• Natural Product Sciences
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• 제29권1호
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• pp.31-37
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• 2023

In this study, we investigated the efficacy of Celtis choseniana Nakai (C. choseniana) as complementary herbal medicine to ameliorate androgenic alopecia (AGA). The effects of C. choseniana on AGA were evaluated using testosterone propionate-induced AGA mouse model and dihydrotestosterone-treated human hair follicle dermal papilla cells. In vivo, C. choseniana treatment deactivated androgen signaling by reducing the concentration of serum dihydrotestosterone level and expressions of 5α-reductase 2 and androgen receptor. Next, C. choseniana treatment increased the hair regrowth rate. Histological studies demonstrated that C. choseniana induced the anagen phase in testosterone propionate-induced AGA mouse model. Cellular proliferation was promoted by C. choseniana treatment via increasing the expression of proliferation factors, such as proliferating cell nuclear antigen and cyclin D1. Furthermore, C. choseniana treatment increased the expression of proteins related to the Wnt/β-catenin signaling pathway. In addition, dickkopf-1, a Wnt inhibitor, was downregulated with C. choseniana treatment. Likewise, C. choseniana treatment promoted cellular proliferation in vitro. This study demonstrated the inhibitory effect of C. choseniana on androgen-induced AGA. Moreover, C. choseniana induced activation of Wnt/β-catenin signaling, resulting in prolonged anagen and cellular proliferation. Therefore, we suggest that C. choseniana can be used as a therapeutic agent to alleviate AGA.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.28-37
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• 2022

Treatment options for patients with chronic kidney disease (CKD) are currently limited; therefore, there has been significant interest in applying mesenchymal stem/stromal cell (MSC)-based therapy to treat CKD. However, MSCs harvested from CKD patients tend to show diminished viability and proliferation due to sustained exposure to uremic toxins in the CKD environment, which limits their utility for cell therapy. The application of melatonin has been demonstrated to improve the therapeutic efficacy of MSCs derived from and engrafted to tissues in patients suffering from CKD, although the underlying biological mechanism has not been elucidated. In this study, we observed overexpression of hexokinase-2 (HK2) in serum samples of CKD patients and MSCs harvested from an adenine-fed CKD mouse model (CKD-mMSCs). HK2 upregulation led to increased production levels of methylglyoxal (MG), a toxic metabolic intermediate of abnormal glycolytic processes. The overabundance of HK2 and MG was associated with impaired mitochondrial function and low cell proliferation in CKD-mMSCs. Melatonin treatment inhibited the increases in HK2 and MG levels, and further improved mitochondrial function, glycolytic metabolism, and cell proliferation. Our findings suggest that identifying and characterizing metabolic regulators such as HK2 in CKD may improve the efficacy of MSCs for treating CKD and other kidney disorders.

• Journal of Ginseng Research
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• 제47권3호
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• pp.385-389
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• 2023

Background: Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance. Previously, we showed that ginseng did not demonstrate estrogenic property in ovariectomized mouse model. However, it is still possible that disruption of steroidogenesis leading to indirect hormonal activity. Methods: The hormonal activities were examined in compliance with OECD guidelines for detecting endocrine disrupting chemicals: test guideline (TG) No. 456 (an in vitro assay method for detecting steroidogenesis property) and TG No. 440 (an in vivo short-term screening method for chemicals with uterotrophic property). Results: Korean Red Ginseng (KRG) and ginsenosides Rb1, Rg1, and Rg3 did not interfere with estrogen and testosterone hormone synthesis as examined in H295 cells according to TG 456. KRG treatment to ovariectomized mice did not show a significant change in uterine weight. In addition, serum estrogen and testosterone levels were not change by KRG intake. Conclusion: These results clearly demonstrate that there is no steroidogenic activity associated with KRG and no disruption of the hypothalamic-pituitary-gonadal axis by KRG. Additional tests will be performed in pursuit of cellular molecular targets of ginseng to manifest mode of action.

• 대한한의학회지
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• 제32권6호
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• pp.41-53
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• 2011

Objectives: This study was performed to investigate the effect of Jaeumgeonbigagamtang (JGT) onrestraint-induced oxidative stress in the mouse brain. Methods: After treatment with JGT, CBC, ROS, MDA, TAC, SOD, activity of catalase, and total GSH content were analyzed. Results: JGT had a strong antioxidant activity by in vitro assay as presented GEAC. JGT treatment significantly ameliorated decrease of blood WBC and increase of platelet count. JGT (50mg/kg) treatment significantly ameliorated increase of MDA and GSH content level in brain tissue. JGT (100mg/kg) treatment significantly ameliorated increase of MDA and activity of TAC level in brain tissue. JGT (200mg/kg) treatment significantly ameliorated increase of ROS, MDA, activity of TAC level and depletion of catalase level in brain tissue. Conclusion: The present study demonstrated antioxidant activity in brain tissue. This result would be consistent with the long clinical efficacy of JGT, and this finding may provide a strong possibility of JGT as a drug candidate for brain-specific multiple disorders and symptoms.

• Current Optics and Photonics
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• 제3권6호
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• pp.555-565
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• 2019

Development of a biomarker for predicting tumor-treatment efficacy is a matter of great concern, to reduce time, medical expense, and effort in oncology therapy. In a preclinical study, we hypothesized that the blood-flow parameter based on laser speckle flowmetry (LSF) could be a potential indicator to estimate the efficacy of breast-cancer treatment. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber applied to a nude mouse, and the change in blood flow rate (BFR) - or the speckle flow index (SFI) is used together as the same meaning in this manuscript - was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily LSF angiogram, several BFR parameters (baseline SFI, normalized SFI, and △rBFR) were compared to tumor size in the normal, treated, and untreated tumor groups. Despite the incomplete tumor treatment, we found that the daily changes in all BFR parameters tended to have partially positive correlation with tumor size. Moreover, we observed that the changes in baseline SFI and normalized SFI responded one day earlier than the tumor shrinkage during chemotherapy. However, daily variations in the hypercapnia-induced △rBFR lagged tumor shrinkage by one day. This study would contribute not only to evaluating tumor vascular response to treatment, but also to monitoring blood-flow-mediated diseases (in brain, skin, and retina) by using LSF in preclinical settings.

• 한방안이비인후피부과학회지
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• 제19권2호
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• pp.1-18
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• 2006

Objective : Although management of asthma has become increasingly effective, its cure remains elusive, necessitating a new modality to prevent or eliminate causes triggering clinical progress. Based in the clinical experiences, a novel decoration Cheongsangbiyeum (CSB), has been developed to treat asthma, which consists of Polyporus, Semen Myristicae, Pericarpium citri Reticulatae, Rhizoma Cimicifugae, Cortex Albizziae, Fructus Rubi, Rhizoma Zedoariae, and Rhizoma Rhei. In the current study, its anti-asthmatic efficacy was evaluated using a mouse model of asthma. Methods : Experimental allergic asthma was induced by repeated intraperitioneal sensitization and intranasal challenge of ovalbumin (OVA). Water extract of CSB (1 mg/mouse/day) was administrated orally whereas control mice on given with identical volume of phosphate-buffered saline (PBS) for 5 days during the course of antigen challenge. When airway hyperreactivity(AHR) measured by ${\bata}-methacoline-induced$ airflow obstruction was compared, AHR of CSB-treated mice was significantly lower than those of control mice, indicating that CM extract can attenuate an asthmatic symptom. Airway recruitment of leukocytes and eosinophils was also markedly reduced by CSB treatment suggesting that oral treatment of CSB can alleviate the airway inflammation. For a better understanding of possible mechanisms underlying anti-asthmatic effet of CSB, cytokine (IL-4, IL-5, IL-13 and $IFN{\gamma}$ levels in bronchoalveola lavage fluid (BALF) and lung tissues were determined. Results : The results showed that cytokine levels were significantly lowered by CSB treatment. Additionally, number of draining lymph node cells was significantly lower than those of control mice. These data indicate that CSB suppress in vivo allergen-specific response. However, notably, levels of type 2 cytokines such as IL-5 and IL-13 were more profoundly influenced. Moreover, in vitro OVA-specific proliferative response and type 2 cytokine (IL-4, IL-5 and IL-13) production lymph node cells was markedly decreased in CSB-treated mice, whereas their $IFN{\gamma}$ production was not significantly altered Thrse data clearly showed a preferential inhibition of type 2 T cell (Th2) response by CSB treatment. This finding was also supported by serum antibody data showing that levels of OVA-specific type 2 antibodies, IgE and IgG1, in CSB-treated mice were significantly lower than in control mice, while type 1 antibody, IgG2a level m rather higher than controls, although the difference was in significant. Conclusions : In conclusion, oral administration of CSB attenuates asthmatic manifestations including AHR ad airway recruitment of eosinophils in a mouse model which possibly results from selective inhibition of Th2 cell response to allergen. Our data suggest a potential clinical application of CSB for control of allergic asthma.

• 대한예방한의학회지
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• 제27권3호
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• pp.35-46
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• 2023

Objectives : Gumiganghwal-tang and its main components have been used for treatment of cough, headache, joint pain and fever. Using a respiratory inflammatory model, we intend to demonstrate the its anti-inflammatory effect and immune mechanism of Gumiganghwal-tang. Methods : We induced the respiratory inflammation mouse model by papain treatment. Female BALB/C mice (8 weeks old) were divided into three groups as follows: saline control group, papain treatment group (vehicle), papain and Gumiganghwal-tang (200 mg/kg) treatment group (n=4). To verify the anti-inflammatory effect of Gumiganghwal-tang extracts, we measured the infiltration of inflammatory cells in bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF). Additionally, the efficacy of Gumiganghwal-tang extracts on Th2 cell population and alveolar macrophage in lung were analyzed by using flow cytometry. Results : Gumiganghwal-tang extracts administration decreased inflammatory cell infiltration in BALF and NALF, especially of eosinophils. Furthermore, interleukin-5 level was reduced in lung by drug administration. Interestingly, Gumiganghwal-tang extracts treatment also decreased the Th2 cell (CD4⁺GATA3⁺) population and increased the alveolar macrophage (CD11b⁺CD11c⁺) population in lung. Conclusions : Our findings indicate that Gumiganghwal-tang extracts have anti-inflammatory effects by mediating Th2 cell and alveolar macrophage cell activation.

• Biomolecules & Therapeutics
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• 제22권4호
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• pp.328-333
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• 2014

Vitiligo is a pigmentary disorder induced by a loss of melanocytes. In addition to replacement of pure melanocytes, cocultures of melanocytes with keratinocytes have been used to improve the repigmentation outcome in vitiligo treatment. We previously identified by in vitro studies, that adipose-derived stem cells (ADSCs) could be a potential substitute for keratinocytes in cocultures with melanocytes. In this study, the efficacy of pigmentation including durability of grafted melanocytes and short-term safety was examined in the nude mouse and Sprague-Dawley rat after grafting of primary cultured human melanocytes, with or without different ratios of primary cultured human ADSCs. Simultaneous grafting of melanocytes and ADSCs, which were separately cultured and mixed on grafting at the ratios of 1:1, 1:2, or 1:3, showed better efficacy than that of pure melanocytes. Grafting of melanocytes cocultured with ADSCs resulted in a similar outcome as the grafting of cell mixtures. Skin pigmentation by melanocytes : ADSCs at the ratios of 1:1 and 1:2 was better than at 1:3. No significant difference was observed between the 1-week and 2-week durations in coculturing. Time-course microscopic examination showed that the grafted melanocytes remained a little longer than 6-week post-grafting. No inflammatory cell infiltration was observed in the grafted skin and no melanocytes were detectable in other organs. Collectively, grafting of melanocytes and ADSCs was equally safe and more effective than grafting of melanocytes alone. Despite the absence of significant differences in efficacy between the group of 1:1 and that of 1:2 ratio, 1:2 ratio for 1-week coculturing may be better for clinical use from the cost-benefit viewpoint.

• 동의생리병리학회지
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• 제16권3호
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• pp.483-489
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• 2002

APA-01, which is an aqueous extract of five Chinese herbs, is a modified formula of Huoxiang-Zhengqi-San. The effect of new herb extract on immune response was investigated. The parameter examined to assess apparent immune response of APA-01 in mice included changes of body weight, relative weight of immune organs, cell proliferation and cytokine gene expression. The body weight and relative weight of immune organs were not significantly changed among the tested groups. In the spleen cell prolijeration assay, APA-01 increased the cell proliferation in a dose-dependent manner. Methotrexate (MTX), an agent of immune suppression, inhibited the spleen cell proliferation (IC/sub 50/: 800㎍/㎖). However, APA-01 significantly inhibited the suppression of mouse spleen cell proliferation. Therefore, it seems that APA-01 has a reducing effect of immune suppression. Immunomodulatory effect of APA-01 was further investigated using reverse transcription polymerase chain reaction (RT-PCR) in mouse spleen cells. In RT-PCR test, APA-01 enhanced the expression of cyclooxygenase-2 (COX-2) mRNA in a dose-dependent manner. In spite of immune suppression by MTX, COX-2 mRNA was induced by co-treatment with APA-01. These results suggest that APA-01 stimulates the proliferation of spleen cells, regulates the expression of COX-2 mRNA, and accelerates the recovery of inhibition of spleen cell proliferation induced by MTX, thus providing the immunological basis for clinical benefit of APA-01.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.231-236
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• 2011

The aim of this study was to investigate the effect of charge carrier lipid on the skin penetration, retention, and hair growth of topically applied finasteride-containing liposomes. Finasteride-containing liposomes were prepared by traditional thin film hydration method using Phospholipon$^{(R)}$ 85 G and cholesterol with or without charge carrier lipid (1,2 dimyristoyl-sn-glycero-3-phosphate or 1,2-dioleoyl-trimethylammonium-propane for anionic and cationic charge, respectively). Freshly prepared finasteride-containing liposome suspension was applied on the hairless mouse skin, and skin penetration and retention were measured using Keshary-Chien diffusion cell. Non-liposomal formulation (ethanol 10% solution containing 0.5 mg/ml of FNS) was also used as a control. The amount of finasteride in the diffusion cell and mouse skin was measured by HPLC. The hair growth was evaluated using depilated male C57BL/6N mice. Mean particle size of all finasteride-containing liposomes was less than a micron, and polydispersity index revealed size homogeneity. Skin penetration and retention studies showed that significantly less amount of finasteride was penetrated when applied as anionic liposome while more amount of the drug was retained. Specifically, in liposome prepared with 10% anionic charge carrier lipid, penetration was 12.99 ${\mu}g/cm^2$ while retention was 79.23 ${\mu}g/cm^2$ after 24 h of application. In hair growth study, finasteride-containing anionic liposomes showed moderate efficacy, but the efficacy was not found when applied as cationic liposomes. In conclusion, topical application of finasteride using anionic liposome formulation appears to be useful option for the treatment of androgenetic alopecia to avoid systemic side effects of the drug.