Publications by authors named "Woong Mo Yang"

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

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

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

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

Standardized hot water extract from the leaves of Hydrangea serrata (Thunb.) Ser. alleviates obesity via the AMPK pathway and modulation of the gut microbiota composition in high fat diet-induced obese mice.

Food Funct 2021 Mar 3;12(6):2672-2685. Epub 2021 Mar 3.

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea.

Obesity is an increasing health problem worldwide as it is the major risk factor for metabolic diseases. In the present study, we investigated the anti-obesity effects of WHS by examining its effects on high fat diet (HFD)-induced obese mice. Male C57BL/6 mice were fed either a normal diet (ND) or a high fat diet (HFD) with or without WHS. At the end of the experiment, we observed the changes in their body weight and white adipose tissue (WAT) weight and lipid profiles in plasma. We performed western blot and histological analyses of WAT and liver to elucidate the molecular mechanisms of action. We also conducted fecal 16S rRNA analysis for investigating the gut microbiota. Our results indicated that pre- and post-oral administration of WHS significantly prevented body weight gain and reduced body fat weight in HFD-induced obese mice. In addition, WHS was found to improve adipocyte hypertrophy and liver fat accumulation by regulating the AMPK and AKT/mTOR pathways. WHS ameliorated hyperlipidemia by reducing total cholesterol and low-density lipoprotein (LDL) and decreased the energy metabolism-related hormones, leptin and insulin, in mouse plasma. Furthermore, we found that WHS modulated gut dysbiosis by normalizing HFD-induced changes. Taken together, our in vivo data implicate that WHS can be considered as a potential dietary supplement for alleviating obesity.
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http://dx.doi.org/10.1039/d0fo02185gDOI Listing
March 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

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

Cancer cell‑specific anticancer effects of Coptis chinensis on gefitinib‑resistant lung cancer cells are mediated through the suppression of Mcl‑1 and Bcl‑2.

Int J Oncol 2020 06 24;56(6):1540-1550. Epub 2020 Mar 24.

Department of Pathology, Korea University College of Medicine, Seoul 02841, Republic of Korea.

The epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitor (TKI), gefitinib, is an effective therapeutic drug used in the treatment of non‑small cell lung cancers (NSCLCs) harboring EGFR mutations. However, acquired resistance significantly limits the efficacy of EGFR‑TKIs and consequently, the current chemotherapeutic strategies for NSCLCs. It is, therefore, necessary to overcome this resistance. In the present study, the anticancer potential of natural extracts of Coptis chinensis (ECC) against gefitinib‑resistant (GR) NSCLC cells were investigated in vitro and in vivo. ECC inhibited the viability, migration and invasion, and effectively induced the apoptosis of GR cells. These effects were associated with the suppression of EGFR/AKT signaling and the expression of anti‑apoptotic proteins, Mcl‑1 and Bcl‑2, which were overexpressed in GR NSCLC cells. Combination treatment with ECC and gefitinib enhanced the sensitivity of GR cells to gefitinib in vitro, but not in vivo. However, ECC increased the survival of individual zebrafish without affecting the anticancer effect to cancer cells in vivo, which indicated a specific cytotoxic effect of ECC on cancer cells, but not on normal cells; this is an important property for the development of novel anticancer drugs. On the whole, the findings of the present study indicate the potential of ECC for use in the treatment of NSCLC, particularly in combination with EGFR‑TKI therapy, in EGFR‑TKI‑resistant cancers.
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http://dx.doi.org/10.3892/ijo.2020.5025DOI Listing
June 2020

Inhibition of the PI3K-AKT-mTOR pathway suppresses the adipocyte-mediated proliferation and migration of breast cancer cells.

J Cancer 2020 10;11(9):2552-2559. Epub 2020 Feb 10.

Department of Science in Korean Medicine and Comorbidity Research Institute, Kyung Hee University, Seoul, Republic of Korea.

: Although it is well known that adipocyte significantly affects breast cancer progression, its mechanism has not been fully understood. Here, we analyzed the effect of adipocytes on breast cancer progression including cell proliferation and migration. : We treated the conditioned media obtained from mouse 3T3-L1-derived or human adipose tissue-derived mesenchymal stem cells (hAMSC)-derived adipocytes to breast cancer cells, MCF-7 and MDA-MB-231. And then, cells viability and proliferation were analyzed using MTT assays and colony forming assays, respectively. Also mRNA expression of inflammatory cytokines and proteins expression in main signal pathway were analyzed by RT-qPCR and immunoblotting, respectively. : Adipocyte-derived conditioned media increased the proliferation and migration of MCF-7 and MDA-MB-231 cells while little effects in a human normal immortalized mammary epithelial cell line MCF10A. In addition, adipocyte-derived conditioned media induced phosphorylation of AKT and mTOR and upregulated the expression of target genes of the PI3K-AKT-mTOR pathway including IL6, IL1β, IL1α and TNFα in breast cancer cells. Furthermore, BEZ235 a dual inhibitor of PI3K and mTOR significantly decreased the adipocyte-mediated the proliferation and migration of breast cancer cells. : Adipocyte-derived conditioned media enhance the proliferation and migration of breast cancer cells through the PI3K-AKT-mTOR pathway, supporting the importance of heterotypic interactions between breast cancer cells and adipocytes in the tumor microenvironment.
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http://dx.doi.org/10.7150/jca.37975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065999PMC
February 2020

Conditioned media from adipocytes promote proliferation, migration, and invasion in melanoma and colorectal cancer cells.

J Cell Physiol 2019 08 9;234(10):18249-18261. Epub 2019 Mar 9.

Department of Korean Pathology, College of Korean Medicine, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.

Epidemiological evidence suggests that obesity can significantly increase the risk of various cancers, although the mechanisms underlying this link are completely unknown. Here, we analyzed the effect of adipocytes on melanoma and colon cancer cells proliferation, migration, and invasion. The potential effects of conditioned media (CM) obtained from differentiated mouse 3T3-L1 cells and human adipose tissue-derived mesenchymal stem cells (hAMSC) on the proliferation, migration, and invasion of B16BL6 melanoma and colon 26-L5 cancer cells were investigated. The 3T3-L1 and hAMSC CM increased cell proliferation, migration, and invasion in both the cell lines. In addition, adipocytes CM increased matrix metalloproteinase 9 (MMP-9) and MMP-2 activity in both B16BL6 and colon 26-L5 cells. These effects were found to be associated with an increased expression of various oncogenic proteins in B16BL6 and colon 26-L5 cells. Also, adipocyte CM induced Akt and mTOR activation in both tumor cell lines, and the pharmacological inhibition of Akt and mTOR blocked the CM induced Akt as well as mTOR activation and CM-stimulated melanoma and colon cancer cell proliferation, migration, and invasion. These data suggest that adipocyte promotes melanoma and colon cancer progression through modulating the expression of diverse proteins associated with cancer growth and metastasis as well as modulation of the Akt/mTOR signaling.
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http://dx.doi.org/10.1002/jcp.28456DOI Listing
August 2019

Osteogenic effects of via up-regulation of Runx2 in osteoporosis.

Biomed Rep 2019 Jan 20;10(1):17-22. Epub 2018 Nov 20.

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

Turcz (labiatae) has been suggested to promote bone growth. However, the anti-osteoporotic effects of have not yet been elucidated. In the present study, the osteogenic effects of were investigated in an osteoporosis model. ICR female mice were ovariectomized (OVX) to induce osteoporosis for 7 weeks. Treatment with 1, 10 and 100 mg/kg was administrated orally to the OVX mice for 6 weeks. At the end of experiment, the microstructure of the capital femoral epiphysis was investigated. The levels of bone mineral density (BMD), bone mineral content (BMC) and serum osteocalcin concentration were evaluated. In addition, mineralized Saos-2 osteoblast cells were treated with 0.01, 0.1 and 1 µg/ml to analyze the expression of osteoblast differentiation-associated factors. Hyperplasia of the growth plate in the femur was recovered by treatment. BMD and BMC were significantly increased in -treated femurs. Serum calcium concentration was increased following treatment. In addition, the ratio of mineralization was markedly increased in -treated differentiated osteoblasts along with increases in Runx2 levels. conferred its osteogenic effects by upregulating Runx2 in osteoporosis. may be a potential therapeutic material for the treatment of osteoporosis.
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http://dx.doi.org/10.3892/br.2018.1172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299205PMC
January 2019

Inhibition of RANKL-stimulated osteoclast differentiation by Schisandra chinensis through down-regulation of NFATc1 and c-fos expression.

BMC Complement Altern Med 2018 Oct 1;18(1):270. Epub 2018 Oct 1.

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

Background: Schisandra chinenesis (SC) has been reported to have ameliorative effect on osteoporosis. However, the mechanisms underlying the anti-osteoporosis activity of SC have not been clearly elucidated. In the present study, we determined the effects of SC on The receptor activator of NF-kB ligand (RANKL)-induced osteoclastogenesis and its potential mechanism.

Methods: Raw 264.7 cells were treated with 0.6, 6 and 60 μg/mL SC in the presence of 100 ng/mL RANKL for 7 days. RANKL-induced osteoclast formation was analyzed by tartrate resistant acid phosphatase (TRAP) staining. The osteoclast differentiation-related factors were confirmed along with TNF-α.

Results: SC inhibits the RANKL-induced osteoclast differentiation in dose-dependent manner within non-toxic concentrations. The supernatant concentrations of TNF-α were significantly decreased by SC treatment. In addition, osteoclastogenesis-related factors, TRAP6 and NF-κB, were markedly decreased by SC in RANKL-induced osteoclasts. Mechanistically, SC reduced the RANKL-triggered NFATc1 and c-fos expressions.

Conclusions: Taken together, our data suggest that SC can modulate bone metabolism by suppressing RANKL-induced osteoclast differentiation.
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http://dx.doi.org/10.1186/s12906-018-2331-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167898PMC
October 2018

(R)-(+)-pulegone suppresses allergic and inflammation responses on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice model.

J Dermatol Sci 2018 Sep 12;91(3):292-300. Epub 2018 Jun 12.

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

Background: (R)-(+)-pulegone (PLG), a biotransformation of monoterpene ketones, is one of essential oils of Labiatae family. Although PLG was reported to have anti-inflammatory and anti-histamine effects, the therapeutic effects of PLG on atopic dermatitis (AD) have not been reported yet.

Objective: This study investigated the anti-AD effects and underlying mechanisms of PLG in AD-induced mice.

Methods: BALB/c male mice were challenged with 2, 4-dinitrochlorobenzene (DNCB, 1%) to induce AD. After 4 days of rest, PLG (0.1, 1 and 10 μM) were topically applied to dorsal skin for 2 weeks with secondary elicitation using 0.5% DNCB. Histological changes were identified by H&E staining and mast cells were evaluated by toluidine blue staining. Pro-inflammatory cytokines and serum IgE levels were analyzed by ELISA. Inflammatory mediators were measured by western blotting assay.

Results: Topical treatment with PLG significantly suppressed skin thickness and scratching behavior compared with control group. Expression of nerve growth factor was also decreased by PLG treatment. PLG administration decreased serum IgE levels and the number of mast cells in mice model of DNCB-induced AD. The levels of IL-4, IFN-γ, IL-6, TNF-α and IL-1β in dorsal skin of PLG-treated group were lower than those in the control group. PLG inhibited the phosphorylation of MAPKs, as well as IκBα degradation and NF-κB activation.

Conclusions: PLG attenuated the symptoms of AD by suppressing cytokines production, the phosphorylation of MAPKs and the activation of NF-κB signaling. These data suggest that PLG may be an effective natural compound for the treatment of inflammatory skin diseases.
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http://dx.doi.org/10.1016/j.jdermsci.2018.06.002DOI Listing
September 2018

Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model.

Cancer Lett 2018 09 29;431:123-141. Epub 2018 May 29.

College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. Electronic address:

Aberrant reactions of signal transducer and transcriptional activator (STAT) are frequently detected in multiple myeloma (MM) cancers and can upregulate the expression of multiple genes related to cell proliferation, survival, metastasis, and angiogenesis. Therefore, agents capable of inhibiting STAT activation can form the basis of novel therapies for MM patients. In the present study, we investigated whether the potential anti-cancer effects of Formononetin (FT), a naturally occurring isoflavone derived from Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, against MM cell lines and human multiple myeloma xenograft tumors in athymic nu/nu mice model are mediated through the negative regulation of STAT3 and STAT5 pathways. Data from the in vitro studies indicated that FT could significantly inhibit cell viability, and induce apoptosis. Interestingly, FT also suppressed constitutive STAT3 (tyrosine residue 705 and serine residue 727) and STAT5 (tyrosine residue 694/699) activation, which correlated with the suppression of the upstream kinases (JAK1, JAK2, and c-Src) in MM cells, and this effect was found to be mediated via an increased production of reactive oxygen species (ROS) due to GSH/GSSG imbalance. Also, FT abrogated STAT3 and STAT5 DNA binding capacity and nuclear translocation. FT induced cell cycle arrest, downregulated the expression of STAT3-regulated anti-apoptotic, angiogenetic, and proliferative gene products; and this correlated with induction of caspase-3 activation and cleavage of PARP. Intraperitoneal administration of FT significantly suppressed the tumor growth in the multiple myeloma xenograft mouse model without exhibiting any significant adverse effects. Overall, our findings indicate that FT exhibits significant anti-cancer effects in MM that may be primarily mediated through the ROS-regulated inhibition of the STAT3 and STAT5 signaling cascade.
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http://dx.doi.org/10.1016/j.canlet.2018.05.038DOI Listing
September 2018

The Application of Embelin for Cancer Prevention and Therapy.

Molecules 2018 03 9;23(3). Epub 2018 Mar 9.

College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones. Recently, several autophagy-inducing agents have been used in the treatment of different human cancers, although they require further exploration before being transferred from the bench to the clinic. Therefore, embelin could be used as a potential agent for cancer therapy.
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http://dx.doi.org/10.3390/molecules23030621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017120PMC
March 2018

Ophiopogonin D modulates multiple oncogenic signaling pathways, leading to suppression of proliferation and chemosensitization of human lung cancer cells.

Phytomedicine 2018 Feb 12;40:165-175. Epub 2018 Jan 12.

College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea. Electronic address:

Background: Ophiopogonin D (OP-D), a steroidal glycoside obtained from the Chinese medicinal plant Ophiopogonin japonicas (the root portion), has been traditionally used to treat fever, inflammation, cough, sputum etc. However, the detailed molecular mechanism(s) underlying its therapeutic actions is still unknown.

Hypothesis: Because nuclear factor-κB (NF-κB), PI3K/AKT, and activator protein-1 (AP-1) signaling cascades have significant functions in cell proliferation, inflammation, and angiogenesis in tumor cells, we hypothesized that OP-D may disrupt these signaling cascades to exert its anticancer effects in human lung-cancer cells.

Methods: We evaluated the effect of OP-D on multiple signaling cascades and its regulated functional responses in lung cancer cells.

Results: OP-D blocked both basal and cytokine-induced proliferation of human lung-cancer cells and caused down-regulation of the expression of diverse oncogenic gene products through the suppression of NF-κB, PI3K/AKT, and AP-1 pathways; but did not affect JNK, p38 and ERK MAP kinases. Interestingly, OP-D suppressed constitutive NF-κB activation in lung cancer cells via interfering with the IκB kinase activation, which inhibited phosphorylation and caused degradation of IκB-α. OP-D also blocked phosphorylation and the nuclear translocation of p65, thereby suppressing NF-κB reporter activity in lung cancer cells. Besides, OP-D could augment cell death induced by paclitaxel in lung-cancer cells.

Conclusion: Overall, the data indicates that OP-D may abrogate diverse signaling cascades linked to tumorigenesis, and can be used in combination with chemotherapeutic agents for cancer therapy.
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http://dx.doi.org/10.1016/j.phymed.2018.01.002DOI Listing
February 2018
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