Exploring the efficacy and safety of herbal medicine on Korean obese women with or without metabolic syndrome risk factors: A study protocol for a double-blind, randomized, multi-center, placebo-controlled clinical trial.

BACKGROUND: The prevalence of obesity among women is increasing. Obesity is associated with various metabolic syndromes; conventional treatments are limited and may induce serious adverse events due to polytherapy regimens. Currently, demands for complementary and alternative medicine that has a proven safety profile for the treatment of obesity with or without metabolic risk factors are increasing.Our team of preclinical experts reported a significant anti-obesity effect of the Korean herbal medicine, Galgeun-tang (GGT). Thus, we designed this trial to explore the effects of GGT among obese women to accumulate optimal clinical evidence.Obesity is not only a component of metabolic syndrome and a factor associated with an increased risk of cardiovascular disease but is also related to insulin resistance. Previous research has confirmed that an increasing body mass index is highly related with increased risk of metabolic syndrome among overweight and obese individuals. The effectiveness of the Korean medicine herbal formula, GGT on obesity has been previously reported. The objective of this study is to assess the efficacy and safety of GGT for weight loss among obese Korean women with or without high risk for metabolic syndrome. METHODS/DESIGN: This study is a randomized, double-blinded, placebo-controlled, multi-center clinical trial. A total of 160 participants will be randomly distributed in 2 groups, the GGT group or the placebo group in a 1:1 ratio using a web-based randomization system. Each group will be administered GGT or placebo 3 times a day for 12 weeks. The primary endpoint is to assess the change in weight from baseline. The secondary endpoints are the following: the changes in body composition measurements, anthropomorphic measurements, obesity screening Laboratory tests, patient self-reported questionnaires, and economic evaluation outcomes. Adverse events will also be reported. DISCUSSION: The findings of this study will confirm methodologies regarding the efficacy and safety of GGT for weight loss among obese Korean women with or without metabolic risk factors.

Acupuncture for perioperative care of total hip arthroplasty: A systemic review of controlled trials and meta-analysis.

INTRODUCTION: This protocol is intended to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of acupuncture in perioperative care of total hip arthroplasty patients. METHODS AND ANALYSIS: The following databases will be searched from their inception to November 2018 without language restrictions: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, Oriental Medicine Advanced Searching Integrated System, Korean Traditional Knowledge Portal, KoreaMed, DBPIA, Research Information Service System, including the China National Knowledge Infrastructure. Any randomized controlled trials related to perioperative care of total hip arthroplasty will be included. The primary outcomes of this study are dosage of analgesics and pain intensity. For secondary outcomes, Harris hip score, incidence of postoperative cognitive dysfunction, mini-mental state exam score, incidence of deep vein thrombosis, D-dimer and fibrinogen level, adverse events will be assessed. Data analysis and synthesis will be carried out using RevMan version 5.3. The methodological quality will be assessed by the Cochrane Collaboration risk of bias tool. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018112123.

Simultaneous Determination of Decursin, Decursinol Angelate, Nodakenin, and Decursinol of Angelica gigas Nakai in Human Plasma by UHPLC-MS/MS: Application to Pharmacokinetic Study.

Coumarins in Cham-dang-gwi, the dried root of Angelica gigas Nakai (AGN), possess pharmacological effects on anemia, pain, infection, and articular rheumatism. The AGN root containes decursin (D), decursinol angelate (DA), nodakenin, and decursinol (DOH), a major metabolite of D and DA. The aim of this study was to develop a simultaneous determination method for these four coumarins in human plasma using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Chromatographic separation was performed on dual columns (Kinetex® C18 column and Capcell core C18 column) with mobile phase consisting of water and acetonitrile at a flow rate of 0.3 mL/min using gradient elution. Multiple reaction monitoring was operated in positive ion mode with precursors to product ion transition values of m/z 328.9→228.8, 328.9→228.9, 409.4→248.8, and 246.8→212.9 to measure D, DA, nodakenin, and DOH, respectively. Linear calibration curves were fitted over concentration range of 0.05⁻50 ng/mL for these four components, with correlation coefficient greater than 0.995. Inter- and intra-day accuracies were between 90.60% and 108.24%. These precisions were within 11.19% for all components. The established method was then applied to a pharmacokinetic study for the four coumarins after usual dosing in Korean subjects.

A sensitive UHPLC-MS/MS method for the simultaneous quantification of three lignans in human plasma and its application to a pharmacokinetic study.

The aim of this study was to develop an analytical method to simultaneously analyze schizandrin, schizandrol B, and gomisin N lignans in human plasma using ultra high performance liquid chromatography with tandem mass spectrometry. The three lignans were separated using a mobile phase of water and acetonitrile containing 0.02% acetic acid equipped with a Kinetex C18 column (2.1 mm × 50 mm, 1.7 µm). This analysis was achieved by multiple reaction monitoring mode in an electrospray interface. The mass transitions were m/z 433.1→384.0 for schizandrin, 398.8→367.8 for schizandrol B, and 400.6→299.8 for gomisin N. Liquid-liquid extraction with methyl tert-butyl ether was used to obtain the three lignans. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. The calibration curves for the three lignans in human plasma were 0.05-50 ng/mL and displayed excellent linearity with correlation coefficients greater than 0.99. Precision for all three lignans was within 11.23%. The accuracy was 88.3-99.0% for schizandrin, 90.6-103.4% for schizandrol B, and 90.2-103.5% for gomisin N. The developed simultaneous analytical method satisfied the criteria of international guidance and could be successfully applied to the pharmacokinetic study of three lignans after oral administration of Schisandrae Fructus extract powder to humans.

Interleukin-1 beta gene polymorphism and traditional constitution in obese women.

In adipose tissue metabolism, cytokines were major regulators. mRNA expression studies show that adipocytes can synthesize both tumor necrosis factor-alpha and several interleukins (ILs), notably IL-1 beta (IL-1beta) and IL-6. In particular, IL-1beta expression is under strong genetic control. We examined the relationship among obesity, polymorphism of the IL-1beta at position +3953 in exon 5, and Sasang constitution. In a group of 181 healthy females with a marked variation in body mass index (BMI), we determined the genotype of IL-1beta by polymerase chain reaction-restriction fragment length polymorphism assays. A significant decrease was found for the IL-1beta T allele in the overweight group (BMI 25 approximately 29 kg/m(2)) compared with the lean group with a BMI < 25 kg/m(2) (P = .049, odds ratio [OR] = 0.296). Carriers of T allele in the heterozygous or homozygous form did not show a significant difference in physical and clinical characteristics. In addition, in Taeumin female subjects, the frequency of IL-1beta T allele was apparently decreased in the overweight group (BMI 25 approximately 29 kg/m(2)) compared with the lean group with a BMI < 25 kg/m(2) (P = .007, OR = 0.152). In overweight women, we found an association between the +3953 C/T polymorphism in the IL-1beta gene and BMI. In addition, we found an association among IL-1beta polymorphism, obesity, and Sasang constitution.

Coptidis rhizoma extract protects against cytokine-induced death of pancreatic beta-cells through suppression of NF-kappaB activation.

We demonstrated previously that Coptidis rhizoma extract (CRE) prevented S-nitroso-N-acetylpenicillamine-induced apoptotic cell death via the inhibition of mitochondrial membrane potential disruption and cytochrome c release in RINm5F (RIN) rat insulinoma cells. In this study, the preventive effects of CRE against cytokine-induced beta-cell death was assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of beta-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with IL-1beta and IFN-gamma resulted in a reduction of cell viability. CRE completely protected IL-1beta and IFN-gamma-mediated cell death in a concentration-dependent manner. Incubation with CRE induced a significant suppression of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, a finding which correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which CRE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation. The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity and p65 subunit levels in nucleus, and IkappaB alpha degradation in cytosol compared to unstimulated cells. Furthermore, the protective effects of CRE were verified via the observation of reduced NO generation and iNOS expression, and normal insulin-secretion responses to glucose in IL-1beta and IFN-gamma-treated islets.

Increased temperature at acupuncture points induced by weight reduction in obese patients: a preliminary study.

This study investigated the temperature changes at acupuncture points resulting from a weight reduction program. A standard method using a digital infrared thermographic imaging device was employed to monitor the temperature at 20 acupuncture points in 32 participants treated for obesity at an Oriental obesity clinic. There were significant temperature increases at all of the acupuncture points except for LI4 (Hegu) and TE5 (Waiguan). The mean total temperature change at the acupuncture points was significantly correlated with the BMI change (r = .588, p < .001). The weight-reduction-induced increase in temperature at acupuncture points may reflect improvements in the circulation of energy flows. However, further study is necessary to understand fully the relationship between the temperature at acupuncture points and weight reduction, including the use of appropriate controls.