• 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.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.683-688
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• 2003

Caffeine (1,3,7-trimethylxanthine), a central nervous system stimulant, is contained in various foods, beverages and over-the-counter medications. Sulfadimethoxine (SDM) is one of the anti-thyroid agents and induces proliferation of thyroid capsule in two stage thyroid carcinogenesis model using N-bis(2-hydroxypropyl)nitrosamine (DHPN). In this study, we examined the effect of caffeine on fibrous proliferation of thyroid capsule in DHPN and SDM-treated rats. Five-week-old male F344 rats were given a single subcutaneous injection of DHPN (2,800 mg/kg, body weight). Starting one week thereafter, SDM (1,000 ppm in drinking water) with or without caffeine (1,500 ppm in diet) was administered for 12 weeks. All animals were autopsied and histopathological examination of the thyroid glands was performed. Thyroid follicular proliferative changes were induced in all rats treated with DHPN+SDM. In addition, the proliferation of perithyroidal fibrous tissue and pleomorphic thyroid follicular cells within the capsule were observed in DHPN+SDM treated group. Caffeine would not be related to these lesions in this experimental condition. although pentoxifylline, a methyl xanthine derivative, has an anti fibrotic effects.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.786-791
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• 1996

Systemic sclerosis is a multisystemic disease of unknown origin charicterized by degenerative fibrotic and inflammatory changes in the skin, vessels, joints, muscles, and visceral organs. Involvement of the lung in systemic sclerosis is common, but pleural effusion is rare. Although vasculitis commonly accompanies many connective tissue disorders, it has been rarely reported in systemic sclerosis. A 43-year-old woman, with a 10-year history of Raynaud's phenomenon, was admitted due to right chest pain. Her hands showed diffuse thickening and swelling of skin. Chest X-ray showed pleural effusions and esophageal manometry showed hypotonic peristalsis and low lower esophageal sphincter tone compatible with scleroderma esophagus. Antinuclear antibodies were present (titer>1 : 160) with a speckled pattern. She was positive for rheumatoid factor, anti scl-70 and RNP antibodies, but negative for anti-Ro, La, and Sm antibodies. Histology of the pleura revealed the presence of leukocytoclastic vasculiti. After adminisrration of prednisolone 30 mg/day, her chest symptom was improved. We report a case of systemic sclerosis with pleural effusions due to leukocytoclastic vasculitis with review of the literatures.

• 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.

• 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.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.45.1-45.22
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• 2023

Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.871-886
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• 2008

Objective : Gypsum fibrosum has been traditionally used in treatment of febrile diseases and recently been shown to have anti-inflammatory effect. Chronic renal failure has a serious clinical symptoms including proteinuria, azotemia, anemia, and hyperlipidemia and has characteristic histopathological changes, glomerular hypertrophy, infiltration of inflammatory cells, and crescentic sclerosis, We investigated the effects of gypsum fibrosum on renal functional and histopathological disorder in chronic renal failure rat model induced 5/6 nephrectomy. Methods : Using Sprague-Dawley rats, CRF was induced by 5/6 nephrectomy. The rats were divided into 3 groups, normal, conrol, and gypsum administered orally with gypsum fibrosum 500mg/kg/day. Body weight, 24 hr proteinuria, hematologic analysis, and histological morphologic changes were followed up after 8 weeks. The glomerular macrophage/monocyte infiltration, $TGF-{\beta}_1$, type IV collagen, and angiotensin II type1 receptor($AT_1$) were evaluated by immunohistochemistry. Resuls : In the CRF control group, functional parameters and histopathologic changes clearly indicated the development of CRF. 24 hr proteinuria significantly increased in the CRF control group over the normal group, and serum creatinine level was lower in the gypsum group than in the control group, LDL-cholesterol was significantly lower in the gypsum group than in the control group. Morphological investigations showed a variety of characteristic features of CRF, glomerular hypertrophy, increasing cellular density of glomerulus, deposition of extra-cellular matrix, fibrotic change, and glomerular sclerosis in the control group, but in the gypsum group, these features diminished significantly. In observation of renal type IV collagen and $AT_1$ expression, positive area significantly increased in the control group over the normal group, and it significantly decreased in the gypsum group compared to the control group. Conclusions : Our findings suggest that gypsum fibrosum inhibits $AT_1$ and type IV collagen expression in renal tissues and attenuates progression of glomerulosclerosis and interstitial fibrosis in chronic renal failure rats, which lead to amelioration of renal function. From these results, we suggest that gypsum fibrosum may have renoprotective effects and could be a useful remedy agent for treating chronic renal failure.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5405-5408
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• 2012

Curcumin (CM), a biphenyl compound, possesses anti-inflammatory, antioxidant and antimicrobial activity. MicroRNAs (miRNAs) are small noncoding RNAs which regulate gene expression and the molecular mechanisms of several biological processes. Liver fibrosis is a major cause of hepatic dysfunction and cancer and there are few effective therapies emphasizing the need for new approaches to control. The present study was conducted to investigate the effect of curcumin (CM) on liver fibrosis through modulating the expression level of miRNAs (199 and 200), the main miRNAs associated with liver fibrosis. Induction of liver fibrosis by carbon tetrachloride ($CCL_4$) was confirmed by histopathological examination. Mice were divided into 3 groups: group 1 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by 4 weeks with olive oil only. Group 2 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by curcumin (5 mg/mouse/day) once daily for the next 4 weeks. The third group was injected with olive oil. The expression level of miR-199 and miR-200 and some of their targeted genes were measured by real time PCR. miRNA (199 and 200) levels were significantly elevated in liver fibrotic tissues compared to control groups. Curcumin was significantly returned the expression levels of mir-199 and -200 with their associated target gene nearly to their normal levels. This is the first study that highlighted the effect of curcumin on liver fibrosis through regulation of miRNAs.

• Herbal Formula Science
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• v.28 no.4
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• pp.429-441
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• 2020

Objectives : Systemic sclerosis(SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs and vasculopathy. The purpose of this study was to investigate the trend in the research on SSc using herbal medicine. Methods : We searched for papers which had both systemic sclerosis and herbal medicine from Pubmed, KCI and NDSL. After searching papers, we classified according to the study design and analyzed selected studies. Results : 18 studies were searched. The types and numbers of study were as follows: 11 were in vitro or in vivo studies using herbal medicine or active components, and 7 were clinical research including case reports. 1. Herbal medicines include the therapeutic effects of "tonifying qi(補氣)" or "active blood(活血)" improved systemic sclerosis in vivo and in vitro studies. 2. Active components isolated from Herbal Medicine such as Astragalus membranaceus(黃芪), Zhizi(梔子), Salvia miltiorrhiza(丹蔘) have anti-fibrotic effects. 3. Clinical trials showed that herbal medicine can improve the symptom of systemic sclerosis including skin fibrosis, Raynaud's phenomenon, pain and gastric dysmotility. Conclusions : This study showed that herbal medicine can be effective for treating SSc. However, further studies are needed to develop novel medicine for SSc.