• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.87-94
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• 2022

Myocardial infarction promotes cardiac remodeling and myocardial fibrosis, thus leading to cardiac dysfunction or heart failure. Peiminine has been regarded as a traditional anti-fibrotic Chinese medicine in pulmonary fibrosis. However, the role of peiminine in myocardial infarction-induced myocardial injury and fibrosis remained elusive. Firstly, rat model of myocardial infarction was established using ligation of the left coronary artery, which were then intraperitoneally injected with 2 or 5 mg/kg peiminine once a day for 4 weeks. Echocardiography and haemodynamic evaluation results showed that peiminine treatment reduced left ventricular end-diastolic pressure, and enhanced maximum rate of increase/decrease of left ventricle pressure (± dP/dt max) and left ventricular systolic pressure, which ameliorate the cardiac function. Secondly, myocardial infarction-induced myocardial injury and infarct size were also attenuated by peiminine. Moreover, peiminine inhibited myocardial infarction-induced increase of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production, as well as the myocardial cell apoptosis, in the rats. Thirdly, peiminine also decreased the myocardial fibrosis related protein expression including collagen I and collagen III. Lastly, peiminine reduced the expression of p38 and phosphorylation of extracellular signal-regulated kinase 1/2 in rat model of myocardial infarction. In conclusion, peiminine has a cardioprotective effect against myocardial infarction-induced myocardial injury and fibrosis, which can be attributed to the inactivation of mitogen-activated protein kinase pathway.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.1
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• pp.49-54
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• 2011

A case of Behcet's syndrome found in a 22 years old male was is reported along with the histological and immunohistochemical studiesfindings. He The patient had had received prolonged medical therapy of anti-inflammatory agents for the conjunctival ulcer, genital ulcer, oral ulcer, and intestinal ulcers since the first onset of the Behcet's syndrome about approximately 7 years agoearlier. Recently, he felt the athickening of both corners of his lip causing that caused mouth opening difficultydifficulties. A plastic rReconstructive surgery was performed to enlarge the size of the oral orifice by multiple Z-plasty incisions, and finallywhich resulted in proper enlargement of the circumferential length of the lip. During the operation, a scar-like thick fibrous tissue was obtained and examined pathologically. In theThe microscopic observation the revealed the submucosal lesion was to be diffusely fibrosed with the a distribution of sclerotic collagen bundles. Particularly, sSeveral foci of collagen degeneration were found observed in the deep connective tissue, and the degenerating collagen bundles were gradually lost their fibrillar appearance. In the immunohistochemical observations, the foci of collagen degeneration was were strongly positive for IgK, but almost negative for TNF${\alpha}$ lysozyme, and MMP-3. Taken together, it was presumed that tThe submucosal fibrosis was presumed to have firstly presented in this study was probablybeeninduced by the prolonged anti-inflammatory therapy, which may inhibit the removal of sclerosed collagen bundles by the cell-mediated immunity and proteolytic digestion of macrophages, and that it was secondarily aggravated by the deposition of immunoglobulins derived from an autoimmune origin. Therefore, even after the successful plastic surgery of the lip to ameliorate the mouth opening difficulty, the recurrent submucosal fibrosis of lip should be carefully managed in the follow-up treatment.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.298-306
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• 2004

Objective : The main purpose of this study was to determine if Rehmanniae Radix has significant effects on lung fibrosis. Materials and Methods : C57BL/6J mice were devided into three groups. These were the normal group, which were not treated, the control group, given Intratracheal instillation(IT) of Bleomycin, the sample group, given IT of bleomycin and water-extracted Rehmanniae Radix. Animals were sacrificed 14 days after IT treatment. Lung fibrosis was evaluated by analysis of bronchoalveolar larvage(BAL) total WBC, percentage of macrophage, lymphocyte and neutrophil. This was done histologically by semiquantitative histological index(SHT) of lung tissue. Results : The sample group in coparison with control group showed a decrease in the BAL, total WBC, lower percentage of lymphocyte and neutrophil(p<0.05) and correspondingly a lower percentage of macrophage(p<0.01). The Sample group showed a significant decrease of collagen accumulation with respect to the control group in SHI of lung tissue(p<0.01). INF-${\gamma}$ and IL-4 levels in BALF of mice significantly decreased in the control group(p<0.05). Conclusions : Results suggest that Rehmanniae Radix has an anti-imflamatory effect and anti-fibrotic effect on the lungs through decrease of IL-4 and total WBC count for not only macrophage, but also lymphocyte and neutrophil. The degradation of INF-${\gamma}$ calls for research beyond the scope of this study.

• Herbal Formula Science
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• v.10 no.2
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• pp.225-241
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• 2002

The inhibitory effects of Injinseulki including extracts of melanian snail plus phytomedicinal plants on $CCl_4$-induced fibrosis, $IFN-{\gamma}$ plus LPS-induced production of NO, PMA-stimulated production $O_2$, and tacrine-induced hepatic injury were investigated in rats, RAW 264.7 or HepG2 cells. The ethanol extracts of melanian snail significantly inhibited tarcrine-induced inury of HepG2 cells. Injinseulki inhibited the production of NO and $O_2$ in a dose-dependent manner in activated RAW 264.7 macrophages. Injinseulki significantly inhibited chemical-induced fibrosis in Rats. These results show that Injinseulki including extracts of melanian snail plus phytomedicinal plants may explain some known biological activities of Injinseulki including their anti-inflammatory and anti-fibrotic effect, and is of considerable benefit in the treatment for live diseases.

• The Korea Journal of Herbology
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• v.28 no.4
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• pp.49-55
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• 2013

Objectives : Mori Folium was popularly used as one of the traditional medicinal herbs. Although M. Folium has been cultivated for rearing silkworm historically, it's use has been expanded as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. However, little has been known about the effect of M. Folium on liver fibrosis. Therefore, we would like to explore an anti-fibrogenic potential of M. Folium extract (MFE) using immortalized human hepatic stellate cell line, LX-2 cells. Methods : We examined the effects of MFE on the transforming growth factor ${\beta}1$ ($TGF{\beta}1$)-induced liver fibrosis in LX-2 cells. Cell viability, Smad binding element-driven luciferase activity, phosphorylations level of Smad 2/3, and expression level of $TGF{\beta}1$-dependent target genes were monitored in the MFE-treated LX-2 cells. Results : Up to 30 ${\mu}g/ml$ MFE treatment did not show any possible toxic effect in LX-2 cells. MFE inhibited $TGF{\beta}1$-inducible Smad binding element-driven luciferase activity and decreased the $TGF{\beta}1$-inducible phosphorylations of Smad 2 and Smad 3 in hepatic stellate cell in a dose dependent manner. Furthermore, increases of plasminogen activator inhibitor type 1, $TGF{\beta}1$ and matrix metalloproteinases 2 genes by $TGF{\beta}1$ were also attenuated by MFE treatment. Conclusions : These findings suggested that MFE would be used as a potential therapeutic agent for the treatment liver fibrosis, which might be mediated by the inhibition of $TGF{\beta}1$-inducible Smad 2/3 transactivation and target genes expression.

• Molecular Medicine Reports
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• v.20 no.4
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• pp.3709-3718
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• 2019

Chronic pancreatitis (CP) is characterized by recurrent pancreatic injury, resulting in inflammation and fibrosis. Currently, there are no drugs for the treatment of pancreatic fibrosis associated with CP. Piperine, a natural alkaloid found in black pepper, has been reported to show anti-inflammatory, anti-oxidative, and antitumor activities. Although piperine exhibits numerous properties in regards to the regulation of diverse diseases, the effects of piperine on CP have not been established. To investigate the effects of piperine on CP in vivo, we induced CP in mice through the repetitive administration of cerulein (50 ㎍/kg) six times at 1-h intervals, 5 times per week, for a total of 3 weeks. In the pre-treatment groups, piperine (1, 5, or 10 mg/kg) or corn oil were administrated orally at 1 h before the first cerulein injection, once a day, 5 times a week, for a total of 3 weeks. In the post-treatment groups, piperine (10 mg/kg) or corn oil was administered orally at 1 or 2 week after the first cerulein injection. Pancreases were collected for histological analysis. In addition, pancreatic stellate cells (PSCs) were isolated to examine the anti-fibrogenic effects and regulatory mechanisms of piperine. Piperine treatment significantly inhibited histological damage in the pancreas, increased the pancreatic acinar cell survival, reduced collagen deposition and reduced pro-inflammatory cytokines and chemokines. In addition, piperine treatment reduced the expression of fibrotic mediators, such as α-smooth muscle actin (α-SMA), collagen, and fibronectin 1 in the pancreas and PSCs. Moreover, piperine treatment reduced the production of transforming growth factor (TGF)-β in the pancreas and PSCs. Furthermore, piperine treatment inhibited TGF-β-induced pSMAD2/3 activation but not pSMAD1/5 in the PSCs. These findings suggest that piperine treatment ameliorates pancreatic fibrosis by inhibiting TGF-β/SMAD2/3 signaling during CP.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.515-523
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• 2023

Background: 20(S)-protopanaxadiol (PPD), one of the main components of ginseng, has anti-inflammatory, anti-estrogenic, and anti-tumor activities. It is known that activated hepatic stellate cells (HSCs) are the primary producers of extracellular matrix (ECM) in the liver, and the Wnt/β-catenin pathway participates in the activation of HSCs. We aimed to explore whether PPD inhibits liver fibrosis is associated with the Wnt/β-catenin pathway inactivation. Methods: The anti-fibrotic roles of PPD were examined both in vitro and in vivo. We also examined the levels of Wnt inhibitory factor 1 (WIF1), DNA methyltransferase 1 (DNMT1) and WIF1 methylation. Results: PPD obviously ameliorated liver fibrosis in carbon tetrachloride (CCl₄)-treated mice and reduced collagen deposition. PPD also suppressed the activation and proliferation of primary HSCs. Notably, PPD inhibited the Wnt/β-catenin pathway, reduced TCF activity, and increased P-β-catenin and GSK-3β levels. Interestingly, WIF1 was found to mediate the inactivation of the Wnt/β-catenin pathway in PPD-treated HSCs. WIF1 silencing suppressed the inhibitory effects of PPD on HSC activation and also restored α-SMA and type I collagen levels. The downregulation of WIF1 expression was associated with the methylation of its promoter. PPD induced WIF1 demethylation and restored WIF1 expression. Further experiments confirmed that DNMT1 overexpression blocked the effects of PPD on WIF1 expression and demethylation and enhanced HSC activation. Conclusion: PPD up-regulates WIF1 levels and impairs Wnt/β-catenin pathway activation via the downregulation of DNMT1-mediated WIF1 methylation, leading to HSC inactivation. Therefore, PPD may be a promising therapeutic drug for patients with liver fibrosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2613-2617
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• 2015

Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (< 6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and profibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.

• Molecules and Cells
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• v.26 no.6
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• pp.625-630
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• 2008

This study was undertaken with the aim of developing an easy and quick means of analyzing the effect of various compounds on the synthesis and secretion of human type I collagen at the protein level. A modification of the ELISA method was used on HFF-1 cells. For the proof of concept, we used thirteen compounds most of which are known to be antioxidants. Each compound was tested at concentrations of 0, 10 and $100{\mu}m$ on HFF-1 cells for 24 h. Thirteen sets of experiments for each compound were performed in ANOVA with three replicates. Duncan multiple range test (DMRT) was used to compare the mean values obtained from the treatment groups. From the results it was concluded that Vitamin C, undecylenic acid, conjugated linoleic acid, glycolic acid, and citric acid at $100{\mu}m$ concentration could be used for anti-wrinkling or protection from premature aging, which requires enhancement of collagen synthesis. Lactic acid, EGCG, resveratrol, and retinol that can inhibit collagen synthesis effectively in a dose-dependent manner may be used for anti-fibrosis treatment purposes.

• The Korea Journal of Herbology
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• v.39 no.4
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• pp.19-28
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• 2024

Objectives : Ephedrae Herba has been used in the East Asian traditional medicine, for treatment of asthma, cold and influenza. Silymarin is an effective antioxidant and its anti-fibrogenic, anti-inflammatory, and hepatoprotective properties have been reported. This study was performed to explore an anti-fibrogenic potential of Ephedrae Herba extract (EHE) + silymarin on immortalized human hepatic stellate cell line, LX-2 cells. Methods : We studied the anti-fibrogenic effects of EHE + silymarin on transforming growth factor β1 (TGF-β1) signaling pathway in LX-2 cells. Cell viability was measured using the MTT assay. mRNA levels were detected by real-time PCR. TGF-β1 signaling-related proteins expression were detected by Western blot. Results : Silymarin 30 ㎍/mL and EHE 100 ㎍/mL showed cytotoxicity on LX-2 cells. Therefore, the concentrations of silymarin and EHE were studied at 10 ㎍/mL, respectively. Silymarin significantly reduced PAI-1 protein expression, Smad binding element (SBE) luciferase activity, and mRNA (PAI-1, MMP2 and 9) expression compared to TGF-β1. EHE significantly reduced SBE luciferase activity and mRNA (PAI-1, MMP2 and 9) expression compared to TGF-β1. More importantly, EHE + silymarin significantly reduced all parameters compared to TGF-β1, and also significantly reduced compared to EHE alone and silymarin alone. Conclusion : The results indicate that EHE + silymarin has anti-fibrogenic effect in LX-2 cells induced by TGF-β1. Additionally, EHE + silymarin shows more effective anti-fibrogenic effect than EHE alone and silymarin alone.