• 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.

• Korean Journal of Food Science and Technology
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• v.53 no.5
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• pp.544-552
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• 2021

This study investigated the anti-fibrotic and antioxidant effects of Paeonia Radix Alba water extract (PR) on thioacetamide (TAA)-induced liver fibrosis in a mouse model and its underlying mechanisms. Liver fibrosis was induced by intraperitoneal injection of TAA (three times a week) for 8 weeks. Furthermore, silymarin (50 mg/kg body weight) and PR (200 mg/kg body weight) were administered for 8 weeks. PR treatment downregulated aspartate aminotransferase (AST), alanine aminotransferase (ALT), ammonia, and myeloperoxidase levels. Moreover, PR treatment downregulated NOX2 and p47phox and upregulated antioxidant enzymes by activating the Nrf2/Keap1 signaling pathway. Furthermore, PR inhibited the factors associated with fibrosis, such as α-SMA and collagen I. AMPK/SIRT1 was upregulated by PR treatment. Overall, these results suggest that PR attenuates liver fibrosis by regulating the Nrf2/Keap1 and AMPK/SIRT1/NF-κB signaling pathways through the inhibition of oxidative stress. Hence, PR has potential as a remedy for preventing and treating liver fibrosis.

• Food Science and Industry
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• v.53 no.4
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• pp.390-396
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• 2020

We investigated the anti-obesity effect of Gelidium elegans extract (GE) on 3T3-L1 preadipocytes and a high-fat-diet (HFD)-induced mouse model. The results of the present study demonstrated that GE prevents weight gain induced by a high-fat diet (HFD) by modulating the adenosine monophosphate-activated protein kinase (AMPK)-PR domain-containing 16 (PRDM16)-uncoupling protein-1 (UCP-1) pathway in a mice model. Moreover, in vitro results show that GE suppressed adipocyte differentiation by modulating adipogenic regulators, stimulated lipolysis by activating ATGL, and inhibited adipogenesis by downregulating various enzymes associated with triglyceride synthesis. GE was also found to upregulate AMPK phosphorylation as well as the expression of UCP1 and PRDM16 proteins, leading to measurable changes in the beige-like phenotype differentiation of 3T3-L1 cells. Taken together, these findings suggest the role of GE as a functional food ingredient extracted from Gelidium elegans to increase energy expenditure and anti-obesity efficacy.

• Journal of Life Science
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• v.23 no.5
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• pp.689-697
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• 2013

In the United States, about 40,000 new cases of oral cancer are diagnosed each year and nearly 7,800 patients died from it in 2012. Omega-3 polyunsaturated fatty acids have been found to have anticancer effects in a variety of cancer cell lines and animal models, but their effect in oral cancer remains unclear. This study was designed to examine the effect of docosahexaenoic acid (DHA, a kind of omega-3 fatty acid) on oral cancer cells and the molecular mechanism of its action. We found that exposure of squamous cell carcinoma-4 (SCC-4) and squamous cell carcinoma-9 (SCC-9) human oral cancer cells to DHA induced growth inhibition in a dose- and time-dependent manner. Meanwhile, in addition to the elevated levels of apoptotic markers, such as cleaved PARP, subG1 portion and TUNEL-positive nuclei, DHA led to autophagic vesicle formation and an increase in autophagic flux, indicating the involvement of both apoptosis and autophagy in the inhibitory effects of DHA on oral cancer cells. Further experiments revealed that the apoptosis and autophagy induced by DHA were linked to inhibition of mammalian target of rapamycin (mTOR) signaling by AKT inhibition and AMP-activated protein kinase (AMPK) activation in SCC-9 cells. Together, our results suggest that DHA induces apoptosis- and autophagy-associated cell death through the AMPK/AKT/mTOR signaling pathway in oral cancer cells. Thus, utilization of omega-3 fatty acids may represent a promising therapeutic approach for chemoprevention and treatment of human oral cancer.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.86-97
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• 2021

Background: Panax ginseng Meyer has been used as a nourishing edible herb in East Asia for thousands of years. 25-OH-PPT was first discovered as a natural rare triterpenoid saponin in ginseng stems and leaves by our group. Research found that it showed strong inhibitory effects on α-glucosidase and protein tyrosine phosphatase 1B, and protected cardiocytes (H9c2) through PI3K/Akt pathway. Methods: In the research, in order to optimize the 25-OH-PPT enrichment process, optimal macroporous resins and optimal purification conditions were studied. Meanwhile, the hypoglycemic effect and mechanism of 25-OH-PPT were evaluated by using STZ to establish insulin-dependent diabetic mice and the spontaneous type 2 diabetes DB/DB mice. Results and Conclusion: Research found that 25-OH-PPT can reduce blood glucose and enhance glucose tolerance in STZ model mice. It increases insulin sensitivity by upregulating GLUT4 and AMPK in skeletal muscle, and activating insulin signaling pathways. In DB/DB mice, 25-OH-PPT achieves hypoglycemic effects mainly by activating the insulin signaling pathway. Meanwhile, through the influence of liver inflammatory factors and lipids in serum, it can be seen that 25-OH-PPT has obvious anti-inflammatory and lipid-lowering effects. These results provide new insights into the study of ginseng as a functional food.

• Mycobiology
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• v.48 no.6
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• pp.512-517
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• 2020

Cordyceps militaris has been reported to the diverse pharmaceutical effects including cancer, inflammatory diseases, and bacteria or virus infection. However, the effect of C. militaris on exercise performance has not yet been elucidated. In this study, we investigated the beneficial effect of C. militaris on exercise performance. To evaluate exercise performance, we prepared C. militaris ethyl acetate extract (CMEE) and conducted grip strength tests every week after administration. Additionally, blood samples were collected at the end of the experiment for biochemical analysis. The administration of CMEE slightly increased grip strength, and this result was similar to the red ginseng treated group. According to the result of biochemical analysis, CMEE had an effect on the biomarkers related to ATP generation pathway but had little influence on the muscle fatigue related biomarkers. Therefore, C. militaris has the possibility of improving exercise performance, which could be associated with the increase in ATP production rather than the decrease in muscle fatigue during exercise.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.5-5
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• 2021

Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.12-19
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• 2024

Skeletal muscle (SM) is the largest organ of the body and is largely responsible for the metabolism required to maintain body functions. Furthermore, the maintenance of SM is dependent on the activation of muscle satellite (stem) cells (MSCs) and the subsequent proliferation and fusion of differentiating myoblasts into mature myofibers (myogenesis). Natural compounds are being used as therapeutic options to promote SM regeneration during aging, muscle atrophy, sarcopenia, cachexia, or obesity. In particular, ginseng-derived compounds have been utilized in these contexts, though ginsenoside Rg1 is mostly used for SM mass management. These compounds primarily function by activating the Akt/mTOR signaling pathway, upregulating myogenin and MyoD to induce muscle hypertrophy, downregulating atrophic factors (atrogin1, muscle ring-finger protein-1, myostatin, and mitochondrial reactive oxygen species production), and suppressing the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in cachexia. Ginsenoside compounds are also used for obesity management, and their anti-obesity effects are attributed to peroxisome proliferator activated receptor gamma (PPARγ) inhibition, AMPK activation, glucose transporter type 4 (GLUT4) translocation, and increased phosphorylations of insulin resistance (IR), insulin receptor substrate-1 (IRS-1), and Akt. This review was undertaken to provide an overview of the use of ginseng-related compounds for the management of SM-related disorders.

• Journal of Korean Medicine Rehabilitation
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• v.31 no.2
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• pp.1-14
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• 2021

Objectives We evaluated the improving effects of Taeksa-tang (TST) using 3T3-L1 cells and C57BL/6 mice were fed on a high-fat diet. Methods The anti-radical activities of TST were studied using 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid). The content of total polyphenol was measured using Folin-Ciocalteu reagent, whereas aluminum chloride colorimetric method was used for the content of total flavonoid. Moreover, the factors related to lipid profile and the protein expressions such as 𝛽-oxidation and anti-oxidant enzyme were analyzed using serum and western blotting of 3T3-L1 cells. Additionally, we examined lipolysis through glycerol appearance in mouse adipose tissue. Results TST treatment showed strong free radical scavenging activities with half maximal inhibitory concentration and the presence of a amount of total polyphenol and total flavonoid. TST treatment significantly increased factors related to 𝛽-oxidation such as carnitine palmitoyl transferase-1 and uncoupling protein 2 via the phosphorlyation of liver kinase B1 (LKB1) and AMP-activated protein kinase (AMPK). Moreover, the protein expressions of anti-oxidant enzyme and lipolysis were significantly elevated by TST administration. In addition, TST supplementation lowered serum malondialdehyde, triglyceride, and total cholesterol levels compared with the control group. Taken together, these data suggest that TST treatment regulated lipid parameters via the increase of 𝛽-oxidation by LKB1-AMPK signaling pathway. Conclusions TST may have a potential remedy in the prevention and treatment of obesity. Therefore, this study may provide the scientific basis for TST use.

• Microbiology and Biotechnology Letters
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• v.47 no.3
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• pp.323-331
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• 2019

White jelly fungus (Tremella fuciformis Berk; TF) has been used as a traditional medicine in Asia; it is known to prevent hypertension, aging, cancer, and arteriosclerosis. This study aimed to investigate the anti-diabetic effects of fermented Tremella fuciformis Berk (FTF) ethanol extracts fermented with L. rhamnosus BHN-LAB 76. We show that FTF increases the ${\alpha}$-glucosidase inhibitory activity and suppress the adipogenesis of 3T3-L1 adipocytes. These inhibitory effects of FTF are accompanied by the regulation of the phosphorylation of AMPK, JNK, and Akt. These data demonstrate that FTF not only inhibits adipogenesis by affecting the adipogenic signaling, but also increases the anti-diabetic effects by regulating the insulin signaling pathway. Therefore, we suggest that the FTF can be used for developing functional food and cosmetics materials.