KISS). Randomized controlled trials describing treatment of CIPN symptoms with acupuncture or EA will be included. The primary outcomes will be scores on a visual analog scale and a numeric rating scale for neuropathic pain. We will also assess the risk of bias by evaluating the available studies using the tools of the Cochrane Collaboration and carry out a meta-analysis. ETHICS AND DISSEMINATION: Ethical approvals and patient consent are not necessary because the meta-analysis will be based on published research. We will submit our meta-analysis to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42018111509.

Effectiveness of collaborative treatment using Korean and Western medicine for mild cognitive impairment or dementia: A protocol for a prospective observational exploratory study.

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).

In Vitro Estrogenic and Breast Cancer Inhibitory Activities of Chemical Constituents Isolated from Rheum undulatum L.

We investigated the estrogenic and breast cancer inhibitory activities of chemical constituents isolated from Rhei undulati Rhizoma (roots of Rheum undulatum L.), which is used as a laxative, an anti-inflammatory, and an anti-blood stagnation agent. Estrogen-like activity was studied using the well characterized E-screen assay in estrogen receptor (ER)-positive MCF-7 cells. The mechanism underlying the breast cancer inhibitory activity of the compounds was studied using human ER-negative MDA-MB-231 and ER-positive MCF-7 cells. The activation of apoptosis pathway-related proteins was investigated by western blotting, using extracts of R. undulatum prepared in three solvent conditions (EX1, EX2, and EX3). The R. undulatum chemical constituents (compounds 1⁻3) showed estrogen-like activity in the concentration range of 10 to 50 µM, by increasing the proliferation of human ER-positive MCF-7 cells. These effects were attenuated by co-treatment with 100 nM fulvestrant, an ER antagonist. Compounds 1⁻3 decreased the viability of MCF-7 cells in a concentration-dependent manner. Compounds 1 (aloe emodin) and 2 (rhapontigenin) induced mitochondria-independent apoptosis by activating the caspase-8 pathway, whereas the cytotoxic effect of compound 3 (chrysophanol 1-O-ß-d-glucopyranoside) was mediated through the mitochondria-dependent apoptotic pathway.

Acupuncture for anxiety: A protocol for a systematic review of controlled trials.

BACKGROUND: Acupuncture has been widely, used in Asian countries since the Yuan Dynasty in China. Moreover, acupuncture has been reported to exhibit anti-allergy effects in many clinical trials. This systematic review will assess the effectiveness, and safety of acupuncture for anxiety treatment. METHODS: Eleven databases, including Asian databases, will be searched for studies conducted through December in the year 2017. We will include randomized controlled trials (RCTs) assessing acupuncture for anxiety. The risk of bias will be evaluated using the Cochrane risk of bias assessment tool, and confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. It will also be disseminated electronically, and in print. The review will be updated to inform, and guide healthcare practices. REGISTRATION NUMBER: PROSPERO 2018 under number CRD42018080034.

Curcuzedoalide contributes to the cytotoxicity of Curcuma zedoaria rhizomes against human gastric cancer AGS cells through induction of apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma zedoaria Roscoe (Zingiberaceae), also known as white turmeric or zedoaria, has been used in Ayurveda and traditional Chinese medicine to treat various cancers, and it possesses several sesquiterpenoid compounds. OBJECTIVE: This study aimed to evaluate the therapeutic effects of a methanolic (MeOH) extract of C. zedoaria rhizomes, as well as its active constituents, against gastric cancer, which is a frequently diagnosed cancer in South Korea. MATERIALS AND METHODS: Repeated column chromatography, together with semi-preparative HPLC purification, was used to separate the bioactive constituents from the C. zedoaria MeOH extract. The cytotoxic effects of the C. zedoaria MeOH extract and its active compounds were measured in human gastric cancer AGS cells. Expression of proteins related to apoptosis was evaluated using Western blotting analysis. RESULTS: The MeOH extract of C. zedoaria rhizomes exerted a cytotoxic effect on AGS cells (IC50: 96.60 ± 4.87µg/mL). Based on the bioactivity-guided fractionation for antiproliferative activity, a chemical investigation of the MeOH extract led to the isolation of five sesquiterpenes including isoprocurcumenol (1), germacrone (2), curzerenone (3), curcumenol (4), and curcuzedoalide (5). Among these, curcuzedoalide demonstrated the strongest effect in suppressing gastric cancer cell proliferation in a dose-dependent manner with an IC50 value of 125.11±2.77µM. Western blotting analysis showed that curcuzedoalide inhibited AGS human gastric cancer cell viability by activating caspase-8, caspase-9, caspase-3, and PARP, which contributed to apoptotic cell death in AGS human gastric cancer cells. CONCLUSION: These data indicate that curcuzedoalide contributed to the cytotoxicity of C. zedoaria by activating the cleavage of caspases and PARP, which are representative markers for apoptosis. Therefore, curcuzedoalide is a positive candidate for the development of novel chemotherapeutics.

Toxicity of Eun-bi San Pharmacopuncture Injection in the Muscle of Rats.

OBJECTIVES: This study was carried out to analyze the single-dose toxicity of Eun-Bi San pharmacopuncture injected into the muscle of Sprague-Dawley (SD) rats. METHODS: All experiments were performed at Biotoxtech, an institution certified to conduct non-clinical studies under the Good Laboratory Practice (GLP) regulations. Six week old SD rats reared by ORIENTBIO were chosen for this pilot study. The reason SD rats were chosen is that they have been widely used in safety tests in the field of medicine, so the results can be easily compared with many other databases. The Eun-Bi San pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, K-GMP). The constituents of the Eun-Bi San pharmacopuncture are Angelicae gigantis radix, Strychni semen and Glycyrrhizae radix. These were extracted at low temperature and low pressure in an aseptic room at the KPI. Doses of Eun- Bi San pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech Co., Ltd. RESULTS: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To determine if abnormalities existed in any organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. CONCLUSION: The results of this study suggest that treatment with Eun-Bi San pharmacopuncture is relatively safe and that its clinical use may be beneficial. Further evaluations and studies on this subject will be needed to provide more concrete evidence in support of these conclusions.