• The Korean Journal of Food And Nutrition
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• v.36 no.2
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• pp.93-102
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• 2023

Centella asiatica (C. asiatica) has been widely used in food, cosmetics, and pharmaceutical industry as a functional material. In a previous study, we have investigated not only pharmacological effects such as antioxidative and anti-inflammatory effects, but also analyzed various functional ingredients. In this study, triterpenoids were analyzed using HPLC-DAD to determine marker compounds among functional ingredients. When triterpenoids were analyzed, asiaticoside from C. asiatica was determined as an optimal marker compound. Next, specificity, linearity, limited of detection (LOD), limited of quantification (LOQ), precision, accuracy, and range were evaluated using HPLC-DAD to determine asiaticoside contents in C. asiatica juice and extracts. The specificity was elucidated by chromatogram and retention time using an established analytical method. The coefficient of correlation obtained was 0.9996. LOD was 4.99 ㎍/mL and LOQ was 15.12 ㎍/mL. Intra- and inter-day precision of asiaticoside were determined to be 0.48~1.68% and 0.08~1.09%, respectively. Furthermore, the recovery rate of asiaticoside was 98.88% and the analytical range of Field-70E was determined to be 0.625~10 mg/mL. As a results of evaluating ABTS, DPPH, and FRAP antioxidative effect, Field-70E showed potent antioxidant activities. Results of this study could be used as basic data for quality standardization of C. astiatica juice and extracts.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.337-346
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• 2023

Background: Ginsenoside Rb2, a major active component of Panax ginseng, has various physiological activities, including anticancer and anti-inflammatory effects. However, the mechanisms underlying the rejuvenation effect of Rb2 in human skin cells have not been elucidated. Methods: We performed a senescence-associated β-galactosidase staining assay to confirm cellular senescence in human dermal fibroblasts (HDFs). The regulatory effects of Rb2 on autophagy were evaluated by analyzing the expression of autophagy marker proteins, such as microtubule-associated protein 1A/1B-light chain (LC) 3 and p62, using immunoblotting. Autophagosome and autolysosome formation was monitored using transmission electron microscopy. Autophagic flux was analyzed using tandem-labeled GFP-RFP-LC3, and lysosomal function was assessed with Lysotracker. We performed RNA sequencing to identify potential target genes related to HDF rejuvenation mediated by Rb2. To verify the functions of the target genes, we silenced them using shRNAs. Results: Rb2 decreased β-galactosidase activity and altered the expression of cell cycle regulatory proteins in senescent HDFs. Rb2 markedly induced the conversion of LC3-I to LC3-II and LC3 puncta. Moreover, Rb2 increased lysosomal function and red puncta in tandem-labeled GFP-RFP-LC3, which indicate that Rb2 promoted autophagic flux. RNA sequencing data showed that the expression of DNA damage-regulated autophagy modulator 2 (DRAM2) was induced by Rb2. In autophagy signaling, Rb2 activated the AMPK-ULK1 pathway and inactivated mTOR. DRAM2 knockdown inhibited autophagy and Rb2-restored cellular senescence. Conclusion: Rb2 reverses cellular senescence by activating autophagy via the AMPK-mTOR pathway and induction of DRAM2, suggesting that Rb2 might have potential value as an antiaging agent.

• Animal Bioscience
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• v.36 no.8
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• pp.1293-1303
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• 2023

Objective: Inflammation and pain management in postpartum hyperprolific sows is currently an important animal welfare issue in the swine industry. The present study investigates effects of ketoprofen treatment on the incidence of post-parturient disorders, feed intake, colostrum yield, piglet colostrum intake, colostrum immunoglobulin G (IgG) and piglet mortality rate during the first 3 days of postnatal life. Methods: In total, 61 Danish Landrace×Yorkshire crossbred sows and their offspring (n = 833) were included in the experiment. The sows were randomly distributed into two groups: i) control (n = 31), sows were treated with tolfenamic acid 2 mg per kg for 2 days postpartum; ii) ketoprofen (n = 30), sows were treated with ketoprofen 3 mg per kg for 2 days postpartum. The farrowing process of the sows was monitored for 24 h daily, and data associated with farrowing were collected. Piglet colostrum intake, sow colostrum yield and colostrum IgG were determined. Results: During the first 3 days postpartum, the incidence of sows that had fever did not differ between control and ketoprofen groups (51.6% and 56.7%, respectively, p = 0.692). Piglet colostrum intake did not differ between control and ketoprofen groups (p = 0.736). However, the proportions of piglets that had inadequate colostrum intake were 71.3%, 22.6%, and 5.4% in those with birth weights of <1.0 kg, 1.0 to 1.29 kg, and ≥1.30 kg, respectively (p<0.001). The piglet mortality rate did not differ between control and ketoprofen groups (p = 0.808). Conclusion: Administration of ketoprofen in postpartum sows for 2 days can control the evidence of post-parturient disorders in sows as effectively as the use of tolfenamic acid. No deleterious effect of ketoprofen was detected on sow colostrum yield, piglet colostrum intake and piglet mortality. Therefore, ketoprofen can be recommended as an alternative anti-inflammatory drug used in postpartum sows.

• Industry Promotion Research
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• v.8 no.1
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• pp.1-10
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• 2023

In this study, a formula (EJ-F101) was prepared to develop a raw material for acne-prone skin improvement using wheat germ extract, and a clinical trial cream was prepared and clinical trials were conducted. As a result of the analysis, when comparing before and after using the product, both the test group and the control group showed significant improvement effects in terms of open comedones, occluded comedones, papules, sebum and oil content in the facial region at 4 weeks after product use, compared to the control group in the test group which showed a more significant improvement effect. As a result of the survey on the efficacy of the product, most items showed higher positive answers in the test product compared to the control product four weeks after the use of the product, and about 43-81% of the study subjects answered positively in the test product, except for the "open surface" item. In addition, for all items related to the usability of the product, about 14-86% of the test group and 38-90% of the control group answered positively at the time point 4 weeks after using the product. As a result of skin safety evaluation, no adverse skin reactions were observed in all subjects of this study. Based on the above results, it is considered that the cream using wheat germ extract is suitable for use on acne-prone skin(non comedogenicity).

• BMB Reports
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• v.56 no.12
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• pp.663-668
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• 2023

C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRP-induced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage.

• Korean Journal of Acupuncture
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• v.41 no.2
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• pp.33-42
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• 2024

Objectives : The sigma-1 receptor is implicated in stress, depression, psychostimulant sensitization, and addiction vulnerability. Prior studies have indicated that ethanol exposure modulates sigma-1 receptor activity within the Ventral Tegmental Area (VTA). Here, we explore the sub-mechanisms underlying sigma-1 receptor activity induced by HT7 (Shinmun) stimulation in behavioral alterations following acute ethanol (ETOH) administration. Methods : Male Wistar rats were investigated for pro- and anti-inflammatory markers after injection of ETOH (1 g/kg) using cytokine enzyme-linked immunosorbent assay (ELISA)s. After confirming that HT7 stimulation changed the total distance traveled in the open field test (OFT), protein changes in the Ventral tegmental area (VTA) were measured by Western blotting. The expression level of inducible nitric oxide synthase (iNOS) after administration of a sigma-1 receptor antagonist (dihydrobromide 1047; BD1047, 10 mg/kg i.p.) and Shenmen (HT7) stimulation was compared. Results : As a result, acute ETOH administration increased proinflammatory marker levels (TNF-𝛼 and IL-6). HT7 stimulation restored the total distance response after acute ethanol administration. In addition, in the VTA, the levels of a microglial marker (iNOS), sigma-1 receptor and protein kinase C, which are predicted to be involved in up- and downregulation, were restored by HT7 stimulation. In particular, HT7 stimulation modulates iNOS expression through effects similar to BD treatment. This study suggests that the stimulatory effect of HT7 may be driven by microglial activation. Conclusions : Microglial activity is regulated by sigma-1 receptor, and sigma-1 receptor activity is regulated by HT7 stimulation. Significantly, we demonstrate that HT7 stimulation ameliorates behavioral alterations induced by acute ETOH administration through microglial activation within the VTA.

• Journal of Pharmacopuncture
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• v.27 no.1
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• pp.14-20
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• 2024

Objectives: Frozen shoulder (FS) is one of the most challenging shoulder disorders for patients and clinicians. Its symptoms mainly include any combination of stiffness, nocturnal pain, and limitation of active and passive glenohumeral joint movement. Conventional treatment options for FS are physical therapy, nonsteroidal anti-inflammatory drugs, injection therapy, and arthroscopic capsular release, but adverse and limited effects continue to present problems. As a result, pharmacoacupuncture (PA) is getting attention as an alternative therapy for patients with FS. PA is a new form of acupuncture treatment in traditional Korean medicine (TKM) that is mainly used for musculoskeletal diseases. It has similarity and specificity compared to corticosteroid injection and hydrodilatation, making it a potential alternative injection therapy for FS. However, no systematic reviews investigating the utilization of PA for FS have been published. Therefore, this review aims to standardize the clinical use of PA for FS and validate its therapeutic effect. Methods: The protocol was registered in Prospero (CRD42023445708) on 18 July 2023. Until Aug. 31, 2023, seven electronic databases will be searched for randomized controlled trials of PA for FS. Authors will be contacted, and manual searches will also be performed. Two reviewers will independently screen and collect data from retrieved articles according to predefined criteria. The primary outcome will be pain intensity, and secondary outcomes will be effective rate, Constant-Murley Score, Shoulder Pain and Disability Index, range of motion, quality of life, and adverse events. Bias and quality of the included trials will be assessed using the Cochrane handbook's risk-of-bias tool for randomized trials. Meta analyses will be conducted using Review Manager V.5.3 software. GRADE will be used to evaluate the level of evidence for each outcome. Results: This systematic review and meta-analysis will be conducted following PRISMA statement. The results will be published in a peer-reviewed journal. Conclusion: This review will provide scientific evidence to support health insurance policy as well as the standardization of PA in clinical practice.

• Journal of Nutrition and Health
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• v.57 no.2
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• pp.211-227
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• 2024

Introduction: Seaweed is a sustainable and underexplored source of bioactive compounds with potent anti-inflammatory activities. However, studies on the interaction between seaweed and genes on inflammation are limited. Purpose: We aimed to evaluate the relationships between seaweed consumption and the polygenic risk scores (PRS) and their interactions with high-sensitivity C-reactive protein (hs-CRP) levels. Methods: Information on seaweed consumption was collected using a food frequency questionnaire, which included laver, kelp, and sea mustard among the items consumed. A total of 31 hs-CRP-related single nucleotide polymorphisms (SNPs) were selected using genome-wide association studies and clumping analysis, and the individual PRS were calculated by weighting the effect size of each allele in the selected SNPs of 39,369 middle-aged (≥40 years) Koreans using the Korean Genome and Epidemiology Study (KoGES)-Health Examinees (HEXA) cohort data. To investigate the interaction between seaweed intake and the PRS on hs-CRP levels >1 mg/L, hazard ratios (HRs) and 95% confidence intervals (CIs) were assessed using multivariable Cox proportional hazards models. Results: During a mean follow-up period of 4.8 years, we recorded 436 patients with elevated hs-CRP levels. Women in the highest tertile of the PRS with the lowest quartile of seaweed intake had an increased incidence of elevated hs-CRP levels compared with women in the lowest tertile of the PRS with the lowest seaweed intake quartile (HR 2.34, 95% CI 1.23-4.45). No significant association was observed among the men. Conclusion: In conclusion, we identified a new interaction between the PRS, seaweed intake, and inflammation in Korean women, and this study suggests that the interaction between the identification of genetic predisposition and dietary seaweed intake may have an impact on determining the risk of developing hyperinflammation in the future.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.823-834
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• 1998

Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.374-383
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• 2006

Background: Ethyl pyruvate (EP) is a derivative of pyruvate that has recently been identified by both various in vitro and in vivo studies to have antioxidant and anti-inflammatory effects. The aim of this study was to determine the effect of EP on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: 5 weeks old, male BALB/c mice were used. ALI was induced by an intratracheal instillation of LPS 0.5mg/Kg/$50{\mu}L$ of saline. The mice were divided into the control, LPS, EP+LPS, and LPS+EP groups. In the control group, balanced salt solution was injected intraperitoneally 30 minutes before or 9 hours after the intratracheal instillation of saline. In the LPS group, a balanced salt solution was also injected intraperitoneally 30 minutes before or 9 hours after instillation the LPS. In the EP+LPS group, 40mg/Kg of EP was injected 30 minutes before LPS instillation. In the LPS+EP group, 40mg/Kg of EP was injected 9 hours after LPS instillation. The TNF-$\alpha$ and IL-6 concentrations in the bronchoalveolar lavage fluid (BALF), and that of NF-$\kappa$B in the lung tissue were measured in the control, LPS and EP+LPS groups at 6 hours after instillation of saline or LPS, and the ALI score and myeloperoxidase (MPO) activity were measured in all four groups 24 and 48 hours after LPS instillation, respectively. Results: The TNF-$\alpha$ and IL-6 concentrations were significantly lower in the EP+LPS group than in the LPS group (p<0.05). The changes in the concentration of these inflammatory cytokines were strongly correlated with that of NF-$\kappa$B (p<0.01). The ALI scores were significantly lower in the EP+LPS and LPS+EP groups compared with the LPS group (p<0.05). In the EP+LPS group, the MPO activity was significantly lower than the LPS group (p=0.019). Conclusion: EP, either administered before or after LPS instillation, has protective effects against the pathogenesis of LPS-induced ALI. EP has potential theurapeutic effects on LPS-induced ALI.