ABSTRACT
BACKGROUND: Ellipticine (Ellip.) was recently reported to have beneficial effects on the differentiation of adipose-derived stem cells into mature chondrocyte-like cells. On the other hand, no practical results have been derived from the transplantation of bone marrow stem cells (BMSCs) in a rabbit osteoarthritis (OA) model. OBJECTIVES: This study examined whether autologous BMSCs incubated with ellipticine (Ellip.+BMSCs) could regenerate articular cartilage in rabbit OA, a model similar to degenerative arthritis in human beings. METHODS: A portion of rabbit articular cartilage was surgically removed, and Ellip.+BMSCs were transplanted into the lesion area. After two and four weeks of treatment, the serum levels of proinflammatory cytokines, i.e., tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2), were analyzed, while macroscopic and micro-computed tomography (CT) evaluations were conducted to determine the intensity of cartilage degeneration. Furthermore, immuno-blotting was performed to evaluate the mitogen-activated protein kinases, PI3K/Akt, and nuclear factor-κB (NF-κB) signaling in rabbit OA models. Histological staining was used to confirm the change in the pattern of collagen and proteoglycan in the articular cartilage matrix. RESULTS: The transplantation of Ellip.+BMSCs elicited a chondroprotective effect by reducing the inflammatory factors (TNF-α, PGE2) in a time-dependent manner. Macroscopic observations, micro-CT, and histological staining revealed articular cartilage regeneration with the downregulation of matrix-metallo proteinases (MMPs), preventing articular cartilage degradation. Furthermore, histological observations confirmed a significant boost in the production of chondrocytes, collagen, and proteoglycan compared to the control group. Western blotting data revealed the downregulation of the p38, PI3K-Akt, and NF-κB inflammatory pathways to attenuate inflammation. CONCLUSIONS: The transplantation of Ellip.+BMSCs normalized the OA condition by boosting the recovery of degenerated articular cartilage and inhibiting the catabolic signaling pathway.
Subject(s)
Cartilage, Articular , Ellipticines , Rabbits , Humans , Animals , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Ellipticines/metabolism , X-Ray Microtomography , Inflammation/veterinary , Proteoglycans/metabolism , Collagen/metabolism , Bone Marrow Cells/metabolismABSTRACT
Progressive aging harms bone tissue structure and function and, thus, requires effective therapies focusing on permanent tissue regeneration rather than partial cure, beginning with regenerative medicine. Due to advances in tissue engineering, stimulating osteogenesis with biomimetic nanoparticles to create a regenerative niche has gained attention for its efficacy and cost-effectiveness. In particular, hydroxyapatite (HAP, Ca10(PO4)6(OH)2) has gained significant interest in orthopedic applications as a major inorganic mineral of native bone. Recently, magnetic nanoparticles (MNPs) have also been noted for their multifunctional potential for hyperthermia, MRI contrast agents, drug delivery, and mechanosensitive receptor manipulation to induce cell differentiation, etc. Thus, the present study synthesizes HAP-decorated MNPs (MHAP NPs) via the wet chemical co-precipitation method. Synthesized MHAP NPs were evaluated against the preosteoblast MC3T3-E1 cells towards concentration-dependent cytotoxicity, proliferation, morphology staining, ROS generation, and osteogenic differentiation. The result evidenced that MHAP NPs concentration up to 10 µg/mL was non-toxic even with the time-dependent proliferation studies. As nanoparticle concentration increased, FACS apoptosis assay and ROS data showed a significant rise in apoptosis and ROS generation. The MC3T3-E1 cells cocultured with 5 µg/mL MHAP NPs showed significant osteogenic differentiation potential. Thus, MHAP NPs synthesized with simple wet chemistry could be employed in bone regenerative therapy.
Subject(s)
Nanoparticles , Tissue Engineering , Tissue Engineering/methods , Durapatite/chemistry , Osteogenesis , Reactive Oxygen Species , Cell Differentiation , Bone and Bones , Nanoparticles/chemistry , OsteoblastsABSTRACT
In the present study, we investigated whether treatment with KRG improve the parameters of immune activity such as the cytotoxicity, populations of CD4+ CD8+T cell, CD3-CD172-CD8+ NK cell and CD172+ monocyte as well as natural cytotoxicity receptors such as Nkp46, Nkp44, Nkp30. In results, KRG significantly increased these immune activities. These results indicate that KRG has distinct immune-enhancing effects by increasing the roles of T cells and NK cell in porcine.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Aiton (Family: Leguminosae), an herbal plant, has been used in East Asian home remedies for centuries for treating ulcers, skin burns, fevers, and inflammatory disorders. In addition, the dried root of S. flavescens was also applied for antipyretic, analgesic, antihelmintic, and stomachic uses. AIM OF STUDY: Nonetheless, how this plant can show various pharmacological activities including anti-inflammatory responses was not fully elucidated. In this study, therefore, we aimed to investigate the curative effects of S. flavescens on inflammation and its molecular mechanism. MATERIALS AND METHODS: For reaching this aim, various in vitro and in vivo experimental models with LPS-treated RAW264.7 cells, HCl/EtOH-induced gastric ulcer, and LPS-triggered lung injury conditions were employed and anti-inflammatory activity of S. flavescens methanol extract (Sf-ME) was also tested. Fingerprinting profile of Sf-ME was identified via LC-MS analysis. Its anti-inflammatory molecular mechanism was also examined by immunoblotting analysis. RESULTS: Nitric oxide production and mRNA expression levels of iNOS, COX-2, IL-1ß, and TNF-α were decreased. Additionally, phosphorylation of Src in the signaling cascade was decreased, and activities of the transcriptional factor NF-κB were reduced as determined by a luciferase reporter assay. Moreover, in vivo, gastritis and lung injury lesions were attenuated by Sf-ME. CONCLUSION: Taken together, these findings suggest that Sf-ME could be a potential anti-inflammatory therapeutic agent via suppression of Src kinase activity and regulation of IL-1ß secretion.
Subject(s)
Lung Injury , Methanol , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Lipopolysaccharides/pharmacology , Lung Injury/drug therapy , NF-kappa B/metabolism , Nitric Oxide/metabolism , Phosphorylation , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , RAW 264.7 Cells , Sophora flavescens , src-Family Kinases/metabolismABSTRACT
Ultraviolet (UV) irradiation induces ROS production, which activates activator protein (AP)-1 and nuclear factor (NF)-κB signaling and downstream molecules, ultimately triggering the generation of matrix metalloproteinases (MMPs) and degradation of collagen. The aim of this study was to investigate the protective effect of methanol extract from Malus baccata (L.) Borkh (Mb-ME) against aging. DPPH and ABTS assays showed that Mb-ME had a significant antioxidant capacity. Flow cytometry results indicated that Mb-ME attenuated UVB and H2O2-stimulated apoptosis and reactive oxygen species (ROS) generation. RT-PCR analysis in HaCaT and HDF cells suggested that Mb-ME treatment blocked the expression of MMPs, COX-2, IL-1ß, IL-6, HYALs, and p53 while promoting the levels of TGM1, FLG, HASs, Sirt1, and Col1A1. Mechanically, Mb-ME inhibited the phosphorylation of MAP kinases and NF-κB signaling. Overall, these results strongly suggest that Mb-ME can be developed as an antiaging therapy.
ABSTRACT
BACKGROUND: Osteoarthritis (OA) is the most common joint complaint resulting in pain, disability, and loss of quality of life. On the other hand, ginsenoside-Rb1 is a plant product derived from ginseng that possesses immune-regulation and anti-inflammatory activities. However, it has been reported that different rout of administration but hydrogel-based Ginsenoside-Rb1 in an OA rabbit model has not been investigated. PURPOSE: The aim of this study was to investigate the potential effects of ginsenoside-Rb1 such as anti-arthritic activity in a rabbit knee OA model via NF- κB, PI3K/Akt, and P38/(MAPK) pathways. STUDY DESIGN: In the current study, rabbit osteoarthritis was induced by hollow trephine on the femur trochlea and the hydrogel-based Ginsenoside-Rb1 sheets were inserted on the rabbit knee to assess the anti-arthritis activity of ginsenoside-Rb1 which is sustained release. METHODS: After the hydrogel-based Rb1 sheet insert on the rabbit knee, macroscopic and micro CT was performed for investigation of chondroprotective effect. Matrix metalloproteinases (MMPs) and apoptotic expression were assessed through Immunohistochemistry and RT-PCR assay. In addition, the flow cytometry technique was used for the investigation of intracellular reactive oxygen species (ROS) production and histological changes were examined by HE, safranin O, and Masson trichrome staining method. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were investigated using Western blot analysis. RESULTS: Macroscopic and micro CT investigation of hydrogel-Rb1 treatment showed a dose-dependent chondroprotective effect. Immunohistochemistry and RT-PCR revealed that expression of matrix metalloproteinases (MMPs) and apoptotic markers TNF-α, caspase-3, and bax are down-regulated in a dose-dependent fashion following implantation of hydrogel-Rb. Higher levels of intracellular reactive oxygen species (ROS) were observed in the OA group. In histopathological investigation of hydrogel-Rb1 exhibited larger amounts of chondro cells, glycosaminoglycan's, and collagen compared to the defect group. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were downregulated by hydrogel-Rb1 while the disease model showed upstream. In the meantime, MMP expression level was considerably down-regulated. CONCLUSIONS: Our results indicate the protective effect of ginsenoside-Rb1 against OA pathogenesis through prevention of apoptosis with suppression of ROS production and activation of NF-κB signaling through downregulation of the MAPK and PI3K/Akt signaling pathways.
Subject(s)
Ginsenosides , Osteoarthritis , Animals , Cartilage , Down-Regulation , Ginsenosides/pharmacology , Ginsenosides/therapeutic use , Hydrogels , NF-kappa B/metabolism , Osteoarthritis/drug therapy , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Quality of Life , Rabbits , Reactive Oxygen Species/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Coronavirus has been spreading rapidly around the world since it broke out in China in 2019. Respiratory diseases caused by coronavirus infection cause various diseases ranging from asymptomatic subclinical infections to severe pneumonia and cardiovascular complications, leading to death. In this regard, natural products are being studied to prevent various diseases caused by COVID-19. In current review, we would like to present mechanisms related to the inhibition of heart disease in ginseng and ginsenoside against SARS-CoV-2. In many previous studies, ginseng and ginsenoside are known to have antioxidant, blood flow improvement, improvement of vascular and heart function, blood pressure control, suppression of myocardial infarction and heart failure, and antiarrhythmia. Therefore, ginseng and ginsenoside have a possibility to suppress cardiovascular complications caused by COVID-19. Many of research provide evidence for ginseng and ginsenoside as treatments for the risk of cardiovascular complications. However, in this review, more specific contents on the proposition of the efficacy of ginseng and ginsenoside for COVID-19 should be presented. Therefore, we hope that researches to reduce cardiovascular complications of ginseng and ginsenoside for COVID-19 should be presented to reduce mortality for COVID-19.
ABSTRACT
Caragana rosea Turcz, which belongs to the Leguminosae family, is a small shrub found in Northern and Eastern China that is known to possess anti-inflammatory properties and is used to treat fever, asthma, and cough. However, the underlying molecular mechanisms of its anti-inflammatory effects are unknown. Therefore, we used lipopolysaccharide (LPS) in RAW264.7 macrophages to investigate the molecular mechanisms that underlie the anti-inflammatory activities of a methanol extract of Caragana rosea (Cr-ME). We showed that Cr-ME reduced the production of nitric oxide (NO) and mRNA levels of iNOS, TNF-α, and IL-6 in a concentration-dependent manner. We also found that Cr-ME blocked MyD88- and TBK1-induced NF-κB and IRF3 promoter activity, suggesting that it affects multiple targets. Moreover, Cr-ME reduced the phosphorylation levels of IκBα, IKKα/ß and IRF3 in a time-dependent manner and regulated the upstream NF-κB proteins Syk and Src, and the IRF3 protein TBK1. Upon overexpression of Src and TBK1, Cr-ME stimulation attenuated the phosphorylation of the NF-κB subunits p50 and p65 and IRF3 signaling. Together, our results suggest that the anti-inflammatory activity of Cr-ME occurs by inhibiting the NF-κB and IRF3 signaling pathways.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Caragana/chemistry , Inflammation/drug therapy , Methanol/chemistry , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cells, Cultured , HEK293 Cells , Humans , Inflammation/chemically induced , Inflammation/metabolism , Interferon Regulatory Factor-3/antagonists & inhibitors , Interferon Regulatory Factor-3/metabolism , Lipopolysaccharides/antagonists & inhibitors , Mice , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Plant Extracts/chemistry , Plant Extracts/isolation & purification , RAW 264.7 Cells , Signal Transduction/drug effects , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/metabolismABSTRACT
An ethanol extract (Pd-EE) of Pinus densiflora Siebold and Zucc was derived from the branches of pine trees. According to the Donguibogam, pine resin has the effects of lowering the fever, reducing pain, and killing worms. The purpose of this study is to investigate whether Pd-EE has anti-inflammatory effects. During in vitro trials, NO production, as well as changes in the mRNA levels of inflammation-related genes and the phosphorylation levels of related proteins, were confirmed in RAW264.7 cells activated with lipopolysaccharide depending on the presence or absence of Pd-EE treatment. The activities of transcription factors were checked in HEK293T cells transfected with adapter molecules in the inflammatory pathway. The anti-inflammatory efficacy of Pd-EE was also estimated in vivo with acute gastritis and acute lung injury models. LC-MS analysis was conducted to identify the components of Pd-EE. This extract reduced the production of NO and the mRNA expression levels of iNOS, COX-2, and IL-6 in RAW264.7 cells. In addition, protein expression levels of p50 and p65 and phosphorylation levels of FRA1 were decreased. In the luciferase assay, the activities of NF-κB and AP-1 were lowered. In acute gastritis and acute lung injury models, Pd-EE suppressed inflammation, resulting in alleviated damage.
Subject(s)
Acute Lung Injury/drug therapy , Gastritis/drug therapy , NF-kappa B/metabolism , Pinus/chemistry , Plant Extracts/pharmacology , Signal Transduction/drug effects , Transcription Factor AP-1/metabolism , Acute Lung Injury/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Cell Line , Cyclooxygenase 2/metabolism , Ethanol/chemistry , Gastritis/metabolism , HEK293 Cells , Humans , Interleukin-6/metabolism , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/metabolism , Plant Extracts/chemistry , RAW 264.7 Cells , RNA, Messenger/metabolismABSTRACT
BACKGROUND: Cocculus hirsutus (L.) W. Thedo., a traditionally well-known plant, has confirmed antitumor properties as well as acute and chronic diuretic effects. However, little is known about its inflammatory activities and the potential effect on inflammatory disease treatment. PURPOSE: Our aim in this study was to explore additional beneficial properties of C. hirsutus ethanol extract (Ch-EE) such as anti-inflammatory activity in vitro and in vivo as well as its underlying mechanisms and to provide a theoretical basis for its role as a candidate natural drug in clinical gastritis and lung disease therapy. STUDY DESIGN: RAW264.7 cells, HEK293T cells, peritoneal macrophages, and mouse models of acute gastritis and acute lung injury were used to assess the anti-inflammatory activity of Ch-EE. METHODS: Decreases in LPS-induced nitric oxide (NO) production and cytokine expression by RAW264.7 cells after Ch-EE treatment were evaluated by Griess assays and PCR, respectively. Transcription factor activity was assessed through luciferase reporter gene assay, and protein expression was determined by Western blotting analysis. Overexpression assays and cellular thermal shift assays were executed in HEK293T cells. Our two in vivo models were an HCl/EtOH-induced gastritis model and an LPS-induced lung injury model. Changes in stomach lesions, lung edema, and lung histology were examined upon treatment with Ch-EE. Components of Ch-EE were determined by liquid chromatography-mass spectrometry. RESULTS: LPS-induced nitric oxide production and Pam3CSK4- and L-NAME-induced NO production were inhibited by Ch-EE treatment of RAW264.7 cells. Furthermore, LPS-induced increases in transcript levels of iNOS, COX2, CCL12, and IL-1ß were reduced by Ch-EE treatment. Ch-EE decreased both MyD88- and TRIF-induced NF-κB promotor activity. Proteins upstream of NF-κB, namely p-p50, p-p65, p-IκBα, p-AKT1, p-Src, and p-Syk, were all downregulated by Ch-EE. Moreover, Src and Syk were targets of Ch-EE. Ch-EE treatment reduced the size of inflammatory stomach lesions induced by HCl/EtOH, lung edema, and accumulation of activated neutrophils caused by LPS. CONCLUSIONS: These results strongly suggest that Cocculus hirsutus can be developed as a promising anti-inflammatory remedy with Src- and Syk-inhibitory functions targeting diseases related to gastritis and lung injury.
Subject(s)
Acute Lung Injury , Cocculus , Acute Lung Injury/drug therapy , Animals , HEK293 Cells , Humans , Lipopolysaccharides , Mice , Mice, Inbred ICR , NF-kappa B , Nitric Oxide , Plant Extracts/pharmacology , RAW 264.7 Cells , Stomach , Syk Kinase , src-Family KinasesABSTRACT
Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.
Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/administration & dosage , Cissus/chemistry , Ethanol/adverse effects , Gastritis/drug therapy , Hydrochloric Acid/adverse effects , Lipopolysaccharides/adverse effects , Macrophages/cytology , Polyphenols/administration & dosage , Acute Lung Injury/chemically induced , Acute Lung Injury/genetics , Administration, Oral , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cytokines/genetics , Disease Models, Animal , Dose-Response Relationship, Drug , Gastritis/chemically induced , Gastritis/genetics , Gene Expression Regulation/drug effects , HEK293 Cells , Humans , MAP Kinase Kinase Kinases/genetics , MAP Kinase Kinase Kinases/metabolism , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Plant Extracts/chemistry , Polyphenols/chemistry , RAW 264.7 Cells , Signal Transduction/drug effects , Treatment Outcome , src-Family Kinases/geneticsABSTRACT
PURPOSE: The pathogenesis of osteoarthritis (OA) is characterized by joint degeneration. The pro-inflammatory cytokine interleukin (IL)-1ß plays a vital role in the pathogenesis of OA by stimulation of specific signaling pathways like NF-κB, PI3K/Akt, and MAPKs pathways. The catabolic role of growth factors in the OA may be inhibited cytokine-activated pathogen. The purpose of this study was to investigate the potential effects of insulin-like growth factor-1 (IGF-1) on IL-1ß-induced apoptosis in rabbit chondrocytes in vitro and in an in vivo rabbit knee OA model. METHODS: In the present study, the OA developed in chondrocyte with the treatment of IL-1ß and articular cartilage ruptures by removal of cartilage from the rabbit knee femoral condyle. After IGF-1 treatment, immunohistochemistry and qRT-PCR were identified OA expression with changes in MMPs (matrix metalloproteinases). The production of ROS (intracellular reactive oxygen species) in the OA was detected by flow cytometry. Further, the disease progression was microscopically investigated and pathophysiological changes were analyzed using histology. The NF-κB, PI3K/Akt and P38 (MAPK) specific pathways that are associated with disease progression were also checked using the Western blot technique. RESULTS: The expression of MMPs and various apoptotic markers are down-regulated following administration of IGF-1 in a dose-dependent fashion while significantly up-regulation of TIMP-1. The results showed that higher levels of ROS were observed upon treatment of chondrocytes and chondral OA with IL-1ß. Collectively, our results indicated that IGF-1 protected NF-κB pathway by suppression of PI3K/Akt and MAPKs specific pathways. Furthermore, the macroscopic and pathological investigation showed that it has a chondroprotective effect by the formation of hyaline cartilage. CONCLUSION: Our results indicate a protective effect of IGF-1 against OA pathogenesis by inhibition of NF-κB signaling via regulation of the MAPK and PI3K/Akt signaling pathways and prevention of apoptosis by suppression of ROS production.
ABSTRACT
Kahweol is a diterpene present in coffee. Until now, several studies have shown that kahweol has anti-inflammatory and anti-angiogenic functions. Due to the limited research available about skin protection, this study aims to discern the potential abilities of kahweol and the possible regulation targets. First, the cytotoxicity of kahweol was checked by 3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay, while 2,20-azino-bis (3ethylbenzothiazoline-6-sulphonic acid) diammonium salt and 1-diphenyl-2-picryl-hydrazyl were used to examine the radical scavenging ability. Polymerase chain reaction analysis was performed to explore the proper time points and doses affecting skin hydration and barrier-related genes. Luciferase assay and Western blotting were used to explore the possible transcription factors. Finally, fludarabine (a STAT1 inhibitor) was chosen to discern the relationship between skin-moisturizing factors and STAT1. We found that HaCaT cells experienced no toxicity from kahweol, and kahweol displayed moderate radical scavenging ability. Moreover, kahweol increased the outcome of HAS1, HAS2, occludin, and TGM-1 from six hours in a dose-dependent manner as well as the activation of STAT1 from six hours. Additionally, kahweol recovered the suppression of HAS2, STAT1-mediated luciferase activity, and HA secretion, which was all downregulated by fludarabine. In this study, we demonstrated that kahweol promotes skin-moisturizing activities by upregulating STAT1.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Diterpenes/pharmacology , Gene Expression Regulation/drug effects , Keratinocytes/physiology , STAT1 Transcription Factor/metabolism , Skin/drug effects , Apoptosis , Cell Proliferation , Cells, Cultured , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , STAT1 Transcription Factor/geneticsABSTRACT
Korean Red Ginseng (KRG) is an herbal oriental medicine known to alleviate cardiovascular dysfunction. To analysis the expression of diabetic cardiac complication-associated genes in db/db mice, we studied the cardiac gene expression following KRG treatment. In result, a total of 585 genes were found to be changed in db/db mice. Among the changed expression, 245 genes were found to 2-fold upregulated, and 340 genes were 2-fold downregulated. In addition, the changed gene expressions were ameliorated by KRG. In conclusion, KRG may be possible to normalize cardiac gene expressions in db/db mice.
ABSTRACT
BACKGROUND: Ginsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis. METHODS: G-Rb1 at a dosage of 3 and 10 µg/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control. RESULTS: The administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1ß, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively. CONCLUSION: Overall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1ß, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.
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Quercetin 3-O-ß-D-glucuronide (Q-3-G), the glucuronide conjugate of quercetin, has been reported as having anti-inflammatory properties in the lipopolysaccharide-stimulated macrophages, as well as anticancer and antioxidant properties. Unlike quercetin, which has been extensively described to possess a wide range of pharmacological activities including skin protective effects, the pharmacological benefits and mechanisms Q-3-G in the skin remained to be elucidated. This study focused on characterizing the skin protective properties, including anti-inflammatory and antioxidant properties, of Q-3-G against UVB-induced or H2O2-induced oxidative stress, the hydration effects, and antimelanogenesis activities using human keratinocytes (HaCaT) and melanoma (B16F10) cells. Q-3-G down-regulated the expression of the pro-inflammatory gene and cytokine such as cyclooxygenase-2 (COX-2) and tumor necrosis factor (TNF)-α in H2O2 or UVB-irradiated HaCaT cells. We also showed that Q-3-G exhibits an antioxidant effect using free radical scavenging assays, flow cytometry, and an increased expression of nuclear factor erythroid 2- related factor 2 (Nrf2). Q-3-G reduced melanin production in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 cells. The hydration effects and mechanisms of Q-3-G were examined by evaluating the moisturizing factor-related genes, such as transglutaminase-1 (TGM-1), filaggrin (FLG), and hyaluronic acid synthase (HAS)-1. In addition, Q-3-G increased the phosphorylation of c-Jun, Jun N-terminal kinase (JNK), Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and TAK1, involved in the MAPKs/AP-1 pathway, and the phosphorylation of IκBα, IκB kinase (IKK)-α, Akt, and Src, involved in the NF-κB pathway. Taken together, we have demonstrated that Q-3-G exerts anti-inflammatory, antioxidant, moisturizing, and antimelanogenesis properties in human keratinocytes and melanoma cells through NF-κB and AP-1 pathways.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Keratinocytes/pathology , Melanins/metabolism , Melanoma, Experimental/pathology , NF-kappa B/metabolism , Quercetin/analogs & derivatives , Transcription Factor AP-1/metabolism , HEK293 Cells , HaCaT Cells , Humans , Hydrogen Peroxide/toxicity , Keratinocytes/drug effects , Keratinocytes/radiation effects , Models, Biological , Quercetin/chemistry , Quercetin/pharmacology , Signal Transduction/drug effects , Signal Transduction/radiation effects , Transcriptional Activation/drug effects , Transcriptional Activation/genetics , Transcriptional Activation/radiation effects , Ultraviolet RaysABSTRACT
Olea europaea is a beneficial edible plant with a number of biological activities like anti-inflammatory, anti-oxidant, antithrombic, antihyperglycemic, and anti-ischemic activities. The mechanisms behind the antiphotoaging and anti-inflammatory effects of Olea europaea are not fully understood. To investigate how an ethanol extract of Olea europaea (Oe-EE) exerts these effects, we explored its activities in human keratinocytes and dermal fibroblasts. We assessed the anti-oxidant effects of Oe-EE via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2[Formula: see text]-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays and measured the expression levels of matrix metalloproteinases (MMPs), cyclooxygenase-2, interleukin (IL)-6, tumor necrosis factor (TNF)-[Formula: see text], and moisturizing factors. Antiphotoaging and anti-inflammatory mechanisms of Oe-EE were explored by assessing signaling molecule activation via immunoblotting. Oe-EE treatment decreased the mRNA expression level of MMPs, cyclooxygenase-2, IL-6, and TNF-[Formula: see text] and restored type I collagen, filaggrin, and sirtuin 1 expression in UVB-irradiated cells. Furthermore, Oe-EE inhibited the activities of several activator protein 1 regulatory enzymes, including extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), and inhibited nuclear factor (NF)-[Formula: see text]B pathway signaling proteins. Therefore, our results indicate that Oe-EE has photoaging-protective and anti-inflammatory effects.
Subject(s)
Anti-Inflammatory Agents , NF-kappa B/metabolism , Olea/chemistry , Plant Extracts/pharmacology , Radiation-Protective Agents , Signal Transduction/drug effects , Signal Transduction/genetics , Transcription Factor AP-1/metabolism , Antioxidants , Dermis/cytology , Fibroblasts/metabolism , Filaggrin Proteins , HaCaT Cells , Humans , Keratinocytes/metabolism , Plant Extracts/isolation & purification , Ultraviolet Rays/adverse effectsABSTRACT
BACKGROUND: Korean Red Ginseng (KRG) has been known to possess many ginsenosides. These ginsenosides are used for curing cardiovascular problems. The present study show the protective potential of KRG against doxorubicin (DOX)-induced myocardial dysfunction, by assessing electrocardiographic, hemodynamic, and biochemical parameters and histopathological findings. METHODS: Animals were fed a standard chow and adjusted to their environment for 3 days before the experiments. Next, the rats were equally divided into five groups (n = 9, each group). The animals were administered with KRG (250 and 500 mg/kg) for 10 days and injected with DOX (20 mg/kg, subcutaneously, twice at a 24-h interval) on the 8th and 9th day. Electrocardiography and echocardiography were performed to study hemodynamics. Plasma levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were measured. In addition, the dose of troponin I and activity of myeloperoxidase in serum and cardiac tissue were analyzed, and the histopathological findings were evaluated using light microscopy. RESULTS: Administration of KRG at a dose of 250 and 500 mg/kg recovered electrocardiographic changes, ejection fraction, fractional shortening, left ventricular systolic pressure, the maximal rate of change in left ventricle contraction (+dP/dtmax), and left ventricle relaxation (-dP/dtmax). In addition, KRG treatment significantly normalized the oxidative stress markers in plasma, dose dependently. In addition, the values of troponin I and myeloperoxidase were ameliorated by KRG treatment, dose dependently. And, KRG treatment showed better histopathological findings when compared with the DOX control group. CONCLUSION: These mean that KRG mitigates myocardial damage by modulating the hemodynamics, histopathological abnormality, and oxidative stress related to DOX-induced cardiomyopathy in rats. The results of the present study show protective effects of KRG on cardiac toxicity.
ABSTRACT
Despite previous reports of anti-aging effects of Korean red ginseng (KRG), the underlying mechanisms remain poorly understood. Therefore, this study investigated possible mechanisms of KRG-mediated anti-aging effects in aged mice. KRG significantly inhibited thymic involution in old mice. Interestingly, KRG only increased protein expression, but not mRNA expression, of aging-related genes Lin28a, GDF-11, Sirt1, IL-2, and IL-17 in the thymocytes of old mice. KRG also modulated the population of some types of immune cells in old mice. KRG increased the population of regulatory T cells and interferon-gamma (IFN-γ)-expressing natural killer (NK) cells in the spleen of old mice, but serum levels of regulatory T cell-specific cytokines IL-10 and TGF-ß were unaffected. Finally, KRG recovered mRNA expression of Lin28a, GDF-11, and Sirt1 artificially decreased by concanavalin A (Con A) in both thymocytes and splenocytes of old mice without cytotoxicity. These results suggest that KRG exerts anti-aging effects by preventing thymic involution, as well as modulating the expression of aging-related genes and immune cell subsets.
Subject(s)
Aging/genetics , Aging/immunology , Gene Expression Regulation , Leukocytes/immunology , Panax/chemistry , Animals , Concanavalin A/pharmacology , Cytokines/metabolism , Gene Expression Regulation/drug effects , Leukocytes/drug effects , Mice, Inbred C57BL , Plant Extracts/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Spleen/drug effects , Spleen/immunology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , Thymus Gland/growth & developmentABSTRACT
Extracts of ginseng species show antihyperglycemic activity. We evaluated the inhibitory effects of diabetic complications for Korean Red Ginseng (KRG), which is enriched in ginsenosides using Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The animals were divided into one of four groups (n = 6â¼9): Long-Evans-Tokushima-Otsuka rats (control rats), OLETF rats, rats given 200 mg/kg KRG, and rats given 400 mg/kg KRG. We examined the protective potential of KRG against type 2 diabetic illnesses. The results exhibited that KRG showed significant antihyperglycemic and antioxidative effects in KRG-treated OLETF rats. And, our results proposed the amelioration of cardiac function through normalized ejection fraction, fractional shortening, and vascular reactivity. Furthermore, histopathological abnormalities in the OLETF rats were prevented by KRG treatment.