• Journal of Life Science
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• v.22 no.10
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• pp.1371-1377
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• 2012

Fibrosis in kidney by internal and external factors causes progressive loss of renal function. Renal fibrosis is the inevitable consequence of an excessive accumulation of the extracellular matrix. TGF-${\beta}$ plays an important role in the process of renal fibrosis and stimulates the synthesis of profibrotic factors, including collagens, fibronectin, and plasminogen activator inhibitor (PAI-1). We examined the effect of Moringa oleifera Lam (moringa) extracts in a rat kidney fibrosis model. We found that moringa root extract suppresses protein expression/mRNA levels of Type I collagen, fibronectin, and PAI-1 induced by TGF-${\beta}$ in renal fibroblasts. Moringa root extract selectively inhibited phosphorylation of TGF-${\beta}$-induced $T{\beta}RII$ and the downstream signaling pathway (e.g., Smad4), and phospho-ERK, but not JNK, p38, or PI3K/AKT. These results suggest that moringa root extract can act against TGF-${\beta}$-induced renal fibrosis in rat kidney fibroblast cells by a mechanism related to its antifibrotic activity, which regulates expression of fibronectin, Type I collagen, and PAI-1 through $T{\beta}RII$-Smad2/3-Smad4 and ERK. Therefore, moringa root extract is an effective substance for fibrosis therapy and provides a new therapeutic strategy for diseases associated with elevated profibrotic factor synthesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.896-902
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• 2008

Yukmijihwang-tang(YM) is used in Oriental medicine for treatments of diverse systemic symptoms including neurological dosorders. The present study was performed to examine potential effects of YM on growth-promoting activity of injured sciatic nerve axons. YM treatment in the injured sciatic nerve induced enhanced distal elongation of injured axons when measured 3 and 7 days after injury. Retrograde tracing of sciatic nerve axons showed YM-mediated increases in the number of DiI-labeled dorsal root ganglion (DRG) sensory neurons and spinal cord motor neurons at 3 days after injury. Hoechst nuclear staining showed that non-neuronal cell population was largely elevated by YM treatment in distal nerve area undergoing axonal regeneration. Furthermore, phospho-Erk1/2 protein levels were upregulated by YM treatment in the injured nerve area. These data suggest that YM may play a role in facilitated axonal regeneration in injured peripheral nerves. Further investigations of individual herbal components would be useful to explore effective molecular components and develop therapeutic strategies.

• Journal of Food Hygiene and Safety
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• v.34 no.5
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• pp.495-501
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• 2019

Aloin [1,8-Dihydroxy-10-(${\beta}$-D-glucopyranosyl)-3-(hydroxymethyl)-9(10H)-anthracenone], is a natural anthraquinone from aloe. It has been shown to have antioxidant and anticancer effects in various types of human cancer cells, but the anticancer effects of aloin in human colorectal cancer cells HT-29 have not been elucidated. In this study, possible mechanisms by which aloin exerts its apoptotic action in cultured human colorectal cancer HT-29 cells were investigated. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that treatment with aloin (0, 100, 200, 300 and $400{\mu}M$) reduced cell viability in a concentration-dependent manner in HT-29 and showed no effects on cell proliferation in A375SM and AGS cells. In addition, it was confirmed that apoptotic body was significantly increased as shown by 4',6-diamidino-2-phenylindole (DAPI) staining, and increased apoptosis rate by flow cytometry in HT-29 cells treated with aloin (0, 200 and $400{\mu}M$). We confirmed by western blotting that aloin activated Bax (pro-apoptotic), cleaved-poly (ADP-ribose) polymerase (PARP) and caspase-3, -8 and Bcl-2 (anti-apoptotic) were not changed compared with the control. Aloin induced up-regulation of phospho-p38 and down-regulation of phospho-extracellular signal-regulated kinase (ERK)1/2. Therefore, aloin suppressed the growth inhibitory effects by the induction of apoptosis in human colorectal cancer cells and has potential as a cancer preventive medicine.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.4
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• pp.39-61
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• 2008

Objectives : The present study was performed to investigate whether acupuncture stimulation in the rats affected regeneration properties of the injured sciatic nerve. A differential effect of acupuncture stimulation on the one point near the spinal nerve root controlling sciatic nerve activity and the other point in the peripheral area subordinated by injured nerve was compared. Materials and Methods: Rat sciatic nerves were injured by crush, and the effects on axonal regeneration on injured sciatic nerves were evaluated by acupuncture stimulation at two different regions. In proximal acupuncture stimulation group, acupuncture stimulation was performed on Huatuo Jiaji(EX B2) points located from L5 to S1 vertebral levels to stimulate the nearest spinal nerve root that innervates sciatic nerves. In distal acupuncture stimulation group, acupuncture stimulation was performed on Zusanli(ST 36) and Weizhong(BL 40) points to stimulate at peripheral area dominated by injured sciatic nerves. Acupuncture stimulation was given every other days for 1 or 2 weeks. Sciatic nerve tissues collected from acupuncture stimulation experimental groups, injury control group, and intact animal group were used for protein analysis by Western blotting or Hoechst nuclear staining. To determine axonal regeneration, Dil fluorescence dye was injected into the sciatic nerve 0.5 cm distal to the injury site in individual animal groups and Dil-labeled cells by retrograde tracing were measured in the DRG at lumbar 5 or in the spinal cord. DRG sensory neurons prepared from individual animal groups were used to measure the extent of neurite outgrowth and for immunofluorescence staining with anti-GAP-43 antibody. Results : Animal groups given proximal or distal acupuncture stimulation showed upregulation of GAP-43 and Cdc2 protein levels in the sciatic nerve at 7 days after injury. Cdk2 protein levels were strongly induced by nerve injury, but did not show changes by acupuncture stimulation. Phospho-Erk1/2 protein levels were elevated by acupuncture stimulation above those present in the injury control animals. These increase in regeneration-associated protein levels appeared to be related with increase cell proliferation in the injured sciatic nerves. Hoechst 33258 staining of sciatic nerve tissue to visualize nuclei of individual cells showed increased Schwann cell number in the distal portion of the injured nerve 7 and 14 days after injury and further increases by acupuncture stimulation particularly at the proximal position. Measurement of axonal regeneration by retrograde tracing showed significantly increased Dil-labeled cells in proximal acupuncture stimulation group compared to distal acupuncture stimulation group and injury control group. Finally, an evaluation of axonal regeneration by retrograde tracing showed increased number of Dil labeled cells in the DRG at lumbar 5 or in the ventral horn of the spinal cord at lower thoracic level at 7 days after nerve injury. Conclusions : The present data show that the proximal acupuncture stimulation at Huatuo Jiaji(EX B2) points governing injured sciatic nerves was more effective for axonal regeneration than the distal acupuncture stimulation. Further studies on functional recovery or associated molecular mechanisms should be critical for developing animal models and clinical applications.

• International Journal of Oral Biology
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• v.33 no.2
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• pp.51-58
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• 2008

A mutation of UNCL, an inner nuclear membrane RNAbinding protein, has been found to eliminate mechanotransduction in Drosophila. UNCL is expressed in human periodontal tissue including in periodontal ligament (PDL) fibroblasts. However, it is unclear how a mechanical stimulus is translated into cellular responses in PDL fibroblasts. The aim of this study was to evaluate the effect of UNCl on mechanical stress related genes in PDL fibroblasts in response to mechanical stress. The mRNA of TGF-$\beta$, COX-2, and MMP-2 was up-regulated after UNCL inactivation in PDL fibroblasts under the compression force. Under the tensile force, inactivation of UNCL decreased the expression of Biglycan, RANKL, MMP-2, and TIMP-2 mRNAs while it increased the expression of TIMP-1. p38-MAPK was expressed in PDL fibroblasts under compression forces whereas phospho-ERK1/2, p65-NFkB, and c-fos were expressed under tension forces. The expression and phosphorylation of the mechanical stress related genes, kinases, and transcription factors were changed according to the types of stress. Furthermore, most of them were regulated by the inactivation of UNCL. This suggests that UNCL is involved in the regulation of mechanical stress related genes through the signaling pathway in PDL fibroblasts.

• The Journal of Internal Korean Medicine
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• v.33 no.2
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• pp.126-144
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• 2012

Background : Peripheral nerves more rapidly recover than central nerves. However, it has been known that the degree of reaction of axons of peripheral nerves is affected by distinctive characteristics of axons and environmental factors near the axons. Taxol is a widely used medicine as for ovarian, breast, lung and gastric cancer. However it causes patients difficulties under treatment due to its toxic and side effects, which include persistent pain. Objectives : This study reviewed how SJT extract in vitro and in vivo affects nerve tissues of a sciatic nerve damaged by Taxol. It also studied how SJT extract in vivo affects axons of the sciatic nerve after the sciatic nerve was damaged by pressing. Methods : After vehicle, Taxol, and Taxol plus SJT were treated respectively for tissue of the sciatic nerve in vitro and then tissues were observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and anti-cdc2. SJT was also oral medicated by injecting Taxol into the sciatic nerve of in vivo rats. Tissues of the sciatic nerve and axons of DRG sensory nerves were then observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and p-Erk1/2. After inflicting pressing damage to the sciatic nerve of in vivo rats, tissues of the sciatic nerve and DRG sensory nerve were observed using Neurofilament 200, Hoechst, $S100{\beta}$, caspase-3, anti-cdc2, phospho-vimentin, ${\beta}1$-integrin, Dil reverse tracking and p-Erk1/2. Results : The group of in vitro Taxol plus SJT treatment had meaningful effects after sciatic nerve tissue was damaged by Taxol. The group of in vivo SJT treatment had effects of regenerating Schwann cells and axons which were damaged by Taxol treatment. The group of in vivo SJT had effects of regenerating axons in damaged areas after the sciatic nerve was damaged by pressing, and also had variations of distribution in Schwann cells at DRG sensory nerves and axons. Conclusions : This study confirmed that SJT treatment is effective for growth of axons in the sciatic nerve tissues and improvement of Schwann cells after axons of the sciatic nerve tissues was damaged. After tissues of sciatic nerve was damaged by pressing in vivo, SJT treatment had effects on promoting regeneration of axon in the damaged area and reactional capabilities in axons of DRG sensory nerves.

• The Journal of Korean Medicine
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• v.32 no.4
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• pp.83-99
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• 2011

Objective: This study aimed to evaluate the protective effects of Socheongryong-tang (SCRT) on elastase-induced lung injury. Materials and Methods: The extract of SCRT was treated to A549 cells and elastase-induced COPD mice model. Then, various parameters such as cell-based cytoprotective activity and histopathological findings were analyzed. Results: SCRT showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. SCRT treatment also revealed the protective effect on elastase-induced COPD mice model. This effect was evidenced via histopathological findings including immunofluoresence stains against elastin, collagen, and caspase 3, and protein level of Cdc2, cyclin B1, and phospho-Erk1/2 in lung tissue. Conclusion: These data suggest that SCRT has pharmaceutical properties on COPD. This study provides scientific evidence for the efficacy of SCRT for clinical application to patients with COPD.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.365-372
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• 2015

Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.45-63
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• 2011

Objective : Atractyloides Chinensis Rhizome (ACR) is widely used in oriental medicine as a remedy for an inflammation and an allergic disease. However, as yet there is no clear explanation of how ACR affects the production of inflammatory cytokine. This study was to determine the effects of ACR on the mast cell-mediated inflammatory responses. Method : The amount of inflammatory cytokine production induced by the phorbol myristate acetate (PMA) plus calcium ionophore(A23187) in the human mast cell line (HMC-1) incubated with various concentrations of ACR was measured. The TNF-${\alpha}$ protein levels were analysised by Western blots. The TNF-${\alpha}$, IL-6 and IL-8 secreted protein levels were measured by the ELISA assay. The TNF-${\alpha}$, IL-6 and IL-8 mRNA levels were measured by the RT-PCR analysis. NF-${\kappa}$B, phospho-I${\kappa}$B and MAPKs were examined by Western blot analysis. The NF-${\kappa}$B promoter activity was examined by a luciferase assay. Results : 1. The expressions of TNF-${\alpha}$ and TNF-${\alpha}$ mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$. 2. The expressions of IL-6 and IL-6 mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$. 3. The expressions of IL-8 and IL-8 mRNA were decreased dose-dependently at 0.05-0.2mg/$m\ell$ of ACR and significantly decreased at 0.2mg/$m\ell$ specially. 4. The expressions of Phosphorylated-JNK were decreased, not p38, ERK 5. The expressions of NF-${\kappa}$B were decreased dose-dependently at 0.1-0.2mg/$m\ell$ of ACR. The expressions of Phosphorylated I${\kappa}$B were significantly decreased at 0.2mg/$m\ell$. In addition, ACR suppressed PMA plus A23187-induced NF-${\kappa}$B promoting activity. Conclusion : It is suggested that ACR should suppress through inhibition of NF-${\kappa}$B activity and cytokine production.

• Journal of Oriental Neuropsychiatry
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• v.21 no.1
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• pp.109-124
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• 2010

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.