Publications by authors named "Mi Hye Kim"

90 Publications

Network Pharmacology Study and Experimental Confirmation Revealing the Ameliorative Effects of Decursin on Chemotherapy-Induced Alopecia.

Pharmaceuticals (Basel) 2021 Nov 11;14(11). Epub 2021 Nov 11.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

Decursin, a pyranocoumarin compound from the root of Nakai as a main constituent, has been reported to have various biological activities, including anti-inflammatory, anticancer, and antioxidant effects. This study aimed to predict and confirm the pharmacological relevance of Decursin on chemotherapy-induced alopecia (CIA) with the underlying molecular mechanisms. Decursin-targeted genes were compared with the gene set of alopecia and investigated through functional enrichment analysis. CIA was induced in C57BL/6J mice by injection of cyclophosphamide, and 1, 10, and 100 μM of Decursin were topically treated to depilated dorsal skin. KGF expression was detected in the dorsal skin tissues. Based on the predicted results, caspase, PIK3/AKT, and MAPKs protein expressions by Decursin were analyzed in the TNF-α-induced keratinocytes. The Decursin network had 60.20% overlapped genes with the network of alopecia. Biological processes, such as cellular response to chemical stimulus, apoptosis, PI3K-AKT signaling pathway, and MAPK signaling pathway, were derived from the Decursin network. In the Decursin-treated skin, there was morphological hair growth and histological restoration of hair follicles in the CIA mice. The KGF fluorescence and protein expressions were significantly increased by Decursin treatment. In addition, caspase-3, -7, and -8 expressions, induced by TNF-α, were dose-dependently decreased along with the inhibition of PI3K, AKT, ERK, and p38 expressions in Decursin-treated keratinocytes. These findings indicated that Decursin would be a potent therapeutic option for hair loss, in response to chemotherapy.
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http://dx.doi.org/10.3390/ph14111150DOI Listing
November 2021

Promotion of osteogenesis by Sweroside via BMP2-involved signaling in postmenopausal osteoporosis.

Phytother Res 2021 Nov 24. Epub 2021 Nov 24.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Phlomis umbrosa has been traditionally used for bone diseases in traditional Korean Medicine. Sweroside (SOS), marker compounds of P. umbrosa, has been known to promote osteoblast differentiation. In this study, ameliorative effects of SOS on osteoporosis and potential target pathway were investigated. Ovariectomized mice were administered three doses of SOS three times a week for 4 weeks after inducing osteoporosis. Bone mineral content (BMC) and bone mineral density (BMD) were analyzed by dual energy X-ray absorptiometry. A human osteosarcoma cell line (SaOS-2) was differentiated to clarify the promoting effects of SOS on osteoblast differentiation and bone formation. Osteoblastic bone-forming markers were evaluated in lumbar vertebrae (LV) and mineralized SaOS-2 cells. SOS markedly elevated BMC and BMD levels and attenuated the bone marrow adipocytes in the femoral shaft. SOS increased the formation of bone matrix in SaOS-2 cells. Bone morphogenetic protein-2 (BMP2) and runt-related transcription factor 2 (CBFA1) in LV and SaOS-2 cells were up-regulated by SOS. SOS increased alkaline phosphatase (ALPL), osteopontin (SPP1), and bone sialoprotein-1 (BSPH1). In conclusion, SOS induced the formation of mineralized bone matrix by regulating BMP2/CBFA1-mediated molecules. Therefore, SOS could be a therapeutic compound of treatment for osteoporosis by producing the new bone matrix.
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http://dx.doi.org/10.1002/ptr.7336DOI Listing
November 2021

Macrophage peroxiredoxin 5 deficiency promotes lung cancer progression via ROS-dependent M2-like polarization.

Free Radic Biol Med 2021 11 9;176:322-334. Epub 2021 Oct 9.

School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, South Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Strategies for cancer treatment have traditionally focused on suppressing cancer cell behavior, but many recent studies have demonstrated that regulating the tumor microenvironment (TME) can also inhibit disease progression. Macrophages are major TME components, and the direction of phenotype polarization is known to regulate tumor behavior, with M2-like polarization promoting progression. It is also known that reactive oxygen species (ROS) in macrophages drive M2 polarization, and M2 polarization promote lung cancer progression. Lung cancer patients with lower expression of the antioxidant enzyme peroxiredoxin 5 (Prx5) demonstrate poorer survival. This study revealed that Prx5 deficiency in macrophages induced M2 macrophage polarization by lung cancer. We report that injection of lung cancer cells produced larger tumors in Prx5-deficit mice than wild-type mice independent of cancer cell Prx5 expression. Through co-culture with lung cancer cell lines, Prx5-deficient macrophages exhibited M2 polarization, and reduced expression levels of the M1-associated inflammatory factors iNOS, TNFα, and Il-1β. Moreover, these Prx5-deficient macrophages promoted the proliferation and migration of co-cultured lung cancer cells. Conversely, suppression of ROS generation by N-acetyl cysteine (NAC) inhibited the M2-like polarization of Prx5-deficient macrophages, increased expression levels of inflammatory factors, inhibited the proliferation and migration of co-cultured lung cancer cells, and suppressed tumor growth in mice. These findings suggest that blocking the M2 polarization of macrophages may promote lung cancer regression.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.10.010DOI Listing
November 2021

LIPOSA pharmacopuncture, a new herbal formula, affects localized adiposity by regulating lipid metabolism .

Exp Ther Med 2021 Nov 13;22(5):1290. Epub 2021 Sep 13.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Localized adiposity is a serious aesthetic problem and a well-known health risk factor. There is a growing interest in minimally invasive treatment options for excessive fat accumulation, such as pharmacopuncture. LIPOSA is a newly developed pharmacopuncture formula from three natural herbs: The tuber of (Thunb.) Breitenb., the whole plant of Dahlst. and the root of Bunge. The present study investigated the effects of pharmacopuncture treatment with LIPOSA on localized adiposity. Male C57BL/6J mice were fed high fat diet for 8 weeks to induce obesity. Then, 100 µl LIPOSA was injected into the left-side inguinal fat pad at various concentrations, including 13.35, 26.7 and 53.4 mg/ml. Normal saline was injected into the right-side inguinal fat pad of each mouse as a control. The treatment was performed three times per week for 2 weeks. The weight and histological changes were analyzed in the inguinal fat pad of the obese mice. The expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), autophagy-related gene (ATG)5, ATG7 and LC3-II, as lipophagy-related factors, were evaluated to confirm the lipid-catabolic effects of LIPOSA. LIPOSA pharmacopuncture markedly decreased the weight of the fat tissue and the size of the adipocytes in the inguinal region of the mouse models of obesity in a dose-dependent manner. The expression levels of ATGL, HSL, ATG5, ATG7 and LC3-II were significantly increased by the LIPOSA treatments. In addition, LIPOSA pharmacopuncture was found to decrease the expression levels of ACC, PPAR-γ and PEPCK. The results indicated that subcutaneous injection of LIPOSA can degrade local fat and induce lipophagic and lipase activation effects. In addition, lipid metabolism related to fat accumulation was regulated by the LIPOSA treatment. The present study suggests that LIPOSA pharmacopuncture can be a non-surgical alternative in the treatment of localized adiposity.
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http://dx.doi.org/10.3892/etm.2021.10725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461519PMC
November 2021

Sex-related Differences in Glial Fibrillary Acidic Protein-positive GABA Regulate Neuropathology Following Pilocarpine-induced Status Epilepticus.

Neuroscience 2021 09 14;472:157-166. Epub 2021 Aug 14.

Department of Physiology, College of Medicine, Dankook University, Cheonan, Republic of Korea. Electronic address:

Status epilepticus (SE) is a life-threatening neurological disorder that causes neuronal death and glial activation. Studies have explained the clinical side effects and lack of effectiveness of neurological disorder treatments based on sex-related differences in brain structure and function. However, the sex-specific outcomes of seizure disorders and the underlying mechanisms remain unknown. We compared SE-induced behavioral and pathophysiological changes in male and female mice. The time taken to reach stage 6 seizure following pilocarpine injection was shorter in male mice than in female mice, and the prevalence of SE was higher in male mice than in female mice. Fluoro-Jade B staining revealed more extensive SE-induced hippocampal neuronal death in male mice than in female mice. Glial cells were more activated in male mice than in female mice. In contrast, astrocyte-derived γ-aminobutyric acid (GABA)-immunostaining was less expressed in male mice than in female mice. Moreover, the mRNA levels of inflammatory cytokines released from activated glial cells were higher in male mice than in female mice. Notably, the mRNA level of astrocytic γ-aminobutyric acid transporter (GAT-3) involved in extracellular GABA uptake was lower in female mice than in male mice, while the mRNA levels of glutamate/aspartate transporter (GLAST (EAAT1)) and glutamate transporter (GLT-1 (EAAT2)) involved in extracellular glutamate uptake were higher in female mice. Our findings suggest that male mice are more vulnerable to SE than female mice, resulting in more extensive neuronal cell death and glial activation in male mice, partly due to increased GAT-3 expression that subsequently leads to reduced glial fibrillary acidic protein (GFAP)-positive GABA content assessed with anti-GABA antibodies.
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http://dx.doi.org/10.1016/j.neuroscience.2021.08.002DOI Listing
September 2021

Pharmacopuncture of Taraxacum platycarpum extract reduces localized fat by regulating the lipolytic pathway.

Biomed Pharmacother 2021 Sep 10;141:111905. Epub 2021 Jul 10.

Department of Convergence Korean Medical Science, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address:

Localized fat deposits are associated with health and aesthetic problems that mainly affect a large proportion of individuals. Recently, bioactive constituents of TP have been reported to affect lipid metabolism. In this study, we performed a network pharmacological analysis to assume potential lipolytic effects of TP and investigated the actual lipolytic effects of TP extract injection on local body fat and its underlying mechanism. Using the genes related to active compounds of TP, the network was constructed. Through the Functional Enrichment Analysis, Lipid Metabolism and Fatty Acid Metabolism were expected to be affiliated with the network, which implied possible lipolytic effects of TP. On the comparison between TP network and Obesity-related Gene Sets, about three-fourths of elements were in common with the gene sets, which indicated a high relevance between TP and obesity. Based on the genes in lipolysis-related pathways, Perilipin, CGI-58, ATGL, HSL and MGL were selected to identify the actual lipolytic effects of TP. TP injection reduced the inguinal fat weight. Also, the diameter of the adipocytes was decreased by the TP treatment in HFD-induced obese mice. In addition, TP suppressed lipid accumulation in differentiated 3T3-L1 adipocytes. Moreover, because the expression of Perilipin was increased, CGI-58, ATGL, HSL and MGL were markedly decreased. Furthermore, glycerol release was down-regulated by the TP treatment. TP exerted its lipolytic effects by regulating the lipolysis machinery through stimulation of lipases. Based on the present findings, TP is expected to be a potent component of injection lipolysis for removing localized body fat.
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http://dx.doi.org/10.1016/j.biopha.2021.111905DOI Listing
September 2021

Truncated Neogenin Promotes Hippocampal Neuronal Death after Acute Seizure.

Neuroscience 2021 08 7;470:78-87. Epub 2021 Jul 7.

Department of Pharmacology, Department of Biomedicine & Health Sciences, Catholic Neuroscience Institute, Institute of Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Protecting hippocampal neurons from death after seizure activity is critical to prevent an alteration of neuronal circuitry and hippocampal function. Here, we present a novel target, a truncated form of neogenin that is associated with seizure-induced hippocampal necroptosis, and novel use of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) as a pharmacological regulator of neogenin truncation. We show that 3 days after pilocarpine-induced status epilepticus in mice, when hippocampal cell death is detected, the level of truncated neogenin is increased, while that of full-length neogenin is decreased. Moreover, phosphorylation of mixed lineage kinase domain-like pseudokinase, a crucial marker of necroptosis, was also markedly upregulated at 3 days post-status epilepticus. In cultured hippocampal cells, kainic acid treatment significantly reduced the expression of full-length neogenin. Notably, treatment with DAPT prevented neogenin truncation and protected cultured neurons from N-methyl-D-aspartate (NMDA)-induced death. These data suggest that seizure-induced hippocampal necroptosis is associated with the generation of truncated neogenin, and that prevention of this by DAPT treatment can protect against NMDA-induced excitotoxicity.
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http://dx.doi.org/10.1016/j.neuroscience.2021.06.039DOI Listing
August 2021

Fat regulatory mechanisms of pine nut oil based on protein interaction network analysis.

Phytomedicine 2021 Jun 27;86:153557. Epub 2021 Mar 27.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Background: Pine nut oil (PNO), a standardized and well-defined extract of Pinus koraiensis (Korean pine), has beneficial effects on wound healing, inflammatory diseases, and cancer. However, the explanation for the mechanism by which PNO reduces body fat remains uncertain. We performed a protein-protein interaction network (PPIN) analysis to explore the genes associated with pinolenic acid using the MEDILINE database from PubChem and PubMed. It was concluded through the PPIN analysis that PNO was involved in a neutral lipid biosynthetic process.

Purpose: This study evaluated the effects of PNO predicted by the network analysis of fat accumulation in chronic obesity mouse models established by feeding a high fat diet (HFD) to C57BL/6J mice and explored potential mechanisms.

Methods: HFD mice were fed only HFD or HFD with PNO at 822 and 1644 mg/kg. After an oral administration of 7 weeks, several body weight and body fat-related parameters were examined, including the following: adipose weight, adipocyte size, serum lipid profiles, adipocyte expression of PPAR-γ, sterol regulatory element binding protein (SREBP)-1c, lipoprotein lipase (LPL) and leptin.

Results: We showed that oral administration of PNO to HFD mice reduces body fat weight, fat in tissue, white adipose tissue weight, and adipocyte size. The serum cholesterol was improved in the HFD mice treated with PNO. Additionally, PNO has significantly attenuated the HFD-induced changes in the adipose tissue expression of PPAR-γ, SREBP-1c, LPL, and leptin.

Conclusions: The findings from this study based on the PPIN analysis suggest that PNO has potential as drug to reduce body fat through fat regulatory mechanisms by PPAR-γ and SREBP-1c.
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http://dx.doi.org/10.1016/j.phymed.2021.153557DOI Listing
June 2021

-Tang, a Korean Medicine, Promotes Bone Formation via BMP-2 Pathway in Osteoporosis.

Front Pharmacol 2021 26;12:643482. Epub 2021 Mar 26.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.

Osteoporosis is a common skeletal disease in post-menopausal women. -tang, an herbal medicine, has been treated for gynecological disease such as anemia, anorexia, anti-fatigue, unspecified menstruation and female infertility in East Asia. In this study, ameliorative effects of -tang soft extracts (PMT), a Korean Medicine, on osteoporosis were investigated. Ovariectomized (OVX) osteoporotic ICR mice were intragastrically administrated PMT for 4 weeks. The level of bone mineral density (BMD) was analyzed in bone tissues by dual X-ray absorptiometry. The bone medullary cavity and deposition of collagen were investigated by histological analysis. In addition, the BMP-2 signaling-related molecules, osteoblastic differentiation and formation markers, were determined in femoral tissues. The levels of BMD and bone mineral content were significantly increased in tibia, femurs and LV by treatment of PMT. PMT replenished bone marrow cavity and increased collagen deposition in bone marrow cells of femur. In addition, administration of PMT recovered serum ALP, bALP, osteocalcin and calcium levels in osteoporotic mice. Moreover, PMT treatment up-regulated the expressions of BMP-2, RUNX2 and OSX with its downstream factors, ALP, OPN and BSP-1, in the femoral tissues. Taken together, PMT restored the bone minerals and improvement of bone integrity by bone-forming BMP-2 signaling pathway. These results demonstrate that PMT could be an ameliorative agent for osteoporosis.
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http://dx.doi.org/10.3389/fphar.2021.643482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032944PMC
March 2021

Comparison of the protective effect of cytosolic and mitochondrial Peroxiredoxin 5 against glutamate-induced neuronal cell death.

Redox Rep 2021 Dec;26(1):53-61

School of Life sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.

: Although glutamate is an essential factor in the neuronal system, excess glutamate can produce excitotoxicity. We previously reported that Peroxiredoxin 5 (Prx5) protects neuronal cells from glutamate toxicity via its antioxidant effects. However, it is unclear whether cytosolic or mitochondrial Prx5 provides greater neuroprotection. Here, we investigated differences in the neuroprotective effects of cytosolic and mitochondrial Prx5.: We analyzed patterns of cytosolic and mitochondrial HO generation in glutamate toxicity using HyPer protein. And then, we confirmed the change of intracellular ROS level and apoptosis with respective methods. The mitochondrial dynamics was assessed with confocal microscope imaging and western blotting.: We found that the level of mitochondrial HO greatly increased compared to cytosolic HO and it affected cytosolic HO generation after glutamate treatment. In addition, we confirmed that mitochondrial Prx5 provides more effective neuroprotection than cytosolic Prx5.: Overall, our study reveals the mechanisms of cytosolic and mitochondrial ROS in glutamate toxicity. Our findings suggest that mitochondrial ROS and Prx5 are attractive therapeutic targets and that controlling these factors be useful for the prevention of neurodegenerative diseases.
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http://dx.doi.org/10.1080/13510002.2021.1901028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971343PMC
December 2021

Derma-Hc, a New Developed Herbal Formula, Ameliorates Cutaneous Lichenification in Atopic Dermatitis.

Int J Mol Sci 2021 Feb 26;22(5). Epub 2021 Feb 26.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

Atopic dermatitis (AD) is a chronic cutaneous disorder that is characterized by severe eczematous inflammation, swelling, and lichenification. Activation of T helper (Th)-22 cells by allergens leads to epidermal hyperplasia with hyperkeratosis at the chronic phase of AD. Derma-Hc is composed of five natural herbs with anti-AD effects, such as BUNGE, Briq., Fabr., Diels, L. In this study, the ameliorative effect of Derma-Hc on cutaneous lichenification in 2,4-dinitrochlorobenzne (DNCB)-induced AD was investigated. The dorsal skin of mice was sensitized with DNCB to induce AD-like skin lesions. The dermatitis score and frequency of scratching were evaluated. Thickness of epidermis and dermis was measured by staining with H&E. In addition, infiltration of the mast cell was observed by staining with toluidine blue. Then, desmosomal cadherin, DSC1 was examined by immunofluorescence. Pathological mechanisms involved in lichenification were analyzed in AD-like skin lesions and TNF-α + IFN-γ-treated with human keratinocytes including keratinocyte differentiation genes and JAK1-STAT3 signaling pathway with IL-22 by RT-PCR and western blotting. Topical treatment of Derma-Hc improved AD-like symptoms such as dryness, edema and lichenefication and decreased the number of scratches. Histopathological analysis demonstrated that Derma-Hc significantly inhibited epidermal hyperplasia, hyperkeratosis, and mast cells infiltration. In addition, the level of DSC1 was highly expressed in the epidermis by Derma-Hc. Moreover, mRNA expression level of FLG, an epidermal differentiation complex gene, was recovered by Derma-Hc treatment. KLK5 and KLK7 were markedly reduced to normalize keratinocyte differentiation in dorsal skin tissues and human keratinocytes. On the other hand, Derma-Hc restored expression level of SPINK5. In addition, Derma-Hc inhibited IL-22 via the blockade of JAK1-STAT3 signal pathway. Taken together, Derma-Hc, a natural herbal formula, regulated keratinocyte differentiation and inhibited epidermal hyperplasia with hyperkeratosis. Therefore, Derma-Hc could be a promising candidate for treating chronic AD through modulating signaling of IL-22-associated skin lichenification.
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http://dx.doi.org/10.3390/ijms22052359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956340PMC
February 2021

Anti-Inflammatory Effects of -Tang, a Traditional Herbal Formula, on Acute Lung Injury in LPS-Sensitized Mice and -Raw 264.7 Cells.

Evid Based Complement Alternat Med 2021 9;2021:6641689. Epub 2021 Feb 9.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Acute lung injury (ALI) is a series of syndromes with persistent inflammation and abnormally increased vascular permeability. -tang (SSHT), a traditional herbal formula consisting of a mixture of seven herbs, has been used to treat allergic reactions and chronic hepatitis disease in East Asia. In this study, we determined whether SSHT has an inhibitory effect against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. 0.05, 0.55, and 5.55 mg/kg of SSHT were orally administered to C57BL/6J mice for 7 days prior to the administration of LPS. After 2 h of LPS sensitization, lung tissues were collected to confirm the lung histology and ALI-related inflammatory factors. SSHT ameliorated the LPS-induced alveolar hemorrhage, alveolar wall thickening, and the shrinkage of the alveolar spaces in the ALI mice model. Proinflammatory cytokines including IL-6, TNF-, and IFN- in the lung tissue were significantly regulated in the SSHT-treated groups compared to the LPS only-treated group. Also, increases of IL-6 and TNF- and decrease of IFN- expressions were dose-dependently modulated by SSHT treatment in LPS-induced raw 264.7 cells. Additionally, the translocation of NF-B into nucleus and phosphorylation of mitogen-activated protein (MAP) kinase were significantly attenuated by the treatment of SSHT in LPS-sensitized ALI mice. SSHT showed anti-inflammatory activities by inhibiting proinflammatory cytokines and NF-B signaling in LPS-induced ALI. This study demonstrates that SSHT has preventive effects on LPS-induced ALI by regulating inflammatory responses as an alternative for treating lung diseases.
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http://dx.doi.org/10.1155/2021/6641689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886507PMC
February 2021

Lipolytic and Lipophagic Effects of Pharmacopuncture on Localized Adiposity.

Evid Based Complement Alternat Med 2021 6;2021:7347639. Epub 2021 Jan 6.

Department of Convergence Korean Medical Science, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.

Localized adiposity is not only a common aesthetic issue but also a health risk factor. Pharmacopuncture can be a therapeutic option for the imbalance of regional fat distribution. The tuber of has been prescribed as antitussive and expectorant as a traditional Korean medicine. This study investigated the effects of pharmacopuncture with water extract (PT) on localized adiposity. Male C57BL/6J mice were fed on a high-fat diet (HFD) for 6 weeks. 100 L of 10 mg/mL of PT was injected into the left-side inguinal fat pad, while saline was injected into the right-side inguinal fat pad as self-control. Treatments were performed 3 times per week for 4 weeks. The inguinal fat weight was analyzed by dual-energy X-ray absorptiometry. PT pharmacopuncture significantly decreased the weight of the inguinal fat pad. The adipocyte size was reduced with increases of lipolytic enzymes and lipophagy-related factors by PT pharmacopuncture. There was marked inhibition of lipid accumulation content in 3T3-L1 adipocytes by PT treatment. The expressions of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), autophagy-related gene (ATG) 5, ATG7, and LC3 were markedly increased by PT treatments and . This study suggests that pharmacopuncture of has ameliorative effects on adiposity by lipid catabolic effects via activating both lipolysis and lipophagy in a localized region.
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http://dx.doi.org/10.1155/2021/7347639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806390PMC
January 2021

Inhalation of Essential Oil from Mentha piperita Ameliorates PM10-Exposed Asthma by Targeting IL-6/JAK2/STAT3 Pathway Based on a Network Pharmacological Analysis.

Pharmaceuticals (Basel) 2020 Dec 22;14(1). Epub 2020 Dec 22.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

Fine particulate matter (PM) exposure exhibits a crucial risk factor to exacerbate airway epithelial remodeling, fibrosis, and pulmonary destruction in asthma. Based on the use of essential oils from aromatic plants on pain relief and anti-inflammatory properties, we investigated the inhibitory effects of essential oil derived from the Mentha species (MEO) against asthma exposed to PM10. The MEO (0.1 / %) was aerosolized by a nebulizer to ovalbumin and PM10-induced asthmatic mice. Histological changes were confirmed in the lung tissues. To define the mode of action of the MEO on asthma, a protein-protein interaction network was constructed using menthol and menthone as the major components of the MEO. Cytokine expression and the JAK2/STAT3 signaling pathway were analyzed in lung epithelial A549 cells co-treated with MEO and PM10. Inhalation of MEO by nebulization inhibited respiratory epithelium hyperplasia, collagen deposition, and goblet cell activation in asthmatic mice. Through a network pharmacological analysis, cytokine-cytokine receptor interaction and JAK/STAT was expected to be underlying mechanisms of MEO on asthma. Treatment with MEO significantly reduced the IL-6 levels with a decrease in pro-inflammatory and T helper 2-specific cytokines. PM10-induced phosphorylation of JAK2 and STAT3 was significantly decreased by MEO. Collectively, MEO may have an inhibitory effect on asthma under the condition of PM10 exposure through the IL-6/JAK2/STAT3 signaling pathway.
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http://dx.doi.org/10.3390/ph14010002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821947PMC
December 2020

Ameliorative effects of Osteo-F, a newly developed herbal formula, on osteoporosis via activation of bone formation.

J Ethnopharmacol 2021 Mar 17;268:113590. Epub 2020 Nov 17.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: The fruit of Schizandra chinensis and Lycium chinense, and the root of Eucommia ulmoides, components of Osteo-F, has traditionally been used for treating bone diseases in Korean Medicine.

Aim Of The Study: The exact role and underlying mechanism of Osteo-F herbal formula on bone formation in osteoporosis was investigated in the present study.

Materials And Methods: OVX mice were treated with 0.9, 9 and 90 mg/kg of Osteo-F for 4 weeks. Bone tissues including fourth to sixth lumbar vertebrae (LV) and femur were collected to analyze the bone mineral density (BMD). In addition, serum biomarkers were estimated by enzyme-linked immunosorbent assay. The expressions of collagen, BMP-2 and osteopontin were determined in tibia to clarify the bone anabolic effects of Osteo-F in osteoporosis.

Results: The levels of BMD in both of fourth to sixth LV and femur were significantly increased by Osteo-F treatment in OVX mice. Bone mineral content (BMC) was also elevated in Osteo-F-treated LV and femoral bone tissues. In addition, serum osteocalcin was markedly increased by Osteo-F in osteoporotic mice. Serum ALP and bALP levels were neutralized in Osteo-F 90 mg/kg-administered mice. Furthermore, Osteo-F treatment dramatically increased the mRNA expressions of collagen type I, BMP-2 and OPN in tibial bone specimens.

Conclusions: Osteo-F ameliorated bone loss by increasing bone forming molecules including BMP-2 and OPN in osteoporosis. Osteo-F, a newly developed herbal formula, may be an alternative material for the management of osteoporosis with bone anabolic effects.
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http://dx.doi.org/10.1016/j.jep.2020.113590DOI Listing
March 2021

Zanthoxylum piperitum alleviates the bone loss in osteoporosis via inhibition of RANKL-induced c-fos/NFATc1/NF-κB pathway.

Phytomedicine 2021 Jan 22;80:153397. Epub 2020 Oct 22.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea. Electronic address:

Background: The fruit of Zanthoxylum piperitum (ZP) is an herbal medicine as well as a spice agent in Asia to treat carminative, stomachic, anthelmintic and degenerative diseases. Z. piperitum was reported to have anti-oxidant, anti-inflammatory, anti-osteoarthritic and osteosarcoma proliferation-control effects.

Purpose And Study Design: This study was conducted to determine the anti-osteoporotic effects and mechanisms of action of ZP.

Methods: Female ICR mice underwent ovariectomies (OVX) and were orally administered ZP at 1, 10 and 100 mg/kg for 6 weeks. The femoral and tibial bones were assessed by dual-energy X-ray absorptiometry and histology to analyze the bone mineral density (BMD) and the number of osteoclasts. Raw 264.7 cells were stimulated by 100 ng/ml receptor activator of nuclear factor-κB ligand (RANKL) for 7 days in the presence of ZP. RANKL-induced signaling molecules were analyzed in osteoclasts.

Results: The levels of femoral and tibial BMD were significantly increased by ZP administration. Serum biomarkers such as osteocalcin, calcium, alkaline phosphatase and bone-specific alkaline phosphatase concentrations were markedly recovered to normal levels in ZP-treated osteoporotic mice. In addition, the number of osteoclasts in the head, trochanter and body of the femur was obviously decreased in the ZP treatment groups. Moreover, ZP treated-cells showed a reduction in the number of TRAP-positive multinuclear cells in RANKL-stimulated Raw 264.7 cells. ZP decreased the RANKL-activated NFATc1 and c-fos, transcription factors of osteoclast formation. The nuclear translocation of NF-κB and phosphorylation of ERK42/44 were inhibited by the ZP treatment in RANKL-induced osteoclasts.

Conclusion: Collectively, ZP exerts its inhibitory effect against bone resorption by regulating RANKL-mediated c-fos/NFATc1/NF-κB in osteoclast. ZP may prove to be a therapeutic agent for osteoporosis.
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http://dx.doi.org/10.1016/j.phymed.2020.153397DOI Listing
January 2021

The Effects of Gardenia Jasminoides on Periodontitis in Ligature-Induced Rat Model.

Oral Health Prev Dent 2020 Sep 4;18(1):799-806. Epub 2020 Sep 4.

Purpose: Periodontitis is characterised by inflammation of periodontium and alveolar bone loss. Gardenia jasminoides is reported to have anti-inflammatory effects. In this study, we investigated the effects of aqueous extract of G. jasminoides (GJ) on periodontitis.

Materials And Methods: Male Sprague-Dawley rats aged 7 weeks were randomly placed in three groups (n = 7); non-ligatured and non-treated (NL group), ligatured and distilled water-treated (L group) and ligatured and 100 mg/kg GJ-treated (GJ group). After oral administration of GJ for 14 days, the mandibles were removed for histology. In addition, RAW 264.7 cells were treated with 100 ng/ml receptor activator of nuclear factor-κΒ ligand (RANKL) and 1, 10 and 100 μg/ml GJ for 7 days to analyse the expression of periodontitis-related factors.

Results: In GJ-treated mice, the score of alveolar bone loss was statistically significantly attenuated compared with the L group. GJ treatment showed inhibition effect in the progress of cementum demineralisation. The expressions of proinflammatory cytokines in gingival tissue were statistically significantly regulated by GJ treatment. Additionally, GJ treatment showed the dose-dependent inhibition of RANKL-induced osteoclast formation. Furthermore, GJ treatment downregulated the RANKL-induced cytokine production in RAW 264.7 cells.

Conclusion: In summary, GJ ameliorated periodontitis-induced alveolar bone loss via inhibiting transcription factors including nuclear factor-κB, c-fos and extracellular signal-regulated kinase signalling. Therefore, GJ might be a therapeutic option for treating periodontitis.
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http://dx.doi.org/10.3290/j.ohpd.a45084DOI Listing
September 2020

Ameliorative and Synergic Effects of Derma-H, a New Herbal Formula, on Allergic Contact Dermatitis.

Front Pharmacol 2020 14;11:1019. Epub 2020 Jul 14.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.

Allergic contact dermatitis (ACD) is characterized by itching, skin inflammation, and allergic responses caused by release of immunoglobulin E and T helper 2-specific cytokines. The aim of this study is to investigate the ameliorative and synergic effects of herbal formula, Derma-H, containing Fisch. ex Bunge (AM) and Benth (NT) which have been used as traditional medicinal herbs for the cure of dryness, edema, and pruritus. 2,4-Dinitrochlorobenzene (DNCB) was applied for ACD induction. AM, NT, and a mixture of AM and NT was topically applied to skin lesions for 11 days. Dermatitis score and number of scratches were significantly diminished in AM, NT, and AM + NT (Derma-H)-treated groups. Especially, Derma-H was more effective than single treatment of AM and NT on skin hyperplasia and mast cell infiltration. Also, NGF expression decreased by NT and a mixture of AM and NT. Additionally, series of TrkA, Raf-1, MEK, and ERK were significantly inhibited by topical AM and NT application. Those findings suggested AM and NT treatment has a synergic effect on DNCB-induced ACD in mice.
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http://dx.doi.org/10.3389/fphar.2020.01019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371928PMC
July 2020

Human placenta induces hair regrowth in chemotherapy-induced alopecia via inhibition of apoptotic factors and proliferation of hair follicles.

BMC Complement Med Ther 2020 Jul 20;20(1):230. Epub 2020 Jul 20.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.

Background: The human placenta (HP) is a complex organ used to alleviate tiredness and promote wound healing. Previous research showed the hair growth-promoting effect of HP. However, no reports have addressed the effects of HP on hair regrowth in chemotherapy-induced alopecia. In this study, we investigated the effects of HP on the apoptosis and proliferation of hair follicles in chemotherapy-induced alopecia.

Methods: Male C57BL/6 mice in telogen were depilated to enter anagen. After 9 days, dystrophic catagen was induced by the intraperitoneal injection of 150 mg/kg cyclophosphamide. During 9 to 16 days, 0.1 and 1 mg/mL HP were topically applied to depilated dorsal skin.

Results: Dystrophic hair follicles by cyclophosphamide were recovered by HP treatment. New hair shafts containing hair fibers appeared to be straight after HP treatment. Immunohistological staining revealed a significant increase of Ki67-positive cells in hair follicles treated with 1 mg/mL HP. Topical HP treatment increased the ratio of Bcl-2/Bax, while it attenuated the expression of pro-apoptotic Bax, p53, and cytochrome c with caspase-9 and -3. In addition, the expression of KGF and the phosphorylation of AKT were upregulated by HP treatment.

Conclusion: These results suggest that HP treatment induced hair growth by inhibiting apoptosis and promoting the proliferation of hair follicles. HP may be useful for treating chemotherapy-induced alopecia.
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http://dx.doi.org/10.1186/s12906-020-03025-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372784PMC
July 2020

Anti-inflammatory effects of Samsoeum, a Korean medicine for health insurance, on chronic bronchitis caused by lipopolysaccharide in rats.

Food Funct 2020 Aug;11(8):6866-6874

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.

Background: Samsoeum (SSE), a Korean medicine, has been used to treat upper respiratory infection including residual coughs after catching a cold, and colds in patients with gastrointestinal disorder. In this study, we investigated the inhibitory effect of SSE against lipopolysaccharide (LPS)-induced bronchitis and characterized its optimal dosing range based on the improvement of SSE concentrations.

Materials And Methods: Male Sprague Dawley rats were intra-nasally administered LPS on day 0, 3 and 6. 2 g kg-1 dose of SSE for rat was determined by the human equivalent dose formula and orally administered once a day from day 3 to day 6. To clarify the optimal administration dose of SSE, various doses including 0.5 (1/4 fold), 1 (1/2 fold), 6 (3 fold), 12 (6 fold), 24 (12 fold) and 36 g kg-1 (18 fold) were also orally administered. In addition, the molecular mechanism of SSE in mucin hyperproduction was investigated in LPS-sensitized A549 cells.

Results: Oral administration of SSE ameliorated alveolar wall thickening and inflammatory cell infiltration of lung tissues in LPS-induced bronchitis at doses of 1/4 fold, 1/2 fold and 1 fold. The total cell and neutrophil numbers in bronchoalveolar lavage fluid (BALF) were reduced in the SSE-treated groups compared with the LPS group. In addition, 0.5, 1 and 2 g kg-1 of SSE suppressed LPS-induced mucin glycoprotein 5AC (MUC5AC) production in BALF. Furthermore, SSE treatment significantly inhibited the pro-inflammatory cytokines, resulting in the decrease of MUC5AC production by the JAK1/STAT6 signaling pathway.

Conclusions: 1, 2 and 6 g kg-1 of SSE ameliorated chronic bronchitis by inhibiting LPS-induced neutrophil infiltration and MUC5AC release in BALF. These findings suggested that SSE with 0.5-3-fold of general daily intake dose would be a therapeutic agent for chronic bronchitis.
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http://dx.doi.org/10.1039/d0fo01171aDOI Listing
August 2020

Peroxiredoxin 2 deficiency reduces white adipogenesis due to the excessive ROS generation.

Cell Biol Int 2020 Oct 16;44(10):2086-2093. Epub 2020 Jul 16.

School of Life Sciences, BK21 Plus KNU Creative Bioresearch Group, Kyungpook National University, Daegu, Republic of Korea.

Reactive oxygen species (ROS) act as signaling molecules to regulate various cell functions. Numerous studies have demonstrated ROS to be essential for the differentiation of adipocytes. Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes in mammalian cells. Prx2 is present in the cytoplasm and cell membranes and demonstrates ROS scavenging activity. We focused on Prx2 involvement in regulating adipogenesis and lipid accumulation and demonstrated that Prx2 expression was upregulated during adipocyte differentiation. In addition, the silencing of Prx2 (shPrx2) inhibited adipogenesis by modulating adipogenic gene expression, and cell death was enhanced via increased ROS production in shPrx2-3T3-L1 cells. These results demonstrate that shPrx2 triggers adipocyte cell death and weakens adipocyte function via ROS production. Taken together, our data suggest the participation of Prx2 in adipocyte function and differentiation. Our results also imply that the downregulation of Prx2 activity could help prevent obesity. Overall, findings support the development of ROS-based therapeutic solutions for the treatment of obesity and obesity-related metabolic disorders.
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http://dx.doi.org/10.1002/cbin.11417DOI Listing
October 2020

Gumiganghwal-tang ameliorates cartilage destruction via inhibition of matrix metalloproteinase.

J Ethnopharmacol 2020 Oct 10;261:113074. Epub 2020 Jun 10.

Department of Convergence Korean Medical Science, College of Korean Medicine, Comorbidity Research Institute, Kyung Hee University, Seoul, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Kyung-Bang Gumiganghwal-tang tablet (GMGHT) is a standardized Korean Medicine that could treat a cold, headache, arthralgia and fever. Although GMGHT has been used for arthritis-related diseases including a sprain, arthralgia, unspecified arthritis and knee arthritis, there is no pre-clinical evidence to treat osteoarthritis (OA). This study determined the drug dosage and the mechanisms of GMGHT for OA.

Methods: OA was induced by intra-articular monoiodoacetic acid (MIA) injection in Sprague-Dawley rats. As calculated from the human equivalent dose formula, GMGHT was orally administered at the doses of 9.86, 98.6 and 986 mg/kg for 4 weeks. The arthritis score was performed by a blind test, and histological changes in articular cartilage were indicated by hematoxylin and eosin, Safranin O and toluidine blue staining. SW1353 chondrocytes were stimulated by interleukin (IL)-1β recombinant to analyze the expressions of Type II collagen, matrix metalloproteinases (MMPs) and nuclear factor (NF)-κB.

Results: Rough and punctate surfaces of the femoral condyle induced by MIA, were recovered by the GMGHT treatment. The arthritis score was significantly improved in the 968 mg/kg of GMGHT-treated cartilage. Loss of chondrocytes and proteoglycan were ameliorated at the deep zone of the subchondral bone plate by the GMGHT administration in OA rats. The expression of Type II collagen was increased, while MMP-1, -3 and -13 levels were decreased in the GMGHT-treated SW1353 chondrocytes. In addition, the GMGHT treatment regulated NF-κB activation along with IL-6, transforming growth factor-β and IL-12 production.

Conclusions: GMGHT promoted the recovery of articular cartilage damage by inhibiting MMPs, accompanied with its anti-inflammatory effects in OA. GMGHT might be an alternative therapeutic treatment for OA.
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http://dx.doi.org/10.1016/j.jep.2020.113074DOI Listing
October 2020

Soshiho-tang protects LPS-induced acute liver injury by attenuating inflammatory response.

J Nat Med 2020 Sep 12;74(4):788-795. Epub 2020 Jun 12.

Department of Convergence Korean Medical Science, Graduate School, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea.

Soshiho-tang (SSHT) has traditionally been used to treat gastrointestinal disorders. In this experiment, we investigated the protective effect of SSHT on inflammatory liver injury in lipopolysaccharide (LPS)-sensitized mice. Male C57BL/6J mice aged 6 weeks were randomly placed in 6 groups (n = 5): normal mice (CTR), LPS-sensitized mice (LPS), LPS-sensitized mice treated with dexamethasone (DEX) and LPS-sensitized mice treated with 0.05, 0.55, and 5.55 g/kg of SSHT (SSHT 0.05, SSHT 0.55, and SSHT 5.55). Various doses of SSHT was given once a day for 7 days. After 2 h of LPS injection, the liver tissue was collected. SSHT pretreatment recovered hemorrhage of liver tissues in LPS-induced acute liver injury. The expressions of MAP Kinase, NF-κB, IκBα, p-IκBα, COX-2, and iNOS protein levels were markedly decreased by SSHT-treated liver tissues. Additionally, SSHT pretreatment significantly regulated the expressions of MCP-1, TNF-α, and IL-6 cytokines. These results suggest the potential of SSHT on the protection of acute liver injury.
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http://dx.doi.org/10.1007/s11418-020-01421-wDOI Listing
September 2020

-Tang Tablet, a Standardized Medicine Attenuates Allergic Asthma via Inhibition of Janus Kinase 1 (JAK1)/ Signal Transducer and Activator of Transcription 6 (STAT6) Signal Pathway.

Molecules 2020 May 8;25(9). Epub 2020 May 8.

Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

Exposure to particulate matter (PM) has been known to be one of the risk factors to cause allergic asthma, leading to development of respiratory disease. -tang tablet (BHT), a standardized Korean Medicine, is prescribed for neurasthenia, laryngopharyngitis and asthma. In this study, we investigated therapeutic effects of BHT on airway inflammation in ovalbumin (OVA) and PM smaller than 10 μm (PM)-induced allergic asthma mice. To establish allergic asthma with airway hyper-responsiveness by PM, BALB/c mice were sensitized and challenged with OVA and PM, and orally administered BHT. Histological staining was performed to assess airway remodeling. Serum and bronchoalveolar lavage fluid (BALF) was collected for measuring immunoglobulin levels and counting inflammatory cells, respectively. Expression levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6), pro-inflammatory cytokines and type 2 T-helper (Th2)-related cytokines were analyzed in vivo and in vitro models. Histopathological analysis demonstrated that BHT suppressed inflammatory cell infiltration, mucus hypersecretion and collagen deposition in the airway. BHT administration effectively decreased number of inflammatory cells in BALF. BHT reduced total serum Immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels. In addition, BHT significantly inhibited the phosphorylation of JAK1 and STAT6 expressions. Release of pro-inflammatory cytokines and Th2-related cytokines were down-regulated by BHT. In conclusion, BHT mitigated airway inflammation by down-regulating pro-inflammatory and Th2-related cytokines via JAK1/STAT6 signaling. BHT might be a promising herbal medicine for preventing airway inflammation. Moreover, an intervention study among humans is needed to further evaluate the possible beneficial effects of BHT in allergic asthma.
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http://dx.doi.org/10.3390/molecules25092206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248972PMC
May 2020

Effects of Processed with KIOM Patent on Bone Remodeling-Related Protein Expression in Human Osteoblast-Like SaOS-2 Cells.

Evid Based Complement Alternat Med 2020 24;2020:4168535. Epub 2020 Apr 24.

Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine (KIOM), 111 Geonjae-ro, Naju-si, Jeollanam-do 58245, Republic of Korea.

This present study evaluated the effects of processed on osteogenesis using Sarcoma osteogenic (SaOS-2) cell lines and osteoclastogenesis of bone marrow-derived macrophage cells (BMM) and to elucidate differences in effect on the expression of bone-related proteins between commercially sold and patented, -propagated Korea Institute of Oriental Medicine (KIOM) . Raw and that were stir-baked and steamed in black bean juice were compared, and western blotting analysis was performed to investigate the expression of bone remodeling-related proteins in SaOS-2 cells. In the cells treated with steamed in black bean juice, the expression of RANKL was decreased, whereas that of osteoprotegerin, alkaline phosphatase, Runx2, and osterix was increased. Owing to these results, we conclude that processed can be used as an alternative treatment for bone diseases such as osteoporosis, osteopenia, periodontitis, and Paget's disease.
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http://dx.doi.org/10.1155/2020/4168535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196996PMC
April 2020

Peroxiredoxin 4 attenuates glutamate-induced neuronal cell death through inhibition of endoplasmic reticulum stress.

Free Radic Res 2020 Apr 5;54(4):207-220. Epub 2020 May 5.

School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea;

High concentrations of glutamate induce neurotoxicity by eliciting reactive oxygen species (ROS) generation and intracellular Ca influx. The disruption of Ca homeostasis in the endoplasmic reticulum (ER) evokes ER stress, ultimately resulting in neuronal dysfunction. Additionally, glutamate participates in the development of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Peroxiredoxins (Prxs) are members of a family of antioxidant enzymes that protect cells from neurotoxic factor-induced apoptosis by scavenging hydrogen peroxide (HO). Prx4 is located in the ER and controls the redox condition within the ER. The present study investigated the protective effects of Prx4 against glutamate-induced neurotoxicity linked to ER stress. HT22 cells in which Prx4 was either overexpressed or silenced were used to elucidate the protective role of Prx4 against glutamate toxicity. The expression of Prx4 in HT22 cells was significantly increased in response to glutamate treatment, while ROS scavengers and ER chemical chaperones reduced Prx4 levels. Moreover, Prx4 overexpression reduces glutamate-induced apoptosis of HT22 cells by inhibiting ROS formation, Ca influx, and ER stress. Therefore, we conclude that Prx4 has protective effects against glutamate-induced HT22 cell damage. Collectively, these results suggest that Prx4 could contribute to the treatment of neuronal disorders.
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http://dx.doi.org/10.1080/10715762.2020.1745201DOI Listing
April 2020

Peroxiredoxin 4 inhibits insulin-induced adipogenesis through regulation of ER stress in 3T3-L1 cells.

Mol Cell Biochem 2020 May 17;468(1-2):97-109. Epub 2020 Mar 17.

School of Life Sciences, BK21 Plus KNU Creative Bioresearch Group, Kyungpook National University, Daegu, Republic of Korea.

Obesity was originally considered a disease endemic to developed countries but has since emerged as a global health problem. Obesity is characterized by abnormal or excessive lipid accumulation (World Health Organization, WHO) resulting from pre-adipocyte differentiation (adipogenesis). The endoplasmic reticulum (ER) produces proteins and cholesterol and shuttles these compounds to their target sites. Many studies have implicated ER stress, indicative of ER dysfunction, in adipogenesis. Reactive oxygen species (ROS) are also known to be involved in pre-adipocyte differentiation. Prx4 specific to the ER lumen exhibits ROS scavenging activity, and we thereby focused on ER-specific Prx4 in tracking changes in adipocyte differentiation and lipid accumulation. Overexpression of Prx4 reduced ER stress and suppressed lipid accumulation by regulating adipogenic gene expression during adipogenesis. Our results demonstrate that Prx4 inhibits ER stress, lowers ROS levels, and attenuates pre-adipocyte differentiation. These findings suggested enhancing the activity of Prx4 may be helpful in the treatment of obesity; the data also support the development of new therapeutic approaches to obesity and obesity-related metabolic disorders.
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http://dx.doi.org/10.1007/s11010-020-03714-wDOI Listing
May 2020

Higher Acid-Base Imbalance Associated with Respiratory Failure Could Decrease the Survival of Patients with Scrub Typhus during Intensive Care Unit Stay: A Gene Set Enrichment Analysis.

J Clin Med 2019 Oct 2;8(10). Epub 2019 Oct 2.

Departments of Medical Science and Anatomy and Cell Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea.

Ninety percent of patients with scrub typhus (SC) with vasculitis-like syndrome recover after mild symptoms; however, 10% can suffer serious complications, such as acute respiratory failure (ARF) and admission to the intensive care unit (ICU). Predictors for the progression of SC have not yet been established, and conventional scoring systems for ICU patients are insufficient to predict severity. We aimed to identify simple and robust indicators to predict aggressive behaviors of SC. We evaluated 91 patients with SC and 81 non-SC patients who were admitted to the ICU, and 32 cases from the public functional genomics data repository for gene expression analysis. We analyzed the relationships between several predictors and clinicopathological characteristics in patients with SC. We performed gene set enrichment analysis (GSEA) to identify SC-specific gene sets. The acid-base imbalance (ABI), measured 24 h before serious complications, was higher in patients with SC than in non-SC patients. A high ABI was associated with an increased incidence of ARF, leading to mechanical ventilation and worse survival. GSEA revealed that SC correlated to gene sets reflecting inflammation/apoptotic response and airway inflammation. ABI can be used to indicate ARF in patients with SC and assist with early detection.
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http://dx.doi.org/10.3390/jcm8101580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832163PMC
October 2019

Peroxiredoxin 5 ameliorates obesity-induced non-alcoholic fatty liver disease through the regulation of oxidative stress and AMP-activated protein kinase signaling.

Redox Biol 2020 01 3;28:101315. Epub 2019 Sep 3.

School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, South Korea; School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, South Korea. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease globally. NAFLD-which can develop into liver fibrosis, nonalcoholic steatohepatosis, cirrhosis, and hepatocellular carcinoma-is defined as an excess accumulation of fat caused by abnormal lipid metabolism and excessive reactive oxygen species (ROS) generation in hepatocytes. Recently, we reported that Peroxiredoxin 5 (Prx5) plays an essential role in regulating adipogenesis and suggested the need to further investigation on the potential curative effects of Prx5 on obesity-induced fatty liver disease. In the present study, we focused on the role of Prx5 in fatty liver disease. We found that Prx5 overexpression significantly suppressed cytosolic and mitochondrial ROS generation. Additionally, Prx5 regulated the AMP-activated protein kinase pathway and lipogenic gene (sterol regulatory element binding protein-1 and FAS) expression; it also inhibited lipid accumulation, resulting in the amelioration of free fatty acid-induced hepatic steatosis. Silence of Prx5 triggered de novo lipogenesis and abnormal lipid accumulation in HepG2 cells. Concordantly, Prx5 knockout mice exhibited a high susceptibility to obesity-induced hepatic steatosis. Liver sections of Prx5-deletion mice fed on a high-fat diet displayed Oil Red O-stained dots and small leaky shapes due to immoderate fat deposition. Collectively, our findings suggest that Prx5 functions as a protective regulator in fatty liver disease and that it may be a valuable therapeutic target for the management of obesity-related metabolic diseases.
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http://dx.doi.org/10.1016/j.redox.2019.101315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736789PMC
January 2020

Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells.

Mol Cell Biol 2019 10 27;39(20). Epub 2019 Sep 27.

School of Life Science, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea

Glutamate is an essential neurotransmitter in the central nervous system (CNS). However, high glutamate concentrations can lead to neurodegenerative diseases. A hallmark of glutamate toxicity is high levels of reactive oxygen species (ROS), which can trigger Ca influx and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Peroxiredoxin 5 (Prx5) is a well-known cysteine-dependent peroxidase enzyme. However, the precise effects of Prx5 on glutamate toxicity are still unclear. In this study, we investigated the role of Prx5 in glutamate-induced neuronal cell death. We found that glutamate treatment induces endogenous Prx5 expression and Ca/calcineurin-dependent dephosphorylation of Drp1, resulting in mitochondrial fission and neuronal cell death. Our results indicate that Prx5 inhibits glutamate-induced mitochondrial fission through the regulation of Ca/calcineurin-dependent dephosphorylation of Drp1, and it does so by scavenging cytosolic and mitochondrial ROS. Therefore, we suggest that Ca/calcineurin-dependent mitochondrial dynamics are deeply associated with glutamate-induced neurotoxicity. Consequently, Prx5 may be used as a potential agent for developing therapies against glutamate-induced neurotoxicity and neurodegenerative diseases where it plays a key role.
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http://dx.doi.org/10.1128/MCB.00148-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766699PMC
October 2019
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