Objective: Anthocyanins belong to a class of flavonoids, exhibiting antioxidant and anti-inflammatory actions have been reported to have anti-cancer effects. Here, we investigated whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in human lung cancer A549 cells, which are critically involved in cancer metastasis. Methods: We used anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) which has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. We have performed cell proliferation assays, cell invasion assay, gelatin zymography, wound healing assay and western blotting to examine whether anthocyanins can inhibit cancer cell proliferation, invasion, and angiogenesis in A549 cells. Result: AIMs did not inhibit cancer cell proliferation on A549 cells. Also, AIMs suppressed cancer migration, and invasion by supressing MMP-2 and MMP-9 expression. The Immuno-blotting results also revealed that AIMs suppressed the proteins involved in cancer proliferation (COX-2, C-myc, cyclin D1), migration and invasion (MMP-2, MMP-9), anti-apoptosis (XIAP, and c-IAP2), adhesion and angiogenesis (ICAM-1, VEGF). Conclusion: This study demonstrates that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat inhibit cancer proliferation, cancer migration, and invasion that is involve in cancer-metastasis. This study provides evidence that AIMs might have anti-cancer effects on human lung cancer.
Jae Young Shin;Ji Hyeon Park;Byoung Ok Cho;Eun Seo Kang;Mi Hyun Joo;Young-Soo Kim;Seon Il Jang
Food Science and Preservation
/
v.31
no.4
/
pp.590-600
/
2024
Angelica keiskei, a perennial herb from Apiaceae family, has been reported to improve diabetes, inhibit thrombosis, alleviate dyslipidemia, and prevent type 2 diabetes, obesity, and atherosclerosis. In this study, the protective effects of A. keiskei extract (AKE) against tumor necrosis factor-alpha (TNF-α)-induced oxidative stress and vascular inflammation in human umbilical vein endothelial cells (HUVECs) were investigated through cell viability analysis, antioxidant enzyme analysis, western blotting, and immunofluorescence staining. The results demonstrated that pretreatment of Angelica keiskei with AKE significantly inhibited the expression of key adhesion molecules such as E-selectin, ICAM-1 and VCAM-1 induced by TNF-α. AKE also showed a substantial reduction in intracellular reactive oxygen species levels and an increase in antioxidant enzyme activity, indicating potential antioxidant capabilities. This study further explained that AKE interfered with the nuclear factor-kappa B (NF-κB) pathway by inhibiting phosphorylation of IκBα and NF-κB, thereby preventing nuclear translocation. Additionally, AKE selectively inhibited the activation of c-Jun N-terminal kinase (JNK) within the mitogen-activated protein kinase (MAPK) pathway, revealing a specific action mechanism. These findings collectively suggest that AKE possesses multi-faceted protective properties, making it a potential therapeutic agent for inflammatory conditions and early atherosclerosis.
Lee, Yun Jung;Yoon, Jung Joo;Lee, So Min;Kho, Min Chul;Kim, Hye Yoom;Ahn, You Mee;Kho, Joung Hyun;Lee, Kee Byoung;Lee, Ho Sub;Choi, Kyung Min;Kwon, Tae Oh;Kang, Dae Gill
Journal of Physiology & Pathology in Korean Medicine
/
v.26
no.5
/
pp.724-731
/
2012
This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM), traditional treatment for diabetes, ameliorates on high fructose-induced steatohepatitis and vascular inflammation. Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose diet alone for 8 weeks, with supplementation with MPM or rosiglitazone, peroxisome proliferators-activated receptor gamma ($PPAR{\gamma}$) agonist, occurring during the final 6 weeks. Treatment with MPM significantly prevented the increase in c-reactive protein (CRP) levels in the high fructose group. MPM suppressed high fructose diet-induced vascular inflammation marker expression such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. MPM also reduced intima/media thickness of thoracic aorta. Histologic observation and oil red O staining demonstrated hepatic tissue damage and lipid accumulation were severe in high fructose group. Treatment with MPM ameliorated hepatic tissue morphology with minimized steatosis. In addition, MPM attenuated hepatitis by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. MPM-fed group showed lower serum GOT and GPT levels comparing with high fructose group. MPM and rosiglitazone (positive control) significantly decreased the size of epididymal adipocytes. Taken together, the administration of MPM inhibited high fructose-induced steatohepatitis and vascular inflammation. These results suggested that MPM is useful in the prevention or treatment of metabolic syndrome-related disorders such as fatty acid metabolism and vascular homeostasis.
Objectives : Crohn's disease (CD) is characterized by a chronic relapsing inflammation of the bowel in which proinflammatory cytokines play an important perpetuating role. Methods : Mice (preventive animal model of gliotoxin) were treated with 5 % 2,4,6-trinitrobenzenesulfonic acid (TNBS) at day 1 and day 7. To investigate preventive effects of acupuncture with Gujin at $LI_{11}$, acupuncture was carried out at day -1, day 1, day 3. And, to investigate therapeutic effects, acupuncture with Gujin was carried out at day 3, day 5, day 7. For the data analysis, we checked weight and width of colon, diarrhea, edema, survival rate, changes of body weight, and myeloperoxygenase (MPO) activity. For analysing protein expression, we carried out immunohistochemical staining and Western blot and we analyzed mRNA expression by RT-PCR. Results : Colon of TNBS treated mice was erosive and shortening compared with the colon of control mice and induced damages of colon epithelial cell layer and induced infiltration of immune cells in all layer of colon. Acupuncture of gujin at $LI_{11}$ in preventive mode suppressed macorscopic damages such as erosive and shortening of colon by TNBS and damages of intestinal epithelial cells and infiltration of immune cells in the colon. The average weight of 5 cm distal colon was increased in TNBS treated mice (758${\mu}g$) compared with in control mice (112${\mu}g$) and width of distal colon was also increased in TNBS treated mice (4.9mm) compared with in control mice (1.3mm). Acupuncture with Gujin at $LI_{11}$ in preventive and therapeutic mode suppressed increase of colon weight and width by TNBS. TNBS induced edema of colon and diarrhea and Acupunctured with Gujin at $LI_{11}$ in preventive and therapeutic mode ameliorated these symptom by TNBS. In preventive and therapeutic mode, the effects of acupuncture with Gujin at $LI_{11}$ were increasing the motility, suppressing body weight decreasing, suppressing MPO activity, reducing expressing of TNF-${\alpha}$, IL-1b, and ICAM-1 in colon compared with that by TNBS Conclusions : This study demonstrates that acupuncture with Gujin at $LI_{11}$ represents a potential therapeutic method of Crohn's disease.
Chang, Woochul;Kim, Ran;Park, Sang In;Jung, Yu Jin;Ham, Onju;Lee, Jihyun;Kim, Ji Hyeong;Oh, Sekyung;Lee, Min Young;Kim, Jongmin;Park, Moon-Seo;Chung, Yong-An;Hwang, Ki-Chul;Maeng, Lee-So
Molecules and Cells
/
v.38
no.7
/
pp.643-650
/
2015
The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.
Na, Ha Gyoon;Park, Yuna;Kim, Min-Ah;Lee, Jin Woo;So, Gyeongseop;Kim, Sung Hyeok;Jang, Ki-Hyo;Kim, Mi-Ja;Namkoong, Seung;Koo, Hyun Jung;Lee, Sung Ryul;Sohn, Eun-Hwa
Journal of Microbiology and Biotechnology
/
v.29
no.5
/
pp.739-748
/
2019
Cheonggukjang and chaga mushrooms have numerous health benefits, and have been used in alternative medicine. Therefore, a powder mixture of 98: Cheonggukjang and 2: Chaga extracts was fermented with Lactobacillus acidophilus KCTC3925 (FCC) and its anti-obesity effects in high-fat diet (HFD)-induced obese mice were determined. Five-week-old male ICR mice were fed a normal diet or HFD in the presence or absence of 3% and 5% FCC by weight (n = 10 per group). After 12 weeks, the mice were sacrificed, and the serum and tissue samples were collected for analysis. Body weight and epididymal fat pad weight were significantly lowered in the 3% and 5% FCC groups compared with those in the HFD control group (p < 0.01). FCC supplementation suppressed serum triglyceride and increased serum HDL-C levels (p < 0.01). Serum GOT, GPT, and leptin levels, hepatic COX-2 mRNA expression, and splenic COX-2 and IL-4 mRNA expression were significantly higher in the HFD groups than in the control group (p > 0.05); however, except for splenic IL-4 levels, the increases were significantly attenuated by FCC supplementation. Expression of ICAM-1, an aortic inflammatory marker, was significantly increased in the HFD group; this effect was suppressed in the 3% FCC group (p < 0.01) but not in the 5% FCC group. FCC suppressed the body weight and epididymal fat pad weight gain, as well as inflammatory responses in the liver and spleen of HFD-fed mice. Thus, FCC supplementation will be beneficial for the treatment of obesity-related effects.
Objective : Asthma is known as chronic airway inflammatory disease. This inflammation is conducted by various inflammatory cells including eosihophil. Chemotaxis is one way that circulating inflammatory cells invade a specific lesion. This study examines the degree to which Lonicerae Flos inhibits eosinophil chemotaxis at pulmonary epithelium after allergic stimulation. Material and Methods : Water extracts of Lonicerae Flos and pulmonary epithelial cell lines A549(human type II-like epithelial cells) and human eosinophils were used. Cytotoxic effects of Lonicerae Flos via MTS assay were estimated, as well as the effects of Lonicerae Flos on chemokines from prestimulated A549 cells by sandwich ELISA and RT-PCR. Chemotaxis assay was conducted on prestimulated eosinophils treated with Lonicerae Flos. Result : In this study $TNF-{\alpha}$ and IL-4, $IL-l{\beta}$ were seen to induced the accumulation of chemokines mRNA in the pulmonary epithelial cell lines A549 in a dose-dependent manner. Chemokines were inhibited by Liripois Tuber in a dose-dependent manner and especially, IL-8 and ICAM-l were inhibited considerably at $100\;{\mu}g/ml$ concentration of Lonicerae Flos. The eosinophil migration is inhibited in high concentration of Lonicerae Flos in a dose-dependent manner. Conclusion : These findings indicate that the supression of the expression of chemokines can be accomplished by Lonicerae Flos treatment, raising the possibility that Lonicerae Flos might be of therapeutic value in diseases such as asthma.
Objectives : Smilacis glabrae rhizoma (SG) has been traditionally used as a herbal medication of musculoskeletal disorders like arthritis, pain, convulsions, and syphilis in traditional Korean medicine. This study was investigated anti-oxidative and anti-inflammatory effect of fractionated extracts of Smilacis Glabrae Rhizoma in Human Umbilical Vein Endothelial Cell (HUVEC). Methods : SG extract prepared with methanol, and then fractionated with hexane, dichloromethane, ethylacetate, n-butanol and water. Inhibitory effect of SG onto free radical generation was determined by measuring DPPH, superoxide anions and nitric oxide scavenging activities in vitro. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymethoxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Intracelluar oxidation was analysed by DCF-DA assay. The nitric oxide (NO) production was measured by Griess reagent system. The levels of ICAM-1 and VCAM-1 expression were confirmed by western blot. And proinflammatory cytokines were measured by ELISA kit. Results : Our results indicated that fractionated extracts, especially ethyl acetate (EA) extract, significantly inhibited free radical generation, the TNF-$\alpha$-induced intracellular oxidation. Furthermore, the EA extract protected TNF-$\alpha$-induced adhesion to THP-1, expression of adhesion molecules accompanied by an attenuation of IL-6 and IL-8 formation in HUVEC. Conclusions : These results indicate that EA extract of SG have potential as an agent of atherosclerosis and other chronic inflammatory diseases including diabetes, hypertension, and arthritis.
Sorbus commixta Hedl. has traditionally been used as a remedy for cough, asthma, and other bronchial disorders. In this study, three major triterpenoids-lupeol, β-sitosterol, and ursolic acid and a coumarin, scopoletin, were isolated from a CHCl3-soluble fragment of the bark of S. commixta. Their structures were identified by spectroscopic analyses, including mass spectrometry (MS), 1D-, and 2D- nuclear magnetic resonance spectroscopy (NMR), as well as by comparing the data with data reported in the literature. Scopoletin was isolated from this plant for the first time. It is a nutraceutical compound contained in many plants that has been reported to exert diverse biological activities, including anti-inflammatory effects. This study examined the inhibitory effect of scopoletin on TNF-α-induced vascular endothelial inflammation. Unlike the marginal impact of other compounds against low-density lipoprotein (LDL) oxidation and vascular endothelial inflammation, scopoletin showed remarkable activity on LDL oxidation (IC50 = 10.2 μM) and exerted vascular anti-inflammatory effects in EA.hy926 human endothelial cells activated by TNF-α. It suppressed the expression of adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, and blocked the adhesion between THP-1 monocytes and EA. hy926 endothelial cells. It also inhibited TNF-α-induced NF-κB translocation from the cytosol to the nucleus. Moreover, IκBα phosphorylation, which was increased by TNF-α treatment, was reduced after treatment with scopoletin. Thus, scopoletin inhibited TNF-α-induced vascular inflammation in endothelial cells by suppressing the NF-κB signaling pathway. These results demonstrate that owing to its anti-inflammatory activity in the vascular endothelium, scopoletin has the potential to inhibit atherosclerosis development.
Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors have been shown to decrease the growth of tumor, in part, by inhibition of neovascularization. Recently, besides mature endothelial cells, endothelial progenitor cells (EPCs) have been shown to contribute neovascularization in angiogenic tissues. In this study, we addressed a question whether nimesulide, a selective COX-2 inhibitor, could affect differentiation of EPCs into adhesive endothelial cells in vitro. Total mononuclear cells were isolated from cord blood by Ficoll density gradient centrifugation, and then the cells were incubated with nimesulide or vehicle control for 7 days. The number of adherent and spindle-shaped cells decreased by nimesulide treatment in a concentration-dependent fashion at a concentration range of 5 - 200 ${\mu}M$. Moreover, the adherent cells double positive for DiI-ac-LDL uptake and lectin binding significantly decreased upon nimesulide treatment. There was no change of expression of CD31 between treatment and control groups, whereas slight reduction was detected upon treatment in expression of VE-cadherin, ICAM-1, vWF, ${\alpha}v$, and ${\alpha}5$. Nimesulide also reduced cell viability during first 3 days' culture and induced apoptosis in adherent EPCs, resulting in increased annexin-V-positive and propidium iodide-negative cells. Taken together, these results suggest that nimesulide could be applied for the inhibition of new vessel formation, in part, by inhibiting differentiation and survival of EPCs.
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