Young-Dal Kwon

Coptidis rhizoma extract protects against cytokine-induced death of pancreatic β-cells through suppression of NF-κB 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 β-cell death was assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of β-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with IL-1β and IFN-γ resulted in a reduction of cell viability. CRE completely protected IL-1β and IFN-γ-mediated cell death in a concentration-dependent manner. Incubation with CRE induced a significant suppression of IL-1β and IFN-γ-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-κ B activation. The IL-1β and IFN-γ-stimulated RIN cells showed increases in NF-κ B binding activity and p65 subunit levels in nucleus, and IκBα 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-1β and IFN-γ-treated islets.

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-1β) and IL-6. In particular, IL-1β expression is under strong genetic control. We examined the relationship among obesity, polymorphism of the IL-1β 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-1β by polymerase chain reaction-restriction fragment length polymorphism assays. A significant decrease was found for the IL-1β T allele in the overweight group (BMI 25 ∼ 29 kg/m2) compared with the lean group with a BMI < 25 kg/m2 (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-1β T allele was apparently decreased in the overweight group (BMI 25 ∼ 29 kg/m2) compared with the lean group with a BMI < 25 kg/m2 (P = .007, OR = 0.152). In overweight women, we found an association between the +3953 C/T polymorphism in the IL-1β gene and BMI. In addition, we found an association among IL-1β polymorphism, obesity, and Sasang constitution.

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.