• Nutrition Research and Practice
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• v.18 no.5
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• pp.602-616
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• 2024

BACKGROUND/OBJECTIVES: Inflammation and ferroptosis are implicated in various diseases and lipopolysaccharides (LPS) have been linked with these disorders. Recently, many edible insects, such as Gryllus bimaculatus, Protaetia brevitarsis larvae (PB) and Tenebrio molitor larvae, have been recommended as alternative foods because they contain lots of nutritional sources. In this study, we explored the potential of PB extract in preventing LPS-induced inflammation and ferroptosis in Hep3B cells. MATERIALS/METHODS: PB powder was extracted using 70% ethanol and applied to Hep3B cells. Co-treatment with LPS was conducted to induce ferroptosis and inflammation. The anti-inflammatory and anti-ferroptosis mechanisms of the PB extract were confirmed using Western blot, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction analysis. RESULTS: PB extract effectively prevented LPS-induced cell death and restored LPS-induced inflammatory cytokine production, NF-κB signaling, endoplasmic reticulum (ER) stress and ferroptosis. Interestingly, PB extract reduced LPS-induced ceramide increase and acid sphingomyelinase (ASMase) expression. The use of the ASMase inhibitor, desipramine, also demonstrated a reduction in these pathways, highlighting the pivotal role of ASMase in inflammation and ferroptosis. Treatment with each inhibitor revealed that ferroptosis causes ER stress and that NF-κB and MAP kinase pathways are involved in inflammation. CONCLUSION: PB emerges as a potential functional food with inhibitory effects on LPS-induced inflammation and ferroptosis, making it a promising candidate for nutritional interventions.

• Applied Biological Chemistry
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• v.17 no.2
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• pp.125-137
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• 1974

The chemical structure of glycolipid of Selenomonas ruminantium cell wall was to be elucidated. The bacterial cells were treated in hot TCA and the glycolipid fractions were extracted by the solvent $CHCl_3\;:\;CH_3OH$ (1 : 3). The extracted glycolipids fraction was further separated by acetone extraction. The acetone soluble fraction was named as the spot A-compound. The acetone insoluble but ether soluble fraction was named as the spot B-compound. These two compounds were examined for elucidation of their chemical structure. The results were as follows: 1. The IR spectral analysis showed that O-acyl and N-acyl fatty acids were linked to glucosamine moiety in the spot A-compound. However in the spot B-compound in addition to O and N-acyl acids phosphorus was shown to be attached to glucosamine. 2. It was recognized by gas liquid chromatography that spot A compound contained beta-OH $C_{13:0}$ fatty acid in predominance in addition to the fatty acid with beta-OH $C_{9:0}$, whereas the spot B compound was composed of the predominant fatty acid of beta-OH $C_{13:0}$ with small amount of beta-OH $C_{9:0}$. 3. According to the paper chromatographic analysis of hydrazinolysis products of the spot A compound, a compound of a similar Rf value as the chitobiose was recognized, which indicated a structure of two molecules glucosamine condensed. The low Rf value of the hydrazinolysis product of the spot B-compound confirmed the presence of phosphorus attached to glucosamine. 4. The appearance of arabinose resulting from. ninhydrin decomposition of the acid hydrolyzate of the spot A compound indicated that the amino group is attached to $C_2$ of glucosamine. 5. The amount of glucosamine in the N-acetylated spot A compound decreased in half of the original content by the treatment. with $NaBH_4$, indicating that there are two molecules of glucosamines in the spot A compound. The presence of 1, 6-linkage between two molecules of glucosamine was suggested by the Morgan-Elson reaction and confirmed by the periodate decomposition test. 6. By the action of ${\beta}-N-acetyl$ glucosaminidase the N-acetylated spot A compound was completely decomposed into N-acetyl glucosamine, whereas the spot B compound was not. This indicated the spot A compound has a beta-linkage. 7. When phosphodiesterase or phosphomonoesterase acted on $^{32}P-labeled$ spot B compound, $^{32}P$ was not released by phosphodiesterase, but completely released by phosphomonoesterase. This indicated that one phosphorus is linked to glucosamine moiety. 8. The spot A compound is assumed to have the following chemical structure: That is glucosaminyl, ${\beta}-1$, 6-glucosamine to which O-acyl and N-acyl fatty acids are linked, of which the predominant fatty acid is beta-OH $C_{13:0}$ fatty acid in addition to beta-OH $C_{9:0}$ fatty acid 9. The spot B compound is likely to have the linkage of $glucosaminyl-{\beta}-1$, 6-glucosamine to which phosphorus is linked in monoester linkage. Furthermore both O-acyl and N-acyl fatty acids contained beta-OH $C_{13:0}$ fatty acid predominantly in addition to beta-OH $C_{9:0}$ fatty acid.

• Journal of Plant Biotechnology
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• v.43 no.2
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• pp.231-239
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• 2016

To study the transcript levels of epigenetically regulated genes in tobacco, we have developed a transgenic line OX1 overexpressing NtROS2a gene encoding cytosine DNA demethylation and a RNAi plant line RNAi13. It has been reported that salt- and $H_2O_2$-stress tolerance of these transgenic lines are enhanced with various phenotypic characters (Lee et al. 2015). In this paper, we conducted microarray analysis with Agilent Tobacco 4 x 44K oligo chip by using overexpression line OX1, RNAi plant line RNAi 13, and wild type plant WT. Differentially expressed genes (DEGs) related to metabolism, nutrient supply, and various stressed were up-regulated by approximately 1.5- to 80- fold. DEGs related to co-enzymes, metabolism, and methylation functional genes were down-regulated by approximately 0.03- to 0.7- fold. qRT-PCR analysis showed that the transcript levels of several candidate genes in OX1 and RNAi lines were significantly (p < 0.05) higher than those in WT, such as genes encoding KH domain-containing protein, MADS-box protein, and Zinc phosphodiesterase ELAC protein. On the other hand, several genes such as those encoding pentatricopeptide (PPR) repeat-containing protein, histone deacetylase HDAC3 protein, and protein kinase were decreased by approximately 0.4- to 1.0- fold. This study showed that NtROS2a gene encoding DNA glycosylase related to demethylation could regulate adaptive response of tobacco at transcriptional level.

• Journal of Life Science
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• v.26 no.12
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• pp.1367-1375
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• 2016

Cilostazol is known to be a selective inhibitor of phosphodiesterase III and is generally used to treat stroke. Our previous findings showed that cilostazol enhanced capillary density through angiogenesis after focal cerebral ischemia. Angiogenesis is an important physiological process for promoting revascularization to overcome tissue ischemia. It is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation. Here, we examined the modulatory effect of cilostazol at each step of the angiogenic mechanism by using human brain microvascular endothelial cells (HBMECs). We found that cilostazol increased the migration of HBMECs in a dose-dependent manner. However, it did not enhance HBMEC proliferation and capillary-like tube formation. We used a cDNA microarray to analyze the mechanisms of cilostazol in cell migration. We picked five candidate genes that were potentially related to cell migration, and we confirmed the gene expression levels by real-time PCR. The genes phosphoserine aminotransferase 1 (PSAT1) and CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$) were up-regulated. The genes tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), and RARRES3 were down-regulated. Our observations suggest that cilostazol can promote angiogenesis by promoting endothelial migration. Understanding the cilostazol-modulated regulatory mechanisms in brain endothelial cells may help stimulate blood vessel formation for the treatment of ischemic diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.1
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• pp.52-58
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• 2017

This study was aimed to examine relaxing effects of Acanthopanacis cortex(AC) through nitric oxide(NO) production and phosphodiesterase type 5(PDE-5) inhibition in corpus cavernosum. In order to define the relaxation effects of AC extract, rabbit corpus cavernous tissues were prepared in $2{\times}2{\times}8mm$ sized strip. AC extract ($0.01-3.0mg/m{\ell}$) were treated in contracted strips induced by phenylephrine(PE) and $N{\omega}$-nitro-L-arginine (L-NNA) was treated before AC extract-treated. And calcium chloride($Ca^{2+}$) 1 mM was infused into precontracted strips after pretreatment of AC extract in $Ca^{2+}-free$ krebs-ringer solution. When AC extract was applied to human umbilical vein endothelial cell(HUVEC), cell viability was measured by MTT assay, and NO concentration was measured by Griess reagent system. Ratio of smooth muscles to collagen fibers and eNOS, PDE-5 positive reaction were measured by histochemical and immunohistochemical process on mice corpus cavernosum. AC extract significantly affected relaxion of the cavernous strips, and the pretreatment of L-NNA inhibited AC extract-induced relaxation. Contraction induced by the addition of $Ca^{2+}$ was inhibited by treatment with the AC extract in $Ca^{2+}-free$ solution. In AC group, NO concentration, ratio of smooth muscle to collagen fibers, and eNOS positive reaction were increased, PDE-5 positive reaction was decreased compared to PE group. As a result of the above experiment, it was thought that AC extract inhibits the inflow of extracellular $Ca^{2+}$ by activating cGMP through the increase of eNOS / NO and the decrease of PDE-5 which inhibits cGMP activity, in the corpus cavernosum.

• Journal of Pharmacopuncture
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• v.27 no.2
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• pp.82-90
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• 2024

Objectives: Nitric oxide is the most important mediator of penile erection after the onset of sexual excitement. It activates cyclic guanosine monophosphate (cGMP), increasing penile blood flow. Most pharmaceutical medications prevent enzyme phosphodiesterase type 5 (PDE-5) from breaking down cGMP, thus keeping its level high. However, due to the adverse effects of pharmacological therapies, herbal drugs that improve sexual function have gained attention recently. This study aimed to investigate the combined effects of ginseng, Tribulus terrestris, and L-arginine amino acid on the sexual performance of individuals with erectile dysfunction (ED) using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Methods: Over three months, 98 men with erectile dysfunction were randomly assigned to receive either 500 mg of herbal supplements or placebo pills. Each herbal tablet contained 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine. Results: The results showed that the changes in the average scores of ILEF-5 within each group before and after the intervention indicated that all parameters related to the improvement of sexual function in patients with erectile dysfunction improved in the herbal treatment group (p < 0.001). The herbal group significantly improved IIEF-5 scores in nondiabetics (p < 0.05). However, there was no significant difference in the changes of IIEF-5 scores between the two intervention and control groups in diabetic patients. Conclusion: In conclusion, ginseng, Tribulus terrestris, and L-arginine have properties that increase energy and strengthen sexual function, making them suitable for patients with sexual disorders.

• Reproductive and Developmental Biology
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• v.35 no.4
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• pp.435-439
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• 2011

Sildenafil citrate (SIL) a phosphodiesterase 5 inhibitor (PDE5I) has been used for long time as a first line oral drug for erectile dysfunction. Though it has beneficial effects on erectile organ it also has some adverse effects in other cells and/or tissues related to reproductive system when exposed to longer duration. The objective of the present study is to evaluate the long term effect of SIL on sperm parameters in Wistar albino rat. The animals are divided into two groups, for group I - rats were treated with saline (vehicle alone) and group - II oral administration of 5 mg/kg b.w. of SIL was administrated orally once in a day for 120 days. At the end of the trial period animals were sacrificed and epididymal sperm were subjected to various analysis. Results showed significant reduction in sperm count, motility, viability and morphologically intact sperm in long term PDE5I exposed animals when compared to control. Acrosomal status and fertility test also showed significant reduction in long term PDE5I exposed animals. The present study clearly indicated that long term SIL has shown to induce alteration in sperm quality and quantity, leading to decline in fertility rate. Indicate that SIL impinge on spermatogenesis as well as epididymal function. Understanding the molecular down-stream events involved in long-term exposure to PDE5 inhibitor can be valuable to supervise on related infertility issues and to suggest corrective measures.

• YAKHAK HOEJI
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• v.36 no.3
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• pp.259-268
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• 1992

A procedure for the determination of KR-30075 and its metabolites in plasma and urine by high performance liquid chromatography is described. For the study of pharmacokinetic properties of KR-30075, a new PDE III inhibitor, the plasma concentration and urinary excretion after an oral administration of KR-30075 (4 mg/kg) in the male rat (Sprague Dawley) were determined by high performance liquid chromatography. The best extraction efficiency of KR-30075 and KR-30072 is obtained with ethyl ether adjusted to pH 4.0. Retention times of both KR-30072 and KR-30075 were within 5 min and resolution was complete at the flow rate of 1.0 ml/min. The sensitivity and specificity of this HPLC assay appears to be satisfactory for the pharmacokinetic study of KR-30075 and its metabolites. One-compartment open model with first-order absorption was applied to evaluate the pharmacokinetic parameters of KR-30075 according to Minimum AIC Estimation. $T_{max}$ was 1 hr, $C_{max}$ was $0.789{\pm}0.31\;{\mu}g/ml$ and elimination half $T_{1/2}$ was 6.31 min after oral administration of 4 mg/kg KR-30075 to male rats.

• Food Science of Animal Resources
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• v.18 no.2
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• pp.185-191
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• 1998

Human milk and bovine milk in normal stage were fractionated four parts : whey, skimmilk membrane, and casein pellet. The specific activity (nmole / mim / mg protein) and distribution ratio(%) of suborganella marker enzymes in each separated milk fraction were determined. Especially, neutral $Ca^{2+}$-ATPase, acid $Ca^{2+}$-ATPase, NADH-cytochrome C reductase, and acid phosphatase were higher in human milk. However, both $Ca^{2+}$-ATPases were not detected in all fractions of bovine milk. On the other hand, 5'-nucleotidase, phosphodiesterase I, alkaline phosphatase, and $\gamma$-glutamyl transpeptidase activities in bovine milk were higher than in human milk. Most of the marker enzymes were highly distributed in cream fraction of either human milk or bovine milk, and their specific activities were high to 24 fold from 3 fold when compared with that of whole milk. These results suggest that marker enzymes in mammary epitherial cell are transfered into cream fraction by the membrane rearrangement, and different biochemical reaction between human and bovine exists for milk secretion in mammary gland.

• Journal of Chest Surgery
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• v.29 no.2
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• pp.191-198
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• 1996

Amrinone is a non-glycosidic, non-adrenergic positive inotropic agent with peripheral and coronary vasodilator effect. It inhibits phosphodiesterase F-III, the cardiac cyclic-AMP specific phosphodiesterase, selectively and potently. In this study, the effects of IV administered amrinone and dopamine were compared in 40 patients who had open heart surgery. Amrinone was administered as a bolus of 1 5~2mglkg for several minutes, followed by continuous infusion at 5~1 Oug/kg/min. The hemodynamic measurements including heart rate, systolic and diastolic pressure, cardiac index, pulmonary wedge pressure, and systemic vascular resistance were recorded immediately for 12~24 hours awl 7th day following operation. In amrinone group, cardiac index increased from 3.73$\pm$1.39 L/min/m2 to 5.44$\pm$2.65 L/min/m2 at the time of posterative 48 hours (n=20, p< 0.05). The decrease in systemic vascular resistance from 1237.5 $\pm$ 637.7 dyne/sec/cm2 to 1000.8 $\pm$ 608.5 dyne/sec/cm2(p<0.05). In Dopamine group, the heart rate increased from 92.1 $\pm$ 13.0/min to 101.0 $\pm$ 13.1/min and the cardiac index decreased from 3.40 $\pm$ 0.50 L/min/m2 to 2.53 $\pm$ 1.15 L/min/m2 at the time of postoperative 12 hours(p<0.05). Systemic vascular resistance increased from 1058.5 $\pm$ 234.6 dyne/sec/cm2 to 1979.7 $\pm$ 759.2 dynelsec/cm2 The comparison of the hemodynamic effects of amrinone and dopamine, both drugs improved cardiac performance. But the administration of amrinone results in a higher cardiac index, diastolic blood pressure and lower systemic vascular resistance than those achieved with dopamine (p<0.05). The uniqueness of the action of amrinone on the heart and its sustained hemodynamic effect suggest it has clinical promise, pos operative care of cardiac surgery