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      Hederagenin의 뼈 형성 관련 작용 기전 연구 = Molecular mechanisms of hederagenin in bone formation

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      https://www.riss.kr/link?id=A108418556

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      다국어 초록 (Multilingual Abstract)

      Purpose: Osteoporosis is characterized by structural deterioration of the bone tissue because of the loss of osteoblastic activity or the increase in osteoclastic activity, resulting in bone fragility and an increased risk of fractures. Hederagenin (H...

      Purpose: Osteoporosis is characterized by structural deterioration of the bone tissue because of the loss of osteoblastic activity or the increase in osteoclastic activity, resulting in bone fragility and an increased risk of fractures. Hederagenin (Hed) is a pentacyclic triterpenoid saponin isolated from Dipsaci Radix, the dried root of Dipsacus asper Wall. Dipsaci Radix has been used in Korean herbal medicine to treat bone fractures. In this study, we attempted to demonstrate the potential anti-osteoporotic effect of Hed by examining its effect on osteoblast differentiation in MC3T3-E1 cells.
      Methods: Osteoblastic MC3T3-E1 cells were cultured in 0, 1, and 10 μg/mL Hed for 3 and 7 days. The activity of alkaline phosphatase (ALP), bone nodule formation and level of expression of bone-related genes and proteins were measured in MC3T3-E1 cells exposed to Hed. The western blot test was used to detect the activation of the bone morphogenetic protein-2 (BMP2)/ Suppressor of Mothers against Decapentaplegic (SMAD)1 pathway.
      Results: Hed significantly increased the proliferation of MC3T3-E1 cells. Intracellular ALP activity was significantly increased in the 1 μg/mL Hed-treated group. Hed significantly increased the concentration of calcified nodules. Furthermore, Hed significantly upregulated the expression of genes and proteins associated with osteoblast proliferation and differentiation, such as Runt-related transcription factor 2 (Runx2), ALP, osteopontin (OPN), and type I procollagen (ProCOL1). Induction of osteoblast differentiation by Hed was associated with increased BMP2. In addition, Hed induced osteoblast differentiation by increasing the activity of SMAD1/5/8. These results suggest that Hed has the potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells via the modulation of the BMP2/SMAD1 pathway.
      Conclusion: The results presented in this study indicate that Hed isolated from Dipsaci Radix has the potential to be developed as a healthcare food and functional material possessing anti-osteoporosis effects.

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      참고문헌 (Reference) 논문관계도

      1 신정민 ; 박찬경 ; 신은주 ; 조태형 ; 황인경, "황금 추출물이 조골세포와 파골세포의 활성에 미치는 영향" 한국식품과학회 40 (40): 674-679, 2008

      2 조황의 ; 손인섭 ; 김선춘 ; 손건호 ; 우미희 ; 문동철, "속단(Dipsaci Radix) 중 Asperosaponins 및 Iridoid glycosides의 LC-ESI-MS에 의한 동시분석" 한국생약학회 43 (43): 137-146, 2012

      3 서현주 ; 어현지 ; 김현준 ; 전권석 ; 박광훈 ; 홍세철 ; 정진부, "산양삼(cultivated wild Panax ginseng) 추출물이 조골세포 활성에 미치는 영향" 한국자원식물학회 33 (33): 227-236, 2020

      4 서현주 ; 손건호 ; 황진현 ; 김동하 ; 박유성 ; 권인숙 ; 조영은, "Vanillic Acid의 MC3T3-E1 조골세포 분화 및 무기질화에 미치는 영향" 한국식품영양과학회 50 (50): 774-782, 2021

      5 Jung KY, "Triterpenoids from the roots of Dipsacus asper" 16 (16): 32-35, 1993

      6 Liu ZG, "The osteoprotective effect of Radix Dipsaci extract in ovariectomized rats" 123 (123): 74-81, 2009

      7 Zhang ZJ, "The herbal medicine Dipsacus asper wall extract reduces the cognitive deficits and overexpression of β-amyloid protein induced by aluminum exposure" 73 (73): 2443-2454, 2003

      8 Wang G, "The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment : Which therapies work best? a network meta-analysis" 6 (6): 452-463, 2017

      9 Wong RW, "The effect of crude extract from Radix Dipsaci on bone in mice" 21 (21): 596-598, 2007

      10 Liu X, "The effect of Astragalus extractive on alveolar bone rebuilding progress of tooth extracted socket of ovariectomied rats" 11 (11): 91-98, 2014

      1 신정민 ; 박찬경 ; 신은주 ; 조태형 ; 황인경, "황금 추출물이 조골세포와 파골세포의 활성에 미치는 영향" 한국식품과학회 40 (40): 674-679, 2008

      2 조황의 ; 손인섭 ; 김선춘 ; 손건호 ; 우미희 ; 문동철, "속단(Dipsaci Radix) 중 Asperosaponins 및 Iridoid glycosides의 LC-ESI-MS에 의한 동시분석" 한국생약학회 43 (43): 137-146, 2012

      3 서현주 ; 어현지 ; 김현준 ; 전권석 ; 박광훈 ; 홍세철 ; 정진부, "산양삼(cultivated wild Panax ginseng) 추출물이 조골세포 활성에 미치는 영향" 한국자원식물학회 33 (33): 227-236, 2020

      4 서현주 ; 손건호 ; 황진현 ; 김동하 ; 박유성 ; 권인숙 ; 조영은, "Vanillic Acid의 MC3T3-E1 조골세포 분화 및 무기질화에 미치는 영향" 한국식품영양과학회 50 (50): 774-782, 2021

      5 Jung KY, "Triterpenoids from the roots of Dipsacus asper" 16 (16): 32-35, 1993

      6 Liu ZG, "The osteoprotective effect of Radix Dipsaci extract in ovariectomized rats" 123 (123): 74-81, 2009

      7 Zhang ZJ, "The herbal medicine Dipsacus asper wall extract reduces the cognitive deficits and overexpression of β-amyloid protein induced by aluminum exposure" 73 (73): 2443-2454, 2003

      8 Wang G, "The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment : Which therapies work best? a network meta-analysis" 6 (6): 452-463, 2017

      9 Wong RW, "The effect of crude extract from Radix Dipsaci on bone in mice" 21 (21): 596-598, 2007

      10 Liu X, "The effect of Astragalus extractive on alveolar bone rebuilding progress of tooth extracted socket of ovariectomied rats" 11 (11): 91-98, 2014

      11 Sang C, "TNF-α promotes osteoclastogenesis through JNK signaling-dependent induction of Semaphorin3D expression in estrogen-deficiency induced osteoporosis" 232 (232): 3396-3408, 2017

      12 Huai Y, "Systems pharmacology dissection of action mechanisms for herbs in osteoporosis treatment" 13 (13): 313-331, 2021

      13 Lee DH, "Studies on the constituents isolated from the Dipsacus asperoides" Andong National University 2013

      14 김난진 ; 류현모 ; 김현정 ; 김영진 ; 남순현, "Smad에 의한 alkaline phosphatase 유전자의 발현 조절기전" 대한소아치과학회 28 (28): 238-246, 2001

      15 Li C, "Protective roles of Asperosaponin VI, a triterpene saponin isolated from Dipsacus asper Wall on acute myocardial infarction in rats" 627 (627): 235-241, 2010

      16 Burstone MS, "Postcoupling, noncoupling, and fluorescence techniques for the demonstration of alkaline phosphatase" 24 (24): 1199-1217, 1960

      17 Oh SR, "In vitro anticomplementary activity of hederagenin saponins isolated from roots of Dipsacus asper" 22 (22): 317-319, 1999

      18 Kanis JA, "European guidance for the diagnosis and management of osteoporosis in postmenopausal women" 24 (24): 23-57, 2013

      19 Huang J, "Ethnopharmacology, phytochemistry, and pharmacology of Cornus officinalis Sieb. et Zucc" 213 : 280-301, 2018

      20 Kim BS, "Effects of the dichloromethane fraction of Dipsaci Radix on the osteoblastic differentiation of human alveolar bone marrow-derived mesenchymal stem cells" 75 (75): 13-19, 2011

      21 Yang L, "Drug efficacies on bone mineral density and fracture rate for the treatment of postmenopausal osteoporosis : a network meta-analysis" 23 (23): 2640-2668, 2019

      22 Antika LD, "Dietary phlorizin enhances osteoblastogenic bone formation through enhancing β-catenin activity via GSK-3β inhibition in a model of senile osteoporosis" 49 : 42-52, 2017

      23 Zeng J, "Current knowledge and development of hederagenin as a promising medicinal agent : a comprehensive review" 8 (8): 24188-24202, 2018

      24 Song L, "Calcium and bone metabolism indices" 82 : 1-46, 2017

      25 Chen D, "Bone morphogenetic proteins" 22 (22): 233-241, 2004

      26 Delany AM, "Basic fibroblast growth factor destabilizes osteonectin mRNA in osteoblasts" 274 (274): C734-C740, 1998

      27 Niu Y, "Asperosaponin VI, a saponin component from Dipsacus asper wall, induces osteoblast differentiation through bone morphogenetic protein-2/p38 and extracellular signal-regulated kinase 1/2 pathway" 25 (25): 1700-1706, 2011

      28 Park JY, "Aqueous extract of Dipsacus asperoides suppresses lipopolysaccharide-stimulated inflammatory responses by inhibiting the ERK1/2 signaling pathway in RAW 264.7 macrophages" 231 : 253-261, 2019

      29 McGuffin M, "American herbal products associations botanical safety handbook" CRC Press 1997

      30 Zhou YQ, "Akebia saponin D, a saponin component from Dipsacus asper Wall, protects PC 12 cells against amyloid-beta induced cytotoxicity" 33 (33): 1102-1110, 2009

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