• Experimental and Molecular Medicine
• /
• 제50권11호
• /
• pp.9.1-9.10
• /
• 2018

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.

• Journal of Ginseng Research
• /
• 제37권4호
• /
• pp.379-388
• /
• 2013

Diabetic nephropathy is one of the serious complications in patients with either type 1 or 2 diabetes mellitus but current treatments remain unsatisfactory. Results of clinical research studies demonstrate that Panax ginseng can help adjust blood pressure and reduce blood sugar and may be advantageous in the treatment of tuberculosis and kidney damage in people with diabetes. The heat-processing method to strengthen the efficacy of P. ginseng has been well-defined based on a long history of ethnopharmacological evidence. The protective effects of P. ginseng on pathological conditions and renal damage associated with diabetic nephropathy in the animal models were markedly improved by heat-processing. The concentrations of less-polar ginsenosides (20(S)-Rg3, 20(R)-Rg3, Rg5, and Rk1) and maltol in P. ginseng were significantly increased in a heat-processing temperature-dependent manner. Based on researches in animal models of diabetes, ginsenoside 20(S)-Rg3 and maltol were evaluated to have therapeutic potential against diabetic renal damage. These effects were achieved through the inhibition of inflammatory pathway activated by oxidative stress and advanced glycation endproducts. These findings indicate that ginsenoside 20(S)-Rg3 and maltol are important bioactive constituents of heat-processed ginseng in the control of pathological conditions associated with diabetic nephropathy.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권4호
• /
• pp.341-354
• /
• 2021

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

• 대한한방내과학회지
• /
• 제40권3호
• /
• pp.425-442
• /
• 2019

Objectives: This study aimed to reveal the pharmacological properties of the newly prescribed herbal mixture, Chenmadansamgamibokhap-tang(CDBT), against hypoxia-induced neuronal cell injury (especially mouse hippocampal neuronal cell line, HT-22 cells) and their corresponding mechanisms. Methods: A cell-based in vitro experiment, in which a hypoxia condition induced neuronal cell death, was performed. Various concentrations of the CDBT were pre-treated to the HT-22 cells for 4 h before 18 h in the hypoxia chamber. The glial cell BV-2 cells were stimulated with $IFN{\gamma}$ and LSP to produce inflammatory cytokines and reactive oxygen species. When the neuronal HT-22 cells were treated with this culture solution, the drug efficacy against neuronal cell death was examined. Results: CDBT showed cytotoxicity in the normal condition of HT-22 cells at a dose of $125{\mu}g/mL$ and showed a protective effect against hypoxia-induced neuronal cell death at a dose of $31.3{\mu}g/mL$. CDBT prevented hypoxia-induced neuronal cell death in a dose-dependent manner in the HT-22 cells by regulating $HIF1{\alpha}$ and cell death signaling. CDBT prevented neuronal cell death signals and DNA fragmentation due to the hypoxia condition. CDBT significantly reduced cellular oxidation, cell death signals, and caspase-3 activities due to microglial cell activations. Moreover, CDBT significantly ameliorated LPS-induced BV-2 cell activation and evoked cellular oxidation through the recovery of redox homeostasis. Conclusions: CDBT cam be considered as a vital therapeutic agent against neuronal cell deaths. Further studies are required to reveal the other functions of CDBT in vivo or in the clinical field.

• 한국콘텐츠학회논문지
• /
• 제19권9호
• /
• pp.338-347
• /
• 2019

본 연구에서는 노인의 삶의 질 향상을 위한 정책과 실천적 제언을 제공하려는 목적으로 노인의 심리 정서적 변인과 노인의 삶의 질에 대한 메타분석을 실시하였다. 총 65편의 학술지 논문을 선정해 위험요인과 보호요인으로 구분하여 메타분석을 진행한 결과, 심리 정서적 변인의 위험요인은 우울, 고독, 외로움, 불안, 스트레스 순으로 중간효과크기가 나타났으며 자살생각과 죽음불안은 작은 효과크기를 보였다. 보호요인으로는 자아존중감이 가장 큰 효과크기를 보였고 자아효능감, 자아통제 순으로 효과크기가 나타났다. 본 연구를 통해서 우울이 노인의 삶의 질에 중요한 영향요인이 되고 있음을 확인할 수 있었으며 노인의 삶의 질 향상을 위해서 우울을 조기발견하고 개입할 수 있는 게이트키퍼의 활용과 찾아가는 상담서비스의 확대가 필요하며 자살생각이나 죽음불안을 경감시키기 위해 죽음준비교육을 일반화시키고 자아존중감을 높이기 위해 노인에게 적합한 일자리를 창출하고 재능기부 및 자원봉사활동 참여 기회의 확대를 제언하였다.

• Biomolecules & Therapeutics
• /
• 제27권1호
• /
• pp.117-125
• /
• 2019

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

• Biomolecules & Therapeutics
• /
• 제29권5호
• /
• pp.536-544
• /
• 2021

5-amino salicylic acid (5-ASA) is a standard therapy for the treatment of mild to moderate forms of inflammatory bowel diseases (IBD) whereas more severe forms involve the use of steroids and immunosuppressive drugs. Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan that has shown epithelium protective effects in experimental colitis recently. In this study, both 5-ASA (30 mg/kg) and HA (15 mg/kg or 30 mg/kg) were administered rectally and investigated for their potential complementary therapeutic effects in moderate or severe murine colitis models. Intrarectal treatment of moderate and severe colitis with 5-ASA alone or HA alone at a dose of 30 mg/kg led to a significant decrease in clinical activity and histology scores, myeloperoxidase activity (MPO), TNF-α, IL-6 and IL-1β in colitis mice compared to untreated animals. The combination of HA (30 mg/kg) and 5-ASA in severe colitis led to a significant improvement of colitis compared to 5-ASA alone. Combined rectal therapy with HA and 5-ASA could be a treatment alternative for severe cases of IBD as it was the only treatment tested that was not significantly different from the healthy control group. This study further underlines the benefit of searching for yet unexplored drug combinations that show therapeutic potential in IBD without the need of designing completely new drug entities.

• 한국식품영양학회지
• /
• 제35권6호
• /
• pp.513-520
• /
• 2022

The purpose of this study was to investigate the effect of Cheonggukjang pills with aronia and blueberries on dextran sulfate sodium (DSS)-induced colitis in mice. There have been several reports that Cheonggukjang is effective for intestinal health, but the efficacy of Cheonggukjang containing fruits has not yet been reported. In this study, we showed the effect of cheonggukjang pills with blueberries and aronia (CPBA) on DSS-induced colitis in BALB/c mice. CPBA was obtained from Soonchang Moonokae foods and orally administered once a day for 2 weeks before DSS treatment. Colitis was induced in mice by feeding 5% (w/v) DSS drinking water for 7 days. The results showed that CPBA treatment significantly alleviated DSS-induced disease activity index associated with a decrease in colon length. CPBA improved DSS-induced histological changes and intestinal epithelial barrier integrity in mice colon. In addition, CPBA administration significantly reduced the levels of DSS-mediated interferon-γ and interleukin-6 in serum and tumor necrosis factor-α in colon tissue. Moreover, the gene expression of COX-2 and iNOS, which are factors involved in inflammatory signaling, was significantly reduced by CPBA treatment. These results suggest that CPBA have a protective effect against DSS-induced mice colitis and may be a candidate for colitis treatment.

• 생약학회지
• /
• 제53권4호
• /
• pp.213-225
• /
• 2022

Schisandra chinensis is widely known to regulate fatigue recovery, lowering blood pressure, and contains several bioactive compounds such as schizadran. In this study, we obtained basic data for the development of health food by measuring the schizandrin content, antioxidant activity, anti-inflammatory, antibacterial activity, and enzyme activity of the hot water extract (SCW) and 40% ethanol extract (SCE) of S. chinensis grown in Sunchang-gun, Korea. Schizandrin content was measured as 7.87 ± 0.01 mg/g for SCW and 10.38 ± 0.05 mg/g for SCE. SCE had higher DPPH and ABTS radical scavenging activity than SCW, and the total polyphenol and flavonoid contents were also higher. Both SCW and SCE (500 ㎍/mL) exhibited more than 55% protective effects against oxidative stress in HepG2 cell lines. Anti-inflammatory efficacy was assessed using RAW 264.7 and Caco-2 cells and both SCW and SCE do not have cytotoxic effects. Anti-inflammatory results showed concentration-dependent NO activity and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) inhibition. The antibacterial activity increased with increasing dose concentrations of SCW and SCE, and the MIC was 25 mg/mL for L. monocytogenes, S. typhimurium, and 75 mg/mL for H. pylori. In addition, amylase and protease enzyme activity was observed in both SCW and SCE.

• 대한본초학회지
• /
• 제28권2호
• /
• pp.83-92
• /
• 2013

Objectives : We investigated differances of physiological functionalities in the steamed Schisandrae Fructus. Methods : The samples were extracts of dryed schisandrae fructus without steaming process (S0), extracts of schisandrae fructus with three times steamed (S3), extracts of schisandrae fructus with five times steamed (S5) and extracts of schisandrae fructus with seven times steamed (S7). We analyzed contents of schisandrin, gomisin, total polyphenol and flavonoid and antioxidant activities. We researched antiinflammation effects for Raw264.7 cells. To evaluate liver protective activity, we measured AST, ALT and gamma-GTP in serum of alcoholic mice. Results : As the steaming number of schisandrae fructus increase, the contents of schisandrin and gomisin were more increased. The contents of total polyphenol of S5 and S7 were significantly increased compared to that of S0. DPPH free radical scavenging activities of S5 and S7 were significantly increased compared to that of S0, ABST radical scavenging activities of S3 and S5 were significantly increased compared to that of S0 in vitro. The NO production of all sample was significantly decreased compared to control, PGE2 release of S3, S5 and S7 were significantly decreased compared to control. IL-$1{\beta}$ release of S5 and S7 were significantly decreased. AST, ALT and gamma-GTP of S3, S5 and S7 were significantly decreased compared to control. Conclusions : We think that extracts of schisandrae fructus with steaming process may have more potential efficacy than a schisandrae fructus without steaming process.