• Korean Journal of Pharmacognosy
• /
• v.36 no.3 s.142
• /
• pp.186-190
• /
• 2005

Searching for inhibitors of lipopolysaccharide (LPS)-induced IL-6 (Interleukin-6) production from medicinal herbs, we isolated two active compounds though bioactivity-guided fractionation from the methanol extract of Chrysanthemum indicum L.. They were determined as kikkanol F monoacetate (1) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (2) by means of spectroscopy techniques such as NMR and MS. The compound 1 and 2 inhibited LPS-induced IL-6 production in the PAW264.7 cells with $IC_{50}$ value of $47\;{\mu}g/ml$ and $27\;{\mu}g/ml$, respectively.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.3
• /
• pp.495-505
• /
• 2024

Gromwell (Lithospermum erythrorhizon, LE) can mitigate obesity-induced skeletal muscle atrophy in C2C12 myotubes and high-fat diet (HFD)-induced obese mice. The purpose of this study was to investigate the anti-skeletal muscle atrophy effects of LE and the underlying molecular mechanism. C2C12 myotubes were pretreated with LE or shikonin, and active component of LE, for 24 h and then treated with 500 μM palmitic acid (PA) for an additional 24 h. Additionally, mice were fed a HFD for 8 weeks to induced obesity, and then fed either the same diet or a version containing 0.25% LE for 10 weeks. LE attenuated PA-induced myotubes atrophy in differentiated C2C12 myotubes. The supplementation of LE to obese mice significantly increased skeletal muscle weight, lean body mass, muscle strength, and exercise performance compared with those in the HFD group. LE supplementation not only suppressed obesity-induced skeletal muscle lipid accumulation, but also downregulated TNF-α and atrophic genes. LE increased protein synthesis in the skeletal muscle via the mTOR pathway. We observed LE induced increase of mitochondrial biogenesis and upregulation of oxidative phosphorylation related genes in the skeletal muscles. Furthermore, LE increased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and the phosphorylation of adenosine monophosphate-activated protein kinase. Collectively, LE may be useful in ameliorating the detrimental effects of obesity-induced skeletal muscle atrophy through the increase of protein synthesis and mitochondrial biogenesis of skeletal muscle.

• Clinical Endoscopy
• /
• v.55 no.1
• /
• pp.150-155
• /
• 2022

We reviewed 7 patients with unsuccessful endoscopic hemostasis using covered self-expandable metal stent (CSEMS) placement for post-endoscopic sphincterotomy (ES) bleeding. ES with a medium incision was performed in 6 and with a large incision in 1 patient. All but 1 of them (86%) showed delayed bleeding, warranting second endoscopic therapies followed by CSEMS placement 1-5 days after the initial ES. Subsequent CSEMS placement did not achieve complete hemostasis in any of the patients. Lateral-side incision lines (3 or 9 o'clock) had more frequent bleeding points (71%) than oral-side incision lines (11-12 o'clock; 29%). Additional endoscopic hemostatic procedures with hemostatic forceps, hypertonic saline epinephrine, or hemoclip achieved excellent hemostasis, resulting in complete hemostasis in all patients. These experiences provide an alert: CSEMS placement is not an ultimate treatment for post-ES bleeding, despite its effectiveness. The lateral-side of the incision line, as well as the oral-most side, should be carefully examined for bleeding points, even after the CSEMS placement.

• Asian-Australasian Journal of Animal Sciences
• /
• v.2 no.3
• /
• pp.226-227
• /
• 1989

• Diabetes and Metabolism Journal
• /
• v.42 no.6
• /
• pp.472-474
• /
• 2018

• Asian-Australasian Journal of Animal Sciences
• /
• v.33 no.11
• /
• pp.1824-1836
• /
• 2020

Objective: On the hypothesis that grazing of cattle prompts organs to secrete or internalize circulating microRNAs (c-miRNAs) in parallel with changes in energy metabolism, we aimed to clarify biological events in adipose, skeletal muscle, and liver tissues in grazing Japanese Shorthorn (JSH) steers by a transcriptomic approach. Methods: The subcutaneous fat (SCF), biceps femoris muscle (BFM), and liver in JSH steers after three months of grazing or housing were analyzed using microarray and quantitative polymerase chain reaction (qPCR), followed by gene ontology (GO) and functional annotation analyses. Results: The results of transcriptomics indicated that SCF was highly responsive to grazing compared to BFM and liver tissues. The 'Exosome', 'Carbohydrate metabolism' and 'Lipid metabolism' were extracted as the relevant GO terms in SCF and BFM, and/or liver from the >1.5-fold-altered mRNAs in grazing steers. The qPCR analyses showed a trend of upregulated gene expression related to exosome secretion and internalization (charged multivesicular body protein 4A, vacuolar protein sorting-associated protein 4B, vesicle associated membrane protein 7, caveolin 1) in the BFM and SCF, as well as upregulation of lipolysis-associated mRNAs (carnitine palmitoyltransferase 1A, hormone-sensitive lipase, perilipin 1, adipose triglyceride lipase, fatty acid binding protein 4) and most of the microRNAs (miRNAs) in SCF. Moreover, gene expression related to fatty acid uptake and inter-organ signaling (solute carrier family 27 member 4 and angiopoietin-like 4) was upregulated in BFM, suggesting activation of SCF-BFM organ crosstalk for energy metabolism. Meanwhile, expression of plasma exosomal miR-16a, miR-19b, miR-21-5p, and miR-142-5p was reduced. According to bioinformatic analyses, the c-miRNA target genes are associated with the terms 'Endosome', 'Caveola', 'Endocytosis', 'Carbohydrate metabolism', and with pathways related to environmental information processing and the endocrine system. Conclusion: Exosome and fatty acid metabolism-related gene expression was altered in SCF of grazing cattle, which could be regulated by miRNA such as miR-142-5p. These changes occurred coordinately in both the SCF and BFM, suggesting involvement of exosome in the SCF-BFM organ crosstalk to modulate energy metabolism.

• Journal of Ginseng Research
• /
• v.44 no.4
• /
• pp.664-671
• /
• 2020

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H₂O₂) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H₂O₂-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H₂O₂-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

• Molecules and Cells
• /
• v.40 no.2
• /
• pp.123-132
• /
• 2017

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

• Diabetes and Metabolism Journal
• /
• v.42 no.6
• /
• pp.496-512
• /
• 2018

Background: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. Methods: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ${\geq}6$ measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. Results: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%). Conclusion: CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

• Diabetes and Metabolism Journal
• /
• v.42 no.6
• /
• pp.529-537
• /
• 2018

Background: Serum albumin and uric acid have been positively linked to metabolic syndrome (MetS). However, the association of MetS incidence with the combination of uric acid and albumin levels has not been investigated. We explored the association of albumin and uric acid with the risk of incident MetS in populations divided according to the levels of these two parameters. Methods: In this retrospective longitudinal study, 11,613 non-MetS participants were enrolled among 24,185 individuals who had undergone at least four annual check-ups between 2006 and 2012. The risk of incident MetS was analyzed according to four groups categorized by the sex-specific medians of serum albumin and uric acid. Results: During 55,407 person-years of follow-up, 2,439 cases of MetS developed. The risk of incident MetS increased as the uric acid category advanced in individuals with lower or higher serum albumin categories with hazard ratios (HRs) of 1.386 (95% confidence interval [CI], 1.236 to 1.554) or 1.314 (95% CI, 1.167 to 1.480). However, the incidence of MetS increased with higher albumin levels only in participants in the lower uric acid category with a HR of 1.143 (95% CI, 1.010 to 1.294). Conclusion: Higher levels of albumin were associated with an increased risk of incident MetS only in individuals with lower uric acid whereas higher levels of uric acid were positively linked to risk of incident MetS regardless of albumin level.