• Toxicological Research
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• v.22 no.3
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• pp.267-273
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• 2006

Tungtungmadic acid(3-caffeoyl, 4-dihydrocaffeoyl quinic acid: CDCQ) is a new chlorogenic acid derivative isolated from the Salicornia herbacea. The suppressive effects of CDCQ on the progress of acute carbon tetrachloride($CCl_4$)-induced hepatic fibrosis were investigated in mice. CDCQ significantly suppressed $CCl_4$-induced hepatic necrosis and inflammation, as determined by serum enzymatic activities of alanine and aspartate aminotransferase and serum TNF-$\alpha$ levels in a dose-dependent manner. In addition, increased hepatic lipid peroxidation and fibrosis after acute $CCl_4$ treatment were suppressed by the administration of CDCQ. CDCQ also significantly prevented the elevation of hepatic hydroxyproline and collagen content and ${\alpha}$-smooth muscle actin(${\alpha}$-SMA) expression in the liver of $CCl_4$-intoxicated mice. These results suggest that the suppressive effects of CDCQ against the acute $CCl_4$-induced hepatic fibrosis possibly related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells.

• Biomedical Science Letters
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• v.24 no.4
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• pp.341-348
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• 2018

The polyherbal drug Gyeongshingangjeehwan 18 (GGEx18) from Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae) has traditionally been used as an antiobesity drug in Korean local clinics. This study investigates the effects of GGEx18 on pancreatic fibroinflammation in high-fat diet (HFD)-fed obese C57BL/6J mice and the molecular mechanism involved in this process. After HFD-fed obese C57BL/6J mice were treated with GGEx18 (125, 250, and 500 mg/kg) for 12 weeks, variables and determinants of obesity, pancreatic inflammation, and fibrosis were measured using histology, immunohistochemistry, and real-time polymerase chain reaction. Administration of GGEx18 at 500 mg/kg/day to obese mice decreased body weight gain, mesenteric adipose tissue mass, and adipocyte size. GGEx18 treatment not only reduced mast cells and CD68-immunoreactive cells, but also decreased collagen levels and ${\alpha}$-smooth muscle actin-positive cells in the pancreas of HFD-fed mice. Concomitantly, GGEx18 decreased the expression of genes for inflammation (i.e., CD68 and tumor necrosis factor ${\alpha}$) and fibrosis (i.e., collagen ${\alpha}1$ and transforming growth factor ${\beta}$) in the pancreas of obese mice. These results suggest that GGEx18 may inhibit visceral obesity and related pancreatic fibroinflammation in HFD-fed obese mice.

• Archives of Pharmacal Research
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• v.29 no.9
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• pp.762-767
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• 2006

Danshen is an herbal medication frequently used in oriental medicine to treat liver or kidney malfunction. In the course of our studies, we observed that compounds purified from Danshen exhibit an inhibitory activity against Discoidin Domain Receptor 2 (DDR2) tyrosine kinase. Through this inhibition, these compounds also inhibited the growth of HSC T6 cells and suppressed the expression of alpha-smooth muscle actin and MMP2, as well as collagen synthesis, all of which are increased in activated liver stellate cells. Given that activation of liver stellate cells is the hallmark of liver fibrosis and that DDR2 plays a critical role in this activation, these results suggest that one of the pharmacological activities of Danshen extract that protects the liver is the inhibition of key cell-signaling kinases, such as DDR2, in liver stellate cells.

• Korean Journal of Veterinary Research
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• v.55 no.1
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• pp.71-73
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• 2015

We report a spontaneous embryonal rhabdomyosarcoma in the abdominal cavity of an aged (88-week-old) Sprague-Dawley rat. The animal had a firm lobulated $5{\times}5{\times}4.5cm$ mass in the abdominal cavity that was whitish to tan with necrotic and hemorrhagic plaques. Microscopically, the mass contained nodules with spindle or globoid shaped neoplastic cells with abundant eosinophilic cytoplasm and round or elongated nuclei mixed with other spindle cells with a filamentous appearance and scanty cytoplasm. Multinucleated cells and cross-striations were also observed. The neoplastic cells were positive for vimentin, desmin, and alpha-smooth muscle actin, especially the small spindle cells.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2005.11a
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• pp.90-91
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• 2005

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.1
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• pp.1-6
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• 2008

Ribbon-type antisense oligonucleotide to TGF-${\beta}1$ (TGF-${\beta}1$ RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by $CCl_4$ injection. When Hepa1c1c7 cells were transfected with TGF-${\beta}1$ RiAS, the level of TGF-${\beta}1$ mRNA was effectively reduced. TGF-${\beta}1$ RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-${\beta}1$ mRNA levels were significantly reduced only in the TGF-${\beta}1$ RiAS-treated group. The results of immunohistochemical studies showed that TGF-${\beta}1$ RiAS prevented the accumulation of collagen and ${\alpha}$-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-${\beta}1$ with efficient uptake can effectively prevent fibrosis of the liver.

• Development and Reproduction
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• v.11 no.2
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• pp.85-96
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• 2007

Mesenchymal stem cells (MSC) are promising candidates for cell-based therapies. One major obstacle for their clinical use is the unsafety of fetal bovine serum (FBS), which is a crucial part of all media currently used for the culture of MSC. We investigated the effect of human cord serum (HCS) on the growth response, mRNA and protein expressions of human amnion-derived stem cells (HAM). HAM were isolated from the amnion after a Caesarean section and cultured in DMEM supplemented with 10% FBS, 5% HCS or 10% HCS. During culture, their biological characteristics at earlier and later passages were analyzed using RT-PCR and immunocytochemistry. Regardless of serum sources, HAM showed the prominent expression of Oct-4, Rex-1, SCF, FGF-5, BMP-4, nestin, GATA-4, NCAM and HLA ABC genes. The expression profile was observed even at later passages. Similarly, HAM cultured in either FBS or HCS exhibited the distinct protein expression of collagen I, II, III and XII, fibronectin, $\alpha$-smooth muscle actin, vimentin, CK18, CD54, FSP, TRA-1-60, SSEA-3, -4 and HLA ABC. However, desmin expression was only observed in HAM cultured in medium supplemented with FBS and vWF expression was only found in HAM cultured in medium supplemented with HCS. Overall pattern of gene and protein expression of HAM was typical of known adult stem cells such as bone marrow-derived MSC. In conclusion, HCS could be as effective as FBS for the culture of HAM.

• Journal of the Korean Society for Precision Engineering
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• v.32 no.8
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• pp.755-760
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• 2015

For proper wound healing, dermal contraction and remodeling are critical; during the natural healing process, differentiated fibroblasts called "myofibroblasts" typically undertake these functions. For severe wounds, however, a critical mass of dermal matrix and fibroblasts are lost, making self-regeneration impossible. To overcome this impairment, synthetic wound patches with embedded functional cells can be used to promote healing. In this study, we developed a polydioxanone (PDO)-based cell-embedded sheet on which dermal fibroblasts were cultured and induced for differentiation into myofibroblasts, whereby the following combinatorial physicochemical stimuli were also applied: aligned topology, electric field (EF), and growth factor. The results show that both the aligned topology and EF synergistically enhanced the expression of alpha smooth-muscle actin (${\alpha}$-SMA), a key myofibroblast marker. Our proof-of-concept (POC) experiments demonstrated the potential applicability of a myofibroblast-embedded PDO sheet as a wound patch.

• Natural Product Sciences
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• v.20 no.4
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• pp.262-268
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• 2014

Rutaecarpine is one of the major alkaloids present in the fruits of Evodia rutaecarpa. In this study, rutaecarpine was evaluated, both in vitro and in vivo, for its hepatoprotective properties against thioacetamide (TAA)-induced hepatic fibrosis. The results showed that rutaecarpine inhibited TAA-induced cytotoxicity, reduced the expression of the fibrogenic cytokine transforming growth factor ${\beta}1$ ($TGF-{\beta}1$), and induced the expression of bcl-2. To evaluate its in vivo effects, animal models with TAA-induced hepatic fibrosis were utilized. Levels of liver tissue injury-associated enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were monitored. $TGF-{\beta}1$ and the ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) were measured as markers of the protective effects on hepatic fibrosis. The AST and ALT levels in blood were greatly enhanced by TAA and completely blunted by rutaecarpine. Rutaecarpine led to the down-regulation of $TGF-{\beta}$ and Bax mRNA expression, as well as the up-regulation of Bcl-2 and $Bcl-X_L$ mRNA levels. In conclusion, rutaecarpine inhibited TAA-induced hepatic fibrosis and apoptosis by inducing the expression of Bcl-2 while blocking $TGF-{\beta}1$ in our TAA-intoxicated model.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.315-320
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• 2008

This study investigated the signaling mechanisms contributed to the vasodilatory effects of HMC05, a herbal prescription. HMC05 acted in an endothelium-independent manner. To elucidate the fundamental mechanisms of its vascular actions, we focused on the signaling molecules involved in actin-myosin filament regulation including 20 kDa myosin light chains (LC20), Rho-associated kinase (ROCK), PKC, JNK and extracellular signal-regulated protein kinase (ERK) in the endothelium-denuded thoracic aorta or isolated smooth muscle cells (SMCs). It lowered the phosphorylation level of LC20 and showed that ROCK, ERK, JNK and $PKC{\alpha}$ pathways played important roles in the effects, as confirmed by the observations with a specific inhibition or activation, and with the activity and the subcellular localization of these molecules. In particular, HMC05 dramatically inhibited the activity of ERK and the downstream signaling of ROCK. It also changed the subcellular localization of the phophorylated $PKC{\alpha}$ as well as the amount of phosphorylation. Taken together, these data indicate that the vascular relaxation effects of HMC05 are attributed to the regulation of these signaling mechanisms.