Acer tegmentosum Maxim Prevents Bone Loss by Inhibiting Osteoclastogenesis and Promoting Osteoblast Mineralization in Ovariectomized Mice

오태우,박광일,도현주,김경호,양혜진,조원경,마진열 한국생약학회 2020 Natural Product Sciences Vol.26 No.1

Osteoporosis is a worldwide disease leading to significant economic and societal burdens globally. Osteoporosis is caused by unbalanced bone remodeling between the rate of osteoclast bone resorption and osteoblast bone formation. Acer tegmentosum Maxim (AT) is a traditional herbal medicine containing multiple biological activities such as anti-oxidant and anti-inflammatory purposes. However, its role in osteoporosis has not been fully studied. Therefore, we investigated whether AT has a potent inhibitory effect on osteoporosis and its mechanism through a systemic evaluation in ovariectomized (OVX) mice. OVX mice were orally administrated with the AT at doses of 50, 100, and 200 mg/kg for 10 weeks. Histological images and histomorphometry analyses were performed by H&E and Toluidine blue satin, and the expression levels of receptor activator for nuclear factor-kB ligand (RANKL), nuclear factor of activated T cells cytoplasm 1 (NFATc1), c-Fos, and matrix metalloproteinase 9 (MMP9) related to the osteoclast differentiation were investigated using immunohistochemical analysis. Administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Further, administration of AT increased periosteal bone formation in a dose-dependent manner. Meanwhile, AT inhibited not only the expression of NFATc1 and c-Fos, which are two major regulators of osteoclastogenesis but also reduced bone resorbed encoding expression of MMP9 and RANKL. Our results indicated that administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Also AT has the bone protective effect through the suppression of osteoclast and promotion of osteoblast, suggesting that it could be a preventive and therapeutic candidate for anti-osteoporosis.

조골세포의 분화에 산겨릅나무 추출물이 미치는 영향

오태우,심기석,김광연,조원경,박광일,마진열 대한한의학방제학회 2017 大韓韓醫學方劑學會誌 Vol.25 No.4

Objectives : The present study, to confirm the osteoblast differentiation effects of Acer tegmentosum Maxim. (AT) extract. Methods : In this experiment, cell viability, Alizarin red S assay, and Alkaline phosphatase (ALP) activity with AT extract (50, 100 ㎍/㎖). Also, we studied the expression of differentiation regulator with AT extract in primary calvarial osteoblasts cells (pOB). Results : As a result of AT treatment, we determined that AT extract stimulates ALP activity and alizarin red activities in the pOB cells for mineralization for 18 days. Moreover, these factors increasing osteogenic markers such as Runt-related transcription factor2 (Runx2), osteocalcin (OC), osteopontin, osterix, smad1, smad5, activating transcription factor4 (ATF4) and collagen type Ⅰ alpha 1. Conclusions : These results indicate that AT extract have effect on bone through the promotion of osteoblastic differentiation, suggesting that it could be used for the treatment of bone diseases.

전뇌 허혈성 흰쥐 모델에서 mBHT의 신경보호효과 연구

오태우,박용기 대한본초학회 2012 大韓本草學會誌 Vol.27 No.6

Objectives: Modified Bo-Yang-Hwan-O-Tang (mBHT) is a polyherbal medicine of twelve herbs traditionally used in the treatment of cerebral and cardiac stroke and vascular dementia. The purpose of this study was to evaluate the neuroprotective effect, pyramidal neuronal cell, inflammation and apoptosis of mBHT against global ischemia in rats. Methods: Global ischemia was produced by two-vessel occlusion (2-VO) in SD male rats. mBHT at dose of 500 ㎎/㎏was orally administrated for 2 weeks or 6 weeks after global ischemia. The histopathological changes of ischemic brain were observed by staining of hematoxylin and eosin (H&E) and Nissl and immunohistochemisty with anti-GFAP (glial fibrillary acidic protein) antibody as a astrocyte marker. The expression of inducible nitric oxide synthase (iNOS) and apoptotic proteins such as Bax, Bcl-2 and caspase-3 was determined by western blot. Results: mBHT treatment significantly inhibited the pyramidal neuronal loss in CA1 of hippocampus of global ischemic rats by 2-VO. mBHT also suppressed the activation of astrocytes in the CA1 at 6 weeks after ischemia. In addition, mBHT significantly increased the expression of anti-apoptotic protein, Bcl-2 on iscemic brain, and significantly attenuated the expression of apoptotic proteins, Bax and caspase-3. Conclusions: These results indicate that mBHT inhibits neuronal cell damage induced in global ischemia by 2-VO, suggesting that mBHT may be a potential candidate for the treatment of vascular dementia.

녹내장 동물모델에서 단풍나무 잎 열수 및 에탄올 추출물의 안압 및 신경세포 보호 효과

오태우,박광일,마진열,Oh, Tae Woo,Park, Kwang-Il,Ma, Jin Yeul 대한한의학방제학회 2021 大韓韓醫學方劑學會誌 Vol.29 No.2

Objectives : This study was conducted to evaluate the Intraocular pressure (IOP) and retina neuroprotective effect of Acer palmatum thumb. extract in glaucoma of DBA2/J mice vivo model. Methods : The amount of change in intraocular pressure(IOP) was measured every two weeks for 30 weeks in the DBA2/J glaucoma animal model. The increased IOP were regrouping into drug treatment groups. EW and EE (1, 2 mg/㎖)extract was eye drop administered twice per day for 8 weeks. After administration of the extract, IOP was measured every 1 week at a fixed time for 8 weeks, and protein expression levels and serological changes related to retinal function were investigated. Results : The DBA2/J mice were IOP increased as time dependent, resulting in damage to the retinal function protein related in glaucoma animal model. However, administration of extracts from Leaves of Acer palmatum thumb. prevented an increase IOP, increased for Brn3α, PKCα, and OPN1SW. Additionally, the experssion of Aterocyte maker, GFAP was decreased in DBA2/J mice. Conclusions : These results demonstrate that both IOP and age can be considered in studies using DBA2/J mice and suggest that the extracts from Leaves of Acer palmatum thumb. regulating of IOP and expression of proteins related to retinal function.

Comparative analysis of acute and chronic stress-induced neurobehavioral alteration and liver injury in mice

오태우,Kim Kwang-Youn,Do Hyun Ju,김영우,박광일 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.4

Backgrounds Recent research has shown that stress has a signifcant infuence on the functions of many organs. Objective The present study investigated the efect of acute or chronic restraint stress on physiological and psychological processes. Results In the acute stress group, body weight and food intake did not change, but in the chronic stress group, food intake signifcantly increased and body weight was signifcantly inhibited. ALT and AST levels were signifcantly increased by both groups. Acute and chronic restraint stress led to diferent behavioral changes. Serum levels of corticosterone and cortisol were more increased in chronic stress than in acute stress. The levels of neurons and astrocyte in the hippocampus, and the NeuN-positive neuronal cells remained unafected by acute stress, but were decreased by chronic stress. GFAP-positive astrocytes were increased by both groups. Conclusion In summary, our study provides evidence of a relationship between liver injury and behavioral change upon exposure to restraint stress.

HK표고버섯균사체의 ConA로 처리된 Jurkat cells에서 NFAT 활성화를 통한 면역증진

오태우,문연규,김훈환,김곤섭,김정옥,하영래 한국생명과학회 2022 생명과학회지 Vol.32 No.9

HK shiitake mushroom mycelium (HKSMM), containing 14% β-glucan, is a health functional food ingredient approved individually for liver health by the Ministry of Food and Drug Safety. The immune-enhancing efficacy of a 50% aqueous ethanol extract of HKSMM (designated HKSMM50) was studied in Jurkat cells activated with concanavalin A (ConA). Active hexose correlated compound (AHCC) was used as a positive control. ConA-activated Jurkat cells were treated with HKSMM50 (0, 25, 50, 100 μg g/ml) or AHCC (100 μg g/ml), and cultured for 3 and 6 hours. The nuclear factor of activated T cells (NFAT) protein content in the cytosol and the nucleus was measured by Western blotting. Interleukin-2 (IL-2), interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2) were determined using enzyme-linked immunosorbent assay (ELISA) kits. HKSMM50 lowered NFAT content in the cytosol, but elevated NFAT content in the nucleus. The IL-2 and IFN-γ productions were elevated. Meanwhile, both COX-2 activity and apoptosis were suppressed. The efficacy of the AHCC treatment showed similar to those of HKSMM50 treatments. These results indicate that the HKSMM50 exhibited immune-enhancing effects in ConA-treated Jurkat cells by activation of NFAT protein, and suggest that HKSMM could be used as a health functional food ingredient to improve immune functions in humans.

WHW®의 랫드에서의 반복경구투여 독성에 관한 연구

오태우,배효상,윤철호,박용기 대한본초학회 2010 大韓本草學會誌 Vol.25 No.3

Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity. Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 ㎎/㎏/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

Neuro-inflammation induced by restraint stress causes impairs neurobehavior in mice

오태우,도현주,김광연,김영우,이병욱,마진열,박광일 대한한의학방제학회 2017 大韓韓醫學方劑學會誌 Vol.25 No.4

Background : Behavioral stress has been suggested as one of the significant factors that is able to disrupt physiological systems and cause depression as well as changes in various body systems. The stressful events can alter cognition, learning, memory and emotional responses, resulting in mental disorders such as depression and anxiety. Results : We used a restraint stress model to evaluate the alteration of behavior and stress-related blood parameter. The animals were randomly divided into two groups of five animals each group. Furthermore, we assessed the change of body weight to evaluate the locomotor activity as well as status of emotional and anxiety in mice. After 7 days of restraint stress, the body weight had significantly decreased in the restraint stress group compared with the control group. We also observed stress-associated behavioral alterations, as there was a significant decrease in open field and forced swim test, whereas the immobilization time was significantly increased in the stress group compared to the control group. We observed the morphological changes of neuronal death and microglia by immunohistochemistry and western blot. In our study restraint stress did not cause change in neuronal cell density in the frontal cortex and CA1 hippocampus region, but there was a trend for an increased COX-2 and iNOS protein expression and microglia (CD11b) in brain, which is restraint stress. Conclusion : Our study, there were significant alterations observed in the behavioral studies. We found that mice undergoing restraint stress changed behavior, confirming the increased expression of inflammatory factors in the brain.

RBL-2H3 세포에서 당귀(當歸) 및 산수유(山茱萸) 복합추출물의 알레르기 개선에 대한 효과

오태우 대한한의학방제학회 2023 大韓韓醫學方劑學會誌 Vol.31 No.4

Objectives : Recently, research has been actively conducted on the efficacy of complexes based on oriental medicine prescriptions for improving immune activity and allergies. In this study, In this study, we aimed to examine the effect of Angelica gigas Nakai and Corni fructus extract (AC), medicinal herbs, among candidate drugs derived through preliminary experiments with various components of oriental medicine prescriptions for allergies, on allergies in RBL-2H3 cells. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in anti-DNP-IgE activated DNP-HSA in RBL-2H3 cells. Cell toxicity was determined by WST-1 assay and the markers of degranulation such as beta-hexosaminidase, histamine, TNF-α and IL-6 production of inflammatory mediators and FcεRI-mediated expression. Results : The results showed that treatment with AC extract (20, 40 and 80 ㎍/㎖) noncytotoxic levels and significantly inhibited the release of β-hexosaminidase, histamine and the production of TNF-α and IL-6 in RBL-2H3 by the antigen stimulation. Conclusions : These results indicate that AC extract exhibits anti-allergic activity through inhibition of degranulation and inhibition of inflammatory mediators and cytokine release. These findings suggest that AC extract may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

허혈,재관류 유도성 신경세포사멸에 대하여 신경보호효과를 가지는 약용식물 추출물의 검색

오태우 ( Tae Woo Oh ),이미영 ( Mi Young Lee ),이혜원 ( Hye Won Lee ),박용기 ( Yong Ki Park ) 대한본초학회 2013 大韓本草學會誌 Vol.28 No.2

Objectives: The purpose of the study is to determine the neuroprotective effects of the water and 80% EtOH extract of some herbal medicine plant on ischemia·reperfusion-induced cell death in SK-N-SH human brain neuronal cells. Methods : SK-N-SH cells were treated with 3mM sodium azide and 10 mM 2-deoxy-D-glucose for 45 min, ptior to the addition of different concentrations of herbal medicine plant extract (0, 10, 25, 50, 100, 250, 500, 1000 μg/ml) for 2 hr and then reperfused with growth medium, incubated for 24 h. Cell viability was determined by WST-1 assay, and ATP/ADP levels were measured by ADP/ATP ratio assay kit. Results: Herbal medicine plant extract significantly inhibited decreasing the cell viability in ischemia-induced SK-N-SH cells. Also increased the ratio of ADP/ATP in ischemia-induced neuronal cells, Conclusions: Our results suggest that herbal medicine plant extract has a neuroprotective property via increasing the energy levels in neuronal cells, suggesting that extract may has a therapeutic potential in the treatment of ischemic brain injury. The exact component and mechanism remains for the future study.