• Journal of Ginseng Research
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• 제45권5호
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• pp.546-554
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• 2021

Background: Diabetes mellitus and hypertension often occur together, amplifying cardiovascular disease (CVD) risk and emphasizing the need for a multitargeted treatment approach. American ginseng (AG) and Korean Red Ginseng (KRG) species could improve glycemic control via complementary mechanisms. Additionally, a KRG-inherent component, ginsenoside Rg3, may moderate blood pressure (BP). Our objective was to investigate the therapeutic potential of coadministration of Rg3-enriched Korean Red Ginseng (Rg3-KRG) and AG, added to standard of care therapy, in the management of hypertension and cardiometabolic risk factors in type-2 diabetes. Methods: Within a randomized controlled, parallel design of 80 participants with type-2 diabetes (HbA1c: 6.5-8%) and hypertension (systolic BP: 140-160 mmHg or treated), supplementation with either 2.25 g/day of combined Rg3-KRG + AG or wheat-bran control was assessed over a 12-wk intervention period. The primary endpoint was ambulatory 24-h systolic BP. Additional endpoints included further hemodynamic assessment, glycemic control, plasma lipids and safety monitoring. Results: Combined ginseng intervention generated a mean ± SE decrease in primary endpoint of 24-h systolic BP (-3.98 ± 2.0 mmHg, p = 0.04). Additionally, there was a greater reduction in HbA1c (-0.35 ± 0.1% [-3.8 ± 1.1 mmol/mol], p = 0.02), and change in blood lipids: total cholesterol (-0.50 ± 0.2 mmol/l, p = 0.01), non-HDL-C (-0.54 ± 0.2 mmol/l, p = 0.01), triglycerides (-0.40 ± 0.2 mmol/l, p = 0.02) and LDL-C (-0.35 ± 0.2 mmol/l, p = 0.06) at 12 wks, relative to control. No adverse safety outcomes were observed. Conclusion: Coadministration of Rg3-KRG + AG is an effective addon for improving BP along with attaining favorable cardiometabolic outcomes in individuals with type 2 diabetes. Ginseng derivatives may offer clinical utility when included in the polypharmacy and lifestyle treatment of diabetes. Clinical trial registration: Clinicaltrials.gov identifier, NCT01578837;

• Korean Journal of Acupuncture
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• 제38권3호
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• pp.140-150
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• 2021

Objectives : The increase of osteoclasts could cause osteoporosis and bone-related diseases. Also, the inhibition of osteoclast differentiation is important in treating bone-related diseases. Traditionally, Psoraleae Semen has been used for geriatric diseases, aging and musculoskeletal diseases. The purpose of this study is to investigate the effect of Psoraleae Semen ethanol extract (PS) on osteoclast differentiation and its function. Methods : To confirm the effect of PS on osteoclastogenesis and bone resorption activity, various levels of concentrations of PS (5, 10, 20 and 40 ㎍/ml) were tested on RAW 264.7 cells cultured with RANKL. We measured tartarate-resistant acid phosphatase (TRAP)-positive cells, TRAP activity, pit formation and F-actin ring formation. The expressions of nuclear factor of activated T-cells (NFATc1) and c-Fos were confirmed through western blot and reverse transcription- polymerase chain reaction (RT-PCR). Also, the expression of bone resorption and fusion-related genes in osteoclast was confirmed by RT-PCR. Results : PS decreased the number of TRAP-positive cells and the TRAP activity. In addition, PS significantly inhibited the formation of pit and F-actin ring. Furthermore, PS decreased the expression of osteoclast related genes. Conclusions : PS inhibits osteoclast differentiation and bone resorption ability through inhibition of the expression of osteoclast-related genes. This indicates that PS may be a potential therapeutic agent to osteoporosis by suppressing osteoclastogenesis.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.321-330
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• 2021

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

• 생명과학회지
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• 제31권4호
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• pp.400-409
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• 2021

천연 benzophenanthridine alkaloid의 일종인 sanguinarine에 의한 인간 암세포에서의 세포사멸 유도는 암 치료를 위한 잠재적 치료 가능성으로 여겨져 왔으나 기본적인 항암 기전은 여전히 불분명하다. 종양 억제제 p53의 결실 또는 돌연변이는 결장암세포의 항암제 내성에 대한 주요 원인으로 작용하다. 따라서, 본 연구에서는 정상 p53을 가진 HCT116 (p53+/+) 및 p53이 결여된 HCT116 (p53-/-) 결장암세포를 대상으로 sanguinarine에 의해 유도되는 세포사멸에서 p53의 역할을 조사하였다. 본 연구의 결과에 의하면, sanguinarine은 HCT116 (p53-/-) 세포에 비하여 HCT116 (p53+/+) 세포의 생존력을 현저히 감소시켰다. 아울러 sanguinarine은 HCT116 (p53-/-) 세포보다 HCT116 (p53+/+) 세포에서 p53 및 cyclin-dependent kinase 억제제 p21^WAF1/CIP1의 발현을 증가시키면서 DNA 손상 및 세포사멸의 유도를 증가시켰다. Sanguinarine은 HCT116 (p53+/+) 세포에서 외인성 및 내인성 세포사멸의 개시에 관여하는 caspase-8 및 caspase-9의 활성을 증가시켰으며, 전형적인 효과기 caspase인 caspase-3을 활성화시켰다. 또한, sanguinarine은 HCT116 (p53+/+) 세포에서 Bax/Bcl-2의 발현 비율을 증가시키고 미토콘드리아 손상을 유발하였지만, HCT116 (p53-/-) 세포에서는 이러한 현상이 관찰되지 않았다. 결론적으로 본 연구의 결과는 sanguinarine은 HCT116 결장암세포에서 p53 의존적으로 외인성 및 내인성 세포사멸의 경로 활성을 통하여 세포사멸을 유도하였음을 의미한다.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.540-549
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• 2021

The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.

• Molecules and Cells
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• 제44권7호
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• pp.468-480
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• 2021

Ubiquitin D (UBD) is highly upregulated in many cancers, and plays a pivotal role in the pathophysiological processes of cancers. However, its roles and underlying mechanisms in oral squamous cell carcinoma (OSCC) are still unclear. In the present study, we investigated the role of UBD in patients with OSCC. Quantitative real-time polymerase chain reaction and Western blot were used to measure the expression of UBD in OSCC tissues. Immunohistochemistry assay was used to detect the differential expressions of UBD in 244 OSCC patients and 32 cases of normal oral mucosae. In addition, CCK-8, colony formation, wound healing and Transwell assays were performed to evaluate the effect of UBD on the cell proliferation, migration, and invasion in OSCC. Furthermore, a xenograft tumor model was established to verify the role of UBD on tumor formation in vivo. We found that UBD was upregulated in human OSCC tissues and cell lines and was associated with clinical and pathological features of patients. Moreover, the overexpression of UBD promoted the proliferation, migration and invasion of OSCC cells; however, the knockdown of UBD exerted the opposite effects. In this study, our results also suggested that UBD promoted OSCC progression through NF-κB signaling. Our findings indicated that UBD played a critical role in OSCC and may serve as a prognostic biomarker and potential therapeutic target for OSCC treatment.

• 산업식품공학
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• 제15권1호
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• pp.1-5
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• 2011

Codonopsis lanceolata L. (Campanulaceae) has long been used in traditional Korean medicine to treat bronchitis, cough, and inflammatory diseases, however, the efficacy of anti-tumor activities remains to be defined. In this study the effects of Codonopsis lanceolata (C. lanceolata) on proliferation, migration and adhesion in lung (A549, H1299) and ovarian cancer (SKOV-3) cells were investigated. To assess and compare the pharmacological effects and production places of C. lanceolata, the ethanolic extracts of C. lanceolata from different places in Korea (Hongseong, Yecheon, Yeongwol, Yanggu, Gangjin, and Hoengseong) were prepared. The extract from Hoengseong county did have only marginal anti-proliferative activity in all the cell lines tested, however, other extracts had little or no effect on cell proliferation. The extracts from Hongseong, Gangjin or Hoengseong county had partial anti-migratory activity in lung cancer cells, but not in ovarian cancer cells. In addition, the extract from Hoengseong county had partial anti-adhesive activity in ovarian cancer cells, however, other extracts did not affect cell adhesion in both lung and ovarian cancer cells. Taken together, these findings provide the first description of anti-tumor efficacy of C. lanceolata from different production places in Korea, and suggest that C. lanceolata from Hoengseong county may have therapeutic potential in lung and ovarian cancers.

• 동의생리병리학회지
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• 제32권6호
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• pp.384-395
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• 2018

The aim of this study was to investigate whether a novel formulation of an herbal extracts has an inhibitory effect on obesity. To determine its anti-obesity effects, we performed anti-obesity-related experiments in vitro and in vivo. Thus, our present study was carried out to evaluate the anti-obesity effect of herbal extracts using a high fat diet (HFD)-induced obese mouse model and 3T3-L1 adipose cells. The effects of each herbal extracts on lipid accumulation in 3T3-L1 cells were examined using Oil Red O staining. Results showed that treatment with each herbal extracts at $10{\sim}100{\mu}g/ml$ had no effect on cell morphology and viability. Without evidence of toxicity, herbal extracts treatment decreased lipid accumulation compared with the untreated adipocytes controls as shown by the lower absorbance of Oil Red O stain. Futhermore, compared with control-differentiated mature adipocytes, each herbal extracts significantly inhibited lipid accumulation in mature 3T3-L1 adipocytes. In the HFD-fed obese mice, body weight, liver weight and white adipose tissue weights were significantly reduced by mixture of herbal extracts administration in mouse skin. Futhermore, we found that mixture of herbal extracts administration suppressed serum triglyceride (TG), and total cholesterol (TCHO) in HFD-induced obese mouse model. The mixture of herbal extracts of permeability was estimated by measuring the transepithelial electrical resistance (TEER) value in pig skin. The optimized formulations of herbal extracts (Test 3 formulation) showed skin permeation. However, test 1 formulation containing essential oil as enhancer showed maximum skin permeation. After confirming the enhanced skin permeability, in vivo studies were performed to assess whether skin irritation potential on the basis of a primary irritation index (PII) in rabbit skin. Reactions were scored for erythema/edema reactions at 24 h, 48 h and 72 h post-application. It was concluded that the test 1 formulation was not irritation (PII = 0). The present study suggests that the test 1 formulation might be of therapeutic interest with respect to the treatment of obesity.

• Parasites, Hosts and Diseases
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• 제57권4호
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• pp.341-357
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• 2019

Acanthamoeba, one of free-living amoebae (FLA), remains a high risk of direct contact with this protozoan parasite which is ubiquitous in nature and man-made environment. This pathogenic FLA can cause sight-threatening amoebic keratitis (AK) and fatal granulomatous amoebic encephalitis (GAE) though these cases may not commonly be reported in our clinical settings. Acanthamoeba has been detected from different environmental sources namely; soil, water, hotspring, swimming pool, air-conditioner, or contact lens storage cases. The identification of Acanthamoeba is based on morphological appearance and molecular techniques using PCR and DNA sequencing for clinico-epidemiological purposes. Recent treatments have long been ineffective against Acanthamoeba cyst, novel anti-Acanthamoeba agents have therefore been extensively investigated. There are efforts to utilize synthetic chemicals, lead compounds from medicinal plant extracts, and animal products to combat Acanthamoeba infection. Applied nanotechnology, an advanced technology, has shown to enhance the anti-Acanthamoeba activity in the encapsulated nanoparticles leading to new therapeutic options. This review attempts to provide an overview of the available data and studies on the occurrence of pathogenic Acanthamoeba among the Association of Southeast Asian Nations (ASEAN) members with the aim of identifying some potential contributing factors such as distribution, demographic profile of the patients, possible source of the parasite, mode of transmission and treatment. Further, this review attempts to provide future direction for prevention and control of the Acanthamoeba infection.

• 생명과학회지
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• 제29권9호
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• pp.941-948
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• 2019

Ziyuglycoside-II ($3{\beta}-3-{\alpha}$-1-arabinopyranosyloxy-19-hydroxyurs-12-en-28-oicacid)는 오이풀(Sanguisorba officinalis L.)의 주요 활성 화합물 중 하나로 지혈작용, 항산화활성, 항염증활성 등의 활성이 보고되어 있다. 그러나 염증성 대장암에서의 ziyuglycoside-II의 활성에 관해서는 아직 보고되지 않아 본 연구에서 azoxymethane (AOM)/dextran sulfate sodium (DSS)으로 유발된 대장암 모델에서 ziyuglycoside-II 항종양활성을 조사하였다. 염증성 대장암을 유발하기 위해 BALB/c 마우스에게 AOM을 1회 복강 주사하고 AOM 투여 1주일 후 총 3 cycle의 2% 농도의 DSS를 음용수로 공급 하였다. Ziyuglycoside-II (1 또는 5 mg/kg)는 1주일에 3회 경구 투여하고, 64일에 대장을 적출하였다. 대장 조직에서의 종양 개수를 관찰한 결과 ziyuglycoside-II의 투여가 종양의 형성을 유의적으로 감소시키는 것을 확인하였다. 또한 Western blot 방법과 면역 조직학 분석의 결과, ziyuglycoside-II의 투여가 대장 조직에서 nuclear factor kappa-B 양성 세포와 염증 관련 단백질의 양을 현저히 감소시킴을 관찰하였다. 또한 ziyuglycoside-II 투여에 의해 대장조직내의 세포사멸이 촉진되었고 cleaved-caspase 3, cleaved-caspase 7과 같은 세포사멸 관련 단백질의 발현이 증가함을 확인하였다. 이러한 결과는 ziyuglycoside-II의 투여가 염증반응을 억제하고 세포 자멸을 유도하여 염증성대장암의 발생을 억제함을 시사하고 있다.