• Journal of Ginseng Research
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• v.43 no.3
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• pp.452-459
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• 2019

Background: Ginsenoside compound K(C-K), a major metabolite of ginsenoside, exhibits anticancer activity in various cancer cells and animal models. A cell signaling study has shown that C-K inhibited nuclear factor-kappa B ($NF-{\kappa}B$) pathway in human astroglial cells and liver cancer cells. However, the molecular targets of C-K and the initiating events were not elucidated. Methods: Interaction between C-K and Annexin A2 was determined by molecular docking and thermal shift assay. HepG2 cells were treated with C-K, followed by a luciferase reporter assay for $NF-{\kappa}B$, immunofluorescence imaging for the subcellular localization of Annexin A2 and $NF-{\kappa}B$ p50 subunit, coimmunoprecipitation of Annexin A2 and $NF-{\kappa}B$ p50 subunit, and both cell viability assay and plate clone formation assay to determine the cell viability. Results: Both molecular docking and thermal shift assay positively confirmed the interaction between Annexin A2 and C-K. This interaction prevented the interaction between Annexin A2 and $NF-{\kappa}B$ p50 subunit and their nuclear colocalization, which attenuated the activation of $NF-{\kappa}B$ and the expression of its downstream genes, followed by the activation of caspase 9 and 3. In addition, the overexpression of Annexin A2-K320A, a C-K binding-deficient mutant of Annexin A2, rendered cells to resist C-K treatment, indicating that C-K exerts its cytotoxic activity mainly by targeting Annexin A2. Conclusion: This study for the first time revealed a cellular target of C-K and the molecular mechanism for its anticancer activity.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.354-360
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• 2019

Ginsenosides, the major active ingredients of ginseng and other plants of the genus Panax, have been used as natural medicines in the East for a long time; in addition, their popularity in the West has increased owing to their various beneficial pharmacological effects. There is therefore a wealth of literature regarding the pharmacological effects of ginsenosides. In contrast, there are few comprehensive studies that investigate their pharmacokinetic behaviors. This is because ginseng contains the complicated mixture of herbal materials as well as thousands of constituents with complex chemical properties, and ginsenosides undergo multiple biotransformation processes after administration. This is a significant issue as pharmacokinetic studies provide crucial data regarding the efficacy and safety of compounds. Moreover, there have been many difficulties in the development of the optimal dosage regimens of ginsenosides and the evaluation of their interactions with other drugs. Therefore, this review details the pharmacokinetic properties and profiles of ginsenosides determined in various animal models administered through different routes of administration. Such information is valuable for designing specialized delivery systems and determining optimal dosing strategies for ginsenosides.

• International Journal of Industrial Entomology and Biomaterials
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• v.39 no.1
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• pp.1-8
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• 2019

Steamed and freeze-dried mature silkworm powder (SMSP) is a natural food containing a large amount of various functional materials and has various health promoting effects. SMSP is known to increase the life expectancy and healthspan, simultaneously. The accomplishment of extension of healthspan should be possible to achieve by activating various signaling pathways delaying aging in various tissues, not by regulating only a few signaling pathways. Consistent with this notion, SMSP increased the resistant to Parkinson disease by enhancing olfaction and mitochondrial activity in neurons of animal models. In addition, SMSP could enhance the gastrointestinal functions. The animals consumed SMSP showed enhanced alcohol metabolisms, reduced cholesterols in bloods, increased resistance to carcinogens causing liver cancers, and protective effects in alcohol induced stomach ulcers. Furthermore, SMSP was also effective in appearance. The SMSP consumed animals showed reduced skin pigmentations and more hair growth compared with control animals. Taken together, the functional enhancement effects of SMSPs in various tissues and organs, which have been discovered to date, are combined to extend healthspan. Therefore, SMSP can be regarded as calorie restriction mimetics. Further studies in the health promoting effects of SMSP will contribute to identifying new applicable diseases, resulted in increased sales of SMSP and incomes of sericulture farmers.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1349-1360
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• 2019

Chronic exposure to ultraviolet (UV) radiation, regarded as a major cause of extrinsic aging or photoaging characterized by wrinkle formation and skin dehydration, exerts adverse effects on skin by causing the overproduction of reactive oxygen species. Agastache rugosa Kuntze, known as Korean mint, possesses a wide spectrum of biological properties including anti-oxidation, anti-inflammation, and anti-atherosclerosis. Previous studies have reported that A. rugosa protected human keratinocytes against UVB irradiation by restoring the anti-oxidant defense system. However, the anti-photoaging effect of A. rugosa extract (ARE) in animal models has not yet been evaluated. ARE was orally administered to hairless mice at doses of 100 or 250 mg/kg/day along with UVB exposure for 12 weeks. ARE histologically improved UVB-induced wrinkle formation, epidermal thickening, erythema, and hyperpigmentation. In addition, ARE recovered skin moisture by improving skin hydration and transepidermal water loss (TEWL). Along with this, ARE increased hyaluronic acid levels by upregulating HA synthase genes. ARE markedly increased the density of collagen and the amounts of hydroxypoline via two pathways. First, ARE significantly downregulated the mRNA expression of matrix metalloproteinases responsible for collagen degradation by inactivating the mitogen-activated protein kinase/activator protein 1 pathway. Second, ARE stimulated the transforming growth factor beta/Smad signaling, consequently raising the mRNA levels of collagen-related genes. In addition, ARE not only increased the mRNA expression of anti-oxidant enzymes but also decreased inflammatory cytokines by blocking the protein expression of nuclear factor kappa B. Collectively, our findings suggest that A. rugosa may be a potential preventive and therapeutic agent for photoaging.

• The Korean Journal of Pain
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• v.32 no.4
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• pp.264-270
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• 2019

Background: To develop a rabbit epidural steroid injection (ESI) model for analyzing steroid retention in the tissue, and to assess the difference in steroid retention in the model according to the location and time elapsed after ESI. Methods: Fluoroscopy-guided ESI was performed using the interlaminar approach between the lowest two lumbar segments in 13 female New Zealand white rabbits. Four rabbits were allocated to each of three different groups according to the time of sacrifice: 3, 7, and 15 days post-ESI; the remaining rabbit was sacrificed immediately post-ESI to obtain baseline data. After sacrifice, two segments were harvested: the lowest two lumbar vertebrae and another two lumbar vertebrae immediately above these. The residual steroid amount (RSA) and residual steroid concentration (RSC) in the collected spinal columns were analyzed. A linear mixed model was used to compare RSAs and RSCs between the injected and adjacent segments, and among the number of days until sacrifice; P < 0.05 was considered statistically significant. Results: Both RSA and RSC of the injected segment were significantly higher than those of the adjacent segment (P < 0.001, both). The RSA and RSC significantly decreased over time (P = 0.009 and P = 0.016, respectively). Conclusions: The developed rabbit ESI model verified that significantly more steroid was retained at the injected segment than at the adjacent segment and the residual steroid decreased over time. This model could be useful not only for comparing current steroid medications, but also for developing new, better steroid formulations.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.349-356
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• 2019

Behavioral analysis in mice provided important contributions in helping understand and treat numerous neurobehavioral and neuropsychiatric disorders. The behavioral performance of animals and humans is widely different among individuals but the neurobehavioral mechanism of the innate difference is seldom investigated. Many neurologic conditions share comorbid symptoms that may have common pathophysiology and therapeutic strategy. The forced swim test (FST) has been commonly used to evaluate the "antidepressant" properties of drugs yet the individual difference analysis of this test was left scantly investigated along with the possible connection among other behavioral domains. This study conducted an FST-screening in outbred CD-1 male mice and segregated them into three groups: high performers (HP) or the active swimmers, middle performers (MP), and low performers (LP) or floaters. After which, a series of behavioral experiments were performed to measure their behavioral responses in the open field, elevated plus maze, Y maze, three-chamber social assay, novel object recognition, delay discounting task, and cliff avoidance reaction. The behavioral tests battery revealed that the three groups displayed seemingly correlated differences in locomotor activity and novel object recognition but not in other behaviors. This study suggests that the HP group in FST has higher locomotor activity and novelty-seeking tendencies compared to the other groups. These results may have important implications in creating behavior database in animal models that could be used for predicting interconnections of various behavioral domains, which eventually helps to understand the neurobiological mechanism controlling the behaviors in individual subjects.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.134-144
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• 2019

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased with the incidence of obesity; however, the underlying mechanisms are unknown. In this study, high-resolution metabolomics (HRM) along with transcriptomics were applied on animal models to draw a mechanistic insight of NAFLD. Wild type (WT) and catalase knockout (CKO) mice were fed with normal fat diet (NFD) or high fat diet (HFD) to identify the changes in metabolic and transcriptomic profiles caused by catalase gene deletion in correspondence with HFD. Integrated omics analysis revealed that cholic acid and $3{\beta}$, $7{\alpha}$-dihydroxy-5-cholestenoate along with cyp7b1 gene involved in primary bile acid biosynthesis were strongly affected by HFD. The analysis also showed that CKO significantly changed all-trans-5,6-epoxy-retinoic acid or all-trans-4-hydroxy-retinoic acid and all-trans-4-oxo-retinoic acid along with cyp3a41b gene in retinol metabolism, and ${\alpha}/{\gamma}$-linolenic acid, eicosapentaenoic acid and thromboxane A2 along with ptgs1 and tbxas1 genes in linolenic acid metabolism. Our results suggest that dysregulated primary bile acid biosynthesis may contribute to liver steatohepatitis, while up-regulated retinol metabolism and linolenic acid metabolism may have contributed to oxidative stress and inflammatory phenomena in our NAFLD model created using CKO mice fed with HFD.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.291-299
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• 2019

Background: Ginsenosides of Korean Red Ginseng extracts (RGE) and its saponin components suppress secretion of inflammasome-mediating cytokines, whereas the nonsaponin fraction (NS) of RGE oppositely stimulates cytokine secretion. Although direct exposure of NS to macrophages in mice induces cytokine production, oral administration of NS has not been studied in inflammasome-related disease in animal models. Methods: Mice were fed RGE or NS for 7 days and then developed peritonitis. Peritoneal cytokines were measured, and peritoneal exudate cells (PECs) were collected to assay expression levels of a set of toll-like receptors (TLRs) and cytokines in response to NS ingestion. In addition, the role of intestinal bacteria in NS-fed mice was assessed. The effect of preexposure to NS in bone marrow-derived macrophages (BMDMs) on cytokine production was further confirmed. Results: NS ingestion attenuated secretion of peritoneal cytokines resulting from peritonitis. In addition, the isolated PECs from NS-fed mice presented lower TLR transcription levels than PECs from control diet-fed mice. BMDMs treated with NS showed downregulation of TLR4 mRNA and protein expression, which was mediated by the $TLR4-MyD88-NF{\kappa}B$ signal pathway. BMDMs pretreated with NS produced less cytokines in response to TLR4 ligands. Conclusion: NS administration directly inhibits TLR4 expression in inflammatory cells such as macrophages, thereby reducing secretion of cytokines during peritonitis.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.699-709
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• 2018

BACKGROUND: Diabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans. METHODS: Current treatment for Type 1 diabetes mellitus mainly includes use of insulin which has its own limitations and also the underlying mechanism of diseases is still not explored. Therefore, alternate methods to cure diabetes are being explored. Stem cells are being investigated as an alternative therapy for treatment of various diseases including diabetes. Few preclinical studies have also been conducted using undifferentiated MSCs as well as in vitro MSCs differentiated into ${\beta}$ islet cells. RESULTS: These stem cell transplant studies have highlighted the benefits of MSCs, which have shown promising results. Few human trials using stem cells have also affirmed the potential of these cells in alleviating the symptoms. CONCLUSION: Stem cell transplantation may prove to be a safe and effective treatment for patients with Type 1 diabetes mellitus.

• Journal of Life Science
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• v.31 no.2
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• pp.137-143
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• 2021

Muscle atrophy refers to a decrease in muscle cells due to damage to muscle fibers. It is reported that muscle atrophy is caused by heart disease, diabetes, and other chronic diseases related to aging. The purpose of this study is to reveal the inhibitory effects of seaweed extracts, which are widely consumed in Korea, and alginic acid on muscle cell damage in muscle atrophy and regeneration models. We found that seaweed extracts (U) and alginic acid (A) attenuated TNF-α-induced muscle atrophy in differentiated C2C12 myoblast cells and inhibited muscle atrophy markers such as MuRF1 and MAFbx. In addition, U and A also regulated ubiquitination marker FoxO1 protein. To confirm the muscle regeneration effect in animal tissue, cardiotoxin (CTX) was used for the regeneration model. Six hours after CTX injection, gastrocnemius muscle volume was increased compared to control. Otherwise, the muscle volume of the U and A treatment groups was not changed. U and A also upregulated regeneration markers MyHC and PGC-1α in a CTX mouse model. These results indicate that seaweed extracts and alginic acid, a seaweed component, are applicable to senile sarcopenia by inhibiting muscle loss and promoting muscle regeneration.