• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.1
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• pp.61-64
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• 2000

A series of 5-oxaproline peptide derivatives was synthesized and evaluated for its ability to inhibit the prolyl 4-hydroxylase in vitro. Structure-activity studies show that the 5-oxaproline sequences, prepared by the 1,3-dipolar cycloaddition of the C-methoxycarbonyl-N-mannosyl nitrone in the presence of the ethylene, are more active than the corresponding proline derivatives. Prolyl 4-hydroxylase belongs to a family of $Fe^{2+}-dependent$ dioxygenase, which catalyzes the formation of 4-hydroxyproline in collagens by the hydroxylation of proline residues in -Gly-Xaa-Pro-Gly- of procollagen chains. In this paper we discover the more selective N-Cbz-Gly-Phe-Pro-Gly-OEt $(K_m\;=\;520\;{\mu}M)$ sequences which are showed stronger binding than others in vitro. Therefore, we set out to investigate constrained tetrapeptide that was designed to mimic the proline structure of pep tides for the development of prolyl 4-hydroxylase inhibitor. From this result, we found that the most potent inhibitor is N-Dansyl-Gly-Phe-5-oxaPro-Gly-OEt $(K_i\;=\;1.6\;{\mu}M)$. This has prompted attempts to develop drugs which inhibit collagen synthesis. Prolyl 4-hydroxylase would seem a particularly suitable target for antifibrotic therapy.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.386-398
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• 2020

Tissue fibrosis is an eventual pathologic change of numerous chronic illnesses, which is characterized by resident fibroblasts differentiation into myofibroblasts during inflammation, coupled with excessive extracellular matrix deposition in tissues, ultimately leading to failure of normal organ function. Now, there are many mechanistic insights into the pathogenesis of tissue fibrosis, which facilitate the discovery of effective antifibrotic drugs. Moreover, many chronic diseases remain a significant clinical unmet need. For the past five years, many research works have undoubtedly addressed the functional dependency of ginsenosides in different types of fibrosis and the successful remission in various animal models treated with ginsenosides. Caveolin-1, interleukin, thrombospondin-1 (TSP-1), liver X receptors (LXRs), Nrf2, microRNA-27b, PPARδ-STAT3, liver kinase B1 (LKB1)-AMPK, and TGF-β1/Smads are potential therapy targeting using ginsenosides. Ginsenosides can play a targeting role and suppress chronic inflammatory response, collagen deposition, and epitheliale-mesenchymal transition (EMT), as well as myofibroblast activation to attenuate fibrosis. In this report, our aim was to focus on the therapeutic prospects of ginsenosides in fibrosis-related human diseases making use of results acquired from various animal models. These findings should provide important therapeutic clues and strategies for the exploration of new drugs for fibrosis treatment.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.619-627
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• 2004

Background : Corticosteroids in combination with cytotoxic drugs are the mainstays of therapy for idiopathic pulmonary fibrosis (IPF). However, there has been no regimen showing any survival benefit. The aim of this study was to describe a short-term clinical experience on interferon gamma-1b (IFN-${\gamma}1b$) therapy for IPF, as an antifibrotic agent. Methods : Medical records of 27 patients who were treated with IFN-${\gamma}1b$ (2 million IU, 3 times a week, subcutaneous injection) were retrospectively reviewed. Treatment response was assessed using ATS/ERS criteria in 17 patients who received IFN-${\gamma}1b$ for more than 6 months. In addition, we compared the efficacy of IFN-${\gamma}1b$ therapy with that of cyclophosphamide${\pm}$prednisolone therapy (n=26). Results : The median age of IFN-${\gamma}$ treated group (M:F=19:8) was 59 years (44-74 years). Compared to the patients who showed a stable response at 6 months (n=12), the deteriorated group (n=5) had worse baseline lung function (FVC, $55.4{\pm}11.3%$ vs. $70.7{\pm}10.9%$, p=0.019; DLco, $50.3{\pm}7.3%$ vs. $76.9{\pm}19.6%$, p=0.014). Lower baseline $PaO_2$ on room air breathing was observed in the deteriorated group ($68.6{\pm}7.8mmHg$ vs. $91.4{\pm}6.6mmHg$ p=0.001). Subcutaneous IFN-${\gamma}1b$ did not show better efficacy than prednisolone. Five patients discontinued IFN-${\gamma}$ because of severe side effects. ARDS developed in one patient, who eventually died. Conclusion : The administration of IFN-${\gamma}1b$ is not desirable for patients diagnosed with IPF with poor lung function. Long-term and large-scaled clinical studies are needed for its efficacy in IPF.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.4
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• pp.251-258
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• 2015

Curcumin, a major polyphenolic compound of turmeric, is well known to prevent non-alcoholic steatohepatitis (NASH) related to obesity. The aim of the study was to investigate the effect of curcumin on hepatic fibrosis induced by carbon tetrachloride ($CCl_4$) in obese mice. $CCl_4$ was administrated in mice fed a normal diet (ND) or a high fat diet (HFD) for 7 weeks together with or without curcumin. It was conducted to examine for metabolic profiles, adipocyte size, and liver fibrosis by serum biochemistry, histology and immunohistochemistry. Also, Apoptosis of hepatic cells was determined by the TUNEL method. Treatment with curcumin significantly lowered the body weight, fasting glucose, serum AST and ALT, and decreased the adipocyte size, the number of macrophage and mast cells in adipose tissue, and collagen deposition in liver tissue in the HFD+$CCl_4$ group compared with the findings of the HFD+$CCl_4$ group. In contrast, treatment with curcumin on the ND+$CCl_4$ group did not show a significant difference except the body weight and mast cell number when compared with the ND+$CCl_4$ group. Furthermore, curcumin significantly reduced the number of parenchymal apoptotic cells, whereas it increased the number of non-parenchymal apoptotic cells, especially resembling an activated hepatic stellate cell in the liver. Taken together, this data suggests that curcumin might be an effective antifibrotic drug for the prevention of liver disease progression in obese mice. Thus, the development of curcumin as a therapy for obesity and liver fibrosis is supported.

• 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.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.366-386
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• 2023

Objective: In this study, a questionnaire survey was conducted for doctors and patients to obtain basic data necessary for the development of an integrated medical system for idiopathic pulmonary fibrosis (IPF). Methods: Questionnaires were developed separately for doctors and patients through an expert group meeting. The survey subjects were recruited online and offline, and finally, responses from 231 doctors and 59 patients were used for statistical analysis. Results: The most important parts in the treatment of IPF for both doctors and patients were the "improvement of respiratory symptoms," "improvement of quality of life," and "prevention of disease progression." Antifibrotic agents were prescribed at a high rate, and 100% of the specialists in Western medicine (WM) and 45.8% of patients reported experiencing side effects. As for the additional payment costs that patients considered as affordable for an integrated medical system, "under 50,000 won (about 38$)" was reported the most in both doctor and patient groups. With regard to the reasons for their reluctance to recommend an integrated medical system for IPF, specialists in WM responded highly to "uncertain evidence for treatment effectiveness." Regarding complementary and alternative medicine therapies that can be beneficial in patients with IPF, "lifestyle management," "diet management," "herb," "relaxation therapy," and "psychotherapy" were ranked high in both doctor and patient groups. Conclusions: In this study, a questionnaire survey on IPF was conducted to review actual treatment status, analyze shortcomings, and identify considerations for the development of an integrated medical system for IPF in the future.