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1.
Int J Mol Sci ; 22(12)2021 Jun 16.
Article in English | MEDLINE | ID: mdl-34208772

ABSTRACT

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells. Isookanin shows inhibitory effects in multiple stages of PGE2-induced angiogenesis, including the growth, proliferation, migration, and tube formation of microvascular endothelial cells. In addition, isookanin induces cell cycle arrest in S phase, which is also the reason for subsequent inhibition of cell proliferation. The mechanism of inhibiting angiogenesis by isookanin is related to the inhibition of PGE2-mediated ERK1/2 and CREB phosphorylation. These findings make isookanin a potential candidate for the treatment of angiogenesis-related diseases.


Subject(s)
Cell Cycle Checkpoints/drug effects , Chalcones/pharmacology , Cyclic AMP Response Element-Binding Protein/metabolism , Dinoprostone/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neovascularization, Physiologic/drug effects , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Humans , Models, Biological , Phosphorylation
2.
Molecules ; 26(2)2021 Jan 06.
Article in English | MEDLINE | ID: mdl-33419109

ABSTRACT

Bidens pilosa L. (Asteraceae) has been used historically in traditional Asian medicine and is known to have a variety of biological effects. However, the specific active compounds responsible for the individual pharmacological effects of Bidens pilosa L. (B. pilosa) extract have not yet been made clear. This study aimed to investigate the anti-inflammatory phytochemicals obtained from B. pilosa. We isolated a flavonoids-type phytochemical, isookanin, from B. pilosa through bioassay-guided fractionation based on its capacity to inhibit inflammation. Some of isookanin's biological properties have been reported; however, the anti-inflammatory mechanism of isookanin has not yet been studied. In the present study, we evaluated the anti-inflammatory activities of isookanin using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We have shown that isookanin reduces the production of proinflammatory mediators (nitric oxide, prostaglandin E2) by inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Isookanin also inhibited the expression of activator protein 1 (AP-1) and downregulated the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-jun NH2-terminal kinase (JNK) in the MAPK signaling pathway. Additionally, isookanin inhibited proinflammatory cytokines (tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß)) in LPS-induced THP-1 cells. These results demonstrate that isookanin could be a potential therapeutic candidate for inflammatory disease.


Subject(s)
Anti-Inflammatory Agents , Bidens/chemistry , Biological Assay , Chalcones , Macrophages/metabolism , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Chalcones/chemistry , Chalcones/isolation & purification , Chalcones/pharmacology , Humans , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/drug effects , Macrophages/pathology , Mice , Monokines/metabolism , RAW 264.7 Cells , THP-1 Cells
3.
Biochem Biophys Rep ; 30: 101256, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35368741

ABSTRACT

Immunostimulants play an important role in the treatment of immunodeficiency. Macrophages are the first line in our immune defense system and play a critical role in the immune response. Therefore, finding new and better substances to induce an immune response by activating macrophages is an attractive research topic, especially in the fields of immunopharmacology and cancer prevention. Keratinocytes actively crosstalk with immune cells during wound repair, so enhancing the function of keratinocytes is also an important part of improving immunity. Beta-glucans are naturally occurring polysaccharides, consisting of d-glucose monomers linked by beta-glycosidic bonds. Several studies have investigated the immunomodulatory effects of beta-glucan, such as its anti-inflammatory and antibacterial properties. However, the use of yeast cell wall glucan has been limited because it is not soluble in water. In this study, we produced low-molecular-weight water-soluble yeast glucan (WSY glucan) and confirmed various aspects of its immune-enhancing effect. The structure of the beta-(1→3) and (1→6) bonds of WSY glucan were confirmed by nuclear magnetic resonance spectroscopy (1H-NMR) analysis. Our results showed that treatment with WSY glucan significantly and dose-dependently induced the production of inflammatory mediators (prostaglandin E2 (PGE2) and nitric oxide (NO)) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-6) in macrophages. In addition, WSY glucan treatment showed changes in the morphological structure of the macrophages and promoted phagocytic activity of the macrophages and wound healing in keratinocytes. Based on these results, WSY glucan is considered as a potential candidate for the treatment of diseases related to the weakening of the immune system without the limitation of insolubility.

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